Cardiac Glycosides from Erysimum Cheiranthoides

Phytochemistry. Nov, 1998  |  Pubmed ID: 11711105

Two new cardiac glycosides were isolated from the seeds of Erysimum cheiranthoides. Their structures were characterized as strophanthidin glycosides of 3-O-alpha-L-rhamnopyranosyl-(1-->4)-3-O-acetyl-beta-D-digitoxopyranosyl and 3-O-beta-D-glucpyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->4)-3-O-acetyl-beta-D-digitoxopyranosyl.

Molecular and Cellular Phenotypic Profiles of Gastric Noninvasive Neoplasia

Laboratory Investigation; a Journal of Technical Methods and Pathology. Dec, 2002  |  Pubmed ID: 12480914

According to the Padova international classification, 52 gastric noninvasive neoplasias (NIN) were classified as follows: 20 low-grade NIN (L-NIN); 9 high-grade NIN including suspicion for carcinoma without invasion (H-NIN); and 23 high-grade NIN including carcinoma without invasion (Ca-NIN). The molecular and cellular phenotypic profiles were investigated and compared. The APC gene was mutated in seven (35%) L-NIN, two (22%) H-NIN, and two (9%) Ca-NIN tumors; APC mutations were significantly more frequent in L-NIN compared with Ca-NIN tumors (p < 0.05). Mutations of the p53 gene were found in five (22%) Ca-NIN tumors but were not observed in L-NIN or H-NIN tumors (p < 0.05). Loss of heterozygosity involving at least one chromosomal locus was detected in 14 (61%) Ca-NIN tumors but was not detected in L-NIN or H-NIN tumors. High-frequency microsatellite instability (MSI-H) was detected in one (5%) L-NIN tumor and in six (26%) Ca-NIN tumors. The frequencies of loss of heterozygosity and MSI-H were significantly higher in Ca-NIN than in L-NIN or H-NIN tumors (p < 0.05). Nuclear accumulation of p53 protein was detected in no L-NIN tumors, 1 (11%) H-NIN tumor, and 10 (44%) Ca-NIN tumors (p < 0.01). All tumors with loss of hMLH1 expression exhibited MSI-H (p < 0.01). Cellular phenotypic analysis revealed that seven (35%) L-NIN tumors and one (4%) Ca-NIN tumor had complete-type intestinal metaplastic phenotype and that one (5%) L-NIN tumor and one (4%) Ca-NIN tumor had a gastric foveolar epithelial phenotype, whereas the remaining tumors exhibited an ordinary phenotype. Thus, the complete-type intestinal metaplastic phenotype was more characteristic of L-NIN tumors than of H-NIN or Ca-NIN tumors (p < 0.01). In summary, the Padova international classification correlated with both the molecular and cellular phenotypic profiles. In practice, p53 and hMLH1 immunohistochemistry discriminated Ca-NIN from L-NIN and H-NIN tumors.

Hypermethylation of the TSLC1 Gene Promoter in Primary Gastric Cancers and Gastric Cancer Cell Lines

Japanese Journal of Cancer Research : Gann. Aug, 2002  |  Pubmed ID: 12716461

The TSLC1 (tumor suppressor in lung cancer-1) gene is a novel tumor suppressor gene on chromosomal region 11q23.2, and is frequently inactivated by concordant promoter hypermethylation and loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). Because LOH on 11q has also been observed frequently in other human neoplasms including gastric cancer, we investigated the promoter methylation status of TSLC1 in 10 gastric cancer cell lines and 97 primary gastric cancers, as well as the corresponding non-cancerous gastric tissues, by bisulfite-SSCP analysis followed by direct sequencing. Allelic status of the TSLC1 gene was also investigated in these cell lines and primary gastric cancers. The TSLC1 promoter was methylated in two gastric cancer cell lines, KATO-III and ECC10, and in 15 out of 97 (16%) primary gastric cancers. It was not methylated in non-cancerous gastric tissues, suggesting that this hypermethylation is a cancer-specific alteration. KATO-III and ECC10 cells retained two alleles of TSLC1, both of which showed hypermethylation, associated with complete loss of gene expression. Most of the primary gastric cancers with promoter methylation also retained heterozygosity at the TSLC1 locus on 11q23.2. These data indicate that bi-allelic hypermethylation of the TSLC1 promoter and resulting gene silencing occur in a subset of primary gastric cancers.

Effects of 10-T Static Magnetic Field on Human Peripheral Blood Immune Cells

Radiation Research. Jun, 2003  |  Pubmed ID: 12751960

The exposure of peripheral blood mononuclear cells (PBMCs) was performed in a 10-T static magnetic field. Without lymphocyte stimulation, there were no significant differences in the viability of the exposed and unexposed CD4(+) T cells, CD8(+) T cells, B cells, and natural killer (NK) cells. The expression of Th1 type chemokine receptor, CXCR3, and Th2 type receptor, CCR3, was unaltered after magnetic-field exposure. No differences were observed in the naive T cells and memory T-cell subclasses in either CD4(+) or CD8(+) T cells. In contrast to the unstimulated condition, the magnetic-field exposure reduced the viability of phytohemagglutinin (PHA)-activated T cells in both the CD4(+) and CD8(+) subclasses. In particular, the number of PHA-treated naive CD8(+) T cells (CD45RA(+)CD4(-)CD8(+)) was markedly decreased after the magnetic-field exposure, while PHA-treated memory CD8(+) cells (CD45RA(-)CD4(-)CD8(+)) were resistant to the exposure. The number of PHA-treated naive CD4(+) T cells (CD45RA(+)CD4(+)CD8(-)) and memory cells (CD45RA(-)CD4(+)CD8(-)) was markedly decreased to a similar degree. Thus the susceptibility of lymphocytes to the magnetic-field exposure differed among activated T-cell subtypes. The magnetic-field exposure significantly increased the death of PHA-stimulated lymphocytes by apoptosis. These results suggest that a strong static magnetic field has acute effects on immune cells during cell division, while the field exposure has a minimal effect on immune cells in a nondividing phase.

Carcinosarcomas (malignant Mullerian Mixed Tumors) of the Uterus and Ovary: a Genetic Study with Special Reference to Histogenesis

International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. Oct, 2003  |  Pubmed ID: 14501818

The histogenesis of carcinosarcomas (malignant mullerian mixed tumors) of the female genital tract is still not completely understood. In the present study, several different molecular pathologic techniques were applied to determine the histogenesis of 15 uterine and ovarian carcinosarcomas. The patterns of X-chromosome inactivation and the presence of p53 and K-ras mutations were analyzed in the carcinomatous and sarcomatous components. Microsatellite analysis was also performed. Ten tumors were monoclonal, one was biclonal (collision tumor), and another was probably biclonal; the other three were of indeterminate histogenesis. These data indicate that most uterine and ovarian carcinosarcomas are monoclonal.

Molecular Cloning and Characterization of a Novel Human Putative Transmembrane Protein Homologous to Mouse Sideroflexin Associated with Sideroblastic Anemia

DNA Sequence : the Journal of DNA Sequencing and Mapping. Oct, 2003  |  Pubmed ID: 14756423

Sideroflexin1 (Sfxn1), the prototype of a novel family of evolutionarily conserved proteins present in eukaryotes, has been found mutated in mice with siderocytic anemia. It is speculated that this protein facilitates the transport of a component required for iron utilization into mitochondrial. During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA encoding a novel sideroflexin protein (SFXN4), which showed 59% identity and 71% similarity to mouse sideroflexin4. According to the search of the human genome database, SFXN4 gene is mapped to chromosome 10q25-26 and spans more than 24.7kb of the genomic DNA. It is 1428 base pair in length and the putative protein contains 305 amino acids with a conserved predicted five-transmembrane-domains structure. RT-PCR result shows that the SFXN4 gene is expressed in many tissues.

Irx4-mediated Regulation of Slit1 Expression Contributes to the Definition of Early Axonal Paths Inside the Retina

Development (Cambridge, England). Mar, 2003  |  Pubmed ID: 12571096

Although multiple axon guidance cues have been discovered in recent years, little is known about the mechanism by which the spatiotemporal expression patterns of the axon guidance cues are regulated in vertebrates. We report that a homeobox gene Irx4 is expressed in a pattern similar to that of Slit1 in the chicken retina. Overexpression of Irx4 led to specific downregulation of Slit1 expression, whereas inhibition of Irx4 activity by a dominant negative mutant led to induction of Slit1 expression, indicating that Irx4 is a crucial regulator of Slit1 expression in the retina. In addition, by examining axonal behavior in the retinas with overexpression of Irx4 and using several in vivo assays to test the effect of Slit1, we found that Slit1 acts positively to guide the retinal axons inside the optic fiber layer (OFL). We further show that the regulation of Slit1 expression by Irx4 is important for providing intermediate targets for retinal axons during their growth within the retina.

Experimental Protection of Mice Against Lethal Staphylococcus Aureus Infection by Novel Bacteriophage Phi MR11

The Journal of Infectious Diseases. Feb, 2003  |  Pubmed ID: 12599078

The protective effects of bacteriophages were assessed against experimental Staphylococcus aureus infection in mice. Of the S. aureus phages isolated in the study, phi MR11 was representatively used for all testing, because its host range was the most broad and it carries no genes for known toxins or antibiotic resistance. Intraperitoneal injections (8 x 10(8) cells) of S. aureus, including methicillin-resistant bacteria, caused bacteremia and eventual death in mice. In contrast, subsequent intraperitoneal administration of purified phi MR11 (MOI > or = 0.1) suppressed S. aureus-induced lethality. This lifesaving effect coincided with the rapid appearance of phi MR11 in the circulation, which remained at substantial levels until the bacteria were eradicated. Inoculation with high-dose phi MR11 alone produced no adverse effects attributable to the phage. These results uphold the efficacy of phage therapy against pernicious S. aureus infections in humans and suggest that phi MR11 may be a potential prototype for gene-modified, advanced therapeutic S. aureus phages.

Microsatellite Instability in Esophageal Squamous Cell Carcinoma is Not Associated with HMLH1 Promoter Hypermethylation

Pathology International. May, 2003  |  Pubmed ID: 12713560

To test whether a subset of esophageal squamous cell carcinomas (SCC) develop through a deficiency in DNA mismatch repair, we examined microsatellite instability (MSI) using 11 microsatellite markers including BAT-26, hMLH1 protein expression by immunohistochemistry, and methylation status of the hMLH1 promoter by methylation-specific polymerase chain reaction (MSP). p53 mutations were also investigated. Microsatellite instability at one or more loci was observed in 40% (12/30) of esophageal SCC tumor samples, although only one of these tumors was categorized as high-frequency MSI (MSI-H) and none showed BAT-26 instability. While immunohistochemistry revealed decreased hMLH1 protein expression in 27% (8/30) of the tumors, hMLH1 promoter hypermethylation was not observed. Absence of hMLH1 protein expression was relatively common in well-differentiated (keratinizing-type) esophageal SCC, but was not associated with hMLH1 promoter hypermethylation. p53 mutation was detected in 37% (11/30) and loss of heterozygosity (LOH) in 90% (27/30) of esophageal SCC samples. Our results suggested that most esophageal SCC develop through defects in tumor suppressor genes (i.e. the suppressor pathway), and that MSI in esophageal SCC probably represent random replication errors rather than being associated with DNA mismatch repair deficiency.

[Studies on the Mechanism of Thermostability and Thermophilicity Change of Thermostable Alkaline Phosphatase and Its Mutants]

Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology. Jul, 2003  |  Pubmed ID: 15969072

The relationship among the substituted amino acids, the 3D structure simulated on PC through CPHmodels Server ( http://www.cbs.dtu. dk/services/CPHmodels/) and the thermostable performance of 4 thermostable alkaline phosphatase(TAP) mutants selected from a clone bank of more than 200 mutants were analyzed to explore the mechanism of thermostability change. These mutants are TAP(A410T) (A410-->T), TAP(P396S) (P396-->S), TAP2(N100S T320-->I) and TAP4(N100-->S P396-->S A410 -->V P490-->S). TAP and the mutants' thermostable performance was evaluated by measuring the highest tolerable temperature (T1/2) and the optimal reaction temperature (Topt). The 3D structure neighboring the substituted amino acids was simulated by Swiss-PDBViewer to observe the relationship between the structure change and the thermostable performance of TAP and its mutants. The results displayed that all these amino acid substitutions except the T320-->I mutant brought about only a little local change on TAP's 3D structure and very little effect on their optimal reaction temperature, but a significant decrease (nearly 10 degrees C) on their highest tolerable temperature. However, the T320-->I mutation due to close to TAP's active sites did bring about a significant descendents of the mutant in both the highest tolerable temperature and the optimal reaction temperature. Thus, it seems to be able to conclude that most of the amino acid substitutions, no matter where they locate and what structure change they may make, can cause TAP's highest tolerable temperature reduced significantly. What's more, if the mutation occurring near or in the active sites, it can also cause TAP's optimal reaction temperature reduced significantly at the same time.

Disruption of Gradient Expression of Zic3 Resulted in Abnormal Intra-retinal Axon Projection

Development (Cambridge, England). Apr, 2004  |  Pubmed ID: 14985256

The targeting of retinal ganglion axons toward the optic disc is the first step in axon pathfinding in the visual system. The molecular mechanisms involved in guiding the retinal axons to project towards the optic disc are not well understood. We report that a gene encoding a zinc-finger transcription factor, Zic3, is expressed in a periphery-high and center-low gradient in the retina at the stages of active axon extension inside the retina. The gradient expression of Zic3 recedes towards the periphery over the course of development, correlating with the progression of retinal cell differentiation and axonogenesis. Disruption of gradient expression of Zic3 by retroviral overexpression resulted in mis-targeting of retinal axons and some axons misrouted to the sub-retinal space at the photoreceptor side of the retina. Misexpression of Zic3 did not affect neurogenesis or differentiation inside the retina, or grossly alter retinal lamination. By stripe assay, we show that misexpression of Zic3 may induce the expression of an inhibitory factor to the retinal axons. Zic3 appears to play a role in intra-retinal axon targeting, possibly through regulation of the expression of specific downstream genes involved in axon guidance.

Role of Alpha4 Integrin and Its Ligand VCAM-1 in the Specific Extravasation of a Tumor-specific TH2 Clone into Tumor Tissue That Initiates Its Rejection

International Journal of Cancer. Journal International Du Cancer. Sep, 2004  |  Pubmed ID: 15239134

The effectiveness of anticancer immunotherapeutic strategies involving the transfer of tumor-specific T cells depends on appropriate lymphocyte-endothelial cell interactions that facilitate the migration of lymphocytes into tumor. Here, we investigated the molecular mechanisms underlying the migration of the antigen-specific Th2 CD4(+) T-cell clone YS1093 into S1509a tumor tissue. YS1093 is specific for the S1509a tumor but does not recognize the S713a tumor. Transfer of YS1093 cells into mice bearing both S1509a and S713a tumors caused only the S1509a tumor to regress. This regression was markedly inhibited by pretreating YS1093 cells with an anti-alpha4 integrin MAb and administering an anti-VCAM-1 MAb at T-cell transfer. Since vascular endothelial cells in S1509a tumor tissues express VCAM-1 and the MHC class II (I-E(k)) molecule restricting YS1093 activity, labeled YS1093 cells migrated specifically into the S1509a tumor, and this migration was also blocked by the anti-TCRbeta F(ab')(2) and anti-I-E(k) MAbs. Furthermore, in vitro assays revealed that anti-CD3 MAb-mediated TCR cross-linkage initiated the binding of alpha4 integrin on YS1093 cells to VCAM-1. This adhesive activity was completely blocked by the anti-alpha4 integrin MAb. These results strongly suggest that i.v.-transferred YS1093 cells act in tumor regression by specifically recognizing their tumor antigen peptide in the context of I-E(k) on vascular endothelial cells in the S1509a tumor, which activates the binding of alpha4 integrin to VCAM-1 on the endothelial cells, facilitating YS1093 extravasation into the tumor. It is likely that this initial migration of specific CD4(+) T cells into tumor tissues promotes the subsequent infiltration into the tumor of other immunocytes that effect tumor destruction.

Overexpression of 5-lipoxygenase in Rat and Human Esophageal Adenocarcinoma and Inhibitory Effects of Zileuton and Celecoxib on Carcinogenesis

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Oct, 2004  |  Pubmed ID: 15475461

Aberrant arachidonic acid (AA) metabolism, especially through the cyclooxygenase (Cox) and 5-lipoxygenase (5-Lox) pathways, has been suggested to play an important role in the development of esophageal adenocarcinoma (EAC). The purpose of this study was to investigate the expression of 5-Lox in EAC of a rat model and in human samples as well as the chemopreventive effects of zileuton (a specific 5-Lox inhibitor) and celecoxib (a specific Cox2 inhibitor) in the rat EAC model.

Promoter Hypermethylation and Inactivation of O(6)-methylguanine-DNA Methyltransferase in Esophageal Squamous Cell Carcinomas and Its Reactivation in Cell Lines

International Journal of Oncology. Mar, 2005  |  Pubmed ID: 15703815

The purpose of this study was to characterize the role of DNA hypermethylation in the loss of expression of O(6)-methylguanine-DNA methyltransferase (MGMT) during the development of esophageal squamous cell carcinoma (ESCC) and to investigate its reactivation in cell lines. Samples were collected from Linzhou City of the Henan province in northern China, a high-risk area of this disease. The hypermethylation of promoter CpG islands of the MGMT gene was examined by methylation-specific PCR in ESCC and neighboring non-tumorous tissues, as well as in laser capture microdissected samples with normal epithelium, basal cell hyperplasia (BCH), and dysplasia (DYS). The MGMT mRNA and protein expression were determined with RT-PCR and immunohistochemistry, respectively. Five of 17 (29%) normal, 10 of 20 (50%) BCH, 8 of 12 (67%) DYS, and 13 of 18 (72%) ESCC samples had DNA hypermethylation in the MGMT promoter region, showing a gradual increase with the progression of carcinogenesis. The frequency of the loss of MGMT mRNA and protein expression progressively decreased from normal to BCH, DYS, and ESCC, and it was highly correlated with MGMT promoter hypermethylation according to Fisher's exact tests. When each individual sample was considered, good concordance between DNA hypermethylation and the loss of expression of MGMT was also observed. In samples from the same patient, if hypermethylation was detected in earlier lesions, it was usually observed in more severe lesions. In the ESCC cell line KYSE 510, treatment with a DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine partially reversed the CpG hypermethylation status and restored mRNA expression of the MGMT gene. Similar reactivation of MGMT gene by dietary polyphenols, (-)-epigallocatechin-3-gallate and genistein, has also been observed. The results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing in the development of ESCC, and this epigenetic event may be prevented or reversed by these polyphenols for the prevention of carcinogenesis.

Hypermethylation of Chfr and HMLH1 in Gastric Noninvasive and Early Invasive Neoplasias

Virchows Archiv : an International Journal of Pathology. Feb, 2005  |  Pubmed ID: 15735977

Human tumors are genetically unstable, and the instability exists at two distinct levels-the chromosomal level and the nucleotide level. Chfr and hMLH1 hypermethylation, which may lead to chromosomal instability (CIN) and microsatellite instability (MSI), respectively, was analyzed in gastric noninvasive neoplasias (NIN, Padova international classification) and submucosal invasive adenocarcinomas and in their corresponding non-neoplastic gastric epithelia. Results were compared with microsatellite status, p53 immunoreactivity, and cellular phenotype. Hypermethylation of Chfr and hMLH1 was observed in: 10% (1/10) and 0% (0/10) of low-grade NIN (L-NIN); 63% (5/8) and 63% (5/8) of high-grade NIN, including suspicion for carcinoma without invasion (H-NIN); 36% (5/14) and 57% (8/14) of high-grade NIN, including carcinoma without invasion; and 35% (7/20) and 25% (5/20) of submucosal invasive adenocarcinomas, respectively. Hypermethylation was less frequent in L-NIN than H-NIN (P<0.05) for Chfr and was also less frequent in L-NIN than the others (P<0.05) for hMLH1. We failed to find a significant correlation between Chfr hypermethylation and chromosomal loss of heterozygosity, although hypermethylation of hMLH1 was significantly associated with high-frequency MSI (P<0.01). Expression of p53 was not associated with Chfr or hMLH1 methylation. As for cellular phenotype, hypermethylation of Chfr and hMLH1 was frequent in tumors exhibiting the foveolar epithelial phenotype (50%, 2/4 and 75%, 3/4, respectively) and the ordinary phenotype (40%, 16/40 and 38%, 15/40, respectively), but never in those with the complete-type intestinal metaplastic phenotype (0%, 0/8 for both). In addition, hypermethylation of Chfr and hMLH1 occurred concurrently (P<0.01); methylation was more frequent in patients over 70 years of age (P<0.01), and it was also present in some samples of non-neoplastic gastric epithelia from elderly patients. Thus, some gastric tumors with the foveolar or ordinary phenotype may develop as a result of age-related methylation of Chfr and hMLH1, although Chfr methylation was not associated with CIN.

Analysis of the DNA Substrate Specificity of the Human BACH1 Helicase Associated with Breast Cancer

The Journal of Biological Chemistry. Jul, 2005  |  Pubmed ID: 15878853

We have investigated the DNA substrate specificity of BACH1 (BRCA1-associated C-terminal helicase). The importance of various DNA structural elements for efficient unwinding by purified recombinant BACH1 helicase was examined. The results indicated that BACH1 preferentially binds and unwinds a forked duplex substrate compared with a duplex flanked by only one single-stranded DNA (ssDNA) tail. In support of its DNA substrate preference, helicase sequestration studies revealed that BACH1 can be preferentially trapped by forked duplex molecules. BACH1 helicase requires a minimal 5 ' ssDNA tail of 15 nucleotides for unwinding of conventional duplex DNA substrates; however, the enzyme is able to catalytically release the third strand of the homologous recombination intermediate D-loop structure irrespective of DNA tail status. In contrast, BACH1 completely fails to unwind a synthetic Holliday junction structure. Moreover, BACH1 requires nucleic acid continuity in the 5 ' ssDNA tail of the forked duplex substrate within six nucleotides of the ssDNA-dsDNA junction to initiate efficiently DNA unwinding. These studies provide the first detailed information on the DNA substrate specificity of BACH1 helicase and provide insight to the types of DNA structures the enzyme is likely to act upon to perform its functions in DNA repair or recombination.

[Intravascular Ultrasound Study of Coronary Remodeling and Determination of Matrix Metalloproteinase and Hypersensitive C-reactive Protein]

Zhonghua Xin Xue Guan Bing Za Zhi. May, 2005  |  Pubmed ID: 15932701

To investigate remodeling characteristics of coronary lesions in patients with acute coronary syndromes (ACS) versus stable angina pectoris (SA) using intravascular ultrasound (IVUS), and to explore the relationship between arterial remodeling and clinical presentation or matrix metalloproteinase (MMPs) or hyper-sensitive C-reactive protein (hs-CRP).

Human Papillomavirus Genotyping by Oligonucleotide Microarray and P16 Expression in Uterine Cervical Intraepithelial Neoplasm and in Invasive Carcinoma in Korean Women

Pathology International. Aug, 2005  |  Pubmed ID: 15998377

For evaluating the diagnostic significance of p16(INK4A) over-expression in the uterine cervical intraepithelial neoplasm and in invasive carcinoma, human papillomavirus (HPV) was detected and genotyped by oligonucleotide microarray in archival tissues of 117 cervical specimens, including 47 invasive squamous cell carcinomas (SCC), 30 cases of cervical intraepithelial neoplasia (CIN), 20 adenocarcinomas, and 20 cases of non-neoplastic cervix. The expression of p16(INK4A) protein was immunohistochemically studied in these cases and in five HPV-positive and one HPV-negative cervical cancer cell lines. HPV was detected in 50% of CIN, 61.7% of SCC, and 45.5% of adenocarcinomas. p16(INK4A) expression was seen in all 20 cases of adenocarcinoma, 78.7% (37/47) of SCC, and 96.7% (29/30) of CIN, but not in any cases of the non-neoplastic cervix. There was no difference in p16(INK4A) expression between the HPV-positive and HPV-negative cervical lesions. All HPV-positive and -negative cervical cancer cell lines expressed p16(INK4A) protein. In conclusion, the presence of p16(INK4A) expression in cervical squamous and glandular epithelium indicates the existence of dysplasia or malignancy in the uterine cervix, regardless of HPV infection.

Molecular Cloning and Characterization of AAAS-V2, a Novel Splice Variant of Human AAAS

Molecular Biology Reports. Jun, 2005  |  Pubmed ID: 16022285

Triple-A syndrome (MIM 231550; also known as Allgrove syndrome) is an autosomal recessive disorder characterized by adrenocorticotropin hormone (ACTH)-resistant adrenal insufficiency, achalasia of the oesophageal cardia and alacrima. Much initial molecular analysis supported that Triple-A syndrome was caused by mutations in AAAS, a WD-repeat protein gene. Here we report cloning and characterization of a novel splice variant of human AAAS, which we named AAAS-v2, which is located on the human chromosome 12p13. The cDNA is 1703 bp, encoding a 513-amino acid polypeptide, which contains three WD40 domains, one less than the original which we called AAAS-v1 (Gen Bank: NM_015665.3). RT-PCR analysis in our work revealed that AAAS-v2 and AAAS-v1 were ubiquitously detected in human multiple tissue cDNA (MTC) panels (CLONTECH).

A Novel Splice Variant of Human Gene NPL, Mainly Expressed in Human Liver, Kidney and Peripheral Blood Leukocyte

DNA Sequence : the Journal of DNA Sequencing and Mapping. Apr, 2005  |  Pubmed ID: 16147865

From the human fetal brain cDNA library constructed by our lab, a novel variant cDNA of a human gene was successfully cloned and identified. Because the gene has been named N-acetylneuraminate pyruvate lyase (NPL), accordingly we term our splice variant NPL_v2. The cDNA of NPL_v2 has a full-length open reading frame (ORF) from the nucleotide position 320 to 1225 that encodes a protein comprising 301 amino acids. SMART analysis showed that our hypothetical protein has one dihydrodipicolinate synthase (DHDPS) domain. Phosphorylation analysis of the deduced protein show that there are five phosphorylation sites including three "serine" and two "threonine" at the region that are not found in other splice variant. RT-PCR experiment revealed that our splice variant of the gene is mainly expressed in human placenta, liver, kidney, pancreas, spleen, thymus, ovary, small intestine and peripheral blood leukocyte.

BACH1 is Critical for Homologous Recombination and Appears to Be the Fanconi Anemia Gene Product FANCJ

Cancer Cell. Sep, 2005  |  Pubmed ID: 16153896

We showed in this study that cells deficient of the BRCA1-associated BACH1 helicase, also known as BRIP1, failed to elicit homologous recombination (HR) after DNA double-stranded breaks (DSBs). BACH1-deficient cells were also sensitive to mitomycin C (MMC) and underwent MMC-induced chromosome instability. Moreover, we identified a homozygous nonsense mutation in BACH1 in a FA-J patient-derived cell line and could not detect BACH1 protein in this cell line. Expression of wild-type BACH1 in this cell line reduced the accumulation of cells at G2/M phases following exposure to DNA crosslinkers, a characteristic of Fanconi anemia (FA) cells. These results support the conclusion that BACH1 is FANCJ.

Reversal of Hypermethylation and Reactivation of P16INK4a, RARbeta, and MGMT Genes by Genistein and Other Isoflavones from Soy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Oct, 2005  |  Pubmed ID: 16203797

We have previously shown the reactivation of some methylation-silenced genes in cancer cells by (-)-epigallocatechin-3-gallate, the major polyphenol from green tea. To determine whether other polyphenolic compounds have similar activities, we studied the effects of soy isoflavones on DNA methylation.

Sema3D, Sema3F, and Sema5A Are Expressed in Overlapping and Distinct Patterns in Chick Embryonic Heart

Developmental Dynamics : an Official Publication of the American Association of Anatomists. Jan, 2006  |  Pubmed ID: 16261621

An increasing number of axon guidance cues have been shown recently to play important roles in the development of non-neural tissues. Semaphorins comprise one of the largest conserved families of axon guidance factors. We analyzed the expression patterns of Sema3D, Sema3F, and Sema5A genes in the chick embryonic heart by in situ hybridization. All three genes are expressed in the cardiac cushion regions, both in the mesenchymal cells, and epithelial cells in the endocardial layer, during the period of cardiac remodeling. In addition to the overlapping expression patterns in the cardiac cushion regions, these genes also exhibit distinct expression patterns in the developing heart: Sema3D is additionally expressed in the tips of the ventricular trabeculae; Sema3F is expressed in a subset of cells scattered throughout the ventricles; and Sema5A is expressed in the newly formed atrioventricular valves. The overlapping and distinct expression patterns of these genes suggest that they may play important roles in heart development.

Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells Via Dopamine Receptor D3

Journal of Immunology (Baltimore, Md. : 1950). Jan, 2006  |  Pubmed ID: 16393968

The nervous systems affect immune functions by releasing neurohormones and neurotransmitters. A neurotransmitter dopamine signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. The secondary lymphoid tissues are highly innervated by sympathetic nerve fibers that store dopamine at high contents. Lymphocytes also produce dopamine. In this study, we examined expression and function of dopamine receptors in lymphocytes. We found that D3 was the predominant subtype of dopamine receptors in the secondary lymphoid tissues and selectively expressed by naive CD8+ T cells of both humans and mice. Dopamine induced calcium flux and chemotaxis in mouse L1.2 cells stably expressing human D3. These responses were almost completely inhibited by pertussis toxin, indicating that D3 was coupled with the Galphai class of G proteins. Consistently, dopamine selectively induced chemotactic responses in naive CD8+ T cells of both humans and mice in a manner sensitive to pertussis toxin and D3 antagonists. Dopamine was highly synergistic with CCL19, CCL21, and CXCL12 in induction of chemotaxis in naive CD8+ T cells. Dopamine selectively induced adhesion of naive CD8+ T cells to fibronectin and ICAM-1 through activation of integrins. Intraperitoneal injection of mice with dopamine selectively attracted naive CD8+ T cells into the peritoneal cavity. Treatment of mice with a D3 antagonist U-99194A selectively reduced homing of naive CD8+ T cells into lymph nodes. Collectively, naive CD8+ T cells selectively express D3 in both humans and mice, and dopamine plays a significant role in migration and homing of naive CD8+ T cells via D3.

Polo-like Kinase and Survivin Are Esophageal Tumor-specific Promoters

Biochemical and Biophysical Research Communications. Apr, 2006  |  Pubmed ID: 16487489

For developing successful cancer gene therapy strategies, tumor-specific gene delivery is essential. In this study, we used esophageal cancer (EC) cells to identify and evaluate esophageal tumor-specific gene promoters. Four genes (polo-like kinase-1/PLK, survivin/BIRC5, karyopherin alpha 2/KPNA2, and pituitary tumor transforming gene protein 1/PTTG1) were identified by a microarray analysis as highly expressed in EC cell lines vs. five normal organ tissues (liver, lung, kidney, brain, and heart). By quantitative RT-PCR, the average mRNA expression levels of these four genes in 20 primary ECs were 2.7-fold (PLK), 6.1-fold (survivin), 2.6-fold (KPNA2), and 2.4-fold (PTTG1) higher than that of each gene in 24 different normal organs. By dual luciferase assay, the promoter activity of PLK and survivin in EC cell lines was 18.9-fold and 28.5-fold higher, respectively, than in normal lung and renal cells. The promoters of PLK and survivin could be useful tools for developing EC-specific gene therapy vectors.

Developmental Expression and Localization of KCNJ10 K+ Channels in the Guinea Pig Inner Ear

Neuroreport. Apr, 2006  |  Pubmed ID: 16543810

The inward rectifier Kir4.1, composed of KCNJ10 K channel subunits, plays an essential role in inner ear K homeostasis. We have investigated the developmental expression and localization of KCNJ10 (Kir4.1) in the guinea pig inner ear using semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Kcnj10 was expressed at low levels from embryonic day 30 (E30), increased from E45, and persisted from E50 to adulthood. KCNJ10 channel protein was detected in spiral ganglion satellite cells of the basal turn at E40, and at E45 its expression proceeded with a base-to-apex gradient along the cochlear spiral. KCNJ10 protein was enriched in the myelin sheath around the cochlear nerve between E40 and E45 and disappeared gradually with age. In the strial intermediate cells, KCNJ10 channel expression was first observed at E50, and lagged behind that of the spiral ganglion. In addition, KCNJ10 channel protein was expressed and localized in vestibular transitional cells. Differential expression of KCNJ10 channel protein suggests roles for KCNJ10 channels in inner ear development and onset of auditory function.

Intrasplenic Electro-transfer of IL-4 Encoding Plasmid DNA Efficiently Inhibits Rat Experimental Allergic Encephalomyelitis

Biochemical and Biophysical Research Communications. May, 2006  |  Pubmed ID: 16564024

Most of the previous studies in which cytokine DNA plasmids were delivered by systemic administration exhibited only marginal therapeutic effects, if any, in the EAE model. One strategy to overcome this limitation would be to determine the optimal delivery route leading to significant beneficial effects both in early (prophylactic) and late (therapeutic) treatments. To address this issue, we directly compared the effects of intrasplenic (i.s.) and intramuscular (i.m.) electro-transfer of interleukin-4 (IL-4) DNA in the rat experimental allergic encephalomyelitis (EAE) model. In the preventive experiment, rats received i.m. (25 or 150 microg) or i.s. (25 microg) administration of IL-4 DNA followed by in vivo electroporation the day before MBP immunization. In the late treatment experiment, rats were treated with i.m. (150 microg) or i.s. (25 microg) administration of IL-4 DNA with electroporation 10 days after MBP immunization. As a control the same amount of vector DNA was used. Macroscopic analysis indicated that the onset of moderate to severe EAE in rats treated with i.s. transfer of 25 microg of IL-4 DNA was prevented on a significant level compared with i.m. 25 microg of the IL-4 DNA transfer group or the control group in the preventive experiments. More importantly, i.s. transfer of 25 microg of IL-4 DNA considerably suppressed the severity of EAE in late treatment experiments while i.m. transfer of 150 microg of IL-4 DNA had little effect. The MBP-specific expression of IFN-gamma from stimulated splenocytes was considerably decreased by the i.s. IL-4 DNA transfer group both in the preventive and therapeutic experiments while i.m. transfer had this effect only in the preventive protocol. Histological analysis showed that spinal cord inflammation was considerably reduced in the i.s. IL-4 DNA transfer group. These data provide the first demonstration that i.s. electro-transfer of IL-4 DNA is more effective both in the prevention and modulation of EAE than i.m. transfer and that i.s. electro-gene transfer may present a new approach to cytokine therapy in autoimmune diseases.

Novel Antiviral Activity of Chemokines

Virology. Jul, 2006  |  Pubmed ID: 16603217

Antimicrobial peptides are a diverse family of small, mostly cationic polypeptides that kill bacteria, fungi and even some enveloped viruses, while chemokines are a group of mostly cationic small proteins that induce directed migration of leukocytes through interactions with a group of seven transmembrane G protein-coupled receptors. Recent studies have shown that antimicrobial peptides and chemokines have substantially overlapping functions. Thus, while some antimicrobial peptides are chemotactic for leukocytes, some chemokines can kill a wide range of bacteria and fungi. Here, we examined a possible direct antiviral activity of chemokines against an enveloped virus HSV-1. Among 22 human chemokines examined, chemokines such as MIP-1 alpha/CCL3, MIP-1 beta/CCL4 and RANTES/CCL5 showed a significant direct antiviral activity against HSV-1. It is intriguing that these chemokines are mostly known to be highly expressed by effector CD8+ T cells. The chemokines with a significant anti-HSV-1 activity commonly bound to HSV-1 virions via envelope glycoprotein gB. Electron microscopy revealed that the chemokines with a significant anti-HSV-1 activity were commonly capable of generating pores in the envelope of HSV-1. Thus, some chemokines have a significant direct antiviral activity against HSV-1 in vitro and may have a potential role in host defense against HSV-1 as a direct antiviral agent.

Molecular Analyses of KCNQ1-5 Potassium Channel MRNAs in Rat and Guinea Pig Inner Ears: Expression, Cloning, and Alternative Splicing

Acta Oto-laryngologica. Apr, 2006  |  Pubmed ID: 16608784

Expression of neuronal Kcnq gene family transcripts in the inner ear provides further evidence for cochlear M-type currents and for complex molecular heterogeneities of voltage-gated potassium channels composed of various KCNQ subunits and/or alternative splice variants. Furthermore, important roles in regulation of cellular excitability in the auditory system, and hearing disorders related to (hyper)excitability, e.g. tinnitus, are implied.

Promoter Methylation and Response to Chemotherapy and Radiation in Esophageal Cancer

Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association. Jun, 2006  |  Pubmed ID: 16678495

Multiple studies have shown that promoter methylation of tumor suppressor genes underlies esophageal carcinogenesis. Hypothetically, methylation resulting in tumor suppressor gene inactivation might result in tumors that are unresponsive to chemotherapy and radiation. Accordingly, our aim was to find methylation markers that could be used to predict response to chemoradiation.

Sema3D and Sema7A Have Distinct Expression Patterns in Chick Embryonic Development

Developmental Dynamics : an Official Publication of the American Association of Anatomists. Aug, 2006  |  Pubmed ID: 16804892

By RT-PCR, we isolated a partial cDNA clone for the chick Semaphorin7A (Sema7A) gene. We further analyzed its expression patterns and compared them with those of the Sema3D gene, in chick embryonic development. Sema3D and Sema7A appeared to be expressed in distinct cell populations. In mesoderm-derived structures, Sema7A expression was detected in the newly formed somites, whereas Sema3D expression was found in the notochord. In ectoderm-derived tissues, Sema3D is expressed broadly in the surface ectoderm, lens and nasal placodes. Sema3D is also expressed in the developing nervous system including diencephalon, dorsal neural tube, optical and otic vesicles. In the limb bud, Sema3D expression was found throughout the ectoderm excluding the apical ectoderm ridge (AER), where Sema7A is concentrated. Although both genes appeared to be expressed in the migrating neural crest cells, Sema3D expression is limited to neural crest cells migrating out of the midbrain/hindbrain regions, while Sema7A expression is widespread in both cranial and trunk neural crest cells.

Auditory Function and Cochlear Morphology in the German Waltzing Guinea Pig

Hearing Research. Sep, 2006  |  Pubmed ID: 16870368

The German waltzing guinea pig is a new strain of animals with a recessively inherited inner ear defect resulting in deafness and severe vestibular dysfunction. Measurements of auditory brainstem responses (ABRs) demonstrated that the homozygotes (gw/gw) are deaf while the heterozygotes (gw/+) have normal hearing. In the gw/gw cochlea, a collapse of Reissner's membrane leads to the absence of scala media. Melanin pigment accumulation was clearly observed in the gw/gw stria vascularis, and both the height and width of stria vascularis were significantly reduced. Ultrastructural observations further detailed the disorganization of stria vascularis in the gw/gw animals: marginal cells lacked basolateral infoldings; intermediate cells (melanocytes) were scarce and degenerated; and basal cells were difficult to identify. The level of degeneration of the organ of Corti varied between individual gw/gw animals. The density of spiral ganglion neurons was significantly decreased in old (1-2 years of age) gw/gw animals. In contrast, no pathological changes were observed in the cochleae of gw/+ animals. Our data suggest that the degeneration originates in the stria vascularis (most likely in the melanocytes), and that this is the primary cause for inner ear defects in the German waltzing guinea pig. Here, we describe the auditory function and cochlear morphology in this spontaneously mutated guinea pig strain.

A Genome-wide Search Identifies Epigenetic Silencing of Somatostatin, Tachykinin-1, and 5 Other Genes in Colon Cancer

Gastroenterology. Sep, 2006  |  Pubmed ID: 16952549

Gene silencing via promoter hypermethylation is a central event in the pathogenesis of cancers. To identify novel methylation targets in colon cancer, we conducted a genome-wide, microarray-based, in silico, and epigenetic search.

Survey of Chemokine Receptor Expression Reveals Frequent Co-expression of Skin-homing CCR4 and CCR10 in Adult T-cell Leukemia/lymphoma

Leukemia & Lymphoma. Oct, 2006  |  Pubmed ID: 17071491

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cell origin with multi-organ involvement. Because the chemokine receptors play crucial roles in tissue-specific homing of mature lymphocytes, particular chemokine receptors expressed on ATLL cells may be involved in their tissue infiltration. We thus performed a comprehensive survey on the chemokine receptor expression in ATLL. ATLL cells expressed transcripts of CCR1, CCR4, CCR7, CCR8, CCR10 and CXCR4 but hardly expressed those of CCR2, CCR3, CCR5, CCR6, CCR9, CXCR1, CXCR2, CXCR3 and CXCR5. These results were confirmed at the protein level by flow cytometric analysis. Notably, patients who have skin lesions showed significantly higher levels of CCR10 mRNA expression than patients without skin lesions. ATLL cells migrated efficiently to the CCR4 ligand, CCL22, and moderately to the CCR10 ligands, CCL27 and CCL28. Moreover, ATLL skin lesions consistently contained transcripts of CCR10 and its ligands CCL27 and CCL28 besides those of CCR4 and its ligands CCL17 and CCL22 that have been reported previously. Collectively, the frequent co-expression of CCR4 and CCR10, the known pair of skin-homing chemokine receptors, may play an important role in ATLL invasion into the skin.

Reprimo Methylation is a Potential Biomarker of Barrett's-Associated Esophageal Neoplastic Progression

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Nov, 2006  |  Pubmed ID: 17121882

Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC).

Host Dependent Frequency Upconversion of Er3+/Yb3+-codoped Bismuth-germanate Glasses

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Aug, 2007  |  Pubmed ID: 17142088

The absorption and upconversion fluorescence spectra of a series of Er3+/Yb3+-codoped xBi(2)O(3)-(90-x)GeO2-10Na(2)O (BGN x, x=31, 36, 41, 46 and 51 mol%) glasses have been studied. Intense green and red emission bands at around 533, 548 and 659 nm, corresponding to the 2H(11/2)-->4I(15/2), 4S(3/2)-->4I(15/2) and 4F(9/2)-->4I(15/2) transitions of Er3+, respectively, were simultaneously observed at room temperature. The dependence of intensities of upconversion emission on excitation power and possible upconversion mechanisms were evaluated and analyzed. The important role of Bi(2)O(3) in upconversion intensity is observed and its influence on the green (533 and 548 nm) and red (659 nm) emissions is compared and discussed. The influence of Bi(2)O(3) on the upconversion emissions has been investigated based on the IR spectra.

Expression of CCR9 in HTLV-1+ T Cells and ATL Cells Expressing Tax

International Journal of Cancer. Journal International Du Cancer. Apr, 2007  |  Pubmed ID: 17205512

Adult T-cell leukemia (ATL) is a highly aggressive mature CD4+ T-cell malignancy that is etiologically associated with human T-lymphotropic virus Type 1 (HTLV-1). ATL is characterized by frequent infiltration of lymph nodes, spleen, liver, skin and gut. Previously, we and others have shown that the majority of ATL cases are strongly positive for CCR4, which may explain the frequent skin invasion of ATL. Here, we examined whether ATL cells express CCR9, which is involved in T-cell homing to the gastrointestinal tract. Human T cell lines carrying HTLV-1 consistently expressed CCR9 together with the HTLV-1-encoded transcriptional activator Tax. Although ATL cells freshly isolated from peripheral blood hardly expressed CCR9, ATL cells cultured for 1 day consistently expressed CCR9 in parallel with the upregulation of Tax. Induction of Tax by Cd2+ in JPX-9, a subline of Jurkat human T cell line carrying Tax under the control of metallothionein promoter, led to upregulation of CCR9. A luciferase reporter gene under the control of the CCR9 promoter was expressed by cotransfection of an expression vector for Tax or in Cd2+-treated JPX-9 cells. Furthermore, immunohistochemical staining demonstrated that ATL cells infiltrating gastrointestinal tract were frequently positive for CCR9. Collectively, CCR9 is inducible in ATL cells expressing Tax and may play a role in the gastrointestinal involvement of ATL.

Assessment of 186Re Chelate-conjugated Bisphosphonate for the Development of New Radiopharmaceuticals for Bones

Nuclear Medicine and Biology. Jan, 2007  |  Pubmed ID: 17210464

The preferable pharmacokinetics of rhenium-186 (186Re)-monoaminemonoamidedithiol-conjugated or 186Re-mercaptoacetyltriglycine-conjugated bisphosphonates (BPs) suggested that the molecular design would be applicable to other radionuclides such as 68Ga, 99mTc, 153Sm and 177Lu. In this study, a key factor affecting the pharmacokinetics of a chelate-conjugated BP was investigated to estimate the validity and the applicability of molecular design.

Malformation of Stria Vascularis in the Developing Inner Ear of the German Waltzing Guinea Pig

Cell and Tissue Research. May, 2007  |  Pubmed ID: 17252244

Auditory function and cochlear morphology have previously been described in the postnatal German waltzing guinea pig, a strain with recessive deafness. In the present study, cochlear histopathology was further investigated in the inner ear of the developing German waltzing guinea pig (gw/gw). The lumen of the cochlear duct diminished progressively from embryonic day (E) 35 to E45 and was absent at E50 because of the complete collapse of Reissner's membrane onto the hearing organ. The embryonic stria vascularis, consisting of a simple epithelium, failed to transform into the complex trilaminar tissue seen in normal animals and displayed signs of degeneration. Subsequent degeneration of the sensory epithelium was observed from E50 and onwards. Defective and insufficient numbers of melanocytes were observed in the developing gw/gw stria vascularis. A gene involved in cochlear melanocyte development, Pax3, was markedly reduced in lateral wall tissue of the cochlea of both E40 and adult gw/gw individuals, whereas its expression was normal in the skin and diaphragm muscle of adult gw/gw animals. The Pax3 gene may thus be involved in the pathological process but is unlikely to be the primary mutated gene in the German waltzing guinea pig. TUNEL assay showed no signs of apoptotic cell death in the developing stria vascularis of this type of guinea pig. Thus, malformation of the stria vascularis appears to be the primary defect in the inner ear of the German waltzing guinea pig. Defective and insufficient numbers of melanocytes might migrate to the developing stria vascularis but fail to provide the proper support for the subsequent development of marginal and basal cells, thereby leading to stria vascularis malformation and dysfunction in the inner ear of the German waltzing guinea pig.

[Effect of Qingdu Suppository-containing Serum on Cervical Carcinoma SiHa Cell MDM2 Gene Expression]

Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. Feb, 2007  |  Pubmed ID: 17343003

To investigate the effect and mechanism of Qingdu Suppository (QDS) in suppressing the growth of SiHa cell of cervical carcinoma on the cytobiologic and molecular biologic level.

Survival, Synaptogenesis, and Regeneration of Adult Mouse Spiral Ganglion Neurons in Vitro

Developmental Neurobiology. Jan, 2007  |  Pubmed ID: 17443776

The inner ear spiral ganglion is populated by bipolar neurons connecting the peripheral sensory receptors, the hair cells, with central neurons in auditory brain stem nuclei. Hearing impairment is often a consequence of hair cell death, e.g., from acoustic trauma. When deprived of their peripheral targets, the spiral ganglion neurons (SGNs) progressively degenerate. For effective clinical treatment using cochlear prostheses, it is essential to maintain the SGN population. To investigate their survival dependence, synaptogenesis, and regenerative capacity, adult mouse SGNs were separated from hair cells and studied in vitro in the presence of various neurotrophins and growth factors. Coadministration of fibroblast growth factor 2 (FGF-2) and glial cell line-derived neurotrophic factor (GDNF) provided support for long-term survival, while FGF-2 alone could strongly promote neurite regeneration. Fibroblast growth factor receptor FGFR-3-IIIc was found to upregulate and translocate to the nucleus in surviving SGNs. Surviving SGNs formed contacts with other SGNs after they were deprived of the signals from the hair cells. In coculture experiments, neurites extending from SGNs projected toward hair cells. Interestingly, adult mouse spiral ganglion cells could carry out both symmetric and asymmetric cell division and give rise to new neurons. The authors propose that a combination of FGF-2 and GDNF could be an efficient route for clinical intervention of secondary degeneration of SGNs. The authors also demonstrate that the adult mammalian inner ear retains progenitor cells, which could commit neurogenesis.

[Surface-modified Paclitaxel-loaded Nanoparticles As Local Delivery System for the Prevention of Vessel Restenosis]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Jan, 2007  |  Pubmed ID: 17520813

The novel paclitaxel-loaded nanopaticle through surface modification with didodecylmethylammonium bromide (DMAB) was prepared and its prevenative against neointimal formation in a rabbit carotid artery injury model was tested. Paclitaxel-loaded nanoparticles were prepared from oil-water emulsions using biodegradable poly (lactic acid-co-glycolic acid) (PLGA). Specific additive for surface conjugation was added after particle formation. To enhance arterial retention using a cationic surfactant, DMAB, was used. The size and distribution, surface morphology and surface charge of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, scanning electron microscope and zeta potential analyzer. The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography (HPLC). Balloon injured rabbit carotid arteries were treated with single infusion of the paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects of vascular smooth muscle cell migration and proliferation were evaluated as end-point. The NPs showed spherical shape with diameter ranging from 200 to 500 nm. The negatively charged PLGA NPs shifted to positive after the DMAB modification. The in vitro drug release profile showed a triphasic release pattern. 28 days later, morphologic analysis revealed that the inhibitory effect of intima proliferation is dose-dependent, and the 30 mg x mL(-1) nanoparticle concentration suspension could completely inhibit proliferation of intima. Paclitaxel-loaded nanoparticles through surface modification with DMAB provide an effective means of inhibiting proliferation response to vascular injury in the rabbit.

Anatomic Study of Maximum Intensity Projection of the Membranous Labyrinth and the Internal Auditory Meatus - MRI Scan in 16 Chinese Adults

Acta Oto-laryngologica. Nov, 2007  |  Pubmed ID: 17851967

Three-dimensional reconstruction of maximum intensity projection (MIP) might document objectively, stereoscopically and directly the minute structures of the membranous labyrinth and internal auditory meatus. In this study, we establish magnetic resonance imaging (MRI) measurement criteria of the inner ear in Chinese adults.

Novel Decapeptides That Bind Avidly and Deliver Radioisotope to Colon Cancer Cells

PloS One. 2007  |  Pubmed ID: 17912343

The rapidly growing field of targeted tumor therapy often utilizes an antibody, sometimes tagged with a tumor-ablating material such as radioisotope, directed against a specific molecule.

Hypermethylation of Tachykinin-1 is a Potential Biomarker in Human Esophageal Cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Nov, 2007  |  Pubmed ID: 17975140

Our aim was to investigate whether and at what stage hypermethylation of the tachykinin-1 (TAC1) gene is associated with human esophageal neoplastic transformation.

Rarity of Somatic Mutation and Frequency of Normal Sequence Variation Detected in Sporadic Colon Adenocarcinoma Using High-Throughput CDNA Sequencing

Bioinformatics and Biology Insights. 2007  |  Pubmed ID: 18389087

We performed high-throughput cDNA sequencing in colorectal adenocarcinoma and matching normal colorectal epithelium. All six hundred three genes in the UCSC database that were expressed in colon cancers and contained open reading frames of 1000 nucleotides or less were selected for study (total basepairs/bp, 366,686). 304,350 of these 366,686 bp (83.0%) were amplified and sequenced successfully. Seventy-eight sequence variants present in germline (i.e. normal) as well as matching somatic (i.e. tumor) DNA were discovered, yielding a frequency of 1 variant per 3,902 bp. Fifty-one of these sequence variants were homozygous (26 synonymous, 25 non-synonymous), while 27 were heterozygous (11 synonymous, 16 non-synonymous). Cancer tissue contained only one sequence-altered allele of the gene ATP50, which was present heterozygously alongside the wild-type allele in matching normal epithelium. Despite this relatively large number of bp and genes sequenced, no somatic mutations unique to tumor were found. High-throughput cDNA sequencing is a practical approach for detecting novel sequence variations and alterations in human tumors, such as those of the colon.

Pituitary Tumor-transforming 1 Increases Cell Motility and Promotes Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma

Cancer Research. May, 2008  |  Pubmed ID: 18451147

Human pituitary tumor-transforming 1 (PTTG1)/securin is a putative oncoprotein that is overexpressed in various tumor types. However, the involvement of PTTG1 in gastrointestinal cancer development and progression remains unclear. In this study, we investigated the clinical significance and biological effects of PTTG1 in esophageal squamous cell carcinoma (ESCC). Immunohistochemical studies performed on 113 primary ESCC specimens revealed a high prevalence of PTTG1 overexpression (60.2%), which was significantly associated with lymph node metastasis (regional, P = 0.042; distant, P = 0.005), advanced tumor stage (P = 0.028), and poorer overall survival (P = 0.017, log-rank test; P = 0.044, Cox proportional hazard model). Eleven ESCC cell lines expressed PTTG1 protein at levels 2.4 to 6.6 times higher than those in normal esophageal epithelial cells (HEEpiC). PTTG1 protein expression was confined to the nucleus in HEEpiC cells but present in both the cytoplasm and nucleus in ESCC cells. Two small interfering RNAs (siRNA) inhibited PTTG1 mRNA and protein expression in three ESCC cell lines by 77% to 97%. In addition, PTTG1 down-regulation by these siRNAs significantly reduced cell motility in all three ESCC cell lines (P < 0.01) in vitro, as well as popliteal lymph node metastases of ESCC cells in nude mice (P = 0.020). Global gene expression profiling suggested that several members of the Ras and Rho gene families, including RRAS, RHOG, ARHGAP1, and ARHGADIA, represented potential downstream genes in the PTTG1 pathway. Taken together, these findings suggest that PTTG1 overexpression promotes cell motility and lymph node metastasis in ESCC patients, leading to poorer survival. Thus, PTTG1 constitutes a potential biomarker and therapeutic target in ESCCs with lymph node metastases.

Generation of Small 32P-labeled Peptides As a Potential Approach to Colorectal Cancer Therapy

PloS One. 2008  |  Pubmed ID: 18575578

Cancers have been revealed to be extremely heterogenous in terms of the frequency and types of mutations present in cells from different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. We describe the generation of multiple, unique small peptides nine to thirty-four amino acids in length which, when labeled with the radioisotope (32)P, bind with vastly differing efficiencies to cell lines derived from different colon adenocarcinomas. In addition, the most effective of these peptides permanently transfers the (32)P radioisotope to colorectal cancer cellular proteins within two hours at a rate that is more than 150 times higher than in cell lines derived from other cancers or from the normal tissues tested. Currently, the only two FDA-approved radioimmunotherapeutic agents in use both employ antibodies directed against the B cell marker CD20 for the treatment of non-Hodgkin's lymphoma. By using the method described herein, large numbers of different (32)P-labeled peptides can be readily produced and assayed against a broad spectrum of cancer types. This report proposes the development and use of (32)P-labeled peptides as potential individualized peptide-binding therapies for the treatment of colon adenocarcinoma patients.

Effect of TGF-beta/Smad Signaling on Sertoli Cell and Possible Mechanism Related to Complete Sertoli Cell-only Syndrome

Molecular and Cellular Biochemistry. Dec, 2008  |  Pubmed ID: 18648910

The roles of TGF-beta and the interaction between TGF-beta and EGFR signaling are critical in Sertoli cell, though the knowledge about them is limited. RT-PCR was used to characterize the status of TGF-beta signaling in clinical testicular specimens with complete Sertoli cell-only syndrome (SCOS). The mouse Sertoli cell TM4 was used to investigate the interaction between TGF-beta and EGFR signaling by using mitogenic assay, luciferase assay, and western blot, while TM3 (mouse leydig cell), 3T3 (mouse embryo fibroblasts), and B82 (mouse lung fibroblasts) were selected as control. The RT-PCR assay indicated that the expression levels of TbetaRII and Smad2 in SCOS testes were upregulated compared to that in the normal controls. In the in vitro experiment, the TGF-beta1 downregulated cellular proliferation of TM3 and B82 cell (P < 0.05), but it did not changed the proliferation of TM4 and 3T3 cells (P > 0.05). On contrast, TGF-beta1 only increased the TGF response elements p3TP-lux activity significantly (P < 0.05) in Sertoli cell TM4. Also, the Western blot assay shows an obvious increase of Smad2 in TM4, 3T3, and TM3 cells after TGF-beta1 treatment while the EGFR expression level was significantly increased in TM4 cells only. In conclusion, the TGF-beta pathway and the cross-link between TGF-beta and EGFR signaling may play an important role on the dysfunction of Sertoli cells which induce germ stem cells' disappearance in SCOS.

Promoter Hypermethylation of CDH13 is a Common, Early Event in Human Esophageal Adenocarcinogenesis and Correlates with Clinical Risk Factors

International Journal of Cancer. Journal International Du Cancer. Nov, 2008  |  Pubmed ID: 18729198

Although the CDH13 gene has been shown to undergo epigenetic silencing by promoter methylation in many types of tumors, hypermethylation of this gene in Barrett's-associated esophageal adenocarcinogenesis has not been studied. Two hundred fifty-nine human esophageal tissues were therefore examined for CDH13 promoter hypermethylation by real-time methylation-specific PCR. CDH13 hypermethylation showed discriminative receiver-operator characteristic curve profiles, sharply demarcating esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma (ESCC) and normal esophagus (NE) (p < 0.0001). CDH13 normalized methylation values (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE (D) and EAC than in NE (p < 0.0000001). CDH13 hypermethylation frequency was 0% in NE but increased early during neoplastic progression, rising to 70% in BE, 77.5% in D and 76.1% in EAC. Both CDH13 hypermethylation frequency and its mean NMV were significantly higher in BE with than without accompanying EAC. In contrast, only 5 (19.2%) of 26 ESCCs exhibited CDH13 hypermethylation. Furthermore, both CDH13 hypermethylation frequency and its mean NMV were significantly higher in EAC than in ESCC, as well as in BE or D vs. ESCC. Interestingly, mean CDH13 NMV was significantly lower in short-segment than in long-segment BE, a known clinical risk factor for neoplastic progression. Similarly, BE segment length was significantly lower in specimens with unmethylated than with methylated CDH13 promoters. 5-aza-2'-deoxycytidine treatment of OE33 EAC and KYSE220 ESCC cells reduced CDH13 methylation and increased CDH13 mRNA expression. These findings suggest that hypermethylation of CDH13 is a common, tissue-specific event in human EAC, occurs early during BE-associated neoplastic progression, and correlates with known clinical neoplastic progression risk factors.

[Gene Therapy in Hereditary Hearing Loss. Future Therapeutic Possibility--maybe Combined with Stem Cells]

Läkartidningen. Sep 3-9, 2008  |  Pubmed ID: 18831451

[Establishment of Mongolian Gerbil Model of Long-term Helicobacter Pylori Infection]

Zhonghua Yi Xue Za Zhi. Jun, 2008  |  Pubmed ID: 18956630

To establish a model of long-term infection with Helicobacter pylori (Hp) in Mongolian gerbil (Meriones unguiculatus), and to investigate if Hp combined with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) has a synergistic effect to induce gastric mucosa injury. To investigate pathological changes of gastric mucosa during long-term Hp infection in Mongolian gerbil model.

Hypermethylation of the Somatostatin Promoter is a Common, Early Event in Human Esophageal Carcinogenesis

Cancer. Jan, 2008  |  Pubmed ID: 17999418

The promoter of somatostatin (SST), a primary inhibitor of gastrin-stimulated gastric acid secretion, is hypermethylated in 80% of human colon cancers. The aim of the current study was to investigate whether and at what stage promoter hypermethylation of SST is involved in human esophageal carcinogenesis.

Spatiotemporal Loss of K+ Transport Proteins in the Developing Cochlear Lateral Wall of Guinea Pigs with Hereditary Deafness

The European Journal of Neuroscience. Jan, 2008  |  Pubmed ID: 18093167

Genetic deafness is one of the most common human genetic birth defects. To understand the molecular mechanisms underlying human hereditary deafness, deaf animal strains have proved to be invaluable models. The German waltzing guinea pig is a new strain of animals with unidentified gene mutation(s), displaying recessively inherited cochleovestibular impairment. Histological investigations of the homozygous animals (gw/gw) revealed a collapse of the endolymphatic compartment and malformation of stria vascularis. RT-PCR showed a significant reduction in expression of the strial intermediate cell-specific gene Dct and the tight-junction gene Cldn11 in the embryonic day (E)40 and adult gw/gw cochlear lateral wall. Immunohistochemical analysis of the gw/gw cochlea showed loss of the tight junction protein CLDN11 in strial basal cells from E40, loss of the potassium channel subunit KCNJ10 in strial intermediate cells from E50, and loss of the Na-K-Cl cotransporter SLC12A2 in strial marginal cells from E50. In addition, a temporary loss of the gap junction protein GJB2 (connexin 26) between fibrocytes in the spiral ligament of the E50 gw/gw cochlea was observed. The barrier composed of tight junctions between strial basal cells was disrupted in the gw/gw cochlea as indicated by a biotin tracer permeability assay. In conclusion, spatiotemporal loss of K+ transport proteins in the cochlear lateral wall is caused by malformation of the stria vascularis in the developing German waltzing guinea pig inner ear. This new animal strain may serve as a good model for studying human genetic deafness due to disruption of inner ear ion homeostasis.

Tax-inducible Production of CC Chemokine Ligand 22 by Human T Cell Leukemia Virus Type 1 (HTLV-1)-infected T Cells Promotes Preferential Transmission of HTLV-1 to CCR4-expressing CD4+ T Cells

Journal of Immunology (Baltimore, Md. : 1950). Jan, 2008  |  Pubmed ID: 18178833

Adult T cell leukemia is a mature CD4+ T cell malignancy which predominantly expresses CCR4 and is etiologically associated with human T cell leukemia virus type 1 (HTLV-1). Because HTLV-1 transmission depends on close cell-cell contacts, HTLV-1-infected T cells may preferentially interact with CCR4+CD4+ T cells for efficient viral transmission. In terms of gene expression and protein secretion, we found a strong correlation between HTLV-1 Tax oncoprotein and CCL22, a CCR4 ligand, in HTLV-1-infected T cells. Transient Tax expression in an HTLV-1-negative T cell line activated the CCL22 promoter and induced CCL22. Additionally, tax gene knockdown by small interference RNA reduced CCL22 expression in the infected T cells. These findings indicate that CCL22 is a cellular target gene of Tax. In chemotaxis assays, the culture supernatants of HTLV-1-infected T cells selectively attracted CCR4+CD4+ T cells in PBMCs. This was blocked by pretreating the supernatants with anti-CCL22 Ab or PBMCs with a synthetic CCR4 antagonist. In coculture experiments, primary CCR4+CD4+ T cells significantly adhered to Tax-expressing cells. This adhesion was blocked by the CCR4 antagonist or pertussis toxin. Interestingly, CCR4 was redistributed to the contact region, and in some cases, this was accompanied by a polarized microtubule-organizing center, which is an indicator of virological synapse formation, in the infected T cells. Finally, anti-CCL22 Ab treatment also blocked HTLV-1 transmission to primary CD4+ T cells in coculture experiments with HTLV-1 producer cells. Thus, HTLV-1-infected T cells produce CCL22 through Tax and selectively interact with CCR4+CD4+ T cells, resulting in preferential transmission of HTLV-1 to CCR4+CD4+ T cells.

Hypermethylation of the AKAP12 Promoter is a Biomarker of Barrett's-associated Esophageal Neoplastic Progression

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Jan, 2008  |  Pubmed ID: 18199717

The A-kinase anchoring protein 12 (AKAP12) is a kinase scaffold protein with known tumor suppressor activity. Recently, AKAP12 promoter hypermethylation was reported in gastric and colorectal cancers. We examined AKAP12 promoter hypermethylation using real-time methylation-specific PCR in 259 human esophageal tissues. AKAP12 hypermethylation showed highly discriminative receiver-operator characteristic (ROC) curve profiles, clearly distinguishing esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma and normal esophagus (P < 0.0001). AKAP12-normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's, and EAC than in normal esophagus (P < 0.0000001). AKAP12 hypermethylation frequency was zero in normal esophagus but increased early during neoplastic progression, to 38.9% in BE from patients with Barrett's alone, 52.5% in dysplastic Barrett's metaplasia, and 52.2% in EAC. AKAP12 hypermethylation levels were significantly higher in normal esophageal epithelia from patients with EAC (mean = 0.00082) than in normal esophagi from patients without Barrett's or esophageal cancer (mean = 0.00007; P = 0.006). There was a significant correlation between AKAP12 hypermethylation and BE segment length, a known clinical neoplastic progression risk factor. In contrast, only 2 (7.7%) of 26 esophageal squamous cell carcinomas exhibited AKAP12 hypermethylation. Treatment of BIC and OE33 EAC cells with 5-aza-2'-deoxycytidine reduced AKAP12 methylation and increased AKAP12 mRNA expression. AKAP12 mRNA levels in EACs with unmethylated AKAP12 (mean = 0.1663) were higher than in EACs with methylated AKAP12 (mean = 0.0668). We conclude that promoter hypermethylation of AKAP12 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker for the early detection of EAC.

Expression of CCL17 and CCL22 by Latent Membrane Protein 1-positive Tumor Cells in Age-related Epstein-Barr Virus-associated B-cell Lymphoproliferative Disorder

Cancer Science. Feb, 2008  |  Pubmed ID: 18271928

Age-related Epstein-Barr virus-positive (EBV(+)) B-cell lymphoproliferative disorder (ALPD) is a disease entity identified from a large-scale re-survey of cases diagnosed as diffuse large B-cell lymphoma. ALPD is a group of EBV(+) polymorphic B-cell lymphoma typically seen in elderly patients. An age-associated decline in host immunity against EBV might be partly responsible for the pathogenesis of ALPD. Histologically, ALPD is often characterized by a minor proportion of EBV-encoded RNA-positive tumor cells in a background of extensive cellular infiltration, similar to that of classical Hodgkin's lymphoma. In contrast to Hodgkin and Reed-Sternberg cells, ALPD tumor cells are clearly positive for B cell markers CD20 and/or CD79a. Hodgkin and Reed-Sternberg cells produce various chemokines, including CCL17 and CCL22, that attract chemokine receptor CCR4-expressing Th2 cells and regulatory T cells. Previously, we have shown that EBV-immortalized B cells also produce CCL17 and CCL22 through latent membrane protein 1 (LMP1)-mediated activation of nuclear factor kappaB. Here we examined expression of CCL17 and CCL22 in ALPD. ALPD tumor cells were often heterogeneous in size in accordance with the differential expression of EBV latent genes at the single cell level. LMP1-expressing tumor cells were typically large in size and selectively positive for CCL17 and CCL22. CCR4(+) cells and forkhead box protein 3(+) regulatory T cells were abundantly present, and the majority of forkhead box protein 3(+) cells were CCR4(+). Collectively, our data show production of CCL17 and CCL22 by LMP1(+) large-sized tumor cells and accumulation of CCR4-expressing cells including regulatory T cells in ALPD.

1,25-dihydroxyvitamin D3 Induces CCR10 Expression in Terminally Differentiating Human B Cells

Journal of Immunology (Baltimore, Md. : 1950). Mar, 2008  |  Pubmed ID: 18292499

In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. In this study, we examined the regulation of CCR10 expression in terminally differentiating human B cells. As reported previously, IL-21 efficiently induced the differentiation of activated human CD19+ B cells into IgD-CD38+ plasma cells in vitro. A minor proportion of the resulting CD19+IgD-CD38+ cells expressed CCR10 at low levels. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the active metabolite of vitamine D3, dramatically increased the proportion of CD19+IgD-CD38+ cells expressing high levels of CCR10. The 1,25-(OH)2D3 also increased the number of CCR10+ cells expressing surface IgA, although the majority of CCR10+ cells remained negative for surface IgA. Thus, 1,25-(OH)2D3 alone may not be sufficient for the induction of IgA expression in terminally differentiating human B cells. To further determine whether 1,25-(OH)2D3 directly induces CCR10 expression in terminally differentiating B cells, we next performed the analysis on the human CCR10 promoter. We identified a proximal Ets-1 site and an upstream potential vitamin D response element to be critical for the inducible expression of CCR10 by 1,25-(OH)2D3. We confirmed the specific binding of Ets-1 and 1,25-(OH)2D3-activated vitamin D receptor to the respective sites. In conclusion, 1,25-(OH)2D3 efficiently induces CCR10 expression in terminally differentiating human B cells in vitro. Furthermore, the human CCR10 promoter is cooperatively activated by Ets-1 and vitamin D receptor in the presence of 1,25-(OH)2D3.

Three-tiered Risk Stratification Model to Predict Progression in Barrett's Esophagus Using Epigenetic and Clinical Features

PloS One. 2008  |  Pubmed ID: 18382671

Barrett's esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett's esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett's esophagus. Moreover, high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency.

[Medical Thoracoscopic Talc Pleurodesis for Malignant Pleural Effusion: an Analysis of 27 Cases]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Dec, 2008  |  Pubmed ID: 19088831

To evaluate the efficacy and safety of talc poudrage pleurodesis via semi-rigid medical thoracoscopy in the treatment of malignant pleural effusions, as well as the factors that may influence the outcomes.

[Effects of Cryopreserved Neural Stem Cells Transplantation on Rat Axonal Regeneration After Spinal Cord Injury]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Jun, 2008  |  Pubmed ID: 19108425

To observe the effects of cryopreserved (-70 degrees C) neural stem cells (NSCs) transplantation on the axon regeneration after the spinal cord injury (SCI) of rats.

[Neural Stem Cells Transplantation Promote the Expressions of Brain Derived Neurotrophic Factor After the Spinal Cord Injury of Rats]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Nov, 2008  |  Pubmed ID: 19143246

To observe the effects of neural stem cells (NSCs) transplantation on the brain derived neurotrophic factor (BDNF) after the spinal cord injury (SCI) of rats, and to investigate the mechanism of repairing the SCI by NSCs transplantation.

A Clinical Study of Microcirculatory Disturbance in Chinese Patients with Sudden Deafness

Acta Oto-laryngologica. Nov, 2008  |  Pubmed ID: 19241603

Cochlear microcirculation disturbance is closely associated with sudden deafness.

MicroRNA-21 is Overexpressed in Human Cholangiocarcinoma and Regulates Programmed Cell Death 4 and Tissue Inhibitor of Metalloproteinase 3

Hepatology (Baltimore, Md.). May, 2009  |  Pubmed ID: 19296468

Cholangiocarcinomas (CCAs) are aggressive cancers, with high mortality and poor survival rates. Only radical surgery offers patients some hope of cure; however, most patients are not surgical candidates because of late diagnosis secondary to relatively poor accuracy of diagnostic means. MicroRNAs (miRs) are involved in every cancer examined, but they have not been evaluated in primary CCA. In this study, miR arrays were performed on five primary CCAs and five normal bile duct specimens (NBDs). Several miRs were dysregulated and miR-21 was overexpressed in CCAs. miR-21 differential expression in these 10 specimens was verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). To validate these findings, qRT-PCR for miR-21 was then performed on 18 additional primary CCAs and 12 normal liver specimens. MiR-21 was 95% sensitive and 100% specific in distinguishing between CCA and normal tissues, with an area under the receiver operating characteristic curve of 0.995. Inhibitors of miR-21 increased protein levels of programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinases 3 (TIMP3). Notably, messenger RNA levels of TIMP3 were significantly lower in CCAs than in normals. Conclusions: MiR-21 is overexpressed in human CCAs. Furthermore, miR-21 may be oncogenic, at least in part, by inhibiting PDCD4 and TIMP3. Finally, these data suggest that TIMP3 is a candidate tumor suppressor gene in the biliary tree.

The MiR-106b-25 Polycistron, Activated by Genomic Amplification, Functions As an Oncogene by Suppressing P21 and Bim

Gastroenterology. May, 2009  |  Pubmed ID: 19422085

Barrett's esophagus (BE) is a highly premalignant disease that predisposes to the development of esophageal adenocarcinoma (EAC); however, the involvement of microRNAs (miRs) in BE-EAC carcinogenic progression is not known.

A Multicenter, Double-blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Cancer Research. May, 2009  |  Pubmed ID: 19435894

Esophageal adenocarcinoma risk in Barrett's esophagus (BE) is increased 30- to 125-fold versus the general population. Among all BE patients, however, neoplastic progression occurs only once per 200 patient-years. Molecular biomarkers are therefore needed to risk-stratify patients for more efficient surveillance endoscopy and to improve the early detection of progression. We therefore performed a retrospective, multicenter, double-blinded validation study of eight BE progression prediction methylation biomarkers. Progression or nonprogression were determined at 2 years (tier 1) and 4 years (tier 2). Methylation was assayed in 145 nonprogressors and 50 progressors using real-time quantitative methylation-specific PCR. Progressors were significantly older than nonprogressors (70.6 versus 62.5 years; P < 0.001). We evaluated a linear combination of the eight markers, using coefficients from a multivariate logistic regression analysis. Areas under the ROC curve (AUC) were high in the 2-year, 4-year, and combined data models (0.843, 0.829, and 0.840; P < 0.001, <0.001, and <0.001, respectively). In addition, even after rigorous overfitting correction, the incremental AUCs contributed by panels based on the 8 markers plus age versus age alone were substantial (Delta-AUC = 0.152, 0.114, and 0.118, respectively) in all 3 models. A methylation biomarker-based panel to predict neoplastic progression in BE has potential clinical value in improving both the efficiency of surveillance endoscopy and the early detection of neoplasia.

Triple Versus Dual Antiplatelet Therapy in Patients with Acute ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Circulation. Jun, 2009  |  Pubmed ID: 19528339

Whether triple antiplatelet therapy is superior or similar to dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in the era of drug-eluting stents remains unclear.

Prokaryotic Expression, Purification and Functional Characterization of Human FHL3

Biotechnology Letters. Oct, 2009  |  Pubmed ID: 19547926

Four and a half LIM domain protein 3 (FHL3) is a member of the family of LIM proteins and is involved in myogenesis, cytoskeleton reconstruction, cell growth and differentiation. The full-length FHL3 cDNA was cloned from human spleen cDNA library and inserted in a prokaryotic expression vector pBV220 and then the recombinant plasmid was transformed into E. coli JM109. The expression of the recombinant protein was induced at 42 degrees C. SDS-PAGE analysis showed that recombinant human FHL3 (rhFHL3) was mainly expressed as an inclusion body. After purification by HisTrap FF crude, the rhFHL3 was renatured by dialysis against renaturing buffer and identified by Western blot analysis using human FHL3 polyclonal antibody. The MTT assay showed that the purified rhFHL3 could inhibit HepG2 cell growth but promote the proliferation of ECV304 cells. In addition, the expression of angiogenin (Ang) gene was increased when ECV304 cells were pretreated with rhFHL3.

[Distribution Characteristics of Common Syndrome Types and Syndrome Elements Extracted by Experts' Experience in Perimenopausal and Postmenopausal Women]

Zhong Xi Yi Jie He Xue Bao = Journal of Chinese Integrative Medicine. Jun, 2009  |  Pubmed ID: 19583933

To compare the distribution characteristics of common syndrome types and syndrome elements of menopause syndrome in perimenopausal and postmenopausal women on the basis of standardized syndrome differentiation extracted by experts' experiences.

CXCR7 is Inducible by HTLV-1 Tax and Promotes Growth and Survival of HTLV-1-infected T Cells

International Journal of Cancer. Journal International Du Cancer. Nov, 2009  |  Pubmed ID: 19623653

Human T-lymphotropic virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia (ATL), encodes the potent transcriptional activator Tax, which is required for HTLV-1-induced immortalization of T cells. CXCR7 is an atypical chemokine receptor frequently expressed by tumor cells and known to promote cell growth and survival. We found that HTLV-1-immortalized T cells expressing Tax consistently expressed CXCR7. Induction of Tax in JPX-9 upregulated CXCR7. Wild-type Tax efficiently activated the CXCR7 promoter via a proximal NF-kappaB site, while a mutant Tax selectively defective in NF-kappaB activation did not. CCX754, a synthetic CXCR7 antagonist, inhibited cell growth and increased apoptosis of HTLV-1-immortalized T cells. Knockdown of CXCR7 by small interfering RNA also reduced cell growth. Stable expression of CXCR7 in a CXCR7-negative ATL cell line promoted cell growth and survival. Taken together, CXCR7 is inducible by Tax and may play an important role in HTLV-1-induced immortalization of T cells by promoting growth and survival of HTLV-1-infected T cells.

Mid-term Angiographic Benefit of Sirolimus-eluting Stents Compared with Paclitaxel-eluting Stents in Patients with Acute Myocardial Infarction

Journal of Cardiology. Aug, 2009  |  Pubmed ID: 19632525

We compared angiographic and clinical outcomes among different drug-eluting stents (DESs) in Korean acute myocardial infarction (AMI) patients.

Chromosomal Abnormalities and Novel Disease-related Regions in Progression from Barrett's Esophagus to Esophageal Adenocarcinoma

International Journal of Cancer. Journal International Du Cancer. Nov, 2009  |  Pubmed ID: 19670330

Barrett's esophagus (BE) is a metaplastic condition caused by chronic gastroesophageal reflux which represents an early step in the development of esophageal adenocarcinoma (EAC). Single-nucleotide polymorphism microarray (SNP-chip) analysis is a novel, precise, high-throughput approach to examine genomic alterations in neoplasia. Using 250K SNP-chips, we examined the neoplastic progression of BE to EAC, studying 11 matched sample sets: 6 sets of normal esophagus (NE), BE and EAC, 4 of NE and BE and 1 of NE and EAC. Six (60%) of 10 total BE samples and 4 (57%) of 7 total EAC samples exhibited 1 or more genomic abnormalities comprising deletions, duplications, amplifications and copy-number-neutral loss of heterozygosity (CNN-LOH). Several shared abnormalities were identified, including chromosome 9p CNN-LOH [2 BE samples (20%)], deletion of CDKN2A [4 BE samples (40%)] and amplification of 17q12-21.2 involving the ERBB2, RARA and TOP2A genes [3.1 Mb, 2 EAC (29%)]. Interestingly, 1 BE sample contained a homozygous deletion spanning 9p22.3-p22.2 (1.2 Mb): this region harbors only 1 known gene, basonuclin 2 (BNC2). Real-time PCR analysis confirmed the deletion of this gene and decreased the expression of BNC2 mRNA in the BE sample. Furthermore, transfection and stable expression of BNC2 caused growth arrest of OE33 EAC cells, suggesting that BNC2 functions as a tumor suppressor gene in the esophagus and that deletion of this gene occurs during the development of EAC. Thus, this SNP-chip analysis has identified several early cytogenetic events and novel candidate cancer-related genes that are potentially involved in the evolution of BE to EAC.

Peripheral Arterial Disease is Associated with Coronary Artery Spasm As Assessed by an Intracoronary Acetylcholine Provocation Test

Clinical and Experimental Pharmacology & Physiology. Nov, 2009  |  Pubmed ID: 19671066

1. Both peripheral arterial disease (PAD) and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS may be expected in patients with PAD. In the present study, we evaluated the incidence and characteristics of CAS in patients with PAD. 2. A total of 78 patients with PAD and 241 age- and gender-matched patients without PAD who had chest pain with normal coronary appearance on coronary angiograms underwent intracoronary acetylcholine (ACh) provocation test. Acetylcholine was injected into the left coronary artery in incremental doses of 20, 50 and 100 microg/min. Significant CAS was defined as a transient > 70% luminal narrowing with concurrent chest pain and/or ST segment changes. 3. Patients with PAD had a significantly higher incidence of ACh-induced significant CAS than those without PAD (60.3 vs 34.0%, respectively P < 0.001), as well as chest pain and ST segment changes during the ACh provocation test. Patients with PAD were more sensitive to lower doses of ACh and had a higher incidence of multivessel spasm than those without PAD. Multivariable logistic analysis showed that age, current smoking, PAD and myocardial bridge were independent predictors of ACh-induced significant CAS. Moreover, of these factors, PAD was the strongest independent predictor (odds ratio 4.25; confidence interval 1.33-13.54; P = 0.014). 4. In patients with chest pain, the presence of arterial disease at another site should still push the clinician towards treating the chest pain as angina, even if the coronary anatomy is normal on a coronary angiogram.

Arrested Maturation of Excitatory Synapses in Autosomal Dominant Lateral Temporal Lobe Epilepsy

Nature Medicine. Oct, 2009  |  Pubmed ID: 19701204

A subset of central glutamatergic synapses are coordinately pruned and matured by unresolved mechanisms during postnatal development. We report that the human epilepsy gene LGI1, encoding leucine-rich, glioma-inactivated protein-1 and mutated in autosomal dominant lateral temporal lobe epilepsy (ADLTE), mediates this process in hippocampus. We created transgenic mice either expressing a truncated mutant LGI1 (835delC) found in ADLTE or overexpressing a wild-type LGI1. We discovered that the normal postnatal maturation of presynaptic and postsynaptic functions was arrested by the 835delC mutant LGI1, and contrastingly, was magnified by excess wild-type LGI1. Concurrently, mutant LGI1 inhibited dendritic pruning and increased the spine density to markedly increase excitatory synaptic transmission. Inhibitory transmission, by contrast, was unaffected. Furthermore, mutant LGI1 promoted epileptiform discharge in vitro and kindling epileptogenesis in vivo with partial gamma-aminobutyric acid(A) (GABA(A)) receptor blockade. Thus, LGI1 represents a human gene mutated to promote epilepsy through impaired postnatal development of glutamatergic circuits.

Lack of Clinical Benefit of Improved Angiographic Results with Sirolimus-eluting Stents Compared with Paclitaxel and Zotarolimus-eluting Stents in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Circulation Journal : Official Journal of the Japanese Circulation Society. Dec, 2009  |  Pubmed ID: 19789418

There is limited information regarding the angiographic and clinical outcomes among the different drug-eluting stents (DESs) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI).

[TRPV1 UTR-3 Polymorphism and Susceptibility of Childhood Asthma of the Han Nationality in Beijing]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Sep, 2009  |  Pubmed ID: 19877503

To explore TRPV1 UTR-3 polymorphism and susceptibility of childhood asthma of Han Nationality in Beijing.

Silencing of Claudin-11 is Associated with Increased Invasiveness of Gastric Cancer Cells

PloS One. 2009  |  Pubmed ID: 19956721

Claudins are membrane proteins that play critical roles in tight junction (TJ) formation and function. Members of the claudin gene family have been demonstrated to be aberrantly regulated, and to participate in the pathogenesis of various human cancers. In the present study, we report that claudin-11 (CLDN11) is silenced in gastric cancer via hypermethylation of its promoter region.

Unexpected Coronary Perforation Following Adjunctive Balloon Postdilation After Overlapping Drug-eluting Stent Implantation Rescued by Successful Stent Graft Implantation

International Journal of Cardiology. Feb, 2009  |  Pubmed ID: 17996967

Aberrant Silencing of the Endocrine Peptide Gene Tachykinin-1 in Gastric Cancer

Biochemical and Biophysical Research Communications. Jan, 2009  |  Pubmed ID: 19046942

Tachykinin-1 (TAC1) is the precursor protein for neuroendocrine peptides, including substance P, and is centrally involved in gastric secretion, motility, mucosal immunity, and cell proliferation. Here we report aberrant silencing of TAC1 in gastric cancer (GC) by promoter hypermethylation. TAC1 methylation and mRNA expression in 47 primary GCs and 41 noncancerous gastric mucosae (NLs) were analyzed by utilizing real-time quantitative PCR-based assays. TAC1 methylation was more prevalent in GCs than in NLs: 21 (45%) of 47 GCs versus 6 (15%) of 41 NLs (p<0.01). Microsatellite instability was also associated with TAC1 methylation in GCs. There was no significant association between TAC1 methylation and age, gender, stage, histological differentiation, or the presence of Helicobacter pylori. TAC1 mRNA was markedly downregulated in GCs relative to NLs. 5-Aza-2'-deoxycytidine-induced demethylation of the TAC1 promoter resulted in TAC1 mRNA upregulation. Further studies are indicated to elucidate the functional involvement of TAC1 in gastric carcinogenesis.

Ototoxicity on Cochlear Nucleus Neurons Following Systemic Application of Gentamicin

Acta Oto-laryngologica. Jul, 2009  |  Pubmed ID: 18855163

The gentamicin-induced pathological alteration in the cochlear nucleus is not exclusively a secondary consequence of the damage in the cochlea. Instead, the toxic effect of gentamicin on the cochlear nucleus may occur simultaneously or even earlier than that on the cochlea.

Expression and Localization of K Channels KCNQ2 and KCNQ3 in the Mammalian Cochlea

Audiology & Neuro-otology. 2009  |  Pubmed ID: 18827480

KCNQ1 and KCNQ4 voltage-gated potassium channel subunits play key roles in hearing. Other members of the KCNQ family also encode slow, low voltage-activated K(+) M currents. We have previously reported the presence of M-like K(+) currents in sensory hair cells, and expression of Kcnq family genes in the cochlea. Here, we describe Kcnq2/3 gene expression and distribution of M channel subunits KCNQ2 and 3 in the cochlea. By using RT-PCR, we found expression of Kcnq2 in the modiolus and organ of Corti, while Kcnq3 expression was also detected in the cochlear lateral wall. Five alternative splice variants of the Kcnq2 gene, one of which has not been reported previously, were identified in the rat cochlea. KCNQ2 and KCNQ3 immunoreactivities were observed in spiral ganglion auditory neurons. In addition, the unmyelinated parts of the nerve fibers innervating hair cells and synaptic regions under hair cells showed KCNQ2 immunoreactivity. KCNQ3 immunoreactivity was also prominent in spiral ganglion satellite cells. These findings suggest that cochlear M channels play important roles in regulation of cellular excitability and maintenance of cochlear K(+) homeostasis in the auditory system.

The Optimal Timing for Non-cardiac Surgery After Percutaneous Coronary Intervention with Drug-eluting Stents

International Journal of Cardiology. Mar, 2010  |  Pubmed ID: 19073354

This study was to assess the optimal timing for non-cardiac surgery (NCS) after drug-eluting stents (DES) implantation in patients who are scheduled for NCS. In conclusions, patients undergoing early NCS within 3 months after the PCI with DES may associate with adverse outcomes. Therefore we suggest that NCS should be deferred at least 3 months after the DES implantation.

Polo-like Kinase 1 Regulates Cell Proliferation and is Targeted by MiR-593* in Esophageal Cancer

International Journal of Cancer. Journal International Du Cancer. Dec, 2010  |  Pubmed ID: 21170987

Polo-like kinase 1 (PLK1) is overexpressed in various human cancers. However, the biological functions and the post-transcriptional regulations of PLK1 in esophageal cancer (EC) are still unknown. The purposes of this study are to determine whether PLK1 can be a molecular target of EC therapy, and to identify a microRNA targeting PLK1. We performed loss-of- and gain-of-function experiments regarding cell proliferation, cell cycle, apoptosis, in vivo tumor formation, and luciferase reporter assays, using siRNAs against PLK1 and microRNA. PLK1 protein was expressed in all 11 EC cell lines, but not in normal esophageal epithelial cells (HEEpiC). Knock-down of PLK1 in EC cells induced G2/M arrest (p<0.001) in cell cycle assay, and reduced cell proliferation (p=0.019) and tumor formation ability in vivo (p<0.0001). MiR-593*, identified as a microRNA targeting PLK1 by a database search, was less expressed especially in six EC cell lines than HEEpiC cells. Moreover, miR-593* expression level was inversely correlated with PLK1 mRNA level in 48 clinical tissue specimens of EC (p=0.006). Introduction of synthetic miR-593* suppressed PLK1 expression by 69-73%, reduced cell proliferation (p=0.008), and increased cell proportion of G2/M phase (p=0.01) in HSA/c (an EC cells), whereas a miR-593* inhibitor up-regulated PLK1 expression by 11-55%. Additionally, luciferase assay demonstrated that miR-593* interacted two binding sites in the PLK1 3'-UTR and reduced 56.8-71.5% of luciferase activity by degrading luciferase mRNA in HSA/c cells. In conclusion, PLK1 is post-transcriptionally regulated by miR-593*, and could be a promising molecular target for EC treatment.

Synthesis and Biological Evaluation of 3,6-diaryl-7H-thiazolo[3,2-b] [1,2,4]triazin-7-one Derivatives As Acetylcholinesterase Inhibitors

Archives of Pharmacal Research. Oct, 2010  |  Pubmed ID: 21052939

Acetylcholinesterase (AChE) inhibitors played an important role in developing a cure for Alzheimer' s disease. In order to study on the influence of modifications at different groups and side chains on the AChE inhibitory ability and the active sites of 7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives, fourteen 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives were designed and synthesized. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control drug. Most of the target compounds exhibited more than 50% inhibition at 10 μM. Some target compounds showed strong inhibition against AChE. The molecular fields analysis and preliminary structure-activity relationships are discussed.

Congenital Unilateral Pulmonary Malformation Misdiagnosed As Bronchial Foreign Body: a Review of 14 Cases

Acta Oto-laryngologica. Aug, 2010  |  Pubmed ID: 20105106

Congenital unilateral pulmonary malformation can easily be misdiagnosed as a bronchial foreign body. Although rigid bronchoscopy helps the proper diagnosis, high risks associated with anesthesia and operative complications may limit its application. However, high-resolution computed tomography (CT) and three-dimensional lung reconstruction provide a non-invasive tool to improve the diagnosis of congenital unilateral pulmonary malformation.

Clinical Characteristics and Mid-term Outcomes of Acute Myocardial Infarction Patients with Prior Cerebrovascular Disease in an Asian Population: Lessons from the Korea Acute Myocardial Infarction Registry

Clinical and Experimental Pharmacology & Physiology. May, 2010  |  Pubmed ID: 20105192

1. The aim of the present study was to evaluated the impact of prior cerebrovascular disease (CVD) on the clinical characteristics and mid-term clinical outcomes of patients with acute myocardial infarction (AMI) in the era of drug-eluting stents. 2. Data from 12 914 patients with acute myocardial infarction who were enrolled in the Korea Acute Myocardial Infarction Registry were analysed retrospectively from November 2005 to December 2007. Prior CVD was defined as having had one or more events of ischaemic or haemorrhagic stroke or a transient ischaemic attack. 3. Of the 12 914 patients reviewed, 906 (7.0%) were found to have had prior CVD. Patients with CVD were older, were more likely to be women and were more likely to have hypertension and diabetes than those without CVD. Patients with prior CVD presented more often with non-ST-segment elevation myocardial infarction and higher Killip class than those without CVD. Furthermore, patients with CVD received less percutaneous coronary intervention (PCI) or thrombolysis compared with those without CVD. Although intensive medical therapy was equal in both groups, clinical outcomes at 8 months showed that patients with CVD had a higher incidence of cardiac death (adjusted odds ratio (OR) 1.42; 95% confidence interval (CI) 1.14-1.76; P = 0.002) and total death (adjusted OR 1.50; 95% CI 1.25-1.81; P < 0.001) than those without CVD. 4. In conclusion, patients with prior CVD presented with worse clinical characteristics on admission and were less likely to receive PCI or thrombolysis than those without CVD. Given the poorer mid-term clinical outcomes, more intensive and aggressive management shouldis recommended for patients with prior CVD to improve their long-term clinical outcome.

Fetal Development of the Retrohepatic Inferior Vena Cava and Accessory Hepatic Veins: Re-evaluation of the Alexander Barry's Hypothesis

Clinical Anatomy (New York, N.Y.). Apr, 2010  |  Pubmed ID: 20112350

The retrohepatic inferior vena cava (IVC) is commonly considered to originate from the right vitelline or omphalomesenteric vein. In contrast, Alexander Barry hypothesized that one of the hepatic veins grows to merge with the subcardinal vein and develops into the retrohepatic IVC. We re-examined fetal development of the retrohepatic IVC and other related veins using serial histological sections of 20 human fetuses between 6 and 16 weeks of gestation. At 6-7 weeks, when a basic configuration of the portal-hepatic vein systems had just been established, one of hepatic veins (i.e., the posterocaudal vein in the present study) had grown caudally to reach the posterocaudal surface of the liver, and notably, extended into the primitive right adrenal gland (five of the eight early-staged fetuses). Because the inferior right hepatic vein (IRHV) and retrohepatic IVC appeared at the same developmental stage, it is likely that any peripheral remnants of the posterocaudal vein would continue to function as primary drainage territory for the IRHV. The caudate vein developed rapidly in accordance with marked caudal and leftward extension of Spiegel's lobe at 12-16 weeks. Thin accessory hepatic veins developed later than the caudate vein and IRHV. The present results supported Barry's hypothesis.

Beta-Bungarotoxin Application to the Round Window: an in Vivo Deafferentation Model of the Inner Ear

Hearing Research. Jun, 2010  |  Pubmed ID: 20184947

Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.

Ramification of Glisson's Sheath Peripheral Branches and Clinical Implications in the Era of Local Ablation Therapy

Surgical and Radiologic Anatomy : SRA. Dec, 2010  |  Pubmed ID: 20204636

Classical anatomical resection does not always guarantee tumor-free margins when the tumor overrides traditional anatomical planes. Surgeons and interventionists frequently need to focus on the peripheral branches of Glisson's sheath in patients with poor hepatic reserves, particularly when the tumor is deep seated. The present study used anatomical liver dissection to investigate the spatial distribution of the branches of Glisson's sheath in each of four liver sectors.

Vestibular Morphology in the German Waltzing Guinea Pig

Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-rhino-laryngologie Et De Chirurgie Cervico-faciale. Apr, 2010  |  Pubmed ID: 20211096

The German waltzing guinea pig is a special strain of animal with a recessively inherited inner ear defect, resulting in deafness and a severe vestibular dysfunction. The hearing loss in the cochlea of the German strain is a result of a collapse of the Reissner membrane and the absence of scala media. The vestibular organ has not yet been described.

Clinical Features and Treatment Options for Chinese Patients with Severe Primary Erectile Dysfunction

Urology. Aug, 2010  |  Pubmed ID: 20299080

To investigate clinical features of Chinese patients with severe primary erectile dysfunction (S-PED) and to identify the ideal treatment options for this population.

Low-molecular-weight Heparin Versus Unfractionated Heparin in Acute ST-segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention with Drug-eluting Stents

American Heart Journal. Apr, 2010  |  Pubmed ID: 20362730

Whether low-molecular-weight heparin (LMWH) is superior to unfractionated heparin (UFH) in acute ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) remains unclear.

Fetal Topographical Anatomy of the Pancreatic Head and Duodenum with Special Reference to Courses of the Pancreaticoduodenal Arteries

Yonsei Medical Journal. May, 2010  |  Pubmed ID: 20376893

The purpose of this study is to provide better understanding as to how the "double" vascular arcades, in contrast to other intestinal marginal vessels, develop along the right margin of the pancreatic head.

Fetal Anatomy of Peripheral Lymphatic Vessels: a D2-40 Immunohistochemical Study Using an 18-week Human Fetus (CRL 155 Mm)

Journal of Anatomy. Jun, 2010  |  Pubmed ID: 20408907

We demonstrated fetal peripheral lymphatic vessels (LVs) using D2-40 immunohistochemistry in a whole female fetus (18 weeks of gestation, CRL 155 mm) except for the head. There were abundant LVs in the thyroid gland, lung, stomach, small intestine, rectum and pancreas, whereas no LVs were seen in the parathyroid gland, spleen and adrenal cortex. In the liver, except for the gallbladder bed, LVs were still restricted to around hilar thick portal veins and around the hepatic vein terminals. Subcutaneous LVs were well developed throughout the body even in areas where no or few perforating LVs connected with the deep LVs. The diaphragm contained abundant, dilated LVs in the pleural half of its thickness. LVs were also seen not only along supplying arteries of muscles and cartilage but also along the epimysium and perichondrium. LVs ran in a space between the obliquus internus and transversus abdominis but not between the obliquus internus and obliquus externus. Some tight connective tissues such as the sacrotuberous ligament contained abundant LVs. The intervertebral foramen contained a lymphatic plexus. The present observations provide a better understanding of peripheral lymphatic development. The fetal lymphatic morphology seems not to represent a mini-version of the adult morphology.

Al-Ghorab Shunt Plus Intracavernous Tunneling for Prolonged Ischemic Priapism

Journal of Andrology. Sep-Oct, 2010  |  Pubmed ID: 20467049

To investigate the efficacy and safety of the corpus cavernosum-corpus spongiosum shunt (Al-Ghorab Shunt) plus intracavernous tunneling (CC-CSS+ICT) for prolonged ischemic priapism (PIP). Twelve patients with PIP were enrolled in this study. The mean age of patients was 38.3 ± 9.2 years old and the mean duration of PIP was 2.8 ± 1.0 days (range, 1.5-4 days). All patients received CC-CSS+ICT for treating PIP. The penile hardness score (PHS) and pain visual analogue score (PVAS) were used to assess the efficacy of the surgery 1, 3, and 5 days after surgery. Color duplex Doppler ultrasonography, International Index of Erectile Function, and quality of life (QOL) were used for evaluating penile morphology, erectile function, QOL, and response to sildenafil treatment. The mean duration of follow up was 21.6 ± 10.1 months. Penile detumescence was successfully restored for all 12 patients postsurgery, with the mean PHS and PVAS significantly decreased compared with that presurgery at different time points (1, 3, 5 days postsurgery; P < .001). The cavernosal arterial blood flow observed with the mean PSV at 1, 3, and 5 days postoperation were 17.79 ± 2.04, 19.14 ± 1.58, and 7.73 ± 2.02 cm/s respectively. All patients suffered from corpus cavernosum fibrosis and erectile dysfunction postoperation; only 2 cases (16.7%) with a short duration of PIP (1.5 days) showed response to sildenafil treatment, and 3 cases (25.0%) with severe fibrosis were satisfied with sexual life after excision of penile corpus cavernosum scar and penile prosthesis implantation. The CC-CSS+ICT could quickly reduce penile rigidity and pain for improving the symptoms of PIP and suggests a safe and effective therapeutic method for PIP.

Human Fetal Anatomy of the Coccygeal Attachments of the Levator Ani Muscle

Clinical Anatomy (New York, N.Y.). Jul, 2010  |  Pubmed ID: 20544951

In contrast to the attachments to the pubis and rectum, there is little information on fetal development of the coccygeal attachment of the levator ani muscles. We find that at 9 weeks, the coccygeus muscle is a large muscle facing the piriformis or gluteus maximus and inserting onto the ischial spine, whereas the levator ani is restricted to the area near the pubis. By 12 weeks, the levator ani also obtains attachment to the ischial spine immediately ventral to the coccygeus muscle. The most superior part of the coccygeus muscle occupies a space at an angle between the pelvic splanchnic and pudendal nerves. Notably, medial to the coccygeus muscle, a third parasagittal muscle (previously termed the sacrococcygeus anterior) appears by 12 weeks, increases in mass by 18 weeks, and connects and mixes with the dorsal end of the levator ani by 18-20 weeks. Thus, the coccygeal attachment of the levator ani appears not to depend on the dorsal extension of the muscle itself but on fusion with the sacrococcygeus anterior. Therefore, the final levator sheet is formed medial (internal) to the coccygeus muscle and originates from two distinct anlage.

Relation Between Normal Rectal Methylation, Smoking Status, and the Presence or Absence of Colorectal Adenomas

Cancer. Oct, 2010  |  Pubmed ID: 20572039

Colorectal cancer (CRC) is 1 of the leading causes of death in the Western world. CRC develops from premalignant lesions, chiefly colorectal adenomas. Currently, the most accurate and recommended screening method for finding colorectal adenomas is colonoscopy performed on all individuals aged>50 years. However, the costs and risks associated with this procedure are relatively high. The objectives of the current study were to correlate epigenetic alterations that occur in normal rectal mucosa, smoking status, and age with the presence or absence of concomitant colorectal adenomas and to assess the potential clinical value of methylation in normal rectal biopsies as a screening assay for the presence of polyps and, hence, the need for a full colonoscopy.

A Comparison Between D2-40 and C-KIT Immunohistochemistry for the Human Fetal Testis and Ovary at the Second Trimester of Gestation

Okajimas Folia Anatomica Japonica. May, 2010  |  Pubmed ID: 20715565

Both M2A (D2-40) and c-KIT have frequently been used as markers of germ cell tumors. However, comparative studies of their immunoreactivities in human fetal gonads have been limited. Using horizontal semiserial whole-abdomen sections of 9 human abortuses at 12 weeks (2 males and 1 females; CRL 70-80 mm), 15 weeks (2 males and 3 females; 115-125 mm) and 18 weeks (1 female; 155 mm) of gestation, we identified germ cells in the testis and ovary on the basis of c-KIT immunoreactivity. M2A was also stained using near or adjacent sections. In 12-week fetuses, c-KIT immunoreactivity was weak, but M2A immunoreactivity was consistently strong. At 15 and 18 weeks of gestation, c-KIT immunoreactivity was found in most germ cells. M2A was expressed in Sertoli cells as well as in germ cells, but was not expressed in ovarian follicles undergoing meiosis. M2A appears to be a more useful marker of germ cells than c-KIT in human fetal testis and ovary at the second trimester. M2A is also reactive in fetal Sertoli cells, but its expression is consistently weaker than in germ cells.

Developmental Changes in the Distribution of Calretinin-immunoreactive Cells in Human Fetal Nasal Epithelium

Okajimas Folia Anatomica Japonica. May, 2010  |  Pubmed ID: 20715566

Immunoreactivity of the calcium binging protein calretinin is often used as a marker of olfactory neurons. Although the immunoreactivity and density of olfactory neurons are known to change between developmental stages in the human fetus, previous descriptions have been limited to the olfactory epithelium and/or the nasal septum and have not included the entire nasal cavity. Using horizontal semi serial sections of heads of six mid-term fetuses (9-15 weeks of gestation), we examined the topographical anatomy of calretinin-positive olfactory neurons. By 9 weeks of gestation, the distribution of calretinin-positive cells reached levels inferior to the developing inferior meatus. By 12 weeks, concentrations in the inferior end had reached the level of the inferior meatus and the middle meatus carried abundant positive cells. However, by 15 weeks, calretinin positive cells were restricted to levels superior to the middle meatus and in the vomeronasal organ. Placode-derived cells are initially distributed antero-inferiorly along the nasal epithelium, but most lose their calretinin immunoreactivity. They might differentiate into the neuroendocrine cells embedded between nasal respiratory epithelial cells. The final differentiation of calretinin-positive cells was likely to require connection to the olfactory bulb and accessory bulb.

[Clinical Efficacy and Patient Satisfaction with Penile Prosthesis Implantation for the Treatment of Severe Erectile Dysfunction]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Aug, 2010  |  Pubmed ID: 20721254

To investigate the clinical efficacy and patient and partner's satisfaction with penile prosthesis implantation (PPI) for treating Chinese patients with severe erectile dysfunction (SED).

[Corpus Cavernosum-corpus Spongiosum Shunt Plus Intracavernous Tunneling for the Treatment of Prolonged Ischemic Priapism]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Aug, 2010  |  Pubmed ID: 20721256

To investigate the efficacy and safety of corpus cavernosum-corpus spongiosum shunt (CC-CSS) plus intracavernous tunneling(CC-CSS+ICT) for the treatment of prolonged ischemic priapism (PIP) were investigated.

Dynamic Changes in the Expression of MicroRNA-31 During Inflammatory Bowel Disease-associated Neoplastic Transformation

Inflammatory Bowel Diseases. Jan, 2011  |  Pubmed ID: 20848542

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer. Aberrant microRNA (miR) expression has been linked to carcinogenesis; however, no reports document a relationship between IBD-related neoplasia (IBDN) and altered miR expression. In the current study we sought to identify specific miR dysregulation along the normal-inflammation-cancer axis.

Contribution of the Anterior Longitudinal Ligament to Ossification and Growth of the Vertebral Body: an Immunohistochemical Study Using the Human Fetal Lumbar Vertebrae

Surgical and Radiologic Anatomy : SRA. Jan, 2011  |  Pubmed ID: 20852859

Using 15 mid-term human fetuses, we examined the role of the spine anterior and posterior longitudinal ligaments (ALL, PLL) in ossification of the lumbar vertebral body. By 18 weeks, a pair of calcified tissue or cortical walls had developed on the anterior and posterior sides of the ossification center. These calcified cortical walls were more highly eosinophilic than trabecular or woven bone in the ossification center. Vimentin-positive osteoblasts were arranged in line along the outer surface of the walls. However, few CD68-positive osteoclasts were evident around the walls, suggesting that the calcification in the walls was similar to periosteal ossification. The anterior cortical wall was connected tightly with the ALL by fiber bundles, but the posterior wall was separated from the PLL by the basivertebral (central) vein and loose tissues. Notably, by 30 weeks, the anterior cortical wall had become attached to and incorporated into the ALL. Thus, the ALL seemed to act as an active periosteum for ossification. Although our materials were limited in number and stage, we hypothesized that, in contrast to the PLL, the mature anterior cortical wall corresponds to a calcified fibrocartilage adjacent to the ALL and forms a bone-ligament interface maintaining an ossification potential.

Identification of the Anterior Sectoral Trunk with Particular Reference to the Hepatic Hilar Plate and Its Clinical Importance

Surgery. Feb, 2011  |  Pubmed ID: 20079912

At the hilum of the liver, there is a structure called the hilar plate, which is of great surgical importance because all variations in the bile ducts and blood vessels occur within this region. The Rex-Cantlie line does not always pass the point of portal bifurcation. Classifying portal vein (PV) variations based on the shape and origin of anterior sectoral trunk (AST) within the hepatic plate system will be of higher anatomical and surgical value than the conventional method based on PV ramification.

Adeno-associated Viral Vector-mediated Expression of NT4-ADNF-9 Fusion Gene Protects Against Aminoglycoside-induced Auditory Hair Cell Loss in Vitro

Acta Oto-laryngologica. Feb, 2011  |  Pubmed ID: 21062116

The present study suggests that adeno-associated viral vector AAV2-mediated expression of activity-dependent neurotrophic factor-9 (ADNF-9) in the cochlea could be a promising approach to protect the cochlea from aminoglycoside-induced impairment, although a further in vivo study is needed.

Increased GABA(A) Channel Subunits Expression in CD8(+) but Not in CD4(+) T Cells in BB Rats Developing Diabetes Compared to Their Congenic Littermates

Molecular Immunology. Jan, 2011  |  Pubmed ID: 21112637

GABA (γ-aminobutyric acid), the main inhibitory neurotransmitter in the central nervous system is also present in the pancreatic islet β cells where it may function as a paracrine molecule and perhaps as an immunomodulator of lymphocytes infiltrating the pancreatic islet. We examined CD4(+) and CD8(+) T cells from diabetes prone (DR(lyp/lyp)) or resistant (DR(+/+)) congenic biobreeding (BB) rats for expression of GABA(A) channels. Our results show that BB rat CD4(+) and CD8(+) T cells express α1, α2, α3, α4, α6, β3, γ1, δ, ρ1 and ρ2 GABA(A) channel subunits. In CD8(+) T cells from DR(lyp/lyp) animals the subunits were significantly upregulated relative to expression levels in the CD8(+) T cells from DR(+/+) rats as well as from CD4(+) T cells from both DR(lyp/lyp) and DR(+/+) rats. Functional channels were formed in the T cells and physiological concentrations of GABA (100 nM) decreased T cell proliferation. Our results are consistent with the hypothesis that GABA in the islets of Langerhans may diminish inflammation by inhibition of activated T lymphocytes.

Tissue Engineering Penoplasty with Biodegradable Scaffold Maxpol-T Cografted Autologous Fibroblasts for Small Penis Syndrome

Journal of Andrology. Sep-Oct, 2011  |  Pubmed ID: 21164145

In this study, we investigated the safety and efficacy of a poly acid-co-glycolide biodegradable scaffold (Maxpol-T) coated by autologous fibroblasts (AF) for penile girth enlargement in small penis syndrome (SPS). Eighty patients with SPS were enrolled in a clinical study at 2 medical centers; 69 patients completed the study protocol. Scrotal skin was harvested under local anesthesia, and AFs were cultured and seeded on a Maxpol-T scaffold; the cografted scaffold was implanted under the Buck's fascia of penile shaft via a circumcising incision. Patients were followed up at 1, 3, and 6 months to evaluate penile girth changes. Patient satisfaction was assessed via Visual Analogue Scale and scored on the International Index of Erectile Function-5 (IIEF-5). Mean preoperative penile girth in the flaccid and erect state was 8.18 ± 0.83 cm and 10.26 ± 1.22 cm, respectively. At the 6-month postoperative follow-up, mean penile girth in the flaccid and erect state was increased to 12.19 ± 1.27 cm and 13.18 ± 1.31 cm, respectively (P < .001 for change in both flaccid and erect state). Sixty-five patients (94.2%) reported satisfaction with the procedure. Among them, 4 cases (5.8%) were dissatisfied, 7 cases (10.1%) were satisfied, 26 cases (37.7%) were very satisfied, and 32 cases (46.4%) were extremely satisfied. All men maintained IIEF-5 scores of more than 22. Complications included prolonged subcutaneous edema in 3 patients (4.3%) and pinpoint erosion at the suture area in 3 patients (4.3%). Implantation of autologous fibroblasts seeded on a Maxpol-T collagen scaffold holds promise as a safe and novel technique for penile girth enhancement in patients with SPS.

GABA is an Effective Immunomodulatory Molecule

Amino Acids. Dec, 2011  |  Pubmed ID: 22160261

In recent years, it has become clear that there is an extensive cross-talk between the nervous and the immune system. Somewhat surprisingly, the immune cells themselves do express components of the neuronal neurotransmitters systems. What role the neurotransmitters, their ion channels, receptors and transporters have in immune function and regulation is an emerging field of study. Several recent studies have shown that the immune system is capable of synthesizing and releasing the classical neurotransmitter GABA (γ-aminobutyric acid). GABA has a number of effects on the immune cells such as activation or suppression of cytokine secretion, modification of cell proliferation and GABA can even affect migration of the cells. The immune cells encounter GABA when released by the immune cells themselves or when the immune cells enter the brain. In addition, GABA can also be found in tissues like the lymph nodes, the islets of Langerhans and GABA is in high enough concentration in blood to activate, e.g., GABA-A channels. GABA appears to have a role in autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis and may modulate the immune response to infections. In the near future, it will be important to work out what specific effects GABA has on the function of the different types of immune cells and determine the underlying mechanisms. In this review, we discuss some of the recent findings revealing the role of GABA as an immunomodulator.

Selective Changes of GABA(A) Channel Subunit MRNAs in the Hippocampus and Orbitofrontal Cortex but Not in Prefrontal Cortex of Human Alcoholics

Frontiers in Cellular Neuroscience. 2011  |  Pubmed ID: 22319468

Alcohol dependence is a common chronic relapsing disorder. The development of alcohol dependence has been associated with changes in brain GABA(A) channel-mediated neurotransmission and plasticity. We have examined mRNA expression of the GABA(A) channel subunit genes in three brain regions in individuals with or without alcohol dependence using quantitative real-time PCR assay. The levels of selective GABA(A) channel subunit mRNAs were altered in specific brain regions in alcoholic subjects. Significant increase in the α1, α4, α5, β1, and γ1 subunit mRNAs in the hippocampal dentate gyrus region, and decrease in the β2 and δ subunit mRNAs in the orbitofrontal cortex were identified whereas no changes in the dorsolateral prefrontal cortex were detected. The data increase our understanding of the role of GABA(A) channels in the development of alcohol dependence.

Horseradish Peroxidase Dye Tracing and Embryonic Statoacoustic Ganglion Cell Transplantation in the Rat Auditory Nerve Trunk

Brain Research. Mar, 2011  |  Pubmed ID: 21215730

At present severe damage to hair cells and sensory neurons in the inner ear results in non-treatable auditory disorders. Cell implantation is a potential treatment for various neurological disorders and has already been used in clinical practice. In the inner ear, delivery of therapeutic substances including neurotrophic factors and stem cells provide strategies that in the future may ameliorate or restore hearing impairment. In order to describe a surgical auditory nerve trunk approach, in the present paper we injected the neuronal tracer horseradish peroxidase (HRP) into the central part of the nerve by an intra cranial approach. We further evaluated the applicability of the present approach by implanting statoacoustic ganglion (SAG) cells into the same location of the auditory nerve in normal hearing rats or animals deafened by application of β-bungarotoxin to the round window niche. The HRP results illustrate labeling in the cochlear nucleus in the brain stem as well as peripherally in the spiral ganglion neurons in the cochlea. The transplanted SAGs were observed within the auditory nerve trunk but no more peripheral than the CNS-PNS transitional zone. Interestingly, the auditory nerve injection did not impair auditory function, as evidenced by the auditory brainstem response. The present findings illustrate that an auditory nerve trunk approach may well access the entire auditory nerve and does not compromise auditory function. We suggest that such an approach might compose a suitable route for cell transplantation into this sensory cranial nerve.

Insulin Reduces Neuronal Excitability by Turning on GABA(A) Channels That Generate Tonic Current

PloS One. 2011  |  Pubmed ID: 21264261

Insulin signaling to the brain is important not only for metabolic homeostasis but also for higher brain functions such as cognition. GABA (γ-aminobutyric acid) decreases neuronal excitability by activating GABA(A) channels that generate phasic and tonic currents. The level of tonic inhibition in neurons varies. In the hippocampus, interneurons and dentate gyrus granule cells normally have significant tonic currents under basal conditions in contrast to the CA1 pyramidal neurons where it is minimal. Here we show in acute rat hippocampal slices that insulin (1 nM) "turns on" new extrasynaptic GABA(A) channels in CA1 pyramidal neurons resulting in decreased frequency of action potential firing. The channels are activated by more than million times lower GABA concentrations than synaptic channels, generate tonic currents and show outward rectification. The single-channel current amplitude is related to the GABA concentration resulting in a single-channel GABA affinity (EC(50)) in intact CA1 neurons of 17 pM with the maximal current amplitude reached with 1 nM GABA. They are inhibited by GABA(A) antagonists but have novel pharmacology as the benzodiazepine flumazenil and zolpidem are inverse agonists. The results show that tonic rather than synaptic conductances regulate basal neuronal excitability when significant tonic conductance is expressed and demonstrate an unexpected hormonal control of the inhibitory channel subtypes and excitability of hippocampal neurons. The insulin-induced new channels provide a specific target for rescuing cognition in health and disease.

Fetal Head Anomaly Restricted to the Eye, the Mandible, and the Pterygoid Process of the Sphenoid: a Histological Study

Clinical Anatomy (New York, N.Y.). Jul, 2011  |  Pubmed ID: 21400609

A report on an unusual combination of anomalies in the head of a female fetus. The authors examined whole body semiserial paraffin sections of a female fetus (155 mm CRL; ∼18 weeks of gestation), with a particular focus on the head region. Cranial autonomic ganglia, nasal olfactory cells, and the orbital muscle were investigated using immunohistochemistry for tyrosine hydroxylase, vasoactive intestinal peptide, calretinin, and smooth muscle actin expression. The surface gross anatomy of the fetus appeared normal. The left eyeball lacked a lens (the eyeballs were otherwise normal). The orbital muscle was very thick and located in the anterolateral side of the extraocular muscles. Conversely, the extraocular muscles made a cluster in the superoposterior side of the orbit. The infratemporal fossa was small due to the bulky, transversely extended lateral pterygoid process in contrast to the small coronoid process of the mandible. The bilateral mandibular bases overlapped at the midline symphysis. The thin orbitosphenoid and thick alisphenoid provided an almost flat, anterior cranial base. Nasal olfactory cells and cranial autonomic ganglia appeared to be normal. No major anomaly was observed in the brain. Because of the changes in topographical anatomy, the orbital muscle probably lost its normal bony attachment and appeared to push the extraocular muscles superoposteriorly. A gene function redundancy rather than mutation may explain the present restricted anomalies in the mandible and pterygoid process.

Current Therapeutic Strategies for Premature Ejaculation and Future Perspectives

Asian Journal of Andrology. Jul, 2011  |  Pubmed ID: 21532601

Premature ejaculation (PE) is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used 'off-label', some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE.

An Open, Comparative, Multicentre Clinical Study of Combined Oral Therapy with Sildenafil and Doxazosin GITS for Treating Chinese Patients with Erectile Dysfunction and Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

Asian Journal of Andrology. Jul, 2011  |  Pubmed ID: 21602833

This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction (ED) and lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH/LUTS). The trial was conducted in hospitals in Beijing, Shanghai, Changsha, Wuhan and Guangzhou, five major cities in China. A total of 250 patients diagnosed with ED and BPH/LUTS aged 50-75 years, and who had International Index of Erection Function-5 (IIEF-5) scores ≤21 and International Prostate Symptom Score (IPSS) ≥10 points, were enrolled and randomly divided into Group A (168 cases; doxazosin GITS 4 mg once daily plus sildenafil 25-100 mg on demand) and Group B (82 cases; sildenafil 25-100 mg on demand). Efficacies were evaluated by IIEF-5 and IPSS scores and a quality of life (QoL) questionnaire, and adverse effects were evaluated during the treatment period. There were no statistically significant differences in mean age, and IIEF-5, IPSS and QoL scores pre-treatment between the two groups. After treatment, IIEF-5, IPSS and QoL scores were significantly improved in Group A, while only IIEF-5 scores were significantly improved in Group B compared with pre-treatment. There were no significant differences in side effects between the two groups. The results indicated that combined therapy with sildenafil and doxazosin GITS for the treatment of ED and BPH/LUTS is safe and effective compared to sildenafil monotherapy.

Computer-assisted Three-dimensional Reconstruction of the Fetal Pancreas Including the Supplying Arteries According to Immunohistochemistry of Pancreatic Polypeptide

Surgical and Radiologic Anatomy : SRA. Jun, 2011  |  Pubmed ID: 21713410

PURPOSE: Computer-assisted three-dimensional reconstruction of the fetal human pancreas was prepared to reconsider topographical relation between the dorsal/ventral anlagen and the vascular supply. METHODS: Tissue sections from the upper abdominal viscera of three fetuses were examined. Sections were immunohistochemically stained to determine pancreatic polypeptide expression, a marker of the ventral pancreas. RESULTS: The immunohistochemical findings were used to create three-dimensional computer-assisted reconstructions to identify pancreatic arteries. The narrowest part of the pancreas, or the neck, corresponding to a part of the dorsal pancreas, was located on the left side of the common bile duct, portal vein and gastroduodenal artery (GDA). The posterior arterial arcade accompanied the ventral pancreas, whereas the anterior arcade did not. In contrast to the GDA, the splenic artery was clearly separated from the neck in fetuses. The GDA appears to be the primary and stable arterial supply for the neck of the pancreas. CONCLUSIONS: This observation may have implications for the preservation of the neck with the GDA during pancreaticoduodenectomy for benign and low-grade malignant diseases.

[Treatments of Erectile Dysfunction Combined with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasis]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Aug, 2011  |  Pubmed ID: 21844982

Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH/LUTS) and erectile dysfunction (ED) are common conditions seen in aging males. Although the exact mechanism of ED combined BPH/LUTS is unknown, treatment with α-adrenergic receptor resistance agents (α-ARAs) contributes to some improvement in ED, and phosphodiesterase-5 inhibitors (PDE-5I) are also of benefit to BPH/LUTS. The action mechanisms of these medications support these observed benefits, which are being studied in the basic science and clinical settings. Much remains to be investigated, but it is clear that the associations between BPH/LUTS and ED lay the foundation for future therapies and possible preventative strategies. This article has mainly summarized the advancement of epidemiology, basic research and treatment of ED combined with BPH/LUTS with α-receptor blockers and phosphodiesterase-5 inhibitors.

Multivessel Versus Single Vessel Spasm, As Assessed by the Intracoronary Acetylcholine Provocation Test, in Korean Patients

Clinical and Experimental Pharmacology & Physiology. Dec, 2011  |  Pubmed ID: 21933225

1. Coronary artery spasm (CAS) is known to be a major cause of myocardial ischaemia. Multivessel coronary spasm (MVS) in particular is likely to induce more severe and prolonged myocardial ischaemia than single vessel spasm (SVS). 2. In the present study, a total of 1082 consecutive patients without significant coronary artery disease who underwent an acetylcholine (ACh) provocation test between March 2004 and April 2009 were investigated. Patients were divided into three groups: an MVS group (n = 275), an SVS group (n = 376) and a non-CAS group (n = 431). Differences in clinical and angiographic characteristics following the ACh provocation test were evaluated between the MVS, SVS and non-CAS groups. 3. At baseline, patients in the MVS group had the highest prevalence of peripheral artery disease (PAD), hyperlipidaemia, smoking and old age, as well as the highest triglyceride levels. Calcium channel blockers were most frequently prescribed in MVS patients before the ACh test. During the ACh test, the highest prevalence of chest pain, ischaemic electrocardiogram changes, baseline spasms and diffuse and severe spasms were observed in the MVS group. The response rate to lower ACh doses that induce CAS was also higher in the MVS group. Multivariate analysis showed that the presence of PAD (odds ratio (OR) 2.0; P = 0.006) and baseline spasm (OR 1.4; P = 0.045) were independent predictors of ACh-induced MVS. 4. In conclusion, ischaemic symptoms, diffuse and severe spasm and baseline spasm were more frequently associated with MVS patients, suggesting more intensive medical therapies and close clinical follow up would be required for this patient group.

The Evaluation of Basic Fibroblast Growth Factor and Fibroblastic Growth Factor Receptor 1 Levels in Saliva and Serum of Patients with Salivary Gland Tumor

DNA and Cell Biology. Sep, 2011  |  Pubmed ID: 21942441

Basic fibroblast growth factor (FGF2) is a well-known endothelial mitogen that regulates endothelial cell proliferation, migration, differentiation, and survival. In the present study, we investigated the levels of FGF2 and fibroblastic growth factor receptor 1 (FGFR1) in saliva and serum of patients with salivary gland tumors. Saliva and serum samples were collected from 43 patients with salivary gland tumors and 40 healthy volunteers. The FGF2 and FGFR1 concentrations in saliva and serum samples were measured by enzyme-linked immunosorbent assay. We found that the levels of FGF2 and FGFR1 in saliva and serum from patients with salivary gland tumors were significantly higher than those from healthy control subjects. These results suggest that salivary FGF2 and FGFR1 can be used as potential biomarkers in the diagnosis of salivary gland tumors.

Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice

Science Translational Medicine. Oct, 2011  |  Pubmed ID: 21974935

People with autism spectrum disorder are characterized by impaired social interaction, reduced communication, and increased repetitive behaviors. The disorder has a substantial genetic component, and recent studies have revealed frequent genome copy number variations (CNVs) in some individuals. A common CNV that occurs in 1 to 3% of those with autism--maternal 15q11-13 duplication (dup15) and triplication (isodicentric extranumerary chromosome, idic15)--affects several genes that have been suggested to underlie autism behavioral traits. To test this, we tripled the dosage of one of these genes, the ubiquitin protein ligase Ube3a, which is expressed solely from the maternal allele in mature neurons, and reconstituted the three core autism traits in mice: defective social interaction, impaired communication, and increased repetitive stereotypic behavior. The penetrance of these autism traits depended on Ube3a gene copy number. In animals with increased Ube3a gene dosage, glutamatergic, but not GABAergic, synaptic transmission was suppressed as a result of reduced presynaptic release probability, synaptic glutamate concentration, and postsynaptic action potential coupling. These results suggest that Ube3a gene dosage may contribute to the autism traits of individuals with maternal 15q11-13 duplication and support the idea that increased E3A ubiquitin ligase gene dosage results in reduced excitatory synaptic transmission.

Low Molecular Weight Heparin Versus Unfractionated Heparin in Patients with Acute Non-ST-segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention with Drug-eluting Stents

Journal of Cardiology. Jan, 2012  |  Pubmed ID: 22079855

Whether low molecular weight heparin (LMWH) enoxaparin is equivalent to unfractionated heparin (UFH) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear.

Epigenomic Program of Barrett's-associated Neoplastic Progression Reveals Possible Involvement of Insulin Signaling Pathways

Endocrine-related Cancer. 2012  |  Pubmed ID: 22194443

Extracranial and Intracranial Complications of Otitis Media: 22-year Clinical Experience and Analysis

Acta Oto-laryngologica. Jan, 2012  |  Pubmed ID: 22224578

Abstract Conclusion: The morbidity of the complications has had a decreased tendency in recent decades, but the category of the complications was rather diverse. There are still many serious complications that require our attention. Surgery is still the most important treatment option. Objective: To investigate otogenic extracranial and intracranial complications in patients with acute and chronic otitis media. Methods: A retrospective study investigated 285 patients with extracranial and intracranial complications among the 2346 inpatients with acute or chronic otitis media with or without cholesteatoma admitted to the Department of Otolaryngology, AnHui Medical University Hospital between 1987 and 2008. Results: In the 285 patients with cranial complications, 253 had a single complication, 29 had two complications, and 3 had more than two complications. Intracranial complications included meningitis (16 cases), brain abscess (42 cases), sigmoid sinus involvement (29 cases), extradural abscess (8 cases), subdural abscess (1 case), and hydrocephalus (2 cases). Extracranial complications included labyrinthitis (90 cases), mastoid abscess (79 cases), facial paralysis (47 cases), Bezold abscess (5 cases), and apicitis pyramidalis (1 case). In all, 267 patients were cured or improved without recurrence. Five patients died from complications, of whom four died of cerebral hernia and one died of multiple abscesses.