Apoptosis Induced by Norcantharidin in Human Tumor Cells

World Journal of Gastroenterology : WJG. Apr, 2000  |  Pubmed ID: 11819571

Developmental Dissociation of T Cells from B, NK, and Myeloid Cells Revealed by MHC Class II-specific Chimeric Immune Receptors Bearing TCR-zeta or FcR-gamma Chain Signaling Domains

Blood. Oct, 2002  |  Pubmed ID: 12351421

The T-cell receptor zeta (TCR-zeta) and FcR-gamma chains play a critical role in mediating signal transduction. We have previously described HIV glycoprotein 120 (gp120)-specific chimeric immune receptors (CIRs) in which the extracellular domain of CD4 is linked to the signaling domain of zeta (CD4zeta) or gamma (CD4gamma). Such CIRs are efficiently expressed following retroviral transduction of mature T cells and specifically redirect effector functions toward HIV-infected targets. In this report, we examine development of CD4zeta- or CD4gamma-expressing T cells from retrovirally transduced hematopoietic stem cells following bone marrow transplantation. Although CD4zeta/gamma-expressing myeloid, NK, and B cells were efficiently reconstituted, parallel development of CD4zeta/gamma-expressing T cells was blocked prior to the CD25(+)CD44(+) prothymocyte stage. In contrast, T cells expressing a signaling-defective CIR were efficiently generated. When major histocompatibility complex (MHC) class II-deficient mice were used as transplant recipients, development of CD4zeta/gamma-expressing T cells was restored. We conclude that CD4zeta/gamma signaling generated following engagement of MHC class II selectively arrests T-lineage development.

Anti-platelet Aggregation and Chemical Constituents from the Rhizome of Gynura Japonica

Planta Medica. Aug, 2003  |  Pubmed ID: 14531028

A novel quinonoid terpenoid, (-)- alpha-tocospirone, a new chromanone, (-)-gynuraone, as well as three new steroids, (22 E,24 S)-7 alpha-hydroperoxystigmasta-5,22-dien-3 beta-ol, (22 E,24 S)-stigmasta-1,4,22-trien-3-one, and (24 R)-stigmasta-1,4-dien-3-one, together with 15 known components, were isolated from the rhizome of Formosan Gynura japonica. Structures of the new compounds were determined through spectral analyses and chemical evidence. Several of the isolated compounds, caryophyllene oxide, 6-acetyl-2,2-dimethylchroman-4-one, vanillin, 2,6-dimethoxy-1,4-benzoquinone, and benzoic acid exhibited significant anti-platelet aggregation activity in vitro.

Renal Angiomyolipoma with Lymph Node Involvement: a Case Report and Literature Review

Chang Gung Medical Journal. Aug, 2003  |  Pubmed ID: 14609043

Renal angiomyolipomas (AMLs) are relatively common tumors containing fatty tissue, blood vessels, and muscular cells in various proportions. Typical AMLs can be diagnosed without histological confirmation by a combination of ultrasound and computed tomography imaging in up to 95% of cases. In contrast, simultaneous involvement of the kidney, renal vein, or lymph nodes is uncommon and might be confused with a metastasizing malignant tumor. We present a pathologically proven case of the very uncommon simultaneous involvement of the kidney and the lymph nodes in AML.

The Methylenetetrahydrofolate Reductase 677C-->T Polymorphism and Lung Cancer Risk in a Chinese Population

Anticancer Research. Nov-Dec, 2003  |  Pubmed ID: 14981981

We examined the relationship of the MTHFR C677T genotype with the risk of lung cancer in a nested case-control study conducted in a cancer screening follow-up study in Taiwan.

A New Aristolactam Alkaloid and Anti-platelet Aggregation Constituents from Piper Taiwanense

Planta Medica. Feb, 2004  |  Pubmed ID: 14994198

A new alkaloid, piperolactam E, and fourteen known compounds have been isolated from the stem of Piper taiwanense. Bioassay-guided fractionation of the methanolic extract led to the isolation, from the chloroform-soluble part, of 4-allylcatechol, eugenol, trans-caffeic aldehyde, 2-hydroxy-1-methoxy-4 H-dibenzo[ de,g]quinoline-4,5-(6 H)-dione, piperolactam B, piperolactam C, and piperolactam E as the active principles of anti-platelet aggregation in vitro. The derived 1,2-diacetoxy-4-allyl-benzene and eugenol acetate exhibit stronger anti-platelet aggregation activities induced by arachidonic acid than 4-allylcatechol and eugenol, respectively.

Comparison Between Extracorporeal Shock Wave Lithotripsy and Semirigid Ureterorenoscope with Holmium:YAG Laser Lithotripsy for Treating Large Proximal Ureteral Stones

The Journal of Urology. Nov, 2004  |  Pubmed ID: 15540749

Management of large impacted upper ureteral calculi remains challenging for urologists. These calculi are frequently associated with obstructive uropathy and deteriorated renal function. Extracorporeal shock wave lithotripsy (SWL) is the least invasive treatment but its success rate is decreased for large impacted upper ureteral calculi. According to the American Urological Association guidelines on ureteral stones published in 1997, the appropriateness of ureteroscopy decreases when stone size exceeds 1 cm. However, the application of advanced ureteroscopy and techniques has increased the success rate of treating proximal ureter calculi. In this study we compared the safety and efficacy of ureterorenoscopic holmium:YAG laser lithotripsy (URSL) with SWL for large impacted proximal ureteral stones.

The MTHFR C677T Polymorphism, Estrogen Exposure and Breast Cancer Risk: a Nested Case-control Study in Taiwan

Anticancer Research. Nov-Dec, 2004  |  Pubmed ID: 15736423

We evaluated the effects of the MTHFR C677T polymorphism and its interaction with estrogen exposure on breast cancer risk in a nested case-control study conducted in Taiwan.

Therapeutic Options for Proximal Ureter Stone: Extracorporeal Shock Wave Lithotripsy Versus Semirigid Ureterorenoscope with Holmium:yttrium-aluminum-garnet Laser Lithotripsy

Urology. Jun, 2005  |  Pubmed ID: 15893812

To compare the safety and cost-effectiveness of ureterorenoscopic holmium:yttrium-aluminum-garnet (YAG) laser lithotripsy (URSL) with extracorporeal shock wave lithotripsy (ESWL) for proximal ureteral stones.

Genetic Polymorphisms of FAS and FASL (CD95/CD95L) Genes in Cervical Carcinogenesis: An Analysis of Haplotype and Gene-gene Interaction

Gynecologic Oncology. Oct, 2005  |  Pubmed ID: 15996722

Whereas human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis, host genetic variations may confer individual susceptibility. Resistance to apoptosis is a hallmark of cancer in which FAS/FAS ligand signaling plays an important role. The present study examines the hypothesis that genetic polymorphisms in FAS and FAS ligand genes, alone or in combination, are associated with cervical carcinogenesis.

Polymorphic Catechol-O-methyltransferase Gene, Duration of Estrogen Exposure, and Breast Cancer Risk: a Nested Case-control Study in Taiwan

Cancer Detection and Prevention. 2005  |  Pubmed ID: 16191465

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens, which are hypothesized to participate in estrogen-induced carcinogenesis.

On the Rigidity of Polynorbornenes with Dipolar Pendant Groups

Chemistry (Weinheim an Der Bergstrasse, Germany). Dec, 2005  |  Pubmed ID: 16278915

A range of polynorbornenes (PNBs) with fused dipolar pendant groups at C-5,6 positions was synthesized by ring-opening metathesis polymerization catalyzed by a ruthenium carbene complex (Grubbs I). Photophysical studies, EFISH measurements, and atomic force microscopy images have been used to investigate the structures and morphology of these polymers. These results suggest that the polymers may adopt rigid rod-like structures. The presence of the double bonds in PNBs appeared to be indispensable for the rigidity of the polymers. Interaction between unsaturated pendant groups may result in coherent alignment leading to a rod-like structure.

Clinical Observations of the Effect of Antidiuretic Hormone on Nocturia in Elderly Men

BJU International. Dec, 2005  |  Pubmed ID: 16287451

To evaluate the effect of desmopressin on nocturia, based on patients' subjective scoring of nocturia, as desmopressin is widely used to treat nocturnal enuresis and nocturnal polyuria.

[Experimental Study on Conduction of Gong Tonality Vibromusic Sound Wave in the Healthy Human Body]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Feb, 2005  |  Pubmed ID: 16312894

To study the conduction of Gong tonality vibromusic sound wave along meridians in healthy human body, and investigate differences of the sensitivity of different meridians and genders to this vibromusic message.

Importance of Cellular Microenvironment and Circulatory Dynamics in B Cell Immunotherapy

Journal of Immunology (Baltimore, Md. : 1950). Jan, 2005  |  Pubmed ID: 15634903

B cell immunotherapy has emerged as a mainstay in the treatment of lymphomas and autoimmune diseases. Although the microenvironment has recently been demonstrated to play critical roles in B cell homeostasis, its contribution to immunotherapy is unknown. To analyze the in vivo factors that regulate mechanisms involved in B cell immunotherapy, we used a murine model for human CD20 (hCD20) expression in which treatment of hCD20(+) mice with anti-hCD20 mAbs mimics B cell depletion observed in humans. We demonstrate in this study that factors derived from the microenvironment, including signals from the B cell-activating factor belonging to the TNF family/BLyS survival factor, integrin-regulated homeostasis, and circulatory dynamics of B cells define distinct in vivo mechanism(s) and sensitivities of cells in anti-hCD20 mAb-directed therapies. These findings provide new insights into the mechanisms of immunotherapy and define new opportunities in the treatment of cancers and autoimmune diseases.

[Advances of Studies on the Biophysical Characteristics of Channels and Acupoints]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Nov, 2005  |  Pubmed ID: 16335213

To summarize recent studies on the biophysical characteristics of meridians and acupoints, so as to provide a basis and thinking for scientific studies.

Modified Bowel Preparation to Reduce Infection After Prostate Biopsy

Chang Gung Medical Journal. Jul-Aug, 2006  |  Pubmed ID: 17051837

Infectious complications after ultrasound guided prostate biopsy are an important issue of concern. We found a higher infection rate with traditional bowel preparation, the phosphate enema, for prostate biopsy and so we modified our technique. In addition, we tried to assess the efficacy of this modified method for aged patients in an agricultural area who have poor compliance or inaccuracy when self-administering bowel preparations.

A Decade of Recurrent Cystitis in a Woman Due to a Giant Vesical Calculus

International Urogynecology Journal and Pelvic Floor Dysfunction. Nov, 2006  |  Pubmed ID: 16328114

A 50-year-old woman suffering from recurrent cystitis for one decade developed a 660-g stone in her bladder. Abdominal plain radiography showed a huge stone shadow measuring 12 x 9 x 8 cm in size.

The Effect of Partial Bladder Outlet Obstruction on Carbonyl and Nitrotyrosine Distribution in Rabbit Bladder

Urology. Dec, 2007  |  Pubmed ID: 18158070

Recent evidence indicates that ischemia and reperfusion (free radical generation) are major etiologic factors in the rabbit bladder subjected to partial outlet obstruction. The current investigation was designed to determine the time course of damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) by measuring the carbonyl and nitrotyrosine content of the bladder.

A Bridging Double Bond As an Electron Acceptor for Optical Nonlinearity of Furan-containing [N.2]cyclophenes

Angewandte Chemie (International Ed. in English). 2007  |  Pubmed ID: 17183500

On the Tacticity of Polynorbornenes with 5,6-endo Pendant Groups That Contain Substituted Aryl Chromophores

Chemistry, an Asian Journal. Jun, 2007  |  Pubmed ID: 17458917

Two dimers and a series of polymers with 5,6-endo pendant aryl groups that contain different substituents at the para positions were synthesized. The conformation and stereochemistry of the dimers and polymers were determined by nonlinear optical analysis (EFISH) as well as UV/Vis and 13C NMR spectroscopy. The chemical shifts of C7 for the polymers appeared as two peaks in the 13C NMR spectra when the substituents are electron-withdrawing groups. The percentage decrease in the relative extinction coefficient of the polymers, epsilon(d), was linearly related to the Hammett constant sigma. Polynorbornenes with electron-withdrawing substituents may adopt isotactic stereochemistry with all pendant groups aligned in one direction. The nature of the interactions between neighboring chromophores may be one of the most important factors in directing the stereoregularity and conformation of these polymers. The corresponding polymers derived from the exo isomers appeared to be less stereoregular.

[Observation on the Receiving Sensibilities of the Points on the Hand's Six Channels for Vibromusic Sound Wave]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Apr, 2007  |  Pubmed ID: 17585672

To understand the receiving sensibility of the points on the hand's six channels for music sound wave in the healthy persons, so as to provide experimental basis for exploring the mechanism of music treatment.

Effect of Aging on the Response of Biochemical Markers in the Rabbit Subjected to Short-term Partial Bladder Obstruction

Molecular and Cellular Biochemistry. Dec, 2007  |  Pubmed ID: 17673951

Partial bladder outlet obstruction (PBOO) results in marked biochemical alterations in the bladder. In this study, we focused on comparison of thapsigargin sensitive sarco/endoplasmic reticulum Ca(2+) ATPase activity (SERCA) and Citrate Synthase after short term PBOO in young versus old rabbits.

Anti-BR3 Antibodies: a New Class of B-cell Immunotherapy Combining Cellular Depletion and Survival Blockade

Blood. Dec, 2007  |  Pubmed ID: 17687108

Removal of pathogenic B lymphocytes by depletion of monoclonal antibodies (mAbs) or deprivation of B-cell survival factors has demonstrated clinical benefit in both oncologic and immunologic diseases. Partial clinical responses and emerging data demonstrating incomplete B-cell depletion after immunotherapy fuels the need for improved therapeutic modalities. Lessons from the first generation of therapeutics directed against B-cell-specific antigens (CD20, CD22) are being applied to develop novel antibodies with additional functional attributes. We describe the generation of a novel class of B-cell-directed therapy (anti-BR3 mAbs) that combines the depleting capacity of a therapeutic mAb and blockade of B-cell-activating factor (BAFF)-BR3 B-cell survival. In mice, treatment with antagonistic anti-BR3 antibodies results in quantitatively greater reduction in some B-cell subsets and qualitatively different effects on bone marrow plasma cells compared with BR3-Fc BAFF blockade or with anti-CD20 treatment. Comparative analysis of BR3-Fc and anti-BR3 mAb reveals a lower B-cell dependence for BAFF-mediated survival in nonhuman primates than in mice. This novel class of B-cell-targeted therapies shows species characteristics in mice and primates that will guide translation to treatment of human disease.

Effect of Letrozole on Urinary Bladder Function in the Female Rabbit

BJU International. Dec, 2007  |  Pubmed ID: 17850373

To investigate the effect of letrozole (a potent aromatase inhibitor that effectively inhibit the synthesis of oestrogen) on bladder contraction with changes in morphology and biochemistry.

Effects of L-arginine and L-NAME on Chronic Partial Bladder Outlet Obstruction in Rabbit

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Dec, 2007  |  Pubmed ID: 17928511

Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS). NOS can be inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and stimulated by supplementing the diet with L-arginine. The aim of this study was to investigate the influence of NOS activity on the response of rabbits to chronic partial bladder outlet obstruction (PBOO). Surgical PBOOs (2 and 8 wk) were performed on male New Zealand White rabbits. Before obstruction, one-third of the animals were premedicated for 7 days with L-NAME and another third with L-arginine. The results are summarized as follows. First, bladder weight after 8-wk PBOO was significantly lower in animals treated with L-arginine compared with both untreated and rabbits treated with L-NAME. Second, contractile function decreased progressively with PBOO duration. However, after 8 wk of PBOO, the L-arginine group had significantly greater contractile function compared with the no-treatment group, and the L-NAME group had significantly lower contractile function compared with the no-treatment group. Third, at 8 wk following PBOO, the level of protein oxidation and nitration was lowest for the L-arginine group and highest in the L-NAME group. These studies clearly demonstrated that increasing blood flow by stimulating NOS significantly protected the bladder from PBOO dysfunctions, whereas inhibiting blood flow by L-NAME enhanced the dysfunctions mediated by PBOO.

[The Key Point of Studying Sub-health is to Solve the Technical Problem]

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. Oct, 2007  |  Pubmed ID: 17990449

Changes in the Smooth Muscle of the Corpora Cavernosum Related to Reversal of Partial Bladder Outlet Obstruction in Rabbits

Journal of Andrology. Mar-Apr, 2008  |  Pubmed ID: 18004011

Previous studies have demonstrated that partial bladder outlet obstruction (PBOO) in the rabbit induces an increase in corpus cavernosum smooth muscle (CCSM) tone, which may make it difficult for the CCSM to relax. Thus, to determine whether the corpus cavernosum restores relaxation after reversal of PBOO, we investigated the physiologic, histologic, and cell biology in penises obtained from rabbits 4 weeks and 8 weeks after reversal of PBOO. CCSM from bladder outlet-obstructed and obstruction-reversed rabbits showed significant decreases in the contractile responses to phenylephrine. The relaxation responses to electrical field stimulation (EFS), ATP, acetylcholine, and sodium nitroprusside (SNP) were decreased in obstructed and reversed for 4 weeks groups. By 8 weeks of reversal, the relaxation of CCSM was increased gradually in response to EFS, SNP, and acetylcholine. However, the response to ATP did not result in the relaxation of CCSM to control levels. The ratio of SM to collagen decreased after obstruction and remained low after reversal. Expression of both isoforms of Rho kinase (ROK) was increased in obstruction groups. At 4 weeks of reversal, the expression of ROK alpha remained at obstruction level, whereas ROK beta expression decreased in comparison with the obstruction group. By 8 weeks of reversal, expression of both ROK alpha and beta significantly decreased when compared with the obstruction group. These results suggested that the poor relaxation response at reversal of 4 weeks was associated with incomplete decreased expression of both isoforms of ROK, whereas the incomplete recovery of the CCSM relaxation response at reversal of 8 weeks may be associated with structural alterations in the CC and irreversible damage from PBOO.

The Effect of Darifenacin on Overactive Bladders in Female and Male Rabbits

International Urology and Nephrology. 2008  |  Pubmed ID: 17680338

Our current study utilized a model of bladder instability to compare the effectiveness of darifenacin, a selective m3 muscarinic antagonist, at inhibiting overactive bladder (OAB) dysfunction in both male and female rabbits. Twenty-four male and female NZ white rabbits were used for this experiment. Each rabbit was anesthetized and the carotid artery was cannulated for blood pressure (BP) monitoring and the left femoral artery was cannulated for acetylcholine (Ach) administration. The bladder dome was catheterized for monitoring bladder pressure and for cystometry. A ligature was placed around the urethra just distal to the bladder to induce OAB. After OAB developed, the response to four IV doses of darifenacin (0.003; 0.01; 0.03; 0.09 mg/kg) evaluated for their effects. Darifenacin: (1) was an equally potent inhibitor of the contractile response of both sexes to intra-arterial Ach, (2) had no effects on BP, (3) was a potent inhibitor of the frequency of OAB, but had a significantly less potent effect on the amplitude, and (4) Darifenacin showed a greater potency in the female rabbits than in the males. These studies provide support for the use of darifenacin in the treatment of OAB.

Coenzyme Q10 Protect Against Ischemia/reperfusion Induced Biochemical and Functional Changes in Rabbit Urinary Bladder

Molecular and Cellular Biochemistry. Apr, 2008  |  Pubmed ID: 18165912

Ischemia, reperfusion, and free radical generation have been recently implicated in the progressive bladder dysfunction. Coenzyme Q10 (CoQ10) is a pro-vitamin like substance that appears to be efficient for treatment of neurodegenerative disorders and ischemic heart disease. Our goal was to investigate the potential protective effect of CoQ10 in a rabbit model of in vivo bilateral ischemia and ischemia/reperfusion (I/R).

A Hydrodynamically Focused Stream As a Dynamic Template for Site-specific Electrochemical Micropatterning of Conducting Polymers

Angewandte Chemie (International Ed. in English). 2008  |  Pubmed ID: 18176924

Free Radical Damage As a Biomarker of Bladder Dysfunction After Partial Outlet Obstruction and Reversal

BJU International. Mar, 2008  |  Pubmed ID: 18190635

To investigate the use of free-radical generation as a result of protein carbonylation and nitrotyrosination to characterize the level of bladder dysfunction after partial bladder outlet obstruction (PBOO) and reversal.

Effect of Co-enzyme Q10 and Alpha-lipoic Acid on Response of Rabbit Urinary Bladder to Repetitive Stimulation and in Vitro Ischemia

Urology. Jul, 2008  |  Pubmed ID: 18280551

To determine the efficacy of coenzyme Q10 (CoQ10) and alpha-lipoic acid (alpha-LA), either alone or in combination, to protect the contractile responses of the rabbit urinary bladder from damage caused by repetitive stimulation in the presence or absence of in vitro ischemia.

The Effect of Low-dose Estrogen Therapy on Ovariectomized Female Rabbit Bladder

Urology. Jun, 2008  |  Pubmed ID: 18295865

To determine whether low-dose estrogen supplementation is as effective as high-dose supplementation in increasing bladder contractile function and mediating bladder hypertrophy and angiogenesis.

Effect of Age on the Role of Rho-kinase in Short-term Partial Bladder Outlet Obstruction

Urology. Mar, 2008  |  Pubmed ID: 18342205

We examined the expression of Rho-kinase (ROK) isoforms in young and old rabbits' detrusor smooth muscles (SM) during the progression of short-term partial bladder outlet obstruction and correlated them with the time course of obstruction.

The Effect of Ovariectomy and Oestrogen Therapy on the Free Fatty Acid Content, Endogenous Lipase Activity, and Phospholipid Content of the Rabbit Urinary Bladder

BJU International. Sep, 2008  |  Pubmed ID: 18485034

To evaluate the effects of ovariectomy (Ovx) and oestrogen therapy on the free fatty acid (FFA) content, endogenous lipase activity, and the phospholipid (PL) content of the urinary bladder, as reduced circulating oestrogen during and after the menopause has been linked to various bladder dysfunctions including incontinence and recurrent urinary tract infections.

The Effect of Chronic Partial Bladder Outlet Obstruction on Corpus Cavernosum Smooth Muscle and Rho-kinase in Rabbits

Neurourology and Urodynamics. 2008  |  Pubmed ID: 18551564

The goal of this study was to investigate the effect of different severities in bladder dysfunction on corpus cavernosum physiology, morphology and expression of Rho-kinase in rabbits.

The Immediate Effect of Nitric Oxide on the Rabbit Bladder After Ovariectomy

Nitric Oxide : Biology and Chemistry / Official Journal of the Nitric Oxide Society. Nov, 2008  |  Pubmed ID: 18619550

Ovariectomy resulted in decreased blood flow and hypoxia to the bladder mucosa and smooth muscle. Nitric oxide (NO) played an important role in regulating bladder function during bladder ischemia and reperfusion. This study was designed to evaluate the role of NO on bladder function in the first few days after ovariectomy. Female rabbits were separated into three groups, one which received no medication, premedicated with N(omega)-nitro-L-arginine methyl ester (L-NAME) and the third treated with L-arginine. Non-ovariectomized controls and at 1 and 3 days post-ovariectomy, animals from each group were euthanized. Cystometry and in vitro isometric contractile responses were recorded and the oxidative stress markers, nitrotyrosine and protein carbonylation were determined. L-NAME treatment did not significantly alter bladder function after ovariectomy. L-Arginine fed, ovariectomized rabbits had lower intravesical pressure and better contractile responses to all forms of stimulation than the ovariectomized rabbits with or without L-NAME. Furthermore, the ovariectomized ones with or without L-NAME had higher oxidative stress markers than L-arginine fed rabbits. This study clearly demonstrates that feeding rabbits with L-arginine can protect the bladder from oxidative free radical damage following short-term ovariectomy.

A Dynamic Micromixer for Arbitrary Control of Disguised Chemical Selectivity

Chemical Communications (Cambridge, England). Aug, 2008  |  Pubmed ID: 18633511

A new type of dynamic micromixer combining the concepts of parallel multi-lamination and hydrodynamic focusing was developed for arbitrary control of disguised chemical selectivity.

Expression of Parathyroid-hormone- Related Protein in the Partially Obstructed Rabbit Bladder

Urologia Internationalis. 2008  |  Pubmed ID: 18645277

Parathyroid-hormone-related protein (PTHrP) is considered as an autocrine/paracrine regulator of growth and/or differentiation in normal and malignant tissues. We determined the distribution and density of the expression of PTHrP in the rabbit bladder during growth in response to partial outlet obstruction and its relation with the smooth muscle/collagen ratio.

Estrogen Administration Attenuates Bladder Outlet Obstruction Induced Oxidative Stress in the Female Rabbit

Neurourology and Urodynamics. 2009  |  Pubmed ID: 18671298

Estrogen administration to female rabbits induces a functional hypertrophy of the bladder. The aim of this study was to investigate whether supplementation of estrogen in the female rabbit with partial bladder outlet obstruction (PBOO) would affect the severity of bladder dysfunction.

Expression of Parathyroid Hormone-related Protein in the Partially Obstructed and Reversed Rabbit Bladder

International Urology and Nephrology. 2009  |  Pubmed ID: 18979176

Parathyroid hormone-related protein (PTHrP), the main factor responsible for malignant hypercalcemia, is produced by a wide range of normal and malignant tissues. Prior studies in the rabbit model demonstrated that partial bladder outlet obstruction results in calcium-dysregulation characterized by a marked increase in free calcium within the smooth muscle compartment and the stimulation of calcium-activated enzymes, such as calpain and phospholipase A(2).

Meta Association of Colorectal Cancer Confirms Risk Alleles at 8q24 and 18q21

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2009  |  Pubmed ID: 19155440

Genome-wide association studies of colorectal cancer (CRC) have identified genetic variants that reproducibly associate with CRC. Associations of 12 single nucleotide polymorphisms at 8q24, 9p24, and 18q21 (SMAD7) and CRC were investigated in a three-center collaborative study including two U.K. case-control cohorts (Sheffield and Leeds) and a U.S. case-control study of CRC cases from high-risk Utah pedigrees.

A Breast Cancer Risk Haplotype in the Caspase-8 Gene

Cancer Research. Apr, 2009  |  Pubmed ID: 19318553

Recent large-scale studies have been successful in identifying common, low-penetrance variants associated with common cancers. One such variant in the caspase-8 (CASP8) gene, D302H (rs1045485), has been confirmed to be associated with breast cancer risk, although the functional effect of this polymorphism (if any) is not yet clear. In order to further map the CASP8 gene with respect to breast cancer susceptibility, we performed extensive haplotype analyses using single nucleotide polymorphisms (SNP) chosen to tag all common variations in the gene (tSNP). We used a staged study design based on 3,200 breast cancer and 3,324 control subjects from the United Kingdom, Utah, and Germany. Using a haplotype-mining algorithm in the UK cohort, we identified a four-SNP haplotype that was significantly associated with breast cancer and that was superior to any other single or multi-locus combination (P=8.0 x 10(-5)), with a per allele odds ratio and 95% confidence interval of 1.30 (1.12-1.49). The result remained significant after adjustment for the multiple testing inherent in mining techniques (false discovery rate, q=0.044). As expected, this haplotype includes the D302H locus. Multicenter analyses on a subset of the tSNPs yielded consistent results. This risk haplotype is likely to carry one or more underlying breast cancer susceptibility alleles, making it an excellent candidate for resequencing in homozygous individuals. An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer.

Prevalence of Antimicrobial Resistance in Helicobacter Pylori Isolates in Taiwan in Relation to Consumption of Antimicrobial Agents

International Journal of Antimicrobial Agents. Aug, 2009  |  Pubmed ID: 19324524

During 1998-2004, a total of 218 Helicobacter pylori isolates were obtained from patients who were randomised to receive one of the following regimens in a medical centre in Taiwan: lansoprazole, amoxicillin and clarithromycin (LAC) therapy; or lansoprazole, metronidazole and clarithromycin (LMC) therapy. In the LMC group, resistance rates for metronidazole and clarithromycin reduced from 48.6% (1998-2000) to 20.4% (2001-2004) (P<0.05) and from 13.5% to 6.3% (P<0.05), respectively. Analysis of annual antimicrobial consumption found that metronidazole use was slowly decreased both in the total population and in gastrointestinal disease patients. The per-protocol analysis revealed a higher eradication rate for patients using LMC therapy in 2001-2004 (82.6% vs. 75.0%), whilst there was similar efficacy for LAC therapy (84.8% vs. 84.2%). This observation suggests an effective programme to control H. pylori antibiotic resistance and hence elevate its cure rate.

A Supramolecular Approach for Preparation of Size-controlled Nanoparticles

Angewandte Chemie (International Ed. in English). 2009  |  Pubmed ID: 19425037

A supramolecular approach has been developed for the preparation of supramolecular nanoparticles (SNPs) with variable sizes (30-450 nm) from three different molecular building blocks using a cyclodextrin/adamantane recognition system. Positron emission tomography (PET) was employed to study the biodistribution and lymph node drainage of the SNPs in mice. The sizes of the SNPs affect their in vivo characteristics (see picture).

The Effect of 2- and 4-week Ovariectomy on Female Rabbit Urinary Bladder Function

Urology. Sep, 2009  |  Pubmed ID: 19501892

To evaluate the effect ovariectomy (OVX) after 2 and 4 weeks on bladder function and biochemistry of the adult female rabbit urinary bladder.

An Integrated Microfluidic Device for Large-scale in Situ Click Chemistry Screening

Lab on a Chip. Aug, 2009  |  Pubmed ID: 19636457

An integrated microfluidic device has been developed to perform 1024 in situ click chemistry reactions in parallel using the bovine carbonic anhydrous II (bCAII) click chemistry system as a proof-of-concept study and a rapid hit identification approach using SPE purification and electrospray-ionization mass spectrometry, multiple reaction monitoring (MRM) analysis, all of which improves the sensitivity and throughput of the downstream analysis.

Genetic Variants in XRCC2: New Insights into Colorectal Cancer Tumorigenesis

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Sep, 2009  |  Pubmed ID: 19690184

Polymorphisms in DNA double-strand break repair gene XRCC2 may play an important role in colorectal cancer etiology, specifically in disease subtypes. Associations of XRCC2 variants and colorectal cancer were investigated by tumor site and tumor instability status in a four-center collaboration including three U.K. case-control studies (Sheffield, Leeds, and Dundee) and a U.S. case-control study of cases from high-risk Utah pedigrees (total: 1,252 cases and 1,422 controls). The 14 variants studied were tagging single nucleotide polymorphisms (SNP) selected from National Institute of Environmental Health Sciences/HapMap data supplemented with SNPs identified from sequencing of 125 cases chosen to represent multiple colorectal cancer groups (familial, metastatic disease, and tumor subsite). Monte Carlo significance testing using Genie software provided valid meta-analyses of the total resource that includes family-based data. Similar to reports of colorectal cancer and other cancer sites, the rs3218536 R188H allele was not associated with increased risk. However, we observed a novel, highly significant association of a common SNP, rs3218499G>C, with increased risk of rectal tumors (odds ratio, 2.1; 95% confidence interval, 1.3-3.3; P(chi2) = 0.0006) versus controls, with the largest risk found for female rectal cases (odds ratio, 3.1; 95% confidence interval, 1.6-6.1; P(chi2) = 0.0006). This difference was significantly different to that for proximal and distal colon cancers (P(chi2) = 0.02). Our investigation supports a role for XRCC2 in colorectal cancer tumorigenesis, conferring susceptibility to rectal tumors.

Cytotoxic Alkyl Benzoquinones and Alkyl Phenols from Ardisia Virens

Phytochemistry. Dec, 2009  |  Pubmed ID: 19833361

Bioassay-guided fractionation of roots and stems of Ardisia virens Kurz (Myrsinaceae) led to isolation of fourteen compounds, (2'R)-6-(2'-acetoxypentadecyl)-5-hydroxy-2-methoxy-1,4-benzoquinone (1), (2'R)-6-(2'-acetoxytridecyl)-5-hydroxy-2-methoxy-1,4-benzoquinone (2), (2'R)-6-(2'-acetoxytridecyl)-2-methoxy-1,4-dihydroxybenzene (3), (2'R)-6-(2'-acetoxytridecyl)-5-formyl-2-methoxy-1,4-dihydroxybenzene (4), 1-(3,5-dihydroxyphenyl)nonan-1-one (5), 1-(3-hydroxy-5-methoxyphenyl)pentan-1-one (6), (2'S)-3-hydroxy-5-methoxyphenyl-2'-tridecanol (7), (2'S)-3-hydroxy-5-methoxyphenyl-2'-pentadecanol (8), (2'S)-5-acetoxy-3-hydroxyphenyl-2'-tetradecanol (9), 1-acetoxy-2-methoxy-6-pentadecyl-4-hydroxybenzene (10), 1-acetoxy-2-methoxy-6-tridecyl-4-hydroxybenzene (11), (2'R)-1-acetoxy-6-(2'-acetoxy-tridecyl)-2-methoxy-4-hydroxybenzene (12), (2'R)-1-acetoxy-6-(2'-acetoxypentadecyl)-2-methoxy-4-hydroxybenzene (13), and 1-acetoxy-6-(2'-ketopentadecyl)-2-methoxy-4-hydroxylbenzene (14), together with thirty-four other known compounds, of which three, 1-(3,5-dihydroxyphenyl)pentan-1-one (15), 1-(3,5-dihydroxyphenyl)heptan-1-one (16), and 1-(3,5-dihydroxyphenyl)pentadecan-1-one (17), were isolated for the first time from a natural source. Their structures were elucidated by analyses of spectroscopic data. Seven cytotoxic constituents were found to be 3, 10-12, ardisianone (18), cornudentanone (19), and ardisianol (31) with cytotoxic properties (IC(50) values < or =4 microg/mL) against MCF-7, NCI-H460 and SF-268 cancer cell lines in vitro.

Integrated Microfluidic Reactors

Nano Today. Dec, 2009  |  Pubmed ID: 20209065

Microfluidic reactors exhibit intrinsic advantages of reduced chemical consumption, safety, high surface-area-to-volume ratios, and improved control over mass and heat transfer superior to the macroscopic reaction setting. In contract to a continuous-flow microfluidic system composed of only a microchannel network, an integrated microfluidic system represents a scalable integration of a microchannel network with functional microfluidic modules, thus enabling the execution and automation of complicated chemical reactions in a single device. In this review, we summarize recent progresses on the development of integrated microfluidics-based chemical reactors for (i) parallel screening of in situ click chemistry libraries, (ii) multistep synthesis of radiolabeled imaging probes for positron emission tomography (PET), (iii) sequential preparation of individually addressable conducting polymer nanowire (CPNW), and (iv) solid-phase synthesis of DNA oligonucleotides. These proof-of-principle demonstrations validate the feasibility and set a solid foundation for exploring a broad application of the integrated microfluidic system.

Photothermal Effects of Supramolecularly Assembled Gold Nanoparticles for the Targeted Treatment of Cancer Cells

Angewandte Chemie (International Ed. in English). May, 2010  |  Pubmed ID: 20391446

A Mouse Knockout Library for Secreted and Transmembrane Proteins

Nature Biotechnology. Jul, 2010  |  Pubmed ID: 20562862

Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.

Microfluidics for Positron Emission Tomography Probe Development

Molecular Imaging. Aug, 2010  |  Pubmed ID: 20643021

Owing to increased needs for positron emission tomography (PET), high demands for a wide variety of radiolabeled compounds will have to be met by exploiting novel radiochemistry and engineering technologies to improve the production and development of PET probes. The application of microfluidic reactors to perform radiosyntheses is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional labeling systems. Microfluidics-based radiochemistry can lead to the use of smaller quantities of precursors, accelerated reaction rates, and easier purification processes with greater yield and higher specific activity of desired probes. Several proof-of-principle examples along with the basics of device architecture and operation and the potential limitations of each design are discussed. Along with the concept of radioisotope distribution from centralized cyclotron facilities to individual imaging centers and laboratories ("decentralized model"), an easy-to-use, stand-alone, flexible, fully automated, radiochemical microfluidic platform can provide simpler and more cost-effective procedures for molecular imaging using PET.

Integrated Microfluidic and Imaging Platform for a Kinase Activity Radioassay to Analyze Minute Patient Cancer Samples

Cancer Research. Nov, 2010  |  Pubmed ID: 20837665

Oncogenic kinase activity and the resulting aberrant growth and survival signaling are a common driving force of cancer. Accordingly, many successful molecularly targeted anticancer therapeutics are directed at inhibiting kinase activity. To assess kinase activity in minute patient samples, we have developed an immunocapture-based in vitro kinase assay on an integrated polydimethylsiloxane microfluidics platform that can reproducibly measure kinase activity from as few as 3,000 cells. For this platform, we adopted the standard radiometric (32)P-ATP-labeled phosphate transfer assay. Implementation on a microfluidic device required us to develop methods for repeated trapping and mixing of solid-phase affinity microbeads. We also developed a solid-state beta-particle camera imbedded directly below the microfluidic device for real-time quantitative detection of the signal from this and other microfluidic radiobioassays. We show that the resulting integrated device can measure ABL kinase activity from BCR-ABL-positive leukemia patient samples. The low sample input requirement of the device creates new potential for direct kinase activity experimentation and diagnostics on patient blood, bone marrow, and needle biopsy samples.

A Rapid Pathway Toward a Superb Gene Delivery System: Programming Structural and Functional Diversity into a Supramolecular Nanoparticle Library

ACS Nano. Oct, 2010  |  Pubmed ID: 20925389

Nanoparticles are regarded as promising transfection reagents for effective and safe delivery of nucleic acids into a specific type of cells or tissues providing an alternative manipulation/therapy strategy to viral gene delivery. However, the current process of searching novel delivery materials is limited due to conventional low-throughput and time-consuming multistep synthetic approaches. Additionally, conventional approaches are frequently accompanied with unpredictability and continual optimization refinements, impeding flexible generation of material diversity creating a major obstacle to achieving high transfection performance. Here we have demonstrated a rapid developmental pathway toward highly efficient gene delivery systems by leveraging the powers of a supramolecular synthetic approach and a custom-designed digital microreactor. Using the digital microreactor, broad structural/functional diversity can be programmed into a library of DNA-encapsulated supramolecular nanoparticles (DNA⊂SNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNA⊂SNPs library identified the DNA⊂SNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNA⊂SNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.

A Digital Microfluidic Droplet Generator Produces Self-assembled Supramolecular Nanoparticles for Targeted Cell Imaging

Nanotechnology. Nov, 2010  |  Pubmed ID: 20935351

Controlling the size distribution of polymer-based nanoparticles is a challenging task due to their flexible core and surface structures. To accomplish such as task requires very precise control at the molecular level. Here we demonstrate a new approach whereby uniform-sized supramolecular nanoparticles (SNPs) can be reliably generated using a digital microfluidic droplet generator (DMDG) chip. A microfluidic environment enabled precise control over the processing parameters, and therefore high batch-to-batch reproducibility and robust production of SNPs with a very narrow size distribution could be realized. Digitally adjustment of the mixing ratios of the building blocks on the DMDG chip allowed us to rapidly scan a variety of synthesis conditions without consuming significant amounts of reagents. Nearly uniform SNPs with sizes ranging from 35 to 350 nm were obtained and characterized by transmission electron microscopy and dynamic light scattering. In addition, we could fine-tune the surface chemistry of the SNPs by incorporating an additional building block functionalized with specific ligands for targeting cells. The sizes and surface properties of these SNPs correlated strongly with their cell uptake efficiencies. This study showed a feasible method for microfluidic-assisted SNP production and provided a great means for preparing size-controlled SNPs with desired surface ligand coverage.

Bladder Volume on Voiding Cystourethrogram Correlates with Indications and Results in Male Infants

Urology. Feb, 2011  |  Pubmed ID: 20974487

To evaluate whether the bladder size on the voiding cystourethrogram (VCUG) might be a proxy for voiding abnormalities. Voiding abnormalities have been implicated in the development of hydronephrosis, reflux, and urinary tract infections.

Microfluidic-based 18F-labeling of Biomolecules for Immuno-positron Emission Tomography

Molecular Imaging. Jun, 2011  |  Pubmed ID: 21496447

Methods for tagging biomolecules with fluorine 18 as immuno-positron emission tomography (immunoPET) tracers require tedious optimization of radiolabeling conditions and can consume large amounts of scarce biomolecules. We describe an improved method using a digital microfluidic droplet generation (DMDG) chip, which provides computer-controlled metering and mixing of 18F tag, biomolecule, and buffer in defined ratios, allowing rapid scouting of reaction conditions in nanoliter volumes. The identified optimized conditions were then translated to bench-scale 18F labeling of a cancer-specific engineered antibody fragments, enabling microPET imaging of tumors in xenografted mice at 0.5 to 4 hours postinjection.

Effect of Hyaluronic Acid on Urine Nerve Growth Factor in Cyclophosphamide-induced Cystitis

International Journal of Urology : Official Journal of the Japanese Urological Association. Jul, 2011  |  Pubmed ID: 21605172

To investigate how hyaluronic acid (HA) affects nerve growth factor (NGF) production and bladder overactivity in a cyclophosphamide (CYP)-induced cystitis rat model.

A Role for XRCC2 Gene Polymorphisms in Breast Cancer Risk and Survival

Journal of Medical Genetics. Jul, 2011  |  Pubmed ID: 21632523

The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer.

Oxidative Stress Biomarkers in Urine and Plasma of Rabbits with Partial Bladder Outlet Obstruction

BJU International. Jun, 2011  |  Pubmed ID: 20875092

What's known on the subject? and What does the study add? It has been known that there is an increase of oxidative damage in the bladder tissues of animals after PBOO. However, no reliable oxidative stress biomarkers in either urine or plasma have been available for the assessment of the severity of PBOO. This study clearly demonstrated that the levels of oxidative stress biomarkers are increased in urine and plasma of the rabbits with PBOO.

Correlation of in Vivo Bladder Blood Flow Measurements with Tissue Hypoxia

World Journal of Urology. Apr, 2011  |  Pubmed ID: 19190918

Obstructive bladder dysfunction is in part due to reduced blood flow and the resulting ischemia of the bladder smooth muscle and mucosa. Our aim was to determine if the severity and localization of ischemia could be determined by measuring blood flow to the bladder with a non-invasive probe placed on the surface of the urothelium.

The Therapeutic Efficacy of Camptothecin-encapsulated Supramolecular Nanoparticles

Biomaterials. Feb, 2012  |  Pubmed ID: 22074663

Nanomaterials have been increasingly employed as drug(s)-incorporated vectors for drug delivery due to their potential of maximizing therapeutic efficacy while minimizing systemic side effects. However, there have been two main challenges for these vectors: (i) the existing synthetic approaches are cumbersome and incapable of achieving precise control of their structural properties, which will affect their biodistribution and therapeutic efficacies, and (ii) lack of an early checkpoint to quickly predict which drug(s)-incorporated vectors exhibit optimal therapeutic outcomes. In this work, we utilized a new rational developmental approach to rapidly screen nanoparticle (NP)-based cancer therapeutic agents containing a built-in companion diagnostic utility for optimal therapeutic efficacy. The approach leverages the advantages of a self-assembly synthetic method for preparation of two different sizes of drug-incorporated supramolecular nanoparticles (SNPs), and a positron emission tomography (PET) imaging-based biodistribution study to quickly evaluate the accumulation of SNPs at a tumor site in vivo and select the favorable SNPs for in vivo therapeutic study. Finally, the enhanced in vivo anti-tumor efficacy of the selected SNPs was validated by tumor reduction/inhibition studies. We foresee our rational developmental approach providing a general strategy in the search of optimal therapeutic agents among the diversity of NP-based therapeutic agents.

Chondroitin Sulfate Synthase 1 (Chsy1) is Required for Bone Development and Digit Patterning

Developmental Biology. Jan, 2012  |  Pubmed ID: 22280990

Joint and skeletal development is highly regulated by extracellular matrix (ECM) proteoglycans, of which chondroitin sulfate proteoglycans (CSPGs) are a major class. Despite the requirement of joint CSPGs for skeletal flexibility and structure, relatively little is understood regarding their role in establishing joint positioning or in modulating signaling and cell behavior during joint formation. Chondroitin sulfate synthase 1 (Chsy1) is one of a family of enzymes that catalyze the extension of chondroitin and dermatan sulfate glycosaminoglycans. Recently, human syndromic brachydactylies have been described to have loss-of-function mutations at the CHSY1 locus. In concordance with these observations, we demonstrate that mice lacking Chsy1, though viable, display chondrodysplasia and decreased bone density. Notably, Chsy1(-/-) mice show a profound limb patterning defect in which orthogonally shifted ectopic joints form in the distal digits. Associated with the digit-patterning defect is a shift in cell orientation and an imbalance in chondroitin sulfation. Our results place Chsy1 as an essential regulator of joint patterning and provide a mouse model of human brachydactylies caused by mutations in CHSY1.