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Find video protocols related to scientific articles indexed in Pubmed.
Successful treatment of genital Bowen's disease with imiquimod 5% cream.
Int J STD AIDS
PUBLISHED: 09-27-2014
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A 64-year-old Japanese woman was diagnosed as having Bowen's disease in the vulva. The histopathological findings revealed papillomatosis, koilocytosis and clumping cells with atypical nuclei. Human papillomavirus DNA was not detected on polymerase chain reaction using consensus primers. The lesion was successfully treated with topical imiquimod 5% cream after two months. Histopathologically, no atypical cells were observed after treatment. Imiquimod can be a potential treatment modality for lesions that are difficult to treat with surgical excision.
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Results of life-supporting galactosyltransferase knockout kidneys in cynomolgus monkeys using two different sources of galactosyltransferase knockout Swine.
Transplantation
PUBLISHED: 09-23-2014
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Various durations of survival have been observed in the xenotransplantation of life-supporting ?-1,3-galactosyltransferase knockout (GalT-KO) porcine kidneys into nonhuman primates. Although others have demonstrated loss of GalT-KO-transplanted kidneys within 2 weeks, we have reported an average survival of 51 days with the cotransplantation of the kidney and vascularized thymus and an average of 29 days with the kidney alone. To determine the factors responsible for this difference in survival time, we performed xenogeneic kidney transplantations into cynomolgus monkeys with an anti-CD40L-based regimen using two different strains of GalT-KO swine, one derived from MGH miniature swine and the other obtained from Meji University.
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Porcine cytomegalovirus infection is associated with early rejection of kidney grafts in a pig to baboon xenotransplantation model.
Transplantation
PUBLISHED: 09-23-2014
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Recent survivals of our pig-to-baboon kidney xenotransplants have been markedly shorter than the graft survivals we previously reported. The discovery of high levels of porcine cytomegalovirus (pCMV) in one of the rejected xenografts led us to evaluate whether this reduction in graft survival might be because of the inadvertent introduction of pCMV into our ?1,3-galactosyltransferase gene knockout swine herd.
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Effectiveness of CT assists for intraarterial chemotherapy: therapeutic outcome of chemoradiation for advanced head and neck cancer extending across the anatomical midline.
Jpn J Radiol
PUBLISHED: 08-27-2014
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The purpose of this study was to evaluate the effectiveness of CT assist for intraarterial chemotherapy in relation to the therapeutic outcomes of intraarterial chemoradiation for advanced head and neck cancer with extension across the anatomical midline (EAM).
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Morphological spectrum of renal pathology and its correlation to clinical features in patients with disseminated intravascular coagulation: a study involving a series of 21 autopsy cases.
Pathol. Int.
PUBLISHED: 08-22-2014
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Disseminated intravascular coagulation (DIC), a thrombohemorrhagic disorder, occurs as a secondary complication in many diseases, but the histopathological features of kidneys in DIC have not been extensively characterized thus far. We reviewed 21 autopsy cases of patients with a clinical diagnosis of DIC and studied the repertoire of renal pathology. Eighteen patients had elevated serum creatinine levels and 15 patients had a variable degree of proteinuria. Underlying disorders included malignant neoplasms in 12 patients, and abdominal aortic aneurysm, acute myocardial infarction, and systemic infections in other patients. Coexistent glomerular pathology, such as focal segmental glomerulosclerosis (FSGS) with different morphological variants, and microthrombi formation, was present in many patients. The microthrombi were histologically similar to that seen in thrombotic microangiopathy, but characteristics associated with DIC were detected by special staining. The presence of FSGS correlated with the degree of urinary protein (P = 0.0044), and the presence of acute tubular injury (ATI) and the extent of global glomerulosclerosis both correlated with serum creatinine levels (P = 0.019 and 0.0003, respectively). FSGS was probably due to endothelial cell damage, another potential etiology for FSGS. Global glomerulosclerosis, a result of previous renal injury, can be a determinant of renal function during the acute phase of DIC.
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A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.
BMC Med
PUBLISHED: 08-21-2014
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To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy.
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Protective effect of neutralization of the extracellular high-mobility group box 1 on renal ischemia-reperfusion injury in miniature Swine.
Transplantation
PUBLISHED: 08-20-2014
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Strategies that reduce ischemia-reperfusion injury (IRI) have the potential to expand the numbers of available organs for transplantation. Recent reports in rodent models have demonstrated that high-mobility group box 1 (HMGB1) acts as an alarm in initiating the inflammatory response resulting from ischemic injury. The aim of this study was to evaluate the cytoprotective effects of anti-HMGB1 antibodies on renal IRI in preclinical large animals.
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Giant Condyloma Acuminatum in the Axilla.
Acta Derm. Venereol.
PUBLISHED: 08-11-2014
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Abstract is missing (Short Communication).
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Impact of advanced age on the short- and long-term outcomes in patients undergoing hepatectomy for hepatocellular carcinoma: a single-center analysis over a 20-year period.
Am. J. Surg.
PUBLISHED: 08-02-2014
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The purpose of this study was to analyze the influence of age on both the risk of hepatectomy and the prognosis in patients with hepatocellular carcinoma (HCC).
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The rejuvenating effects of leuprolide acetate on the aged baboon's thymus.
Transpl. Immunol.
PUBLISHED: 05-27-2014
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We have previously demonstrated that the juvenile thymus plays an essential role in tolerance induced by both renal transplantation and a short course of calcineurin inhibitors. Aged thymi have a decreased ability to induce tolerance. Luteinizing hormone-releasing hormone (LHRH) is known to pharmacologically rejuvenate the thymus in rodents. In order to develop a clinically applicable regimen of transplantation tolerance in adults, we sought to determine if thymic rejuvenation would occur with LHRH agonism in non-human primates.
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Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for ?5(IV) and ?2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy.
Clin. Exp. Nephrol.
PUBLISHED: 05-19-2014
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The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis.
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Clinical effects of ghrelin on gastrointestinal involvement in patients with systemic sclerosis.
Endocr. J.
PUBLISHED: 05-17-2014
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The majority of patients with systemic sclerosis (SSc) have gastrointestinal (GI) tract involvement, but therapies using prokinetic agents are usually unsatisfactory. Ghrelin stimulates gastric motility in healthy human volunteers. In this study, we investigated whether ghrelin could improve gastric emptying in patients with gastrointestinal symptoms due to SSc. The study was performed in a randomized, double-blind, placebo-controlled crossover fashion on two occasions. Ten SSc patients with GI tract involvement received an infusion of either ghrelin (5.0 ?g/kg) or saline, and gastric emptying rate was evaluated by (13)C-acetic acid breath test. Gastric emptying was significantly accelerated by ghrelin infusion in patients with SSc (ghrelin vs. saline: 43.3 ± 11.4 min vs. 53.4 ± 5.4 min, P=0.03). No serious adverse effects were observed. Our results suggest that ghrelin might represent a new therapeutic approach for GI tract involvement in patients with SSc.
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Characterisation of cytoplasmic DNA complementary to non-retroviral RNA viruses in human cells.
Sci Rep
PUBLISHED: 05-02-2014
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The synthesis and subsequent genomic integration of DNA that is complementary to the genomes of non-retroviral RNA viruses are rarely observed. However, upon infection of various human cell lines and primary fibroblasts with the vesicular stomatitis virus (VSV), we detected DNA complementary to the VSV RNA. The VSV DNA was detected in the cytoplasm as single-stranded DNA fully complementary to the viral mRNA from the poly(A) region to the 7-methyl guanosine cap. The formation of this DNA was cell-dependent. Experimentally, we found that the transduction of cells that do not produce VSV DNA with the long interspersed nuclear element 1 and their infection with VSV could lead to the formation of VSV DNA. Viral DNA complementary to other RNA viruses was also detected in the respective infected human cells. Thus, the genetic information of the non-retroviral RNA virus genome can flow into the DNA of mammalian cells expressing LINE-1-like elements.
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Prospective signs of cleidocranial dysplasia in Cebpb deficiency.
J. Biomed. Sci.
PUBLISHED: 04-07-2014
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Although runt-related transcription factor 2 (RUNX2) has been considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (Cebpb) is a key factor of Runx2 expression and our previous study has reported two CCD signs including hyperdontia and elongated coronoid process of the mandible in Cebpb deficient mice. Following that, this work aimed to conduct a case-control study of thoracic, zygomatic and masticatory muscular morphology to propose an association between musculoskeletal phenotypes and deficiency of Cebpb, using a sample of Cebpb-/-, Cebpb+/- and Cebpb+/+ adult mice. Somatic skeletons and skulls of mice were inspected with soft x-rays and micro-computed tomography (?CT), respectively. Zygomatic inclination was assessed using methods of coordinate geometry and trigonometric function on anatomic landmarks identified with ?CT. Masseter and temporal muscles were collected and weighed. Expression of Cebpb was examined with a reverse transcriptase polymerase chain reaction (RT-PCR) technique.
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Pigmented condyloma acuminatum.
J. Dermatol.
PUBLISHED: 02-24-2014
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We herein report a case of pigmented condyloma acuminatum in the genital region. A histopathological examination revealed keratinocyte proliferation, papillomatosis and basal pigmentation. Cellular atypia was rarely observed. The patient also had ordinary skin-colored nodules on the coronal sulcus. Polymerase chain reaction amplification with consensus primers for human papillomavirus (HPV) and subsequent sequencing confirmed an infection of HPV type 6. Pigmented condyloma acuminatum is not rare; however, making the differential diagnosis between bowenoid papulosis and seborrheic keratosis is sometimes difficult. The mechanism of pigmentation in such cases remains unknown and requires further investigation. HPV typing is a useful method for diagnosing the disease.
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Bowenoid papulosis successfully treated with imiquimod 5% cream.
J. Dermatol.
PUBLISHED: 02-09-2014
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A 24-year-old healthy Japanese female was diagnosed as having bowenoid papulosis in the genital area. The histopathological findings revealed acanthosis, papillomatosis, dyskeratotic cells and clumping cells with mild atypical nuclei. Human papillomavirus type 16 was detected in the lesion. The lesion was successfully treated with topical imiquimod 5% cream after 2 months. Imiquimod 5% cream is a potentially effective treatment modality for lesions that are difficult to treat with surgical excision.
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Liver failure after hepatocellular carcinoma surgery.
Langenbecks Arch Surg
PUBLISHED: 01-27-2014
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The aim of this study was to construct a prediction model for posthepatectomy liver failure (PHLF), as defined by the International Study Group of Liver Surgery, and evaluate its accuracy in hepatocellular carcinoma (HCC) patients with cirrhosis or chronic hepatitis.
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Rituximab treatment prevents the early development of proteinuria following pig-to-baboon xeno-kidney transplantation.
J. Am. Soc. Nephrol.
PUBLISHED: 01-23-2014
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We previously reported life-supporting ?1,3-galactosyltransferase knockout (GalTKO) thymokidney xenograft survival of >2 months in baboons. However, despite otherwise normal renal function, recipients developed proteinuria with morphologic changes (podocyte effacement), a condition that presents a major obstacle to long-term studies in this model. A recent clinical study showed that rituximab therapy after allogeneic transplant prevented proteinuria possibly associated with loss of sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b). Here, we demonstrate that rituximab prevents the disruption of pig podocytes in an SMPDL-3b-dependent manner in vitro and the early development of proteinuria after xenogeneic kidney transplantation in baboons. Immunofluorescence showed SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig podocytes with naive baboon sera, which has preformed antipig natural antibodies, reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased podocyte proliferation, whereas pretreatment with rituximab prevented these effects. Six baboons received rituximab before transplantation to deplete B cells and again in the peri-transplant period; 18 baboons treated only before transplantation served as historical controls. The onset of post-transplant proteinuria was significantly delayed in a B cell-independent manner in the animals that received peri-transplant rituximab treatment. Although further optimization of this protocol is required, these data provide intriguing clues to the mechanisms of post-transplant proteinuria in xenogeneic kidney transplantation and a potential strategy for its prevention.
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Fine-tuned bee-flower coevolutionary state hidden within multiple pollination interactions.
Sci Rep
PUBLISHED: 01-20-2014
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Relationships between flowers and pollinators are generally considered cases of mutualism since both agents gain benefits. Fine-tuned adaptations are usually found in the form of strict one-to-one coevolution between species. Many insect pollinators are, however, considered generalists, visiting numerous kinds of flowers, and many flower species (angiosperms) are also considered generalists, visited by many insect pollinators. We here describe a fine-tuned coevolutionary state of a flower-visiting bee that collects both nectar and pollen from an early spring flower visited by multiple pollinators. Detailed morphology of the bee proboscis is shown to be finely adjusted to the floral morphology and nectar production of the flower. Behavioral observations also confirm the precision of this mutualism. Our results suggest that a fine-tuned one-to-one coevolutionary state between a flower species and a pollinator species might be common, but frequently overlooked, in multiple flower-pollinator interactions.
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Preclinical validation of talaporfin sodium-mediated photodynamic therapy for esophageal squamous cell carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.
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Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1) regulate supernumerary organ formations.
PLoS ONE
PUBLISHED: 01-01-2014
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Bone morphogenetic proteins (BMPs) are highly conserved signaling molecules that are part of the transforming growth factor (TGF)-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1) suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.
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Functional evaluation of activation-dependent alterations in the sialoglycan composition of T cells.
J. Biol. Chem.
PUBLISHED: 12-02-2013
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Sialic acids (Sias) are often conjugated to the termini of cellular glycans and are key mediators of cellular recognition. Sias are nine-carbon acidic sugars, and, in vertebrates, the major species are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), differing in structure at the C5 position. Previously, we described a positive feedback loop involving regulation of Neu5Gc expression in mouse B cells. In this context, Neu5Gc negatively regulated B-cell proliferation and Neu5Gc expression was suppressed upon activation. Similarly, resting mouse T cells expressed principally Neu5Gc, and Neu5Ac was induced upon activation. In the present work, we used various probes to examine sialoglycan expression by activated T cells in terms of the Sia species expressed and the linkages of Sias to glycans. Upon T-cell activation, sialoglycan expression shifted from Neu5Gc to Neu5Ac and the linkage from ?2,6 to ?2,3. These changes altered the expression levels of siglec (sialic acid-binding immunoglobulin-like lectins) ligands. Expression of sialoadhesin and Siglec-F ligands increased, and that of CD22 ligands decreased. Neu5Gc exerted a negative effect on T-cell activation, both in terms of the proliferative response and in the context of activation-marker expression. Suppression of Neu5Gc expression in mouse T and B cells prevented the development of nonspecific CD22-mediated T cell-B cell interactions. Our results suggest that an activation-dependent shift from Neu5Gc to Neu5Ac and replacement of ?2,6 by ?2,3 linkages, may regulate immune cell interactions at several levels.
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The effects of transovarian exposure to p,p-DDT and p,p-DDE on avian reproduction using Japanese quails.
J Toxicol Sci
PUBLISHED: 11-12-2013
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In the 1950s to 1970s developed countries reported declines in populations of raptorial and fish-eating birds and dichlorodiphenyltrichloroethane (DDT) and its metabolites were considered causative substances because they accumulated significantly in the tissues of wild birds and animals. However, except for the estrogenic effects of o,p-DDT, a minor component of commercial DDT, there has been no compelling evidence that DDT directly affects avian reproductive systems. To assess the possible impact of DDT on development and reproduction of birds, exposure experiments to the major component of commercial DDT, p,p-DDT, and its persistent metabolite, p,p-dichlorodiphenyldichloroethylene (DDE), were performed using Japanese quail (Coturnix japonica) eggs; the test substances (3 to 100 ?g/g) were injected into the yolk prior to incubation, and hatched chicks were raised to adulthood. p,p-DDT had no significant effects on the morphology and function of the reproductive systems, although the hatchability of treated eggs was reduced at the highest dose (100 ?g/g). High doses of p,p-DDE slightly enhanced the eggshell forming ability of female quails; eggshell mass and thickness were increased at 30 ?g/g or more although no morphological changes were observed in the oviduct. Transcriptions of the CYP11A1 gene in the ovaries, and of AHR and ARNT in the livers, of adult females were significantly increased at 3 ?g/g or more of p,p-DDT. Except for low hatchability, transovarian exposure to p,p-DDT or p,p-DDE did not markedly impair the avian reproductive systems, but the hormonal actions of these compounds are likely to change reproductive and hepatic functions even after maturation.
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Intravenous cyclophosphamide pulse therapy in Japanese children with systemic lupus erythematosus.
J Nippon Med Sch
PUBLISHED: 11-06-2013
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Intravenous cyclophosphamide (IVCY) pulse therapy has been used for lupus nephritis since the latter half of the 1980s; it has been shown to be effective for lupus nephritis and vasculitis and has become a standard therapy for the diffuse proliferative type of lupus nephritis in adults. IVCY therapy has also come to be used in children. This paper reports the long-term outcomes of IVCY therapy in children.
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Seroconversion of hepatitis B envelope antigen by entecavir in a child with hepatitis B virus-related membranous nephropathy.
J Nippon Med Sch
PUBLISHED: 11-06-2013
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Membranous nephropathy (MN) is caused by subepithelial deposition of immune complexes in the glomerular basement membrane, with secondary MN arising in association with infection. In secondary MN caused by hepatitis B virus (HBV), seroconversion has been known to occur after the onset of MN, particularly in children. In patients with high serum concentrations of HBV DNA, treatment with interferon-?2b or a nucleoside analog has been reported to induce seroconversion and suppress HBV-DNA levels. We treated a 7-year-old boy who presented with proteinuria and liver dysfunction. He had a history of HBV infection since shortly after birth, as his mother was HBV-positive, and he was neither vaccinated nor treated with immunoglobulin at birth. Chronic hepatitis related to HBV was diagnosed following percutaneous needle biopsy of the liver. Percutaneous renal biopsy revealed HBV-related glomerulonephritis with diffuse global subepithelial and focal segmental mesangial and subendothelial deposits. Therefore, HBV-associated MN was diagnosed. Treatment with the nucleoside analog lamivudine was started to reduce serum HBV-DNA levels, but lamivudine was discontinued and treatment with entecavir was started at a dosage of 0.5 mg/day after 6 weeks because of possible adverse effects. Tests for HB envelope antibody were positive in week 16 of treatment, and proteinuria had resolved by week 22. Elevated levels of aspartate aminotransferase and alanine aminotransferase were seen with both treatments but were probably attributable to the developing immune response to HBV. In the present case, HBV levels needed to be reduced to: 1) lower elevated serum HBV-DNA titers, which put the patient at high risk of hepatocellular carcinoma; and 2) remove the immune complexes causing MN. Use of nucleoside analogs to suppress the HBV load may facilitate early remission of MN, and entecavir therapy did not cause any serious adverse reactions in this case. Given the advent of lamivudine-resistant HBV, entecavir appears promising for patients with elevated serum levels of HBV DNA.
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Vascularized composite allograft transplant survival in miniature Swine: is MHC tolerance sufficient for acceptance of epidermis?
Transplantation
PUBLISHED: 09-24-2013
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We have previously reported that Massachusetts General Hospital miniature swine, which had accepted class I-mismatched kidneys long-term after 12 days of high-dose cyclosporine A, uniformly accepted donor-major histocompatibility complex (MHC)-matched kidneys without immunosuppression but rejected donor MHC-matched split-thickness skin grafts by day 25, without changes in renal graft function or antidonor in vitro responses. We have now tested whether this "split tolerance" would also be observed for the primarily vascularized skin of vascularized composite allografts (VCAs).
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Snail expression and outcome in T1 high-grade and T2 bladder cancer: a retrospective immunohistochemical analysis.
BMC Urol
PUBLISHED: 09-20-2013
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Neoadjuvant chemotherapy has been shown to have benefit in T1 high-grade or T2 bladder cancer. However, neoadjuvant chemotherapy fails in some patients. Careful patient selection for neoadjuvant chemotherapy is therefore needed. Several reports show that Snail is associated with resistance to chemotherapy. We hypothesized that Snail expression could predict survival in T1 high-grade and T2 bladder cancer patients treated with neoadjuvant chemotherapy.
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Efficacy of steroid pulse therapy in combination with mizoribine following tonsillectomy for immunoglobulin a nephropathy in renally impaired patients.
J Nippon Med Sch
PUBLISHED: 09-03-2013
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The long-term prognosis of immunoglobulin A nephropathy is poor. Treatment is intended to achieve complete remission in the early stage or to preserve renal function in the advanced stages. In Japan, aggressive steroid pulse therapy following tonsillectomy (tonsillectomy-pulse therapy) has recently been used to treat early IgA nephropathy and has achieved favorable outcomes. However, steroid doses are sometimes limited because of adverse reactions s and the efficacy of tonsillectomy-steroid pulse therapy has not been established in patients with renal dysfunction. In our current treatment protocol, the total steroid dose has been significantly reduced through the use of the immunosuppressant mizoribine in combination with tonsillectomy-steroid pulse therapy for the treatment of active IgA nephropathy in patients with renal impairment.
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Three isozymes of peptidylarginine deiminase in the chicken: Molecular cloning, characterization, and tissue distribution.
Comp. Biochem. Physiol. B, Biochem. Mol. Biol.
PUBLISHED: 08-12-2013
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Peptidylarginine deiminase (PAD; EC 3.5.3.15) is a post-translational modification enzyme that catalyzes the conversion of protein-bound arginine to citrulline (deimination) in a calcium ion dependent manner. Although PADI genes are widely conserved among vertebrates, their function in the chicken is poorly understood. Here, we cloned and sequenced three chicken PADI cDNAs and analyzed the expression of their proteins in various tissues. Immunoblotting analysis showed that chicken PAD1 and PAD3 were present in cells of several central neuron system tissues including the retina; the chicken PAD2 protein was not detected in any tissue. We expressed recombinant chicken PADs in insect cells and characterized their enzymatic properties. The chicken PAD1 and PAD3 recombinant proteins required calcium ions as an essential cofactor for their catalytic activity. The two recombinant proteins showed similar substrate specificities toward synthetic arginine derivatives. By contrast to them, chicken PAD2 did not show any activity. We found that one of the conserved active centers in mammalian PADs had been altered in chicken PAD2; we prepared a reverse mutant but we did not detect an activity. We conclude that chicken PAD1 and PAD3 might play specific roles in the nervous system, but that chicken PAD2 might not be functional under normal physiological conditions.
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Assessing the effect of immunosuppression on engraftment of pancreatic islets.
Transplantation
PUBLISHED: 07-26-2013
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In addition to ischemia and immunologic factors, immunosuppressive drugs have been suggested as a possible contributing factor to the loss of functional islets after allogeneic islet cell transplantation. Using our previously described islet-kidney (IK) transplantation model in miniature swine, we studied whether an islet-toxic triple-drug immunosuppressive regimen (cyclosporine+azathioprine+prednisone) affects the islet engraftment process and thus long-term islet function.
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Microsporum canis infection mimics pemphigus erythematosus.
Indian J Dermatol
PUBLISHED: 06-01-2013
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We report a 55-year-old Japanese woman with a two-month history of multiple pruritic erythema and erosion on her face and neck. Based on the clinical appearance, we initially diagnosed her as having pemphigus erythematosus. However, the results of a histopathological examination and a direct immunofluorescence study did not support the initial diagnosis. Additionally, anti-desmoglein 1 and 3 antibodies were all negative. Subsequently, a microscopic examination of scales revealed filaments of fungi and a fungal culture was negative for macroconidium. Using molecular biology techniques, we identified the fungus as Microsporum canis, which causes a zoonotic infection. The immune reaction to the fungi could be drastic and therefore, the eruption sometimes displays atypical clinical manifestations.
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Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo-embolization.
Int. J. Clin. Oncol.
PUBLISHED: 05-22-2013
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The aim of the present study was to evaluate whether serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) trends might be correlated with overall survival rates in patients with recurrent hepatocellular carcinoma (HCC) undergoing trans-catheter arterial chemo-embolization (TACE).
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Novel collagen/gelatin scaffold with sustained release of basic fibroblast growth factor: clinical trial for chronic skin ulcers.
Tissue Eng Part A
PUBLISHED: 04-27-2013
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Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing and are a costly problem in healthcare. We have developed a novel artificial dermis, collagen/gelatin sponge (CGS), which is capable of sustained release of basic fibroblast growth factor (bFGF) for more than 10 days. The objective of this study was to investigate the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. Patients with chronic skin ulcers that had not healed in at least 4 weeks were treated with CGS impregnated with bFGF at 7 or 14 ?g/cm(2) after debridement, and the wound bed improvement was assessed 14 days after application. Wound bed improvement was defined as a granulated and epithelialized area on day 14 with a proportion to the baseline wound area after debridement of 50% or higher. The wound area, the wound area on day 14, and the granulation area on day 14 were independently measured by blinded reviewers in a central review using digital images of wounds taken with a calibrator. Patients were followed up until 28 days after application to observe the adverse reactions related to the application of CGS. From May 2010 to June 2011, 17 patients were enrolled and, in 16 patients, the wound bed improved. Among the randomized patients in step 2, no significant difference was seen between the low-dose group and the high-dose group. No serious adverse reactions were observed. Adverse reactions with a clear causal relationship to the study treatment were mild and patients quickly recovered from them. This study is the first-in-man clinical trial of CGS and showed the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. This combination therapy could be a promising therapy for chronic skin ulcers.
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Surgical technique of orthotopic liver transplantation in rats: the Kamada technique and a new splint technique for hepatic artery reconstruction.
J Nippon Med Sch
PUBLISHED: 03-09-2013
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Orthotopic liver transplantation (OLT) in rats is technically feasible and useful for the assessment of clinical liver transplantation and analysis of inflammatory liver diseases. OLT in rats was pioneered by Lee et al. in 1973 using hand-suture techniques of all vessels. This model has not been widely used due to the long operative time and technical demand. The cuff method was introduced by Kamada in 1979, and today, the Kamada technique is the one most commonly used worldwide. However, this technique does not include hepatic artery reconstruction, although this procedure is routinely performed in clinical transplantation. Nevertheless, several techniques for hepatic artery reconstruction in rat OLT have been reported recently, and our group also developed a simple splint technique from recipient right renal artery to donor celiac axis bearing the hepatic artery. In the present article, we describe the Kamada technique, as a standard surgical method for rat OLT. In addition, we also describe our splint technique for hepatic artery reconstruction. Then, we compare the features of Kamada technique and our splint technique for hepatic artery reconstruction and all other surgical techniques currently in use for rat OLT. The widespread use of the rat OLT model should help to provide full assessment of transplant immunology and the mechanism and treatment of inflammatory liver diseases.
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Production of cloned NIBS (Nippon Institute for Biological Science) and ?-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates.
Xenotransplantation
PUBLISHED: 02-28-2013
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BACKGROUND: Nuclear transfer (NT) technologies offer a means for producing the genetically modified pigs necessary to develop swine models for mechanistic studies of disease processes as well as to serve as organ donors for xenotransplantation. Most previous studies have used commercial pigs as surrogates. METHOD AND RESULTS: In this study, we established a cloning technique for miniature pigs by somatic cell nuclear transfer (SCNT) using Nippon Institute for Biological Science (NIBS) miniature pigs as surrogates. Moreover, utilizing this technique, we have successfully produced an ?-1, 3-galactosyltransferase knockout (GalT-KO) miniature swine. Fibroblasts procured from a NIBS miniature pig fetus were injected into 1312 enucleated oocytes. The cloned embryos were transferred to 11 surrogates of which five successfully delivered 13 cloned offspring; the production efficiency was 1.0% (13/1312). In a second experiment, lung fibroblasts obtained from neonatal GalT-KO MGH miniature swine were used as donor cells and 1953 cloned embryos were transferred to 12 surrogates. Six cloned offspring were born from five surrogates, a production efficiency of 0.3% (6/1953). CONCLUSIONS: These results demonstrate successful establishment of a miniature pig cloning technique by SCNT using NIBS miniature pigs as surrogates. To our knowledge, this is the first demonstration of successful production of GalT-KO miniature swine using miniature swine surrogates. This technique could help to ensure a stable supply of the cloned pigs through the use of miniature pig surrogates and could expand production in countries with limited space or in facilities with special regulations such as specific pathogen-free or good laboratory practice.
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Comparison of the indocyanine green fluorescence and blue dye methods in detection of sentinel lymph nodes in early-stage breast cancer.
Ann. Surg. Oncol.
PUBLISHED: 02-21-2013
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To assess the diagnostic performance of sentinel lymph node (SLN) biopsy using the indocyanine green (ICG) fluorescence method compared with that using the blue dye method, a prospective multicenter study was performed.
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Canonical thermal pure quantum state.
Phys. Rev. Lett.
PUBLISHED: 02-15-2013
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A thermal equilibrium state of a quantum many-body system can be represented by a typical pure state, which we call a thermal pure quantum (TPQ) state. We construct the canonical TPQ state, which corresponds to the canonical ensemble of the conventional statistical mechanics. It is related to the microcanonical TPQ state, which corresponds to the microcanonical ensemble, by simple analytic transformations. Both TPQ states give identical thermodynamic results, if both ensembles do, in the thermodynamic limit. The TPQ states corresponding to other ensembles can also be constructed. We have thus established the TPQ formulation of statistical mechanics, according to which all quantities of statistical-mechanical interest are obtained from a single realization of any TPQ state. We also show that it has great advantages in practical applications. As an illustration, we study the spin-1/2 kagome Heisenberg antiferromagnet.
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Distribution of glomerular density in different cortical zones of the human kidney.
Pathol. Int.
PUBLISHED: 02-13-2013
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Our studies have demonstrated that a low glomerular density in renal biopsies is a plausible predictor of a worse renal outcome in patients with primary glomerular diseases. However, there remains a concern regarding the diversity that may exist in the distribution of glomerular density within the same kidney. This study therefore aimed to determine the differences in the glomerular density between anatomically different cortical zones of the human kidney. A total of 89 autopsy kidneys were analyzed to accurately measure the glomerular density in different parts of the renal cortex. As a whole, compared to the glomerular density in the superficial cortex (3.0?±?0.7/mm(2)), the average glomerular density in the juxtamedullary cortex (2.2?±?0.6/mm(2)) was approximately two-thirds. The glomerular density showed maximal 3.5-fold variations between individuals and was inversely correlated with the mean glomerular volume in both cortical areas. A low glomerular density of the superficial cortex was predominantly associated with the increase of global glomerulosclerosis. On the other hand, a low glomerular density of the juxtamedullary cortex was predominantly associated with an increase in the kidney weight. Thus, there are significant zonal differences in the distribution of the glomerular density in human kidneys independent of the potential variations observed between individuals.
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Japan Renal Biopsy Registry and Japan Kidney Disease Registry: Committee Report for 2009 and 2010.
Clin. Exp. Nephrol.
PUBLISHED: 02-06-2013
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The Japan Renal Biopsy Registry (J-RBR) was started in 2007 and the Japan Kidney Disease Registry (J-KDR) was then started in 2009 by the Committee for Standardization of Renal Pathological Diagnosis and the Committee for the Kidney Disease Registry of the Japanese Society of Nephrology. The purpose of this report is to describe and summarize the registered data from 2009 and 2010. For the J-KDR, data were collected from 4,016 cases, including 3,336 (83.1 %) by the J-RBR and 680 (16.9 %) other cases from 59 centers in 2009, and from 4,681 cases including 4,106 J-RBR cases (87.7 %) and 575 other cases (12.3 %) from 94 centers in 2010, including the affiliate hospitals. In the J-RBR, 3,165 native kidneys (94.9 %) and 171 renal grafts (5.1 %) and 3,869 native kidneys (94.2 %) and 237 renal grafts (5.8 %) were registered in 2009 and 2010, respectively. Patients younger than 20 years of age comprised 12.1 % of the registered cases, and those 65 years and over comprised 24.5 % of the cases with native kidneys in 2009 and 2010. The most common clinical diagnosis was chronic nephritic syndrome (55.4 % and 50.0 % in 2009 and 2010, respectively), followed by nephrotic syndrome (22.4 % and 27.0 %); the most frequent pathological diagnosis as classified by the pathogenesis was IgA nephropathy (31.6 % and 30.4 %), followed by primary glomerular diseases (except IgA nephropathy) (27.2 % and 28.1 %). Among the primary glomerular diseases (except IgA nephropathy) in the patients with nephrotic syndrome, membranous nephropathy was the most common histopathology in 2009 (40.3 %) and minor glomerular abnormalities (50.0 %) were the most common in 2010 in native kidneys in the J-RBR. Five new secondary and longitudinal research studies by the J-KDR were started in 2009 and one was started in 2010.
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Renal inflammatory changes in acute hepatic failure-associated acute kidney injury.
Am. J. Nephrol.
PUBLISHED: 02-01-2013
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Acute kidney injury (AKI) is a common complication in advanced liver dysfunction. Our aim is to clarify the mechanisms of acute hepatic failure (AHF)-associated AKI.
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The prevalence of Merkel cell polyomavirus in Japanese patients with Merkel cell carcinoma.
J. Dermatol. Sci.
PUBLISHED: 02-01-2013
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A novel polyomavirus, the Merkel cell polyomavirus (MCPyV) has been implicated in the pathogenesis of Merkel cell carcinoma (MCC); however, the prevalence of MCPyV in Japan has not been extensively investigated.
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Evasion from accelerated blood clearance of nanocarrier named as "Lactosome" induced by excessive administration of Lactosome.
Biochim. Biophys. Acta
PUBLISHED: 01-18-2013
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Nanoparticle of Lactosome, which is composed of poly(l-lactic acid)-base depsipeptide with diameter of 35nm, accumulates in solid tumors by the enhanced permeability and retention (EPR) effect. However, a pharmacokinetic alteration of Lactosome was observed when Lactosome was repeatedly administered. This phenomenon is named as the Lactosome accelerated blood clearance (ABC) phenomenon. In this study, the effect of Lactosome dose on the ABC phenomenon was examined and discussed in terms of immune tolerance.
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An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model.
Mol. Vis.
PUBLISHED: 01-01-2013
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We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPAR?) agonist on corneal inflammation and wound healing after alkali burn injury in rats.
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Pathologic characteristics of transplanted kidney xenografts.
J. Am. Soc. Nephrol.
PUBLISHED: 11-23-2011
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For xenotransplantation to become a clinical reality, we need to better understand the mechanisms of graft rejection or acceptance. We examined pathologic changes in ?1,3-galactosyltransferase gene-knockout pig kidneys transplanted into baboons that were treated with a protocol designed to induce immunotolerance through thymic transplantation (n=4) or were treated with long-term immunosuppressants (n=3). Hyperacute rejection did not occur in ?1,3-galactosyltransferase gene-knockout kidney xenografts. By 34 days, acute humoral rejection led to xenograft loss in all three xenografts in the long-term immunosuppression group. The failing grafts exhibited thrombotic microangiopathic glomerulopathy with multiple platelet-fibrin microthrombi, focal interstitial hemorrhage, and acute cellular xenograft rejection. Damaged glomeruli showed IgM, IgG, C4d, and C5b-9 deposition. They also demonstrated endothelial cell death, diffuse endothelial procoagulant activation with high expression of tissue factor and vWF, and low expression of the ectonucleotidase CD39. In contrast, in the immunotolerance group, two of four grafts had normal graft function and no pathologic findings of acute or chronic rejection at 56 and 83 days. One of the remaining kidneys had mild but transient graft dysfunction with reversible, mild microangiopathic glomerulopathy, probably associated with preformed antibodies. The other kidney in the immunotolerance group developed unstable graft function at 81 days and developed chronic xenograft glomerulopathy. In summary, the success of pig-to-primate xenotransplantation may necessitate immune tolerance to inhibit acute humoral and cellular xenograft rejection.
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Human T-cell leukemia viruses are highly unstable over a wide range of temperatures.
J. Gen. Virol.
PUBLISHED: 11-23-2011
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The biological properties of human T-cell leukemia virus type I (HTLV-I) and HTLV type II (HTLV-II) are not well elucidated as cell-free viruses. We established new assay systems to detect the infectivity of cell-free HTLVs and examined the stability of cell-free HTLVs at different temperatures. HTLVs lost infectivity more rapidly than did bovine leukemia virus (BLV), which is genetically related to HTLVs. The half-lives of three HTLV-I strains (two cosmopolitan strains and one Melanesian strain) at 37 °C were approximately 0.6 h, whereas the half-life of a BLV strain was 8.5 h. HTLV-I rapidly lost infectivity unexpectedly at 0 and 4 °C. We examined the stability of vesicular stomatitis virus pseudotypes with HTLV-I, HTLV-II or BLV Env proteins, and the Env proteins of HTLVs were found to be more unstable at 4 and 25 °C than the Env proteins of the BLV. Over the course of the viral life cycle, heat treatment inhibited HTLV-I infection at the phase of attachment to the host cells, and inhibition was more marked upon entry into the cells. The HTLV-I Env surface (SU) protein (gp46) was easily released from virions during incubation at 37 °C. However, this release was inhibited by pre-treatment of the virions with N-ethylmaleimide, suggesting that the inter-subunit bond between gp46 SU and gp21 transmembrane (TM) proteins is rearranged by disulfide bond isomerization. HTLVs are highly unstable over a wide range of temperatures because the disulfide bonds between the SU and TM proteins are labile.
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Progression of pancreatitis prior to diabetes onset in WBN/Kob-Lepr(fa) rats.
J. Vet. Med. Sci.
PUBLISHED: 08-12-2011
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We established the WBN/Kob-Lepr(fa) rat as a new congenic strain for the fa allele of the leptin receptor gene (Lepr). Homozygous (fa/fa) WBN/Kob-Lepr(fa) rats provide a model of non-insulin-dependent diabetes, although its onset is secondary to pancreatitis. In the present study, we compared histopathological observations of pancreatitis in each genotype of this rat, to examine its suitability as a model of pancreatitis. The histopathological findings of the pancreatitis revealed intense changes dependent on age, such as hemorrhage or hemosiderin deposition. The pancreatitis in homozygous (fa/fa) WBN/Kob-Lepr(fa) rats were more severe than those of WBN/Kob rats.
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First experience with the use of a recombinant CD3 immunotoxin as induction therapy in pig-to-primate xenotransplantation: the effect of T-cell depletion on outcome.
Transplantation
PUBLISHED: 08-09-2011
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We have previously reported life-supporting kidney xenograft-survival greater than 80 days using a steroid-free antithymocyte globulin (ATG)-based induction regimen (ATG regimen) in a GalT-KO pig-to-baboon thymokidney (TK) model. We evaluated two induction regimens, a newly developed anti-monkey CD3 recombinant immunotoxin (anti-CD3 rIT) and an anti-human CD2 antibody (LoCD2), by assessing T-cell depletion (TCD) and graft survival.
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Renal thrombotic microangiopathy associated with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Pathol. Int.
PUBLISHED: 07-12-2011
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Thrombotic microangiopathy (TMA) is a major complication after hematopoietic stem cell transplantation (HSCT). In this study, we examined the clinical and pathologic features of 2 patients and 5 autopsy cases with HSCT-associated renal TMA to clarify the association between graft-versus-host disease (GVHD) and renal TMA. The median interval between HSCT and renal biopsy or autopsy was 7 months (range 3-42 months). Clinically, acute and chronic GVHD occurred in 7 and 4 patients, respectively. Clinical evidence for TMA was detected in 2 patients, while chronic kidney disease developed in all patients. The main histopathological findings were diffuse endothelial injury in glomeruli, peritubular capillaries (PTCs), and small arteries. In addition, all cases showed glomerulitis, renal tubulitis, and peritubular capillaritis with infiltration of CD3+ T cells and TIA-1+ cytotoxic cells, suggesting that GVHD occurred during the development of TMA. Diffuse and patchy C4d deposition was noted in glomerular capillaries and PTCs, respectively, in 2 biopsy and 2 autopsy cases, suggesting the involvement of antibody-mediated renal endothelial injury in more than 50% of renal TMA cases. In conclusion, the kidney is a potential target of chronic GVHD that may induce the development of HSCT-associated TMA. Importantly, some cases are associated with chronic humoral GVHD.
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Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis.
Bone
PUBLISHED: 06-03-2011
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Maxillofacial dysmorphogenesis is found in 5% of the population. To begin to understand the mechanisms required for maxillofacial morphogenesis, we employed the inhibitors of the differentiation 2 (Id2) knock-out mouse model, in which Id proteins, members of the regulator of basic helix-loop-helix (bHLH) transcription factors, modulate cell proliferation, apoptosis, and differentiation. We now report that spatially-restricted growth defects are localized at the skull base of Id2 KO mice. Curiously, at birth, neither the mutant Id2 KO nor wild-type (WT) mice differed, based upon cephalometric and histological analyses of cranial base synchondroses. In postnatal week 2, a narrower hypertrophic zone and an inhibited proliferative zone in presphenoid synchondrosis (PSS) and spheno-occipital synchondrosis (SOS) with maxillary hypoplasia were identified in the Id2 mutant mice. Complementary studies revealed that exogenous bone morphogenetic proteins (BMPs) enhanced cartilage growth, matrix deposition, and chondrocyte proliferation in the WT but not in the mutant model. Id2-deficient chondrocytes expressed more Smad7 transcripts. Based on our results, we assert that Id2 plays an essential role, acting downstream of BMP signaling, to regulate cartilage formation at the postnatal stage by enhancing BMP signals through inhibiting Smad7 expression. As a consequence, abnormal endochondral ossification was observed in cranial base synchondroses during the postnatal growth period, resulting in the clinical phenotype of maxillofacial dysmorphogenesis.
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Focal segmental glomerulosclerosis after renal transplantation.
Clin Transplant
PUBLISHED: 06-01-2011
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Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic syndrome of proteinuria, usually of nephrotic range, associated with focal and segmental sclerotic glomerular lesions. Therefore, FSGS is diagnosed by clinical features and histopathological examination of renal biopsy. The natural history of the condition varies, and although it may respond to treatment, FSGS is an important disease in the etiology of end-stage renal disease (ESRD). Furthermore, after kidney transplantation, approximately 30% of patients with FSGS develop recurrent FSGS. The risk factors for recurrence of FSGS include childhood onset and age <15 yr, rapid progression of the primary FSGS to ESRD, recurrence of FSGS in a previous allograft, diffuse mesangial hypercellularity in the native kidney, collapsing FSGS, and podocin gene mutation. In addition, after kidney transplantation, de novo FSGS also develops in approximately 10-20% of allografts, associated with a complication of hyperfiltration injury, chronic transplant glomerulopathy, and calcineurin inhibitor toxicity. FSGS is considered a podocyte disease, and the pathology is characterized by segmental FSGS lesion with glomerular epithelial hypercellularity. The pathological diagnosis of FSGS is based on the 2004 Columbia classification system. In the present minireview, we discuss the pathology of recurrence and de novo FSGS after kidney transplantation.
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Kaposis sarcoma-associated herpesvirus vFLIP and human T cell lymphotropic virus type 1 Tax oncogenic proteins activate IkappaB kinase subunit gamma by different mechanisms independent of the physiological cytokine-induced pathways.
J. Virol.
PUBLISHED: 05-18-2011
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Activation of I?B kinase subunit ? (IKK?), a key regulator of the classical NF-?B pathway, by the vFLIP protein of Kaposis sarcoma-associated herpesvirus (KSHV) and the Tax protein of human T cell lymphotropic virus type 1 (HTLV1) is essential for virus-associated cancer. We show that vFLIP and Tax activate this pathway by different interactions with IKK? and independently of the ubiquitin-mediated signaling pathways induced by cytokines. Our data provide new insights into the mechanisms by which IKK? can be activated and show that NF-?B activation by oncogenic viruses can be targeted without affecting physiologically important pathways.
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COP35, a cholangiocarcinoma-binding oligopeptide, interacts with the clathrin heavy chain accompanied by GRP78.
Mol. Cancer Res.
PUBLISHED: 05-13-2011
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Cholangiocarcinoma (CCA) is a common carcinoma of the liver, and the majority of patients with CCA have a poor prognosis due to the lack of effective nonsurgical therapies in addition to its rapid progression and inoperability at the time of diagnosis. The development of novel nonsurgical therapeutics that efficiently target CCA could significantly improve the prognosis for patients presenting with CCA. Here, we describe the iterative production and characterization of a novel peptide, designated COP35 (CCA-binding oligopeptide 35), which binds selectively to human CCA, identified by bacteriophage biopanning using the intrahepatic CCA cell line RBE and the normal cholangiocyte cell line MMNK-1. COP35 was found to augment the growth inhibitory effects of 5-fluorouracil (5-FU) against RBE cells. Utilizing pull-down assay and liquid chromatography, we identify the clathrin heavy chain accompanied by GRP78/BiP as a COP35-binding partner. In summary, we identify COP35 as a possible candidate for peptide-targeted therapies for CCA.
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Development of a new selective medium for isolation of methicillin-resistant Staphylococcus aureus.
J. Vet. Med. Sci.
PUBLISHED: 04-28-2011
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A new selective medium containing cephem antibiotics was developed for isolation of methicillin-resistant Staphylococcus aureus (MRSA). MRSA colonies on a medium containing ceftazidime (CAZ) were most easily identifiable and a medium containing cefoperazone (CPZ) was superior in suppressing the growth of other bacteria. With the medium containing a couple of CAZ and CPZ, MRSA and methicillin-resistant coagulase-negative staphylococci (MRCNS) were detected from 2 and 1 of 15 chicken meat samples respectively. The MRSA and MRCNS recovery test showed that the medium was effective for MRSA isolation, suppressing the growth of other bacteria efficiently. These results suggested that the medium containing a couple of CAZ and CPZ was useful for MRSA detection from foods and animals.
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Runx3 is required for full activation of regulatory T cells to prevent colitis-associated tumor formation.
J. Immunol.
PUBLISHED: 04-22-2011
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Inflammation is increasingly recognized as an essential component of tumorigenesis, which is promoted and suppressed by various T cell subsets acting in different ways. It was shown previously in Runx3-deficient mice that differentiation of CD8 T and NK cells is perturbed. In this study, we show that Runx3 is also required for proper differentiation and function of regulatory T cells. In Runx3-deficient mice, T cells were unable to inhibit inflammation and to suppress tumor development. As expected, recombination activating gene 2-deficient mice bearing Runx3-deficient lymphocytes spontaneously developed colon tumors. However, tumor formation was completely blocked by transfer of either regulatory T cells or CD8 T cells derived from wild-type mice to mutant mice or by housing mutant mice in a specific pathogen-free condition. These results indicate that Runx3-deficient lymphocytes and microorganisms act together to induce inflammation and consequently induce the development of colon tumors.
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Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin.
Jpn J Radiol
PUBLISHED: 04-12-2011
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Cisplatin has shown a high tumor response rate among head and neck carcinomas, and the tumor response is related to the cisplatin dosage. The purpose of this study was to evaluate the efficacy and toxicity of selective intraarterial chemoradiation therapy for oropharyngeal carcinomas with high-dose cisplatin.
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Increased risk of temporomandibular joint closed lock: a case-control study of ANKH polymorphisms.
PLoS ONE
PUBLISHED: 03-24-2011
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This study aimed to carry out a histological examination of the temporomandibular joint (TMJ) in ank mutant mice and to identify polymorphisms of the human ANKH gene in order to establish the relationship between the type of temporomandibular disorders (TMD) and ANKH polymorphisms.
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[Two cases of rapidly progressive nephritic syndrome complicated with alcoholic liver cirrhosis].
Nihon Jinzo Gakkai Shi
PUBLISHED: 03-05-2011
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It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through the use of steroids and immune system suppressors. Case 1 was a 55-year-old male. He was being treated for alcoholic liver cirrhosis, but as bloody urine was noticed macroscopically, his renal function rapidly decreased. Specimens from a renal biopsy showed endocapillary proliferative lesions accompanying necrotic lesions. Granular deposition of IgA (IgA1) and C3 was seen along the capillary walls and in the mesangial areas. After the combined treatments of bilateral palatotonsillectomy, three courses of steroid semi-pulse therapy and post-therapy with steroids and mizoribin (MZR)were started, his hematuria and proteinuria disappeared and renal function improved markedly. Case 2 was a 37-year-old male with alcoholic liver cirrhosis complicated with hepatic encephalopathy. Although he was being treated at another hospital, nephritic syndrome occurred with rapidly worsening renal function and massive ascites. After continuous drainage of the ascites, we performed a renal biopsy. Mild proliferative lesions and notable wrinkling, thickening and doubling of the basal membrane were seen. Crescent formations were found in about half of the glomeruli. The fluorescent antibody technique showed positive pictures of IgA (IgA1) and C3. When three courses of steroid semi-pulse therapy and post therapy with steroids and MZR were combined, his proteinuria and serum Cre level decreased and stagnated ascites markedly decreased. The two cases were diagnosed as having secondary IgA nephropathy induced by the deposition of the IgA1 derived mainly from the intestinal tract, which had increased in the blood due to alcoholic liver cirrhosis. Active use of immune system suppressor therapy was effective.
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A novel synthetic material for spinal fusion: a prospective clinical trial of porous bioactive titanium metal for lumbar interbody fusion.
Eur Spine J
PUBLISHED: 02-16-2011
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The objective of this study was to establish the efficacy and safety of porous bioactive titanium metal for use in a spinal fusion device, based on a prospective human clinical trial. A high-strength spinal interbody fusion device was manufactured from porous titanium metal. A bioactive surface was produced by simple chemical and thermal treatment. Five patients with unstable lumbar spine disease were treated surgically using this device in a clinical trial approved by our Ethics Review Committee and the University Hospital Medical Information Network. Clinical and radiological results were reported at the minimum follow-up period of 1 year. The optimal mechanical strength and interconnected structure of the porous titanium metal were adjusted for the device. The whole surface of porous titanium metal was treated uniformly and its bioactive ability was confirmed before clinical use. Successful bony union was achieved in all cases within 6 months without the need for autologous iliac crest bone grafting. Two specific findings including an anchoring effect and gap filling were evident radiologically. All clinical parameters improved significantly after the operation and no adverse effects were encountered during the follow-up period. Although a larger and longer-term follow-up clinical study is mandatory to reach any firm conclusions, the study results show that this porous bioactive titanium metal is promising material for a spinal fusion device.
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Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety.
J Transl Med
PUBLISHED: 02-01-2011
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Hepatocyte growth factor (HGF) stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF), including a phase I/II study of patients with fulminant hepatitis (FH) or late-onset hepatic failure (LOHF), in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule.
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Functions of Runx in IgA class switch recombination.
J. Cell. Biochem.
PUBLISHED: 01-27-2011
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Runt-related (Runx) transcriptional regulators play essential roles in various cell fate determination processes, and dysfunction of these regulators causes many human diseases. Considerable insight into the functions of Runx proteins was provided mainly by studies of hematopoietic and skeletal disorders. Recently, extensive investigations have revealed new functions of these transcription factors in immune cell differentiation and functioning. In the present review, we discuss the mechanisms of selective IgA production in the intestine and report the involvement of Runx proteins in this process.
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Cross-priming of CD8(+) T cells in vivo by dendritic cells pulsed with autologous apoptotic leukemic cells in immunotherapy for elderly patients with acute myeloid leukemia.
Exp. Hematol.
PUBLISHED: 01-01-2011
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The prognosis for elderly patients with acute myeloid leukemia (AML) remains dismal. To explore the potential of immunotherapy for improving clinical outcomes for these patients, we performed a phase I clinical trial of dendritic cell (DC)-based immunotherapy for elderly patients with AML.
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Beneficial effects of perioperative low-dose inhaled carbon monoxide on pulmonary allograft survival in MHC-inbred CLAWN miniature swine.
Transplantation
PUBLISHED: 11-16-2010
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We have recently reported that perioperative low-dose carbon monoxide (CO) inhalation decreases lung ischemia-reperfusion injury in miniature swine. The aims of this study were to establish a large animal model of pulmonary allograft rejection using polymerase chain reaction-typed major histocompatibility complex (MHC)-inbred CLAWN miniature swine and to examine the effects of CO on allograft survival.
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Renal thrombotic microangiopathy associated with chronic humoral graft versus host disease after hematopoietic stem cell transplantation.
Pathol. Int.
PUBLISHED: 11-05-2010
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Thrombotic microangiopathy (TMA) is a known complication of hematopoietic stem cell transplantation (HSCT). The pathogenesis of TMA is controversial but considered to involve various factors such as total body irradiation, use of calcineurin inhibitors for prophylaxis against graft versus host disease (GVHD), viral infection, and GVHD. Herein we describe a case with renal TMA after HSCT, which was probably associated with antibody-mediated endothelial cell injury from chronic GVHD (termed here chronic humoral GVHD). A 49-year-old man presented two years after HSCT with renal dysfunction and proteinuria but without the clinical features of TMA. Histopathological examination of renal biopsy showed chronic glomerular endothelial cell injury with double contour of the glomerular basement membrane, microthrombi and the deposition of complement split product C4d along the glomerular capillaries. Renal tubulitis and peritubular capillaritis were also noted with a multilayered basement membrane and patchy C4d deposition on peritubular capillaries. These findings resemble those of chronic antibody-mediated rejection after kidney transplantation. Furthermore, C4d deposition suggests complement activation. Although circulating anti-blood type and anti-human leukocyte antigen antibodies were not detected, the renal TMA in this case was probably associated with chronic humoral GVHD.
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The influence of dietary restriction on the development of diabetes and pancreatitis in female WBN/Kob-fatty rats.
Exp. Anim.
PUBLISHED: 10-30-2010
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Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr(fa)) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.
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Inhibition of matrix metalloproteinases reduces ischemia-reperfusion acute kidney injury.
Lab. Invest.
PUBLISHED: 10-18-2010
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Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix and involved in ischemic organ injuries. The present study was designed to determine the role of MMP-2 in the development of ischemic acute kidney injury (AKI). AKI was induced in MMP-2 wild-type (MMP-2(+/+)) mice by 30, 60, 90, and 120?min renal ischemia and reperfusion. Renal histology, expression and activity of MMP-2 and MMP-9, and renal function were examined during the development of AKI. AKI was also induced in MMP-2-deficient (MMP-2(-/-)) mice and MMP-2(+/+) mice treated with inhibitor of MMPs (minocycline and synthetic peptide MMP inhibitor). In MMP-2(+/+) mice, MMP-2 and MMP-9 activities increased significantly at 2 to 24?h, peaked at 6?h, after reperfusion. Immunohistochemical analysis identified MMP-2 in the interstitium around tubules and peritubular capillaries in the outer medulla. Acute tubular injury (ATI), including apoptosis and necrosis, was evident in the outer medulla at 24?h, along with renal dysfunction. As ischemia period increases, MMP-2 and MMP-9 activities at 6?h and severity of AKI at 24?h increased depending on the duration of ischemia between 30 and 120?min. However, the kidneys of MMP-2(-/-) mice showed minimal ATI; serum creatinine 24?h after reperfusion was significantly low in these mice. Inhibitors of MMPs reduced ATI and improved renal dysfunction at 24?h. We conclude that MMPs, especially MMP-2 have a pathogenic role in ischemia-reperfusion AKI, and that inhibitors of MMPs can protect against ischemic AKI.
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Isolation of Staphylococcus aureus from raw fish in relation to culture methods.
J. Vet. Med. Sci.
PUBLISHED: 10-12-2010
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Five hundred and fifty fish samples from various stages in the course of distribution in Hyogo Prefecture (209 retailed in super markets, 173 obtained from fishery cooperatives at a harbor, 91 caught by trawling and 77 caught by rod fishing) were examined for contamination with Staphylococcus aureus (S. aureus). S. aureus was detected in 41 (19.6%) of the retail fish samples and 46 (26.6%) of the samples from the fishery cooperatives. No S. aureus was isolated from the live fish (91 trawled and 77 fished by rod). With regard to the retail fish, the contamination rate of processed fish (26.0%) was significantly higher than that of unprocessed fish (14.2%). For 88 samples, the efficacy of the selective medium was compared using Baird-Parker agar and mannitol salt agar supplemented with egg yolk (MSEY agar) by the direct plate and enrichment culture methods. Using the direct culture method, the S. aureus positive rate with the Baird-Parker agar (30.7%) was significantly higher (P<0.01) than that with the MSEY agar (6.8%). The enrichment culture method remarkably raised the S. aureus detection rate. Seventy-eight (85.7%) of 91 isolates belonged to the human ecovar. Sixty-two (68.1%) of the 91 isolates had some enterotoxin genes, including 44 (48.4%) with the sea gene. These data showed that the fish were contaminated with S. aureus after landing and that Baird-Parker agar had an advantage in detecting S. aureus with a direct plate culture.
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Renoprotective effect of erythropoietin against ischaemia-reperfusion injury in a non-human primate model.
Nephrol. Dial. Transplant.
PUBLISHED: 10-08-2010
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The renoprotective effect of erythropoietin (Epo) against ischaemia-reperfusion injury (IR/I) was evaluated in a non-human primate model.
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Evaluation of the impact of in-ovo exposure to dicofol on avian reproduction.
Environ. Toxicol. Chem.
PUBLISHED: 09-28-2010
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To assess the possible impact of the currently used organochlorine insecticide, dicofol, on the development and reproduction of avian species, in ovo exposure experiments to its p,p and o,p isomers were performed using Japanese quail (Coturnix japonica) eggs. o,p-Dicofol (0.3-100?µg/g of egg) and p,p-dicofol (3-100?µg/g) were injected into the yolk prior to incubation and hatched chicks were raised to adulthood. In ovo treatment with o,p-dicofol impaired the eggshell-forming ability of female quails after sexual maturity; eggshell strength, mass, and thickness were significantly reduced at minimum dosages of 3, 1, and 0.3?µg/g, respectively. o,p-Dicofol also caused abnormal development of the right oviduct independently of the dose; even a female exposed at the lowest dose tested (0.3?µg/g) possessed a large right oviduct. Minor but significant mass reductions of both the left oviduct and the testis were observed only at 10?µg/g. In addition, the transcript of a gene encoding cytochrome P450 cholesterol side-chain cleavage in the gonads of male hatchlings was markedly reduced by o,p-dicofol treatment. p,p-Dicofol did not have any marked effects on the reproductive systems, although some significant changes in eggshell formation and oviduct morphology were observed. The results indicate that transovarian exposure, especially to o,p-dicofol, could damage avian reproduction mainly through eggshell thinning.
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The short-term effect of diacylglycerol oil consumption on total and dietary fat utilization in overweight women.
Obesity (Silver Spring)
PUBLISHED: 09-02-2010
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Diacylglycerol (DAG) is a natural component of edible oils with metabolic characteristics distinct from those of triacylglycerol (TAG). Consumption of DAG oil (containing > 80% DAG) induces greater fat oxidation than consumption of TAG oil. We compared the effects of 4 days of DAG oil consumption with those of TAG oil consumption on total and dietary fat oxidation over 24 h in overweight women using a whole-room respiratory chamber. Overweight (BMI (kg/m²) ? 25) females participated in this double-blind, crossover-controlled trial. The subjects consumed test diets containing either TAG or DAG oil as 15% of their total caloric intake (mean test oil intake was 33.0 ± 3.1 g/day) during each 4-day treatment. Fat oxidation and energy expenditure were measured in a respiratory chamber on the 4th day of each treatment. Compared with TAG oil, DAG oil consumption significantly increased total fat oxidation and dietary fat oxidation in overweight subjects. Total energy expenditure (TEE) and carbohydrate (CHO) oxidation did not significantly differ between DAG oil and TAG oil consumption in overweight subjects. Compared with TAG oil, DAG oil consumption enhanced total fat oxidation and dietary fat oxidation in overweight subjects. The enhanced fat metabolism in overweight subjects that consumed DAG oil partly explains the greater loss of body weight and body fat related to DAG oil consumption in weight-loss studies.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.