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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 181 records · Page 10Linked to original sources
PubMed1997

Surgical strategy for patients with pancreaticobiliary maljunction without choledocal dilatation.

It is well known that the frequency of an associated gallbladder cancer in patients with pancreaticobiliary maljunction (PBM) without congenital choledochal dilation (CCD) is very high, while that of bile duct cancer with CCD is remarkably high, and that of bile duct malignancy without CCD is low. However, recent statistical evaluations have demonstrated that the coincidence rates of gallbladder and bile duct cancer with CCD are 11.5% and 4.6%, respectively, whereas without CCD the rates are 57.1% and 4.1%, respectively. Rates of bile duct cancer with CCD are comparable to those without CCD. We have performed biliary reconstruction after resection of extrahepatic bile ducts along with the gallbladder for PBM patients who had neither CCD nor cancer. Our surgical strategy for these patients without CCD with PBM was assessed from K-ras point mutations and overexpression of p53 protein in the epithelia of the cancerous portions and non-neoplastic portions of the gallbladder and bile duct affected by PBM regardless of choledochal dilatation. The mutation rate in the non-neoplastic gallbladder epithelium without CCD was 80%, that of the bile duct without CCD 57%, not significantly different from the 50% and 40%, respectively, with CCD. The frequency of p53 overexpression in the non-neoplastic bile duct epithelium without CCD was 14%, comparable to the 11% in gallbladder epithelium with CCD. Judging from the statistical data and the molecular biological data, resection of an extrahepatic bile duct with the gallbladder should be the treatment of choice for carcinogenesis prevention.

Biliary Tract↗
PubMed1997

Decrease in the concentrations of transforming growth factor-beta 1 in the sera of patients with Kawasaki disease.

Kawasaki disease (KD) is one of the most important forms of vasculitis, and is characterized by the initiation of a proinflammatory cytokine cascade. To further characterize the immunological profile of KD, we measured the serum levels of transforming growth factor-beta 1 (TGF-beta 1) as a regulatory cytokine. We determined the concentration of TGF-beta 1 in the sera of the patients with KD, anaphylactoid purpura (AP), and scarlet fever, using a sandwich enzyme linked immunosorbent assay. The serum levels of TGF-beta 1 were decreased in patients with KD, but not in patients with AP or scarlet fever during the acute stage. We found an inverse correlation between TGF-beta 1 and soluble tumor necrosis factor (TNF) receptor levels in KD patients during the acute and subacute stage. Decreased levels of TGF-beta 1, in particular to suppress TNF alpha (TNF-alpha) production, is an important part of the regulatory system of increased TNF-alpha production which cause vasculitis.

Adolescent↗
PubMed1997

Identification of rat and human cytochrome P450 forms involved in the metabolism of the thromboxane A2 receptor antagonist (+)-S-145.

(+)-S-145 [5-(+)-(Z)-7-[(1R, 2S, 3S, 4S)-3-phenylsulfonylaminobicyclo[2.2.1]hept-2-yl]-heptenoic acid] and its beta-oxidized metabolites [two [bisnor or dihydro (DH)-bisnor] or four (tetranor) carbon-shortened products at the carboxyl side chain] are hydroxylated at the C-5 or C-6 position of the bicyclo ring by microsomal monooxygenases. We investigated the oxidative metabolism of (+)-S-145 and its beta-oxidized metabolites with liver microsomes from rats and humans to identify which cytochrome P450 (P450) forms are involved in these reactions. In rats, phenobarbital or dexamethasone treatment significantly increased 5- and 6-hydroxylation activities toward (+)-S-145 and its beta-oxidized metabolites, suggesting the involvement of P4503A forms. Immunoinhibition studies suggested that P4503A2 was mainly responsible for the 5-hydroxylation of (+)-S-145, bisnor, and DH-bisnor and the 6-hydroxylation of bisnor and tetranor. Furthermore, P4502C6, a phenobarbital-inducible 2C form in the rat, was involved in the 6-hydroxylation of (+)-S-145, bisnor, and DH-bisnor. P4502C11, the major constitutive form (male rats), was partly involved in the 5-hydroxylation of DH-bisnor and the 6-hydroxylation of bisnor and DH-bisnor. Reconstitution studies with purified human enzymes and immunoinhibition studies suggest that P4503A4 is primarily involved in the 5-hydroxylation of (+)-S-145 and bisnor and the 6-hydroxylation of tetranor; P4502C9/10 mainly catalyzed the 5-hydroxylation of tetranor and the 6-hydroxylation of (+)-S-145. Results of the present study indicated that the same subfamily P450 forms are responsible for the oxidative metabolism of (+)-S-145 in rats and humans. P4503A enzymes were shown to be involved in the formation of 6-hydroxy tetranor, the main metabolite of S-1452 in vivo.

Animals↗
PubMed1997

[Indocyanine green infrared fluorescence angiography and histopathological correlation in experimental choroidal circulatory disturbance. Report 1].

We performed an experimental study on choroidal circulatory disturbance to clarify basic problems about interpretation of retino-choroidal lesions in indocyanine green fluorescence angiography (ICG angiography). We severed all of the posterior temporal ciliary arteries, to produce choroidal circulatory disturbance. Fluorescein angiography and ICG angiography were performed using scanning laser ophthalmoscope immediately, and 2 days after occlusion. These findings were compared with histopathological findings from the same specimen. Immediately after occlusion, choroidal vessels were filled with the red blood cells in the lesion that showed hypofluorescence in both types of angiography. Two days after occlusion, the fundus had a grayish white edematous appearance which was similar to choroidal infarction. The retinal pigment epithelial cells. (RPEs) in infarcted lesion progressed to liquefied necrosis. Fluorescein angiography showed hyperfluorescence in the lesion, and ICG angiography showed hypofluorescence in the early phase, but hyperfluorescence at the margin of the lesion in the late phase. This result showed that damaged RPEs were stained by ICG dye. In reading ICG angiography, we have to consider that the ICG angiogram is greatly modified by the condition of the RPEs.

Animals↗
PubMed1997

[Indocyanine green infrared fluorescence angiography and histopathological correlation in experimental choroidal circulatory disturbance. Report 2].

We performed an experimental study on choroidal circulatory disturbance to clarify basic problems about interpretation of retino-choroidal lesions in indocyanine green fluorescence angiography (ICG angiography). We severed the posterior ciliary arteries to produce choroidal circulatory disturbance. Fluorescein angiography and ICG angiography were performed at one week, and one month after occlusion. These findings were compared with histopathological findings. One week after occlusion, the area of choroidal infarct showed occlusion of choriocapillaris and proliferation of the retinal pigment epithelial (RPE) cells, this area showed hypofluorescence in the early phase ICG angiography. The hypofluorescence area increased in the late phase. One month after occlusion, the lesion showed loss of choriocapillaris at the center and proliferation of fibroblast-like cells at the edge of the lesion. The subretinal strand showed hyperfluorescence in late phase ICG angiography. Proliferated RPE cells masked ICG fluorescence in the late phase. Fibroblast-like cells showed tissue staining. When reading ICG angiography, we have to take into account that the ICG angiogram is greatly modified by condition of the RPE.

Animals↗
PubMed1997

A mechanism of cisplatin action: antineoplastic effect through inhibition of neovascularization.

Though cisplatin (cis-diamminedichloroplatinum; CDDP) has been widely used for the treatment of malignant tumors, the mechanism of its action has not been well understood. Neovascularization, which accompanies tumor growth and metastasis, is required for cell proliferation in order to supply both oxygen and nutrients. We have studied in this investigation the effect of CDDP on endothelial cell (EC) proliferation in vitro and on rabbit corneal neovascularization in vivo. DNA synthesis of human umbilical EC was inhibited by CDDP in a dose-dependent fashion. Significant inhibition was observed at concentration over 10(-8) M, which is attainable in the serum of treated patients. Rabbit corneal neovascularization in vivo was also suppressed by intravenous injection of 0.5 mg/kg of CDDP for 10 days. These results suggest that CDDP might have an indirect anti-neoplastic effect through the suppression of neovascularization required for the tumor growth.

Animals↗
PubMed1996

Pantropic retroviral vectors integrate and express in cells of the malaria mosquito, Anopheles gambiae.

The lack of efficient mechanisms for stable genetic transformation of medically important insects, such as anopheline mosquitoes, is the single most important impediment to progress in identifying novel control strategies. Currently available techniques for foreign gene expression in insect cells in culture lack the benefit of stable inheritance conferred by integration. To overcome this problem, a new class of pantropic retroviral vectors has been developed in which the amphotropic envelope is completely replaced by the G glycoprotein of vesicular stomatitis virus. The broadened host cell range of these particles allowed successful entry, integration, and expression of heterologous genes in cultured cells of Anopheles gambiae, the principle mosquito vector responsible for the transmission of over 100 million cases of malaria each year. Mosquito cells in culture infected with a pantropic vector expressing hygromycin phosphotransferase from the Drosophila hsp70 promoter were resistant to the antibiotic hygromycin B. Integrated provirus was detected in infected mosquito cell clones grown in selective media. Thus, pantropic retroviral vectors hold promise as a transformation system for mosquitoes in vivo.

Animals↗
PubMed1996

Production of transgenic dwarf surfclams, Mulinia lateralis, with pantropic retroviral vectors.

A pantropic pseudotyped retroviral vector containing the envelope protein of vesicular stomatitis virus was used as a gene transfer vector in the dwarf surfclam, Mulinia lateralis. These pantropic retroviral vectors have an extremely broad host cell range and can infect many nonmammalian species. Newly fertilized dwarf surfclam eggs were electroporated at 700 V in the presence of 1 x 10(4) colony-forming units of pantropic pseudotyped retroviral particles. Infection was well tolerated and did not affect the survival rate of the embryos. Gametes collected from P1 presumptive transgenic animals were analyzed for the presence of provirus by PCR, and in different experiments 13-33% of the gamete pools were positive for the transgene. Dot blot hybridization of DNA samples from the F1 offspring of two different crosses between infected P1 and wild-type individuals revealed that 28% and 31% of F1 offspring were transgenic, respectively. Southern blot analysis of DNA isolated from PCR-positive F1 animals confirmed integration of a single copy of the provirus into the host genome. Thus, the germ lines of these two P1 transgenic animals were mosaic for the transgene. Expression of beta-galactosidase encoded by the provirus was detected in transgenic but not control surfclam embryos. Pantropic pseudotyped retroviral vectors provide a useful method for the stable introduction of foreign genetic information into surfclams and may facilitate the introduction of desirable genetic traits into commercially important shellfish and crustaceans.

Animals↗
PubMed1996

K-ras point mutations in cancerous and noncancerous biliary epithelium in patients with pancreaticobiliary maljunction.

BACKGROUND: Pancreaticobiliary maljunction (PBM), an anomalous union of the pancreatic duct with the common bile duct, has frequently been shown to be associated with biliary carcinoma. However, the mechanism of carcinogenesis is unknown. METHODS: Mutations of the K-ras oncogene were examined in cancerous and noncancerous biliary tract epithelium of 20 patients with PBM by an extraction of DNA from surgically resected histologic specimens. DNA was analyzed by a polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) method and direct sequencing. RESULTS: An abnormally mobilized DNA band was detected not only in cancerous epithelium but also in hyperplastic, metaplastic, and inflammatory epithelium of the gallbladder and/or common bile duct in patients with PBM. Among the biliary epithelium of patients with PBM, point mutation of K-ras oncogenes were detected in 4 of 5 (80%) cancerous epithelium, 7 of 12 (58%) hyperplastic and metaplastic epithelium, and 8 of 18 (44%) inflammatory epithelium, whereas no point mutation of the K-ras oncogene was detected in the gallbladder epithelium in 3 control patients without PBM. Direct sequence analysis of the K-ras oncogene revealed the mutation at codon 12 substituting the wild-type glycine (GGT) for aspartic acid (GAT) in all cancerous lesions of patients with PBM. Simultaneous two-point mutations from the wild-type glycine (GGC) to arginine (CGC) at codon 13 associated with the mutation at codon 12 were also found in one case of gallbladder carcinoma and one case of bile duct carcinoma. CONCLUSIONS: K-ras gene mutation is involved in the carcinogenesis of biliary tract epithelium in patients with PBM, and appears to be a high risk factor for carcinogenesis of the biliary tract.

Adult↗
PubMed1996

Rapidly progressive hepatitis C in a patient with common variable immunodeficiency.

UNLABELLED: A 15-year-old girl with common variable immunodeficiency contracted hepatitis C, which progressed to liver cirrhosis and finally to hepatic failure 5 years later. Since she was agammaglobulinaemic, hepatitis C virus (HCV) infection was diagnosed on the basis of HCV-RNA detection. Quantification of her sera showed high levels of HCV-RNA (more than 10(7) copies of RNA/mL), which implied active viral replication. There were no other hepatotoxic factors except HCV infection. The initial liver biopsy at 16 years of age and the autopsy confirmed a rapid progression in liver histopathological change over 4 years. CONCLUSION: Contrary to the widely held view of a benign short-term prognosis in paediatric hepatitis C, progressive fatal liver disease can develop in some patients with HCV infection. Such a rapid progression of liver injury provides the rationale for antiviral therapy in at least certain high risk groups of these children. Hepatitis C may progress rapidly in an immune deficiency condition.

Adolescent↗
PubMed1996

Retrovirol gene transfer in Xenopus cell lines and embryos.

A new class of retroviral vector pseudotypes have an expanded host species range and can be concentrated to high titers by ultracentrifugation. These pantropic vectors contain the genome of the murine leukemia virus-based vectors and the envelope protein of vesicular stomatitis virus substituted for the amphotropic envelope protein. We tested (a) the ability of pseudotyped (pantropic) and unmodified (amphotropic) vectors to stably infect three different Xenopus laevis cell lines, including one derived from the embryonic retina; and (b) the ability of the concentrated pseudotyped virus to infect embryos and to mediate foreign gene expression in the embryonic CNS. Expression of the neomycin phosphotransferase gene and single copy integration of the provirus into the genome of the cell lines was demonstrated. Surprisingly, the amphotropic and pantropic vectors generated neomycin-resistant clones with similar efficiency. PCR amplification of genomic DNA from single stage 10, 20, and 25 embryos microinjected in the blastocoel or neural tube cavities with concentrated pantropic vector (10(8) cfu/ml) revealed proviral DNA. Microinjection of a concentrated pantropic vector containing the coding sequence for the beta-galactosidase gene into the neural tube lumen of 24-h embryos yielded beta-galactosidase expressing cells in the brain. Thus, retroviral vectors provide an additional approach to existing strategies for gene transfer in Xenopus embryos and cell lines.

Animals↗
PubMed1996

Spinal cord MRI in neuro-Behçet's disease.

We report the case of a 10-year-old boy with neuro-Behçet's disease. Spinal cord MRI showed signal abnormalities in the cervical and thoracic cord, but cerebral CT and MRI revealed no abnormality.

Behcet Syndrome↗
PubMed1996

Gastrointestinal hemorrhage complicating aspirin therapy in acute Kawasaki disease.

Although gastrointestinal hemorrhage is a well-recognized complication of aspirin therapy, this side effect has not been previously reported in patients with Kawasaki disease (KD). We describe two children with typical KD who had massive gastrointestinal bleeding that required hospitalization and transfusion. Physicians caring for patients with KD should instruct parents on the signs and symptoms of aspirin toxicity. Fortunately, gastrointestinal hemorrhage appears to be a rare complication of salicylate therapy in patients with Kawasaki disease.

Acute Disease↗
PubMed1996

Genotyping of hepatitis C virus: coinfection by multiple genotypes detected in children with chronic posttransfusion hepatitis C.

The distribution of genotypes of the hepatitis C virus (HCV) was studied in 24 children with chronic posttransfusion hepatitis C. Genotypes were determined by reverse transcription-nested polymerase chain reaction with type-specific primers. Twenty (83%) were infected by a single genotype: 14 by type II [1b], 3 by III [2a], and 3 IV [2b]. Four (17%) were coinfected by two genotypes. The amount of blood transfusion given to the patients infected by multiple genotypes was significantly larger than to those infected by a single genotype (mean +/- SD, 15.2 +/- 14.4 vs 78.6 +/- 42.0 U). Three of the four patients infected by multiple genotypes were considered to be immunocompromised by anticancer therapy for malignant disease. Eighteen patients showed a raised level of alanine aminotransferase throughout the follow-up, while the remaining six patients (three of type II [1b], two of IV [2b], and one of III [2a] + IV [2b]) achieved biochemical remission. Liver biopsy was performed on 19 patients. Compared to those with type III [2a] or IV [2b], those with type II [1b] appeared to show more severe histological changes with higher histological activity index scores, although there was no significant difference. The positive rates of antibody to C100-3 or 5-1-1 in patients with type III [2a] or IV [2b] were lower than in those with type II [1b] (33 and 33 vs 43 and 50%), whereas the antibody to C33C or C22-3 was detected in nearly all patients regardless of their genotypes. In the present study, we found a high incidence of multiple-genotype infection among children with chronic posttransfusion hepatitis C.

Adolescent↗