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M Ishibashi

Publications and source records attributed to M Ishibashi.

At least 19 recordsLinked to original sources
PubMed1992

In vivo and in vitro mechanisms of cardiac allograft acceptance in the rat after short treatment with 15-deoxyspergualin.

15-Deoxyspergualin (DSG) has been reported to be a useful immunosuppressive agent already used to inhibit acute rejection in clinical transplantation. In the present study, the survival of heart allograft in rats after a short course of DSG treatment and the mechanisms underlying DSG-induced heart allograft acceptance were studied. Male LEW rats were used as recipients. Male ACI and Wistar rats were used as donors and third-party donors, respectively. Survival of ACI heart grafts in LEW recipients treated with a short course of DSG starting on day 4 after grafting was markedly prolonged, with a mean survival time of 16.6 +/- 5.8 days and 29.8 +/- 3.0 days at doses of 2.5 mg/kg per day and 5 mg/kg per day, respectively. On day 20 after grafting, the mechanism of inducing allograft survival after DSG treatment at a dose of 5 mg/kg per day was analyzed by testing the activation of spleen cells or serum in several assay systems. Spleen cells from DSG-treated rats with surviving heart allografts showed almost no proliferative response against donor strain stimulator cells compared with controls. The cytotoxic activity towards donor strain target cells of spleen cells from DSG-treated rats with surviving heart allografts was lower than that of spleen cells from rats with rejected heart allografts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Electron microscopic study of hepatitis B virus-associated antigens on the infected liver cell membrane in relation to analysis of immune target antigens in chronic hepatitis B.

To clarify the characteristics of cell surface Pre-S2 Ag, HBcAg and HBeAg immunohistochemically and to explore their relationship with a cellular immune target antigen, 31 liver biopsy specimens from chronic HBV carriers were examined by immunoperoxidase staining. By immune light microscopy, Pre-S2 Ag was detected on the liver cell membrane in 18 (58%) of the 31 cases, HBcAg in 4 cases (13%) and HBeAg in 4 cases (13%). Pre-S2 Ag frequently showed a honeycomb-like membrane expression pattern which was present regardless of liver inflammation, whereas HBcAg and HBeAg exhibited a scattered membrane expression pattern detected in areas of marked inflammation. Of the 18 cases showing a honeycomb-like Pre-S2 Ag expression, 3 concomitantly showed a scattered membrane expression pattern. Immunoelectron microscopy revealed these two distinct membrane expression patterns. In areas showing a honeycomb-like membrane expression pattern, Pre-S2 Ag was demonstrated in the intercellular space and on the basolateral membranes of hepatocytes, but was not detected on the cell membranes in areas of the intercellular space lacking an immunoreaction. Cytoplasmic expression of Pre-S2 Ag was less extensive in these hepatocytes. These findings suggest that the honeycomb-like membrane expression of Pre-S2 Ag results from attachment of extracellular antigen to the liver cell membrane. In contrast, in areas showing a scattered membrane expression pattern, Pre-S2 Ag, HBcAg and HBeAg were each detected as single-layered linear deposits along the cell membrane, but were absent in the intercellular space. Each antigen was also expressed abundantly in the cytoplasm, and the immunoproducts appeared to fuse with the cell membrane. These findings suggest that the scattered membrane expression of these antigens results from intrahepatic transfer of antigen synthesized in the liver cell to the cell membrane, possibly serving as a target for the host immune-mediated response in connection with inflammation.

Adult↗
PubMed1992

Differences in transforming activity and coded amino acid sequence among E6 genes of several papillomaviruses associated with epidermodysplasia verruciformis.

Using the polymerase chain reaction technique, we cloned and sequenced DNA fragments containing the E6 genes of the epidermodysplasia verruciformis (EV)-associated HPVs 5, 8, 14, 20, 21, 25, and 47, of which only the sequences of HPVs 5, 8, and 47 have previously been reported. Based on the deduced amino acid sequence homology (57.3 to 83.0%), these HPVs could be divided into two clusters: HPVs 5, 8, and 47, and HPVs 14, 20, 21, and 25. The E6 genes of three HPVs from each cluster were examined for transforming activity toward a cultured rat fibroblast cell line, 3Y1, using the retrovirus-mediated gene transfer technique, and all were found to induce morphological transformation. However, the E6 genes of the first cluster were more potent than those of the second. Since HPVs 5 and 8 are the most frequently found HPVs in malignant lesions of EV patients, the observed in vitro transforming activities of the E6 genes may reflect their oncogenic potential in humans.

Amino Acid Sequence↗
PubMed1992

Analysis of the eicosapentaenoic acid (EPA) metabolite delta 17-6-keto-PGF1 alpha in human plasma by GC/SIM using [18O] delta 17-6-keto-PGF1 alpha.

A method of the microdetermination of delta 17-6-keto-PGF1 alpha, a hydrolyzed metabolite of PGI3, is described. An authentic delta 17-6-keto-PGF1 alpha (120 mg) was prepared from eicosapentaenoic acid (EPA) incubated with homogenate of bovine aortic intima. [18O]delta 17-6-Keto-PGF1 alpha was synthesized by repeating base-catalyzed hydrolysis of methyl ester derivatives in [18O]water, to obtain an internal standard in gas chromatography/selected ion monitoring (GC/SIM) of delta 17-6-keto-PGF1 alpha. Good linear response over the range of 10 pg-10ng was demonstrated. Chromatographic conditions using a MP-65HT column presented nearly baseline separation of delta 17-6-keto-PGF1 alpha and 6-keto-PGF1 alpha. We were able to detect delta 17-6-keto-PGF1 alpha in the range from 6 to 26 pg/ml of the human plasma. The present method can be applied to the determination of delta 17-6-keto-PGF1 alpha in the human urine and plasma.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Separation and concentration of delta 17-6-keto-PGF1 alpha using monoclonal antibody to omega 3-olefin structure of trienoic prostanoids.

A monoclonal antibody against cis-3-hexen-1-ol was prepared and used to separate and/or concentrate delta 17-6-keto-prostaglandin F1 alpha (PGF1 alpha) in the human sera. cis-3-Hexen-1-ol was conjugated with the human serum albumin (HSA) according to the N-succinimidylester method and hyperimmunized to BALB/c mouse. The monoclonal antibodies were obtained from hybridoma clones established by a fusion between SP2/0-Ag14-k13 mouse myeloma cells and splenocytes of a mouse. A monoclonal antibody, named 4G9-12B, recognized the epitope characteristic for omega 3-olefin structure. The 4G9-12B antibody became more specific for delta 17-6-keto-PGF1 alpha than 6-keto-PGF1 alpha by applying inhibition ELISA using amino-residue coating plates. Using the prepared immunoaffinity columns of this antibody, delta 17-6-keto-PGF1 alpha was clearly detected in 6 pg/ml of the human blood sera by GC/MS analysis. These results suggest that the monoclonal antibody to the partial structure of trienoic prostanoid, omega 3-olefin unit, and that its immunoaffinity columns are useful in separating and concentrating delta 17-6-keto-PGF1 alpha in the human blood or urine.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

The in vitro immunosuppressive effect of deoxymethylspergualin in man as compared with FK506 and cyclosporine.

The effect of deoxymethylspergualin (MeDSG) on in vitro human lymphocyte response was assessed in comparison with FK506 and cyclosporine. Peripheral blood mononuclear cells from normal human volunteers were used for assay of mixed lymphocyte reaction, cell mediated lympholysis, and blastogenesis by PHA, IL-2, and OKT3. MeDSG suppressed only allogeneic stimulation (MLR and CML) and IL-2-induced blastogenesis, not PHA- or OKT3-induced blastogenesis, although the other immunosuppressive agents showed some suppressive effect for all assays. A kinetic study of MLR showed that the suppressive activity did not decrease even when MeDSG was added at day 3 or day 4. The other agents, however, showed a weak suppressive effect when added at a later phase of MLR.

Cyclosporine↗
PubMed1992

FK506-induced kidney tubular cell injury.

Some renal changes associated with cyclosporine, such as tubular vacuolization and glomerular thrombosis, have also been reported with FK506. Furthermore, FK506 therapy is associated with a decrease in glomerular filtration rate and renal plasma flow and an increase in renal vascular resistance. We studied the in vitro tubular cell sensitivity to FK506 in comparison with CsA, the ultrastructural changes induced by FK506 and CsA, and the effect of both drugs on tubular cell growth in vitro. We also investigated whether FK506 and CsA induced endothelin-1 (ET-1) secretion of cultured tubular cells and whether this stimulatory effect coincided with a change in the endothelin systemic synthesis. Exposure of tubular cells to high concentrations of FK506 or CsA (10, 50, 100 microM) induced a time- and dose-dependent cell injury in vitro. The damage induced by FK506 and CsA was characterized by a direct cytotoxic effect on tubular cells, as expressed by release of 3H thymidine from prelabeled cells, N-acetyl-beta-D-glucosaminidase release, and cell detachment. Ultrastructural changes (vacuolizations, swelling, and mitochondrial enlargement) and inhibition of the growth of cultured tubular cells were also observed at high concentrations of FK506 and CsA. Low concentrations of FK506 and CsA (1, 0.1, 0.01, 0.001 microM) were not cytotoxic and induced only a minimal inhibitory effect on the growth of tubular cells in vitro. We demonstrated that FK506 (1, 0.1, 0.01 microM) time-dependently stimulated the secretion of endothelin by cultured tubular cells. CsA 10, 1, 0.1, 0.01 also exerted an enhancing effect on ET-1 secretion in cultured tubular cells. We observed that the concentration of CsA that induced the most important enhancing effect was 10 or 100 times higher than that required for FK506 to observe the same effect. The concentrations of FK506 or CsA that induced ET-1 secretion were not cytolytic for tubular cells in vitro. FK506- or CsA-treated rats showed an increase in serum level of ET-1 in comparison with the control. Through the stimulatory effect on endothelin secretion by tubular cells, FK506 and CsA may induce a perturbation of renal hemodynamics. Concentrations of FK506 and CsA, higher than established serum levels but close to those reached in tissues, are cytotoxic for tubular cells and induced ultrastructural changes and a significant delayed regeneration.

Acetylglucosaminidase↗
PubMed1992

Cytopathic effects of Helicobacter pylori on cultured mammalian cells.

Cytopathic effects of broth-culture filtrates from eight clinical isolates and one reference strain of Helicobacter pylori on three cultured mammalian cell lines were investigated. All the strains, including NCTC 11637, produced cytotoxic factors that caused intracellular vacuolation on these cell lines. AGS and SflEp cells were more sensitive than HEp-2 cells. To examine the role of urease in the cytotoxic effect, a urease-negative mutant was produced. Filtrates from both wild-type and mutant strains produced similar vacuolation on SflEp cells in the absence of urea, suggesting that H. pylori produces a cytotoxic substance other than urease. In contrast, ammonia alone, or jack bean urease with urea, also induced rounding and detachment of SflEp cells, whereas ammonium salts induced the production of small vacuoles. The combination of the broth filtrate of the wild-type strain and urea induced vacuolation followed by rounding and detachment of SflEp cells. Evidence is presented that the latter changes are due to ammonia produced during incubation. Nevertheless, the amounts produced were less than that needed to induce cytopathic effects by itself. These results suggest that the cytotoxic substance induces intracellular vacuolation, and that the vacuolated cells are more susceptible to killing by ammonia. Thus both the cytotoxic substance and urease may contribute to the lethal cytotoxicity of H. pylori in vitro.

Ammonia↗
PubMed1992

A case of adenocarcinoma of the lung with a spindle cell component.

We report a 60-year-old man, who was admitted to the hospital with complaints of cough and sputum. His chest x-ray showed an abnormal mass in the right upper lobe. After admission he noticed the painful gingival tumor. Right upper lobectomy and resection of the gingival tumor were performed. Their histological features showed that the tumor consisted of a papillary and tubular adenocarcinoma mixed with a component of spindle cells. Immunohistochemical study demonstrated a positive reaction in the epithelial component for keratin and epithelial membrane antigen, and not only these epithelial markers but also vimentin were expressed in some spindle tumor cells. Electron microscopic study confirmed the biphasic pattern, showing gland formation and undifferentiated cells. We diagnose this case as adenocarcinoma of the lung with a spindle cell component and the gingival tumor was metastatic. Autopsy showed that metastatic lesions were found in the left adrenal gland and in the left kidney. The tumor cells in the left adrenal gland were composed of spindle cells and the tumor in the left kidney showed gland formation. Immunohistochemical and electron microscopic findings of surgical and autopsy specimen suggest that this tumor is of epithelial origin, and the spindle cells are derived from immature mesenchymal cell transformation of epithelial cells.

Adenocarcinoma↗
PubMed1992

A case of primary sarcoma of the pulmonary artery.

A 39-year-old male was admitted complaining of nonproductive cough and dyspnea on exertion. Death occurred eight months after onset of the symptoms. Autopsy examination showed that the pulmonary trunk and left main pulmonary artery were markedly dilated and completely occluded by a tumor. The tumor had infiltrated into the left upper lobe and mediastinal lymph nodes, and metastatic nodules were found in both lungs and in the left adrenal gland. Small foci of infarction were noted in the lower lobes of both lungs. The tumor cells were of two types; pleomorphic spindle cells and bizarre multinucleated giant cells. Immunohistochemically, they were positive for vimentin, myosin, and lysozyme, but negative for desmin and muscle-specific actin. The cytoplasm of the tumor cells was showed by electron microscopy to contain microfilaments, dense bodies, and pinocytotic vesicles. We diagnosed this case as undifferentiated sarcoma of the pulmonary artery. Approximately 100 cases of pulmonary artery sarcoma have been reported. Histopathologically, almost all of the reported cases showed both spindle cells and pleomorphic giant cells, indicating a biologically anaplastic neoplasm.

Adult↗
PubMed1992

Hypolipidemic effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) in rats.

We examined the effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) with high purity on circulating lipids in rats under several experimental conditions. In normolipidemic rats, EPA-E decreased the lipids in a dose-dependent manner. Clofibrate (100 mg/kg/day) was more potent in lowering the lipids than EPA-E (1000 mg/kg/day). In high cholesterol diet-fed rats, EPA-E (300 mg/kg/day) decreased the total cholesterol. However, clofibrate (300 mg/kg/day) had little effect on the total cholesterol. In hypertriglycemic rats induced by corn oil, EPA-E (300 mg/kg/day) or clofibrate (100 mg/kg/day) reduced the rise of triglycerides. EPA-E (300 mg/kg/day), clinofibrate (100 mg/kg/day) or clofibrate (300 mg/kg/day) caused a significant reduction in the lipids induced by the injection of Triton WR-1339. Furthermore, EPA-E (300 mg/kg/day) or clinofibrate (100 mg/kg/day) decreased the elevation of lipids produced by feeding the rats a casein-rich diet. These results show that EPA-E possesses potent inhibitory activity on experimental hyperlipidemia induced either exogenously or endogenously.

Animals↗
PubMed1992

Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency.

The occurrence of adrenal myelolipomas is reported in an untreated patient with congenital adrenal 21-hydroxylase deficiency. Laparotomy demonstrated the presence of two lesions, a large tumor which arose from an ectopic adrenal cortex and a smaller tumor in the left adrenal gland. Six cases of adrenal myelolipomas and congenital adrenal hyperplasia have been reported in the literature. All patients were associated with excessive ACTH secretion for a long period of time. The relative frequency of this association, coupled with the observation by Selye and Stone (Am J Pathol 26:211, 1950) that anterior pituitary extracts cause myelolipomatous changes in rats, may indicate a possible role for ACTH in the development of myelolipomas.

Adrenal Gland Neoplasms↗
PubMed1992

[Studies on caries of Ishibashi rat--III. Experimental caries in Ishibashi rat].

Dental caries was experimentally induced in the Ishibashi rats (ISR) by feeding them with conventional diets or with caries-producing diets, and the pattern and severity of their induced carious lesions were compared with those of the Sprague-Dawley rats (SD). Simultaneously, serum antibody titers against Streptococcus mutans and calcium and phosphorus concentration in the sera and in the femurs were compared between the ISR and SD. The results were as follows: 1. When judged by cavities, ISR showed a higher carious incidence and average number of cavities per one rat than the SD, whichever diet the rats were fed. 2. When judged by fissure caries observed on the thin sections of the teeth, both the carious incidence and average number of fissure lesions in the ISR were not always high compared with those in the SD, and there seemed to be a great variation of caries-susceptibility in the ISR. 3. Caries in the ISR seemed to be more progressive than that in the SD. 4. There were no differences in the serum antibody titers against the S. mutans between the ISR and SD. 5. No differences in the concentration of calcium and phosphorus in the sera and femurs were observed between the ISR and SD, whichever diet they were fed.

Animals↗
PubMed1992

[The experience of administration of 15-deoxyspergualin on rejection in kidney transplant recipients].

We report here the favorable results of clinical application of 15-deoxyspergualin (DSG) as a rescue therapy for rejection episodes in kidney transplant recipients. DSG was discovered in Japan and was proved to be a novel immunosuppressant in various animal transplantation models. The immunosuppressive mechanism of DSG is unclear yet, but its point of action is supposed to be in the early immuno response to allogeneic stimulation without the regulation of cytokine production. We performed the administration of DSG in fifteen patients, who had rejection episodes, with a dosage of 3 mg/kg/day or 5 mg/kg/day for five days by drip infusion. In the group of recipients who had rejection episodes within six months after kidney transplantation, DSG proved effective on six out of seven acute rejection episodes and induced favorable remission. And in the group of recipients who had rejection episodes after six months since kidney transplantation, DSG proved effective on all of ten rejection episodes. There was not a difference of effectiveness in respect to the dosage of DSG. The side effect of DSG treatment was mainly leukopenia but in most cases these leukopenia was remitted just under careful observation. Some patients complained the sense of abdominal discomfort. But so far, we did not encounter serious or critical side effects and complications during all the time of progression. Another benefit was that DSG was able to reverse the rejection episode even in the patient who had already treated with anti lymphocyte globulin and/or anti CD3 monoclonal antibody OKT3. We concluded that the administration of DSG as a rescue therapy was not accompanied by the serious side effects and was most effective against acute rejection after kidney transplantation.

Adult↗
PubMed1992

The producer and biological activities of SO-75R1, a new mutactimycin group antibiotic [corrected].

The producer of SO-75R1, a new anthracycline group antibiotic was identified as Nocardia brasiliensis. SO-75R1 was active against Gram-positive bacteria, but not active against Gram-negative bacteria or fungi. All tested Nocardia brasiliensis strains as well as the producer itself were resistant to SO-75R1, although four other pathogenic Nocardia, i.e. N. asteroides, N. nova, N. farcinica and N. otitidiscaviarum were sensitive [corrected].

Animals↗