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N Matsuhashi

Publications and source records attributed to N Matsuhashi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Specific clonal T cell accumulation in intestinal lesions of Crohn's disease.

The initial cellular events that take place at the outset of autoimmune diseases and that may be the most important in terms of understanding their pathogenesis are poorly understood, especially in humans. This is mainly due to the difficulties in the identification of primary lesions and the accessibility to such material. In this respect, it is noteworthy that the appearance of small reddish erosions, known as aphthoid lesions, is known to be an early event in Crohn's disease. In the present study, accumulation of lesion-specific clonal TCR bands in the intestinal lesions of Crohn's disease patients was demonstrated by means of a highly sensitive method based on single strand conformational polymorphism. Such clonal accumulation was demonstrated in both aphthoid and discrete ulcer lesions. There were several TCR BV bands that were present in both aphthoid lesions and discrete ulcer lesions, but some were specific to the aphthoid lesions. In addition, the same aphthoid lesion-specific/dominant T cell clones were found to be expanded in separate aphthoid lesions of a single patient, and were absent from intervening, non-inflamed mucosa. Some of these bands may represent T cell clones activated primarily at the onset of disease.

Adolescent↗
PubMed1996

Interaction between the two signal transduction systems of the histamine H2 receptor: desensitizing and sensitizing effects of histamine stimulation on histamine-dependent cAMP production in Chinese hamster ovary cells.

The histamine H2 receptor is a member of the family of G-protein-coupled receptors and is linked to the activation of adenylate cyclase phospholipase C (PLC). In this study we examined the effects of protein kinase C (PKC) activation in Chinese hamster ovary (CHO) cells stably expressing canine histamine H2 receptors. Pretreatment with 100 nM phorbol 12-myristate 13-acetate at 37 degrees C for 15 min led to significant potentiation of histamine-dependent and forskolin-dependent cAMP production, whereas the biologically inactive phorbol ester, 4 alpha-phorbol 12, 13-didecanoate, was without effect. These potentiating effects were abolished by preincubation with 0.5 microM bisindolylmaleimide, a PKC inhibitor. Thus the activation of PKCs seems to be involved in the potentiation of cAMP production by acting on a post-receptor mechanism. Preincubation of a CHO cell line, CHO-H2R, with 10 microM histamine for 30 min had two effects. Maximal histamine-dependent cAMP production and forskolin-dependent cAMP production were potentiated by 36% and 105.2% respectively. The other effect was a desensitization of the histamine-dependent adenylate cyclase response as demonstrated by a three-fold increase in EC50. Administration of 0.5 microM bisindolylmaleimide before preincubation of CHO-H2R with 10 microM histamine did not alter the desensitizing effect on cAMP production, but did abolish the sensitizing effect. Preincubation of CHO-H2R cells with 10 nM histamine resulted in moderate potentiation, which was also abolished by bisindolylmaleimide, but not in desensitization of the histamine-dependent cAMP production. Thus these results suggest that preincubation with histamine had a sensitizing effect on cAMP production mediated by PLC and PKC activation, as well as a desensitizing effect on the H2 receptor. The former effect is dependent on the intensity of PLC and PKC signals delivered by H2 receptors. The latter effect requires a higher concentration of histamine.

Animals↗
PubMed1996

Chronic intestinal pseudoobstruction associated with autoantibodies against proliferating cell nuclear antigen.

Autoantibodies against proliferating cell nuclear antigen (PCNA) have been detected almost exclusively in sera from patients with systemic lupus erythematosus (SLE). Because of the extremely low prevalence of anti-PCNA, however, it has been difficult to establish its disease specificity and clinical associations. We present 2 cases in which patients with anti-PCNA developed severe gastrointestinal dysfunction that led to chronic intestinal pseudoobstruction. Neither patient had manifestations suggestive of SLE. Although sclerodermatous skin changes were minimal or absent in these patients, physical and radiographic findings indicated that systemic sclerosis was a likely cause of the gastrointestinal dysfunction. The similarity of the clinical features in these patients implies that the unusual detection of this unique autoantibody may not be a coincidence.

Autoantibodies↗
PubMed1996

Three histologically different tiny gastric cancers developing adjacent to each other, resected endoscopically in a single mucosal piece.

In this report, we describe a case with triple tiny cancers of the stomach developing adjacent to each other and resected endoscopically in a single mucosal piece. The three cancers differed from each other histologically. The surrounding mucosa was atrophic pyloric gland mucosa with moderate to severe intestinal metaplasia. Both histological and serological examinations were negative for Helicobacter pylori. Each of the three cancer lesions was positive for mutant p53 product immunohistochemically. None of the cancers were positive for Epstein-Barr virus sequence in an in situ hybridization analysis. These lesions suggest that certain local conditions in the gastric mucosa can result in carcinogenesis of different histological types of gastric cancers.

Adenocarcinoma↗
PubMed1995

Structural and functional analysis of the canine histamine H2 receptor by site-directed mutagenesis: N-glycosylation is not vital for its action.

G-protein-coupled receptors generally share a similar structure containing seven membrane-spanning domains and extracellular site(s) for N-glycosylation. The histamine H2 receptor is a member of the family of G-protein-coupled receptors, and has three extracellular potential sites for N-glycosylation (Asn-4, Asn-162 and Asn-168). To date, however, no information has been presented regarding N-glycosylation of the H2 receptor. To investigate the presence, location and functional roles of N-glycosylation of the H2 receptor, site-directed mutagenesis was performed to eliminate the potential site(s) for N-glycosylation singly and collectively. The wild-type and mutated H2 receptors were expressed stably in Chinese hamster ovary (CHO) cells or transiently in COS7 cells. Immunoblotting of the wild-type and mutated H2 receptors with an antiserum directed against the C-terminus of the H2 receptor showed that mutation at Asn-162, but not at Asn-168, resulted in a substantial decrease in the molecular mass. A mutation at Asn-4 led to a further decrease in the molecular mass. Tunicamycin treatment of the transfected cells yielded a sharp band with a molecular mass identical to that of the mutant devoid of all three potential sites for N-glycosylation. These findings indicate that the H2 receptor is N-glycosylated, and that N-glycosylation takes place mainly at two sites, Asn-4 and Asn-162. Neither the affinity for tiotidine nor that for histamine was affected by the mutagenesis. Immunocytochemistry and tiotidine binding showed that the mutated receptors were exclusively distributed on the cell surface in a fashion similar to that of the wild-type. In addition, the glycosylation-defective receptor was capable of activating adenylate cyclase and elevating the intracellular Ca2+ concentration in response to histamine in stable CHO cell lines. Thus N-glycosylation of the H2 receptor is not required for cell surface localization, ligand binding or functional coupling to G-protein(s).

1-Methyl-3-isobutylxanthine↗
PubMed1995

HLA-linked susceptibility and resistance genes in Crohn's disease.

BACKGROUND & AIMS: Previous studies have shown a positive association of HLA-DR4-DQ4 with Crohn's disease in the Japanese population, but the association between Crohn's disease and HLA genes has yet to be fully elucidated. The aim of this study was to determine the Crohn's disease/HLA association using a DNA typing method. METHODS: A total of 90 unrelated patients with Crohn's disease and 336 healthy controls were typed for HLA class II genes including DP using DNA typing with the polymerase chain reaction-sequence-specific oligonucleotide probes method. RESULTS: Allelic analysis showed that DRB1*0405, DRB1*0410, DQA1*03, DQB1*0401, and DQB1*0402 are positively associated and DRB1*1501, DRB1*1302, and DQB1*0602 negatively associated with Crohn's disease. DP genes showed no significant association with Crohn's disease. Haplotype analysis showed positive associations with DRB1*0405-DQA1*03-DQB1*0401, DRB1*0410-DQA1*03-DQB1* 0402, and DRB1*0802-DQA1*03-BQB1-0402 haplotypes and negative associations with DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1302-DQA1*0102-DQB1*0604 haplotypes. CONCLUSIONS: In Crohn's disease in the Japanese population, the HLA-linked disease susceptibility gene is primarily associated with DQB1*04, in which leucine at the 56th position is a unique amino acid, and the disease resistance allele is suggested to be DQA1*0102.

Base Sequence↗
PubMed1995

A rare case of cardiac sarcoidosis in a patient with progressive systemic sclerosis, Sjogren's syndrome, and polymyositis.

A 56-year-old woman with overlap syndrome of progressive systemic sclerosis (PSS), Sjogren's syndrome, and polymyositis is reported. She developed complete atrioventricular (AV) block and progressive bilateral hilar adenopathy, and was diagnosed as having sarcoidosis by histological examination of the hilar lymph nodes biopsied thoracoscopically. Although coexistence of one or two autoimmune diseases with sarcoidosis is not uncommon, coexistence of three or more autoimmune diseases with sarcoidosis is rare. To our knowledge, the described case is the first case in which the three above-mentioned autoimmune diseases were accompanied by myocardial sarcoidosis.

Cardiomyopathies↗
PubMed1994

Pancreatic carcinoma accompanied by pseudocyst: report of two cases.

Two cases of pancreatic cancer accompanied by pseudocyst are reported. Case 1 was a 60-year-old man who was admitted to our hospital complaining of left lower abdominal discomfort. A cystic lesion, about 3 cm in diameter, was found in the pancreatic tail by ultrasonography (US) and computed tomography (CT). No signs of chronic pancreatitis were found. At operation, an elastic, hard, white tumor, about 1 cm in diameter, was felt adjacent to the cystic lesion on the duodenal side. Histologically, this tumor was a duct cell carcinoma with an adjacent pseudocyst upstream of the pancreas. Case 2 was a 57-year-old man who complained of back pain and loss of body weight. US and CT examination revealed a cystic lesion, 11 x 7 cm in size, in the tail of the pancreas. Histological examination of the resected specimen revealed both a duct cell carcinoma, 3 cm in size, in the body of the pancreas and a pseudocyst, 9 cm in size. Pseudocysts accompanying carcinoma are thought to develop from obstruction of the pancreatic duct by the carcinoma, followed by intraductal high pressure and disruption of ductules upstream of the pancreas. Thus, we should pay careful attention to pseudocyst of the pancreas, especially when signs of diffuse chronic inflammation cannot be found, to help identify duct cell carcinoma in the early stage. Further detailed examinations of the cyst fluid or pancreatic juice, such as cytology, tumor marker determinations, or establishment of K-ras codon 12 mutation, are needed.

Carcinoma, Ductal, Breast↗
PubMed1994

Retroperitoneal fibrosis leading to extrahepatic portal vein obstruction.

A very rare case of highly probable retroperitoneal fibrosis leading to extrahepatic portal obstruction is described. The patient was a 44-year-old woman with right pleural effusion and splenomegaly. Computed tomography indicated a large accumulation of soft tissues in the retroperitoneum, and abdominal angiography showed extensive portal obstruction. A twenty-year-long abuse of analgesics is suspected to have caused the retroperitoneal fibrosis.

Adult↗
PubMed1994

Expression of histamine H2 receptor in Chinese hamster ovary cells: a probe to study the desensitization mechanism.

Canine histamine H2 receptor DNA, cloned by polymenase chain reaction (PCR), was transfected into Chinese hamster ovary cells using an expression vector. The expression of H2 receptors was demonstrated by immunoblotting with specific antibodies and the binding of tiotidine, an H2 receptor antagonist. H2 receptor-specific cAMP production was observed only in cells expressing canine H2 receptors. Preincubation of transfected cells with 10 microM histamine for 10 or 60 min at 37 degrees C decreased both the maximal response and the sensitivity of the subsequent histamine-stimulated cAMP production, showing desensitization. Under these circumstances, decreases in tiotidine binding without changes in affinity in intact cells and also in the membrane were observed, whereas there was no decrease in total H2 receptor number. Thus, desensitization of histamine H2 receptor was associated with the sequetration of receptors.

Animals↗
PubMed1993

Desensitization of canine histamine H2 receptor expressed in Chinese hamster ovary cells.

Canine histamine H2 receptor DNA was transfected into Chinese hamster ovary cells using an expression vector. Expression of H2 receptors was demonstrated by immunoblotting with specific antibodies and the binding of tiotidine, an H2 receptor antagonist. H2 receptor-specific cAMP production was observed only in the cells expressing canine H2 receptor with 10(-9)-10(-4) M histamine in a dose-dependent manner. Preincubation of transfected cells with 10 microM histamine for 10 min or 60 min at 37 degrees C decreased both the maximal response and the sensitivity of the subsequent histamine-stimulated cAMP production, showing desensitization. Under these circumstances, tiotidine binding was decreased by 25% in intact cells. A similar decrease in the tiotidine binding was observed also in the membrane without changes in the affinity, whereas no decrease in total H2 receptor number was observed. Thus, desensitization of histamine H2 receptor was associated with the sequestration of receptors.

Adenylyl Cyclases↗
PubMed1993

Negative feedback regulation of acid secretion: linkage of acid secretion and mucosal defense.

To regulate inappropriate or excessive acid secretion that may be harmful not only to surrounding mucosal cells but also parietal cells themselves, versatile mechanisms operate to control acid secretion. In this article elaborate mechanisms that participate in the control of acid secretion are described with our data and a review of relevant findings in the literature concerning the action or secretion of key regulatory molecules. The analysis of the regulatory mechanisms revealed that appropriate secretory control can be achieved by multiple feedback regulations, which are closely coordinated with mucosal defense. In the feedback circuits, the regulatory factors cannot be simply categorized into either aggressive or defensive factors. Therefore we propose that the mucosal integrity and tissue homeostasis would be better understood by a feedback loop model rather than by a dualistic balance model.

Animals↗
PubMed1992

Treatment of hepatocellular carcinoma associated with advanced cirrhosis by transcatheter arterial chemoembolization using autologous blood clot: a preliminary report.

Twenty-two patients with hepatocellular carcinoma were treated by a new method of transcatheter arterial chemoembolization using an autologous blood clot as an embolizing agent. All had underlying advanced cirrhosis (14 Child's class B and 8 Child's class C patients). The median follow-up interval was 11 mo (range = 2 to 30 mo). The results of the treatment were compared with those of conventional chemoembolization using gelatin sponge particles for 19 Child's class B patients as historical controls. The survival rate for Child's class B patients treated by the new procedure estimated by the Kaplan-Meier method was 100% at 2 yr, whereas the survival rate for Child's class B patients treated by conventional chemoembolization was 89% at 1 yr and 72% at 2 yr. The survival rate for Child's class C patients was 75% at 1 yr and 50% at 2 yr. Side effects such as pyrexia of more than 38 degrees C or an elevation of the serum bilirubin level of more than 1.5-fold were less common in patients treated by the new method than in those treated by conventional chemoembolization, and thus the new procedure could be performed even for Child's class C patients. The autologous blood clot did not collapse the hepatic arteries even when the embolization was performed repeatedly, and thus fine collateral vessels feeding recurrent hepatocellular carcinoma did not develop. The results suggest that the new chemoembolization using an autologous blood clot is a promising therapeutic procedure in the management of hepatocellular carcinoma associated with advanced cirrhosis.

Aged↗
PubMed1992

Multiple strictures of the small intestine after long-term nonsteroidal anti-inflammatory drug therapy.

A 60-yr-old female patient with rheumatoid arthritis presented with nonsteroidal anti-inflammatory drug (NSAID)-induced ileal ulcers which caused intestinal bleeding and multiple strictures. Results of investigations, including radiological, pathological, and bacteriological examinations, were not consistent with Crohn's disease or intestinal tuberculosis. Rather, the lesion was characteristic of "diaphragm disease" caused by NSAIDs. Discontinuance of NSAIDs in combination with administration of ornoprostil (prostaglandin E1-derivative), sucralfate, and sulfasalazine put an end to the intestinal bleeding. This is a rate case of a patient with multiple strictures of the small intestine caused by NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Tolerogenic ability of thymocytes in organ-cultured thymus lobes.

It is generally believed that macrophages and dendritic cells are the major cell populations that present tolerogenic self antigens to developing thymocytes. However, it is still controversial whether self antigens expressed on thymocytes themselves work as tolerogens in the thymus. To evaluate this possibility, Thy-1 bright cells were sorted out from fetal thymus cells on the 15th gestation day, and were colonized into 2'-deoxyguanosine-treated allogeneic thymus lobes. The repopulated thymus lobes were organ-cultured, and the allo-specific killer activity of thymocytes recovered from the lobes was examined. These cells were tolerant to class I but not to class II-MHC of the donor haplotype, indicating that class I molecules expressed on the thymocytes worked as tolerogen. Tolerogenic ability of Thy-1+ cells was also demonstrated in another system. Upon intimate contact with allogeneic thymus lobes on a polycarbonate filter, thymus lobes fused with each other and Thy-1+ cells co-migrated (Eur. J. Immunol. 19:1525-1530, 1989). In thymus lobes rendered parabiotic from day 5, CTL tolerance was achieved against class I but not to class II MHC. These data indicate that thymocyte-thymocyte interaction is sufficient to induce class I CTL tolerance in developing thymocytes.

Animals↗
PubMed1991

Multiple diffuse hemangiomas of the large intestine.

A 54-year-old male case with multiple, diffuse hemangiomas of the large intestine is described. Large diffuse hemangiomas were located at the rectosigmoid and the ascending colon. Some polypoid lesions were located on the transverse colon. Tiny calcifications representing phleboliths were detected in those lesions. No skin hemangiomas were present. Although he did not manifest systemic bleeding tendency, blood examinations demonstrated the presence of mild consumption coagulopathy.

Colonic Polyps↗