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Biomedical subjects

Y Fujiyama

Publications and source records attributed to Y Fujiyama.

At least 109 records · Page 6Linked to original sources
PubMed1996

Regulation of complement C3 synthesis by interleukin-1 and transforming growth factor-beta in rat non-transformed intestinal epithelial cell line, IEC-6.

Intestinal epithelial cells are an important source of many biologically active molecules that modulate immune responses in the mucosa. The purpose of this study was to demonstrate the synthesis of complement C3 component in the rat non-transformed crypt-like intestinal epithelial cell line, IEC-6. Unstimulated IEC-6 cells secreted a low level of C3 protein and showed weak expression of C3 mRNA. The addition of interleukin (IL)-1 beta induced a dose- and time-dependent increase in C3 production. These effects of IL-1 beta were observed at a concentration as low as 0.01 ng/ml and reached a plateau at a concentration of 5 ng/ml. The effects were observed at the mRNA level as early as 6 h after the beginning of incubation. Transforming growth factor (TGF)-beta alone had no effect. However, TGF-beta at low concentrations (0.001-1 ng/ml) enhanced the effect of IL-1 beta in increasing C3 production; this enhancement was not observed at high concentrations (5-10 ng/ml). These effects of TGF-beta were also observed at the mRNA level. The present findings indicate that intestinal epithelial cells are indeed capable of synthesizing complement C3 in response to IL-1 beta and TGF-beta.

Animals↗
PubMed1996

Altered polyamine biosynthesis with aging after massive proximal small bowel resection in rat.

We examined the effect of aging on polyamine biosynthesis in the small intestine. Two groups of male Wistar rats (young; 10-week-old, n = 40; old; 24-month-old, n = 40) underwent either a jejunal transection and reanastomosis or 90% proximal small bowel resection. The rats were sacrificed on the 1st, 2nd, 4th, and 7th postoperative day (POD). The mucosa was submitted for histological examination, weighed, and assayed for protein, DNA, RNA, and polyamine content. Ornithine decarboxylase (ODC) activity was measured and ODC mRNA in the mucosa was determined by Northern blot analysis. Compared with the values for wet weight and protein content in old rats, young rats showed significantly higher values for wet weight on the 1st and 2nd POD, and for protein content on the 1st POD, but there were no differences between young and old rats after the 4th POD. The values for ODC activity and ODC mRNA were significantly lower in old rats than in young rats on the 1st POD, but there were no differences between young and old rats after the 2nd POD. The value for putrescine in old rats was significantly lower on the 2nd POD, but was significantly higher on the 4th POD than that in young rats. The present study showed that, in old rats, the residual intestine after small bowel resection preserved sufficient adaptive capacity, but that the adaptive response was decreased. The findings in this study also suggest that a decrease in ODC mRNA expression is involved in the decreased adaptive response that occurs with aging.

Adaptation, Physiological↗
PubMed1996

Morphological identification of and collagen synthesis by periacinar fibroblastoid cells cultured from isolated rat pancreatic acini.

Rat pancreatic periacinar fibroblastoid cells (PFCs) appear to be involved in intralobular fibrosis and acinar cell regeneration. We isolated pancreatic acini of the rat, cultured the fibroblastoid cells, and characterized the cells morphologically and immunohistochemically. Isolated acini were seeded on culture dishes, and spindle-shaped cells migrated and proliferated. On Electronmicroscopic examination, microfilament bundles were seen, and the intracellular localization of vimentin, alpha-smooth muscle actin, and non-muscle myosin was identified immunohistochemically. These findings strongly suggest that the cells were myofibroblast-like. The PFCs were also demonstrated, immunohistochemically, to contain prolyl hydroxylase, type-I procollagen, type-III procollagen, type-IV collagen, fibronectin, and laminin. Stimulation by transforming growth factor beta 1 (TGF beta 1) increased intracellular immunoreactive prolyl hydroxylase and collagen synthesis in the PFCs. These findings indicate that PFCs proliferate in culture as myofibroblast-like cells and synthesize extracellular matrix components. It is possible that PFCs are involved in intralobular fibrosis in response to stimulation with TGF beta 1.

Animals↗
PubMed1996

Ulcerative colitis complicated by gastroduodenal lesions.

A case of ulcerative colitis complicated with gastric and duodenal lesions is reported. The patient was a 17-year-old male who was admitted with bloody diarrhea and abdominal pain. Based on the endoscopic and histological findings of the colon, a diagnosis of ulcerative colitis was made. Upper gastrointestinal endoscopy showed multiple erosions and granular changes in the antral greater curvature of the stomach and descending portion of the duodenum. Histological examination of the stomach and duodenum revealed marked inflammatory cell infiltration and crypt abscesses. Clinically, the gastric and duodenal lesions did not respond to antiulcer drugs, but were alleviated by steroid. It was concluded that the pathogenesis of the gastric and duodenal lesions in this patient was similar to that of the colonic lesions of ulcerative colitis.

Adolescent↗
PubMed1996

Interleukin 4 acts as an inducer of decay-accelerating factor gene expression in human intestinal epithelial cells.

BACKGROUND & AIMS: Decay-accelerating factor (DAF) protects host tissues from the attack of autologous complement activation. In this study, we attempted to define the cytokine regulation of DAF messenger RNA (mRNA) expression in human intestinal epithelial cells. METHODS: The effects of cytokines on DAF mRNA accumulation were evaluated by Northern blot analysis. The DAF protein expression was analyzed by both immunoprecipitation and immunoblotting. RESULTS: Interleukin (IL)-4 induced a marked increase in DAF mRNA accumulation in HT-29 cells. In this line, IL-1 beta evoked only weak induction, and IL-6, IL-8, IL-10, and interferon gamma had no effect. The effect of IL-4 was observed in a dose-dependent manner and confirmed at the protein level. The increase in DAF mRNA accumulation reached a maximum at 3-6 hours and then gradually decreased. These effects of IL-4 on DAF mRNA and protein expression were also observed in T84 cells. The mRNA stability studies suggested that IL-4 regulates DAF gene expression mainly at the transcriptional level. CONCLUSIONS: In human intestinal epithelial cells, IL-4 acts as a potent inducer of DAF mRNA expression, suggesting a cytoprotective role for IL-4 against autologous complement activation.

CD55 Antigens↗
PubMed1996

Local secretion of complement C3 in the exocrine pancreas: ductal epithelial cells as a possible biosynthetic site.

BACKGROUND & AIMS: The complement system participates in the local immune system in various tissues. In this study, we investigated the local secretion of complement C3 into the pancreatic fluid and attempted to determine a possible biosynthetic site. METHODS: C3 protein in human pancreatic fluid was analyzed by, immunoblotting. The C3 messenger RNA (mRNA) expression in several pancreatic carcinoma cell lines was analyzed by the polymerase chain reaction and/or Northern blotting. The secretion of C3 by these pancreatic carcinoma cells was assessed by metabolic labeling and immunoprecipitation experiments. RESULTS: In five samples of human pancreatic fluid, C3 was detected as a molecule composed of alpha and beta chains. C3 mRNA expression was observed in the ductal cell carcinoma lines (PANC-1 and MIA PaCa-2) but not in the acinar cell line (HPC-YO and AR-42J). C3 production in these cells was enhanced by interleukin 1 beta and tumor necrosis factor alpha at both the protein and the mRNA levels. CONCLUSIONS: (1) Complement C3 is secreted into the exocrine fluids of the pancreas. (2) Ductal epithelial cells are possible biosynthetic sites for C3. (3) The proinflammatory cytokines, interleukin 1 beta and tumor necrosis factor alpha are effective stimulators of local C3 production in the pancreas.

Adult↗
PubMed1996

Severe anemia in a patient with isolated adrenocorticotropin deficiency.

A 64-year-old man was referred to our hospital for evaluation of progressive anemia. On admission, he had a severe normocytic normochromic anemia [hemoglobin 7.5 g/dl] requiring a blood transfusion. Endocrinological studies demonstrated an isolated ACTH deficiency. After receiving glucocorticoid replacement therapy, his anemia was rapidly corrected, his hematocrit and hemoglobin remained elevated for approximately 4 months. We present evidence that glucocorticoid plays an important role in the physiological regulation of human erythropoiesis.

Adrenocorticotropic Hormone↗
PubMed1996

[Mechanisms of enhanced erythrocyte destruction in patients with erythrocyte membrane disorders].

Factors causing erythrocyte destruction in patients with congenital erythrocyte membrane disorders include 1) decreased cell deformability, 2) increased cell viscosity, 3) decreased membrane stability, 4) increased intracellular Ca2+ concentrations, 5) changes in membrane permeability, 6) extracellular conditions such as hypoxia and acidic pH, or 7) hypersplenism. erythrocytes with shape changes due to abnormality of membrane skeleton lose deformability to negotiate the interendothelial slits into the splenic venous sinus, and stagnate within the cordal space where metabolic stress reduces membrane stability. Thereafter, erythrocytes are ingested by cordal macrophages, resulting in extravascular hemolysis.

Anemia, Hemolytic, Congenital↗
PubMed1995

Effects of serine protease inhibitors on accumulation of polymorphonuclear leukocytes in the lung induced by acute pancreatitis in rats.

The administration of a high-dose of a serine protease inhibitor is recommended in patients complicated by multiple organ failure (MOF), including adult respiratory distress syndrome (ARDS), induced by acute pancreatitis. The accumulation of polymorphonuclear leukocytes (PMN) in affected organs is considered to be one of the causative factors of MOF. Adhesion to endothelial cells (EC), via adhesion molecules, and the transendothelial migration of PMN is closely associated with the accumulation of PMN. We examined the effects of two serine protease inhibitors, ulinastatin (UT) and gabexate mesilate (GM), on EC-PMN adhesion and transendothelial migration in human umbilical vein EC and 51Cr-labeled PMN in vitro. EC-PMN adhesion, and the expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ELAM-1) on EC induced by IL-1 beta and TNF alpha, were reduced by the pretreatment of EC with these inhibitors. The transendothelial migration of PMN stimulated by IL-8 was also inhibited by pretreating PMN with UT or GM. We also examined whether these inhibitors reduced PMN accumulation in the lung in rats with acute pancreatitis induced by a closed duodenal loop. The myeloperoxidase activity in and histological findings of the lung suggested that UT and GM reduced PMN accumulation. In conclusion, serine protease inhibitors may inhibit PMN accumulation in ARDS due to acute pancreatitis.

Acute Disease↗
PubMed1995

Effects of short-term administration of the CCK receptor antagonist, KSG-504, on regeneration of pancreatic acinar cells in acute pancreatitis in rats.

Cholecystokinin (CCK) receptor antagonists have been reported on have an inhibitory effect on acute experimental pancreatitis, but their long-term administration is also reported to block pancreatic regeneration. We examined whether the short-term administration of KSG-504 (KSG), a synthetic CCK-A receptor antagonist, inhibited the regeneration of pancreatic acinar cells after ethionine-induced acute pancreatitis in rats. KSG (50 mg/kg), given 12 times by subcutaneous injection at 6-h intervals, prevented the reduction of protein, amylase, and trypsinogen levels, and the DNA content of the pancreas and facilitated the recovery of these values. Ornithine decarboxylase activity in pancreatic tissue and a 5-bromo-2'-deoxyuridine labeling study indicated that DNA synthesis was accelerated in rats treated with KSG. These findings suggest that the short-term administration of KSG inhibits the development of ethionine-induced acute pancreatitis and facilitates the regeneration of acinar cells.

Acute Disease↗
PubMed1995

Band 4.2 Shiga: 317 CGC-->TGC in compound heterozygotes with 142 GCT-->ACT results in band 4.2 deficiency and microspherocytosis.

A novel compound heterozygous mutation of 317 CGC-->TGC with 142 GCT-->ACT in human red cell band 4.2 deficiency is described. A proband and his son suffered from compensated haemolysis with nearly complete deficiency of red cell band 4.2. Their red cell morphology exhibited microspherocytosis resembling classic hereditary spherocytosis (HS). Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed band 4.2 to be nearly missing (< 1% of normal controls) with the presence of 74 kD and 72 kD isoforms in trace amounts. Other family members (daughters older and younger than the son) exhibited nearly normal amounts of 72kD as a wild form of band 4.2 on SDS-PAGE with the presence of the 74kD isoform in a trace amount. The proband and his son demonstrated two compound heterozygous mutations in trans: i.e. nucleotide (nt) 949 CGC-->TGC (codon 317 Arg-->Cys) in exon 7 and nt 424 GCT--ACT (codon 142 Ala-->Thr) in exon 3 of the band 4.2 gene. The two daughters demonstrated only the mutation of nt 949 CGC-->TGC in exon 7 in heterozygous states, but no 142 mutation. Therefore the proband and his son were compound heterozygotes of these two mutations in trans. It is interesting to note that the 74 kD isoform of band 4.2 protein existed in a trace amount in the two daughters in spite of the absence of the 142 Ala-->Thr mutation. In addition, even in the presence of the 142 mutation in one allele in the proband and his son, their red cell morphology demonstrated classic HS with microspherocytosis, although a homozygous state of the 142 mutation known as the Nippon type of band 4.2 deficiency exhibits ovalostomatocytosis.

Aged↗
PubMed1995

Small intestinal perforation due to cytomegalovirus infection in patients with non-Hodgkin's lymphoma.

We describe two patients with non-Hodgkin's lymphoma (NHL) who suffered cytomegalovirus (CMV)-related small intestinal perforations during the course of chemotherapy. Surgical specimens from both patients revealed histologic evidence of occlusive vasculitis and tissue destruction caused by CMV-affected cells in the submucosa and muscular walls, that may have played an important role in the pathogenesis of these perforations. Although such intestinal perforations are rare complications in NHL patients, CMV infection should be recognized as a primary etiological factor in acute abdominal crises when treating NHL patients with pharmaceutical agents including steroids. Emergency surgery and the anti-CMV agent, ganciclovir, would improve the prognoses of such patients.

Combined Modality Therapy↗
PubMed1995

Thalassemia incidentally found by marked erythrocytosis due to an ochre mutation at codon 35 in a Japanese man.

We present a patient with beta-thalassemia minor diagnosed on the basis of the incidental findings of marked hypochromic and microcytic erythrocytosis. Hemoglobin analysis revealed increased hemoglobin (Hb) A2 levels and decreased beta/alpha synthesis ratio in both the propositus and his mother. Further molecular studies identified a single base substitution of TCA to TAA within codon 35 in heterozygous state, which creates a premature terminator resulting in a defect of effective beta globin synthesis. This is the first report of beta-thalassemia due to a nonsense mutation at codon 35 of beta-thalassemia gene in the Japanese population.

Adult↗
PubMed1995

The pathogenic role of Bacteroides vulgatus in patients with ulcerative colitis.

To clarify the role played by Bacteroides vulgatus in the pathogenesis of ulcerative colitis, the serum antibody titer to the outer membrane protein of B. vulgatus, obtained from the inflamed rectal mucosa, and measured by enzyme-linked immunosorbent assay, was investigated in patients with ulcerative colitis. High serum antibody titers to the outer membrane protein of B. vulgatus were found in these patients. The specific outer membrane protein of B. vulgatus reactive to serum antibody was recognized as a 26-kDa protein. These findings indicate that B. vulgatus containing a 26-kDa protein in the outer membrane may be implicated in the pathogenesis of ulcerative colitis.

Antibodies, Bacterial↗
PubMed1993

Differential cytokine regulation of complement C3, C4, and factor B synthesis in human intestinal epithelial cell line, Caco-2.

In the intestinal tract, the local synthesis of C3 and components of both the classical (C4) and alternative (factor B) C activation pathway has previously been demonstrated in vivo. However, the cellular source of this local C synthesis has not been identified. In this study, we demonstrated the syntheses of C3, C4, and factor B in the human colonic adenocarcinoma cell line Caco-2, which is regarded as a good experimental model of normal human intestinal epithelial cells. The results of metabolic labeling experiments indicated that the intra- and extracellular molecular sizes and subunit structures of Caco-2-derived C3, C4, and factor B were compatible with previously reported values for these components in other cells. The functional activities of C3 and C4 in the supernatants were also demonstrated by hemolytic titration assay. Furthermore, C syntheses in this line were independently upregulated by several human cytokines: C3 synthesis was dose-dependently enhanced by the addition of IL-1 beta or TNF-alpha; C4 synthesis was enhanced by the addition of IL-6 or IFN-gamma in the same manner; and the addition of IL-1 beta or IL-6 also induced a dose-dependent increase in factor B synthesis. These enhancing effects were confirmed to be specific for individual cytokines by experiments using anti-human cytokine antibodies. It is likely that intestinal epithelial cells are local production sites of C3, C4, and factor B, and that local C syntheses in the intestine are independently regulated by several cytokines, derived from monocytes/macrophages and T cells resident in the mucosal microenvironment.

Adenocarcinoma↗
PubMed1993

Treatment of ulcerative colitis with camostat mesilate, a serine protease inhibitor.

We were able to induce and maintain remission with camostat mesilate, a serine protease inhibitor, in two patients with ulcerative colitis, to whom salicylazosulfapyridine could not be administered due to previous side effects. The enzymatic activity of proteases from granulocyte, pancreatic juice and bacteria is possibly harmful to the inflamed colonic mucosa. Camostat mesilate can be expected to have an anti-inflammatory effect on the damaged mucosa of inflammatory bowel disease.

Adult↗
PubMed1993

[Effect of combination chemotherapy for elderly patients with malignant lymphoma].

The remedial effect in elderly patients with malignant lymphoma in two groups treated with combination chemotherapy, one including doxorubicin (ADM) (A group) and the other excluding ADM (V group) were compared. Forty patients aged 65 years or more with malignant lymphoma were entered from January 1982 to December 1991. The A group was made up of 10 patients and the V group of 18 patients. As to pathological classification, two of the A group had low grade malignancy lymphoma, four had intermediate grade and three had high grade. Four of the V group had low grade, eight had intermediate grade and five had high grade. In terms of clinical stage, three of the A group were in stage II, 3 in stage III and 4 in stage IV. Two of the V group were in stage II, 7 in stage III and 9 in stage IV. The effective rate for the A group was 90% and the V group was 61%. The survival rate over five years in the A group was 37.5% and 21.8% in the V group. There were no adverse effects on the cardiovascular system in the A group. No significant differences of effects were shown in this study, however, the A group showed a higher tendency in terms of the CR rate and the survival rate. Cases of early death during chemotherapy were few and the quality of life of the patients was raised by discharge in the A group. Combination chemotherapy including ADM appears to be satisfactory in aged patients with malignant lymphoma.

Aged↗