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Biomedical subjects

G Ohshio

Publications and source records attributed to G Ohshio.

At least 91 records · Page 5Linked to original sources

Radical pancreatectomy for ductal cell carcinoma of the head of the pancreas.

Seventy-four patients were treated with a radical or a nonradical pancreatectomy for ductal cell carcinoma of the head of the pancreas. Their survival rates and the selection of the operative procedure were evaluated. In 32 patients, a radical pancreatectomy was attempted where there was sufficient clearance of regional or juxta-regional lymph nodes beyond the group of suspected metastatic nodes, as well as a resection of a greater margin of soft tissue around the pancreas. These patients' cumulative 5-year survival rate was 33.4%. In 14 Stage I or Stage II patients, the cumulative 5-year survival rate was 46.4%. In 18 Stage III or Stage IV patients, the cumulative 5-year survival rate was 20.7%. For 42 patients treated with a nonradical pancreatectomy with the dissection of lymph nodes adjacent to the pancreas or of regional lymph nodes but with insufficient clearance of the soft tissue around the pancreas, the cumulative 2-year and 3-year survival rates were 5.4% and 0%, respectively. In seven patients with Stage II carcinoma, the survival rate was 16.7% after 2 years and 0% after three years. In 35 Stage III or Stage IV patients, the survival rate was 3.2% after 2 years and 0% after 3 years. Thus, the survival rates were significantly higher in patients treated with radical operation than in patients who had nonradical operation. These results indicate that a radical pancreatectomy with sufficient lymph node clearance with the surrounding connective tissue around the pancreas is indispensable to cure patients with ductal cell carcinoma of the pancreas.

Adult↗

Distribution of vitamin B12 R-binder in lung tumors. Implications for cell differentiation.

Expression of vitamin B12 R-binder, a specific binding protein for vitamin B12, was studied immunohistochemically in normal lung tissues and 107 lung tumors of various types. In normal tissues, vitamin B12 R-binder (R-binder) expression was restricted to the mucous cells of bronchial or bronchiolar epithelium and submucosal glands as well as to nonciliated bronchiolar (Clara) cells. Among lung carcinomas, 38% of squamous cell carcinomas, 42% of adenocarcinomas and 23% of large cell carcinomas showed positive staining for R-binder whereas small cell carcinomas did not. These findings offer the possibility that a majority of the histologic types of lung carcinoma have common histogenetical characteristics with mucous or Clara cells. Of the bronchial gland tumors, R-binder could be detected in a mucoepidermoid carcinoma but not in adenoid cystic carcinomas. Epithelial components in both pulmonary blastomas and hamartomas showed a reactivity for R-binder, suggesting that these tumors contained components composed of cells with bronchiolar cell differentiation. The immunohistochemical examination of lung tumors, using anti-R-binder antibody, may have some implications in the cell differentiation of lung tumors.

Bronchi↗

Failure of a potent cholecystokinin antagonist to protect against diet-induced pancreatitis in mice.

The effects of a potent cholecystokinin (CCK) receptor antagonist, L-364,718, on two forms of experimental acute pancreatitis in mice were evaluated. The antagonist prevented the hyperamylasemia, pancreatic edema, and acinar cell vacuolization that followed administration of a supramaximally stimulating dose of the cholecystokinin analogue cerulein. In contrast, the same dose of L-364,718 (1 mg/kg/6 h) and an even higher dose (10 mg/kg/6 h) failed to prevent the hyperamylasemia, acinar cell necrosis, and mortality that followed administration of a choline-deficient ethionine-supplemented diet. These observations are at variance with those previously reported to follow administration of the relatively weak cholecystokinin antagonist proglumide (Niederau C et al. J Clin Invest 1986;78:1056-63). The observations reported in this communication suggest that cholecystokinin does not play an important role in diet-induced pancreatitis and that CCK receptor antagonists are unlikely to be of benefit in the treatment of clinical acute pancreatitis.

Animals↗

Effect of endotoxin on digestive enzyme and superoxide dismutase in mouse pancreas.

In order to clarify the effect of endotoxin on pancreatic lesions, changes in the level of activity of pancreatic proteolytic enzymes and superoxide dismutase (SOD) were measured following the intraperitoneal administration of Escherichia coli endotoxin in mice. Microscopic examination revealed that congestion of zymogen granules in acinar cells appeared in the early stages. The accumulation increased gradually and was widespread at 24 h after E. coli endotoxin administration. The serum amylase level increased significantly from its basal level of 1,630 +/- 128 SU to 2,395 +/- 42 SU at 4 h (p less than 0.05), 3,172 +/- 513 SU at 8 h (p less than 0.05), and 2,572 +/- 229 SU at 12 h (p less than 0.05) after E. coli endotoxin administration. The serum lipase level also increased significantly from its basal level of 37.6 +/- 1.6 IU/l to 65.8 +/- 8.9 IU/l at 12 h (p less than 0.05). The level of trypsinogen in the pancreas increased markedly from its basal level of 161.8 +/- 15.7 U/g tissue to 270.0 +/- 9.6 U/g tissue at 2 h (p less than 0.001) after E. coli endotoxin administration and showed continued increases at 8 h (313.3 +/- 10 U/g tissue, p less than 0.001) and 24 h (352.9 +/- 19.3 U/g tissue, p less than 0.001); however, the level of net stimulated secretion of trypsinogen in the medium decreased significantly at 4 h (p less than 0.05) and 8 h (p less than 0.01) after E. coli endotoxin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

Esterase inhibitors prevent lysosomal enzyme redistribution in two noninvasive models of experimental pancreatitis.

Earlier studies have indicated that lysosomal enzymes such as cathepsin B become redistributed within pancreatic acinar cells during the early stages of both diet- and secretagogue-induced acute pancreatitis. As a result, cathepsin B and digestive zymogens became colocalized within large cytoplasmic vacuoles. As cathepsin B can activate trypsinogen, this colocalization could result in intracellular digestive enzyme activation. The present study investigates the protective effects of gabexate mesilate (FOY) and camostate (FOY 305) on both of these noninvasive models of experimental pancreatitis. These esterase inhibitors prevented the hyperamylasemia, pancreatic edema, and acinar cell vacuolization that characterize secretagogue-induced pancreatitis and the hyperamylasemia and mortality that characterize diet-induced pancreatitis. In addition, FOY and FOY 305 were found to significantly decrease the subcellular redistribution of cathepsin B that occurs in both models. These findings indicate that enzyme activity sensitive to inhibition by FOY and FOY 305 may be critical to the redistribution phenomenon that characterizes both of these models of pancreatitis.

Amylases↗

Serum secretory IgA levels in patients with Behçet disease.

Serum IgA, IgC, IgM and secretory IgA levels in patients with Behçet disease were examined. Among them, serum IgA and secretory IgA levels, which increase in mucosal inflammation, were significantly higher than controls (p less than 0.001, p greater than 0.01). These results indicate that mucosal inflammation, oral and gastrointestinal inflammation, may lead to gram-negative bacterial infection and endotoxin-induced uveitis in patients with Behçet disease.

Adult↗

Autoimmune abnormalities in a murine model of accelerated senescence.

Immunopathological abnormalities in senescence-accelerated mice (SAM) were studied by comparison of senescence-prone (SAM-P/1) and senescence-resistant (SAM-R/1) mice. Sera from SAM-P/1 mice contained a number of autoantibodies, including natural thymocytotoxic autoantibody (NTA), anti-nuclear antibodies (ANA) and IgG anti-single-stranded and anti-double-stranded (ss and ds) DNA antibodies. Furthermore, an earlier increase in serum IgG2 levels and an earlier appearance of IgG circulating immune-complexes (CIC) associated with low C3 levels, were observed in SAM-P/1 mice. These serological findings were distinctive features in SAM-P/1 mice, which could almost discriminate these mice from SAM-R/1 mice. In addition, age-associated glomerular mesangial and capillary lesions with granular IgG and C3 deposition were frequently observed in SAM-P/1 mice, whereas SAM-R/1 mice even at 10 months of age showed only mild mesangial lesions. These findings suggest that autoimmune abnormalities may contribute to the accelerated senescence in these mice.

Aging↗

Lectin histochemistry in ulcerative colitis and Crohn's disease.

The glycoconjugate composition of intestinal goblet cell mucin was characterized according to the anatomical distribution of lectin-binding sites in surgically resected intestinal tissues and mucosal biopsy specimens obtained from 38 control subjects, and from 32 patients with the active phase of ulcerative colitis, and 12 with Crohn's disease. Immunoperoxidase labeling studies found that in control tissues binding by Soybean Agglutinin (SBA), Dolichos Biflorus Agglutinin (DBA), Wheatgerm Agglutinin (WGA), and Ricinus Communis Agglutinin-120 (RCA-120) was consistently higher than that of Peanut Agglutinin (PNA), Ulex Europaeus Agglutinin-1 (UEA-1), Concanavalin A (ConA) and Helix Pomatia Agglutinin (HPA). Tissues from ulcerative colitis and Crohn's disease patients, showed increases in DBA and SBA binding, a reduction in HPA binding, and changes in the distribution of PNA, UEA-1, RCA-120, and HPA labeling sites. These results demonstrated that the expression of lectin-binding sites on human intestinal goblet mucin was specifically altered in ulcerative colitis and Crohn's disease, thus possibly providing another approach to the assessment of neoplastic risk on these diseases.

Adolescent↗

Small carcinoma of the pancreas. Clinical and pathologic evaluation of 17 patients.

The clinical and pathologic characteristics of 17 small carcinomas (less than 2 cm in diameter) of the pancreas are reviewed in this article. All the tumors were located in the head of the pancreas, and the clue to the diagnosis was jaundice in ten patients and abdominal pain in seven. Carcinoembryonic antigen (CEA) and CA 19-9 were not reliable markers for detecting small carcinomas of the pancreas. Ultrasonography (US), computerized tomography (CT), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP) were useful diagnostic tools. Lymph node metastases were found in 41% of affected patients, capsular invasion in 24%, retroperitoneal invasion in 24%, and portal system involvement in 29%. In five patients the carcinoma was Stage I; in eight patients, Stage II; in two patients, Stage III, and in two patients, Stage IV. Fifteen patients with Stages I to III and one patient with Stage IV underwent curative pancreaticoduodenectomy or total pancreatectomy, and one patient with liver metastasis and Stage IV underwent noncurative pancreaticoduodenectomy. The cumulative 4-year survival rate was 37%. Although four patients with Stage I disease lived for more than 48 months, the survival period of the 12 patients with Stages II to IV disease was less than 25 months. Thus, small carcinoma of the pancreas is not always curable; however, a small, localized lesion without any extratumoral extension can be resected with a chance of cure.

Abdomen↗

Immunohistochemical examination of Peyer's patches in autoimmune mice.

The distribution of T-cells and B-cells in Peyer's patches was examined in three autoimmune model mice, MRL/Mp-lpr/lpr, BXSB, NZBWF1/J mice and normal BALB/c mice, between one and ten months old. A multiple layering technique was used for immunohistochemical detection of lymphocyte surface antigens of T-cells (Thy1.2, Lyt1, Lyt2) and B-cells (surface IgM) and peanut agglutinin receptor for germinal center cells. The T-cell population of female MRL/Mp-lpr/lpr mice increased markedly with age, and the B-cell population of the male BXSB mouse tended to increase. However, little change was observed with age in the NZBWF1/J mice. The immunohistochemical properties of the Peyer's patches in the three autoimmune model mice were different.

Animals↗

Comparative studies on immunoglobulins, complement component (C3), albumin, and immunoglobulin A-containing circulating immune complexes in serum and bile of patients with biliary obstruction.

We measured the concentrations of IgA, IgG, IgM, secretory IgA, albumin, complement component (C3), and IgA-containing circulating immune complex (IgA-CIC) in the serum and bile of patients with biliary obstruction. The bile-to-serum (BS) ratio of the concentrations of albumin and IgG increased with the increase in total serum bilirubin. This indicates that the permeability from blood to bile increases with the degree of biliary obstruction, and the blood-bile barrier function breaks down. The BS ratios of IgA and IgM, which are selectively secreted into bile, did not show a significant correlation with total serum bilirubin. The index of the BS ratio to the BS ratio of albumin (BS/BS-Alb index) of IgA and IgM was significantly larger than that of IgG. This indicates that the selective transport of IgA and IgM into bile is present even in patients with obstructive jaundice. Since the BS/BS-Alb index of C3 is larger than that of IgG, and the SGOT correlated directly with the BS ratio of C3, some of the C3 in bile may come from damaged hepatocytes.

Albumins↗

Vitamin B12 R-binder localization in the human uterus: an immunohistochemical study.

The localization of vitamin B12 R-binder in the uterus was studied by use of an immunoperoxidase technique. Positive staining by anti-R-binder antiserum was observed in the columnar epithelium of the endocervix (18/18 cases) and in the surface epithelium of the endometrium (8/21 cases). Staining was usually seen in the apical portion of the epithelium; cytoplasmic staining in the endocervical columnar epithelium was intense. The secretory products in the endocervical glands showed positive staining. The endometrial glandular epithelium did not stain (0/24 cases). Metaplastic squamous epithelium of the endocervix showed positive staining (3/18 cases). The native squamous epithelium as well as the stromal components of the cervix, endometrium, and myometrium were negative for R-binder. This study shows that R-binder is localized in the uterus, especially in the endocervical glands. The R-binder in the endocervix may have antimicrobial activity in the uterus as in other organs, such as the intestines and mammary glands.

Adult↗

Circulating immune complex, endotoxin, and biliary infection in patients with biliary obstruction.

Immunoglobulin A-containing circulating immune complexes, immunoglobulin G-containing circulating immune complexes, and endotoxin were measured in the sera of patients with obstructive jaundice. The bile of patients with percutaneous transhepatic biliary drainage was also cultured for bacteriologic studies. There was a significantly positive correlation between the endotoxin levels and both immunoglobulin A-containing circulating immune complex and immunoglobulin G-containing circulating immune complex. The endotoxin levels of the patients with gram-negative infections were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin G-containing circulating immune complex levels of the patients with bacteria in bile were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin A-containing circulating immune complex levels of the patients with bacteria in bile were slightly increased, but the difference did not reach statistical significance. These results indicate that one of the causes of increased circulating immune complex levels may be endotoxemia in combination with biliary infection in patients with biliary obstruction.

Antigen-Antibody Complex↗

The effect of splenectomy on antibody response to lipopolysaccharide (E. coli) immunization.

The influence of splenectomy on the antibody response to lipopolysaccharide (LPS: E. coli 0128:B12) was investigated in mice. Splenectomy had little effect on the primary response to the LPS. However, the level of IgG anti-LPS antibodies of splenectomized mice was significantly lower than that of sham-operated mice when the mice were immunized 1, 3, and 7 days after the operation and reimmunized 7 days after the first immunization. There was no significant difference in those immunized 30 days after the operation and reimmunized 7 days later. In mice immunized before splenectomy and reimmunized 30 days after splenectomy, the level of IgG anti-LPS antibodies was low, even in the mice splenectomized 30 days after primary immunization. Our results indicate that splenectomy impairs the antibody response to lipopolysaccharides.

Animals↗

Pathogenesis of lupus dermatoses in autoimmune mice. X. Evaluation of histamine-N-methyltransferase activity in the skin of autoimmune.

We measured histamine concentration and its metabolizing enzymes in the skin of MRL/Mp-lpr/lpr (MRL/l) and BXSB mice to clarify the contribution of histamine metabolism to the mechanisms of the development of lupus dermatoses. The concentration of histamine seemed to differ with the mouse strain. The activity of histamine-N-methyltransferase (HMT), one of two major metabolizing enzymes, was significantly lower in the tail and back skin of MRL/l mice at the age of 5 months than in the control MRL/Mp-+/+(MRL/n) mice, although there were no characteristic differences among several mouse strains of 1 mo of age. In the back skin of MRL/l mice, an age-dependent decrease of HMT activity was observed along with a corresponding decrease in histamine concentration, whereas an age-dependent increase of both HMT activity and histamine concentration was demonstrated in BXSB mice and other control mouse strains. Autoimmune-prone male BXSB mice and non-autoimmune female BXSB mice at 5 mo of age showed similar HMT activity. Corticosteroid treatment restored HMT activity in the skin of MRL/l mice but not in MRL/n mice. In addition, the change in HMT activity in MRL/l mice treated with corticosteroid appeared earlier than changes in clinicopathological examinations including skin eruptions, dermatopathology and proteinuria. Diamine oxidase (DAO) activity, another major metabolizing enzyme, was not detected in the skin of any autoimmune or control mouse strains. These findings suggest that the low activity of HMT in the skin of MRL/l mice plays a significant pathological role in the development of spontaneous lupus-like eruption. In other mouse strains, it is assumed that HMT activity is regulated by genetic factors.

Abdomen↗

Effects of sera from patients with obstructive jaundice on the generation of oxygen intermediates by normal polymorphonuclear leukocytes.

Recently it has been suggested that oxygen intermediates play an important role in the pathogenesis of tissue damage. The effect of sera from patients with obstructive jaundice on the generation of oxygen intermediates by normal polymorphonuclear leukocytes (PMNs) was investigated. Sera from patients with obstructive jaundice increased superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxol radical (OH.) generation compared with sera from healthy individuals or patients with biliary tract stones and/or tumors of the biliary tract or pancreas (without obstructive jaundice). In particular, the hydroxyl radical, which is one of the most potent oxidants capable of causing tissue damage, was produced in large quantities. Sera from patients with obstructive jaundice have a strong capacity to induce production of oxygen intermediates from PMNs, and oxygen intermediates may play a role in the pathogenesis of hepatic and other organ injury in obstructive jaundice.

Cholestasis↗

Distribution of vitamin B12 R-binder in carcinomas of the digestive tract.

To evaluate whether the increase in serum transcobalamin I, seen in patients with carcinoma, is caused by synthesis of R-binder to tumour cells, the distribution of vitamin B12 R-binder in 125 malignant growths of the digestive tract was studied. Positive staining for R-binder with immunoperoxidase was observed in 85 (70%) carcinomas. Positive staining for R-binder was observed in all four cholangiocarcinomas studied, but was absent in nine hepatocellular carcinomas. These findings suggest that determination of R-binder in liver tumours may be of some value in differentiating hepatocellular carcinomas and cholangiocarcinoma, and that synthesis of R-binder by tumour cells causes an increase in serum transcobalamin I.

Adenocarcinoma↗