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Biomedical subjects

H Wakasugi

Publications and source records attributed to H Wakasugi.

At least 55 records · Page 3Linked to original sources

Angiopathies in pancreatic diabetes resulting from chronic pancreatitis.

CONCLUSION: Marked diabetic micro- and macroangiopathies were recognized in three autopsy cases with pancreatic diabetes resulting from chronic pancreatitis. BACKGROUND: Recent reports have suggested that diabetic retinopathy occurs as one of the microangiopathies in patients with secondary diabetes following chronic pancreatitis. METHODS: We report three autopsy cases with pancreatic diabetes. Cases 1 and 2 showed alcoholic chronic pancreatitis. Case 3 was a patient with chronic pancreatitis resulting from hyperparathyroidism. All three cases had pancreatic calcification and markedly decreased exocrine pancreatic function. There was no family history of diabetes in these patients. The HbA1 values were elevated, with diminished secretion of both insulin and glucagon. RESULTS: The common features of the clinical courses were poor glycemic control, including insulin-induced hypoglycemic attacks in the early stage and microangiopathy, followed by difficulties in treatment for hypertension in the late stage of pancreatic diabetes. Autopsies, performed after 12-18 yr of diabetes, revealed fibrosis of the pancreas, disappearance of acinar cells in the exocrine pancreas, atrophy, a diminished number of islets of Langerhans, and diabetic glomerulosclerosis, with arteriosclerosis in the brain, heart, and kidneys. Cerebral hemorrhage, heart failure, and myocardial infarction were suggested to be the main causes of death. Although the serum lipid levels were rather low in cases 1 and 2, arteriosclerosis was marked by the age of 60, and serum protein levels were also low in all three cases.

Adult↗

Induction of thioredoxin in human lymphocytes with low-dose ionizing radiation.

Induction of the expression of the thioredoxin (TRX) gene, producing a key protein in regulating cellular functions through redox reaction as well as being a radioprotector, was followed after ionizing irradiation of lymphocytes from human donors. The TRX mRNA level increased to a peak, 5.7-fold higher than the control at maximum, 6 h after irradiation, and then decreased. The optimum radiation dose for enhancement of induction of the TRX mRNA was 0.25 Gy. The TRX protein also increased to a peak, a 3-fold increase at maximum, with the same timing as that for TRX mRNA.

Blotting, Northern↗

[EBV-related malignancies and thioredoxin].

Thioredoxin (TRX) is a ubiquitous protein with two redox-active half-cystine residues. 3B6-IL-1, which was first reported as an interleukin 1-like protein produced by Epstein-Barr virus (EBV)-transformed human B cell line (3B6), proved to be a human homologue of TRX. TRX is multifunctional in that it regulates DNA replication and transcription intracellularly and has various cytokine activities extracellularly associated with cell proliferation, immunological response, etc. It also functions to protect the cells from oxidative stress. In various tumors including EBV-related malignancies, an elevated expression of TRX is reported, but the role of TRX in such tumors has not yet been clarified. This review presents recent progress concerning the relation between TRX and neoplasms.

Herpesvirus 4, Human↗

A study of malabsorption in pancreatic cancer.

The type, incidence, and severity of malabsorption in patients with pancreatic cancer were investigated. The following absorption tests were performed; pancreatic function diagnostant (PFD) test, measurement of serum carotene levels, and 5 g D-xylose absorption test. Rates of abnormality in the tests were 75.7% of 37, 54.2% of 48, and 54% of 50 patients with pancreatic cancer, respectively. In particular, a marked decrease of values in the xylose absorption test was characteristic and more often recognized in patients with carcinoma of the pancreas with occlusion of the superior mesenteric vein. The presence of malabsorption (disturbed transport through the portal vein), in addition to maldigestion of nutrients, is suggested to induce severe malnutrition in patients with pancreatic cancer.

Adult↗

Analysis of Ki-ras codon 12 mutations in the duodenal juice of patients with pancreatic cancer.

BACKGROUND & AIMS: Point mutations of the Ki-ras gene at codon 12 have been frequently identified in pure pancreatic juice of patients with pancreatic cancer in studies examining pancreatic cancer tissues. The aim of this study was to examine mutations of the Ki-ras codon 12 in the duodenal juice collected from patients with various pancreatic disorders. METHODS: The duodenal juice was collected through a Dreiling tube installed in the duodenum during a secretin test. Analysis of the Ki-ras mutations was performed using the enriched polymerase chain reaction--single-strand conformation polymorphism technique. RESULTS: Point mutations were detected in 12 of 19 patients with pancreatic cancer; of the 12 patients, 10 had ductal tubular adenocarcinoma and 2 intraductal papillary adenocarcinoma. Mutational patterns included GAT (n = 4), GTT (n = 3), CGT (n = 1), and double mutations of GTT and GAT (n = 3) and GAT and CGT (n = 1). In 41 patients with benign pancreatic disorders, a point mutation was detected in only 1 patient with chronic pancreatitis. CONCLUSIONS: Analysis of the Ki-ras codon 12 mutations in the duodenal juice is useful in the diagnosis of pancreatic cancer.

Base Sequence↗

Ethics and health in a changing world.

Seven advisers from a wide variety of health-related professions met with some 30 staff at WHO to discuss ethical issues currently arising in health and international cooperation. Far-reaching questions of responsibility and legitimacy were raised. The following observations are adapted from the final report on the meeting.

Ethics↗

[An autopsy case of renal failure as its cause of death in a patient with primary hyperparathyroidism associated with chronic pancreatitis].

This paper presents a 59-year-old man who was admitted to our hospital because of abdominal pains in 1973. He had pancreatic calcification and showed high levels of serum amylase, Ca, and PTH. He was diagnosed as primary hyperparathyroidism with chronic pancreatitis. After excision of an ectopic parathyroid adenoma, serum Ca levels were decreased and normalized by dihydrotachysterol p.o. At the same time his symptoms disappeared. The exocrine and endocrine pancreatic functions, however, decreased gradually. Diabetes mellitus appeared in 1975 and he required insulin injection since 1983. In spite of the treatment, his diabetic control was poor. Seventeen years later in 1992, he showed hypertension and edema (nephrotic syndrome). Because of renal failure, he underwent hemodialysis and passed away due to myocardial infarction in 1993. Autopsy findings showed existence of diabetic nephropathy as the cause of renal failure. Clinical course of this patient suggests that severe complications occur even in pancreatic diabetes and that we have to control diabetes strictly in pancreatic diabetes as well as in primary diabetes.

Chronic Disease↗

Frequent development of murine T-cell lymphomas with TcR alpha/beta+, CD4-/8- phenotype after implantation of human inflammatory breast cancer cells in BALB/c nude mice.

Tumors developed quite frequently in some of the visceral organs, including spleen and liver, in BALB/c nude mice upon subcutaneously xenografting surgical specimens from five different inflammatory breast cancer patients. All of these tumors developed within two and a half months to one year after the subcutaneous inoculation of surgical specimens. From these tumors, five independent transplantable tumors, including tMK-2, tHK-1, tYK-1, tYK-2 and tTY-1 have been established. Chromosome analysis, morphologic studies by light and electron microscopy and phenotype analysis indicated that these tumors are of mouse origin. The tMK-2 tumor was highly metastatic to the spleen and liver when it was subcutaneously transplanted into the right scapular region. In addition, the region where the tMK-2 tumor cells were subcutaneously inoculated showed an apparently inflammatory process represented by erythema. After subcutaneous inoculation into the right scapular region, tHK-1, tYK-1, 2, and tTY-1 tumors also metastasized to some of the visceral organs, including spleen and liver. From these tumors, in vitro cell lines were established. The cells grew in a stromal-cell dependent manner under in vitro culture conditions. The cells were again tumorigenic at the inoculated region and metastasized to various organs, including liver and spleen, of BABL/c nude mice. Histological examination revealed that the tumors showed features of malignant lymphoma. Phenotypically, these five tumors expressed early T lymphocyte markers as revealed by anti-mouse anti-TcR alpha/beta, anti-CD3, CD4 and CD8 monoclonal antibodies. To our knowledge, these cell lines are the first T-cell lines showing the phenotype of extrathymically differentiated T-cells in the liver.

Animals↗

Juvenile-onset pancreatic diabetes to whom a healthy infant was born.

A rare case of pregnancy and successful transvaginal delivery in secondary diabetes due to chronic pancreatitis is reported. At the age of 16 the patient was diagnosed as having chronic pancreatitis probably caused by hyperlipemia. Three years later diabetes and calcification of the pancreas was found. Blood glucose was well controlled using both self-monitoring of blood glucose and multiple subcutaneous insulin injection just before she became pregnant at age 23. The dose of insulin was slightly increased and no acute exacerbation of pancreatitis occurred during pregnancy, partly due to an appropriate low fat diet with digestive enzyme preparations.

Adult↗

[Immunopotentiation by OK-432 ointment to apply to the mouse abdominal skin].

The immunopotentiating effect of a streptococcal preparation, OK-432 (Picibanil), mixed with an ointment based Lanolin, was examined. The mixture was applied to mouse abdomen. The effect of OK-432 ointment was compared with those of OK-432 ip and sc. The leucocyte count in the abdominal cavity increased in 3.6 x 10(6) and 12.5 x 10(6) on the 3rd day after ointment application and ip injection of 5 KE OK-432, respectively. The result indicated that OK-432-Lanolin applied to the abdominal skin wall affected the abdominal cavity. IL-6 and IFN-gamma in the abdominal cavity increased in 1.4 ng and 9 ng, respectively, after applying 5 KE OK-432 ointment. From these results the treatment with OK-432 ointment on the abdominal skin exhibited an immunomodulatory effect on the abdominal cavity.

Abdomen↗

Thioredoxin increases the proliferation of human B-cell lines through a protein kinase C-dependent mechanism.

Thioredoxin (Trx) catalyzes thiol-disulfide oxidoreductions. We and others recently showed that human Trx could function as an autocrine growth factor for human lymphoid cells immortalized by the human T-lymphotrophic virus type I or the Epstein-Barr virus. Here we report that reduced Trx from Escherichia coli generated by NADPH and thioredoxin reductase increases the proliferation of an Epstein-barr virus(+)-B cell line 1G8, which constitutively produces low amounts of human Trx. This proliferative effect involved the activation of protein kinase C through its translocation to the membrane. Staurosporin and calphostin C, two inhibitors of protein kinase C, but not of H8, a protein kinase A inhibitor, were able to block Trx-dependent proliferation. The addition of Trx to 1G8 cells resulted in the formation of inositol 1,4,5-triphosphate and sn-1,2-diacylglycerol by a phosphoinositide-specific phospholipase C, as well as increased free calcium concentration. Diacylglycerol showed a biphasic increase; the first phase, corresponding to an early peak (30 s) of inositol 1,4,5-triphosphate and a second larger, prolonged phase. The second phase was inhibited by propranolol, a specific inhibitor of phosphohydrolase, indicating that it is most likely derived from phosphatidylcholine hydrolysis by the sequential action of phospholipase D and phosphatidic acid phosphohydrolase. Our data suggest that enhanced phosphoinositide-specific phospholipase C activity induced by the dithiol form of Trx in 1G8 cells is associated to protein kinase C activation, and thus plays a role in the permanent growth of Epstein-Barr virus-infected B cells.

B-Lymphocytes↗

Effectiveness of chemotherapy for advanced adenocarcinoma of the pancreas in combined modality therapy.

Because it is difficult to diagnose at an early stage, pancreatic carcinoma is usually well advanced by the time it is diagnosed. The combined use of intraoperative radiotherapy, gastrointestinal and/or biliary tract bypass operation, celiac plexus nerve block, and chemotherapy is widely applied in treatment, with favorable results reported in some patients with advanced disease. To evaluate the efficacy of chemotherapy in such combinations, we compared the effect of 5-fluorouracil, its analogues, and mitomycin C on the survival of patients with advanced stage pancreatic cancer. We found no significant difference between the patients treated or not treated with these drugs. Clearly, there is a need for new agents having greater efficacy against pancreatic carcinoma.

Adenocarcinoma↗

Gene expression of erythropoietin in hepatocellular carcinoma.

A 68-year-old man with hepatocellular carcinoma complicated by erythrocytosis showed an increased plasma level of immunoreactive erythropoietin (EPO). Northern blot analysis and RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. Histological and immunocytochemical examination showed that the tumor was a hepatocellular carcinoma with predominant immunostaining for EPO. The erythrocytosis improved and the high serum EPO level decreased after resection of the tumor. This is the first demonstration of EPO mRNA expression in hepatocellular carcinoma tissue by RT-PCR.

Aged↗

Goodpasture's-like syndrome and effect of extracorporeal membrane oxygenator support.

A 49-year-old man was admitted because of general fatigue, cough and hematuria. During the hospital course, acute renal failure, hemoptysis and dyspnea developed. A percutaneous renal biopsy revealed a diffuse crescentic glomerulonephritis, and direct immunofluorescence showed a linear pattern of IgG along the glomerular basement membrane. Although serum anti-glomerular basement membrane (anti-GBM) antibody was not detected. Goodpasture's-like syndrome was suspected, and methylprednisolone pulse therapy and plasmapheresis were administered. Concomitantly, extracorporeal membrane oxygenation (ECMO) was instituted because of deterioration in respiratory status due to a severe pulmonary hemorrhage despite maximal ventilatory support. Temporarily, the patient improved and ECMO was discontinued. ECMO may be a useful therapeutic support for hypoxia resulting from pulmonary hemorrhage in Goodpasture's syndrome (GPS) and Goodpasture's-like syndrome.

Anti-Glomerular Basement Membrane Disease↗

[Establishment of a human colon cancer-derived cell line (KC-1) which produces CEA, CA 19-9 and sialyl SSEA-1(SLX)].

A human colon cancer-derived cell line, KC-1, was established from the surgical specimen of mucinous adenocarcinoma of the colon. The cells grew as monolayers, showing formation of irregular aggregation of cells and pleomorphic nuclei. The doubling time in vitro was 56.6 hours. The cells produced CEA, CA19-9 and sialyl SSEA-1(SLX). Chromosome numbers were distributed between 79 and 83 with many structural abnormalities. A point mutation of the Ki-ras gene in codon 61 (CAA-->CAT) was found. The cells have been subcultured 13 times during these three years. This cell line can be useful for investigations of colon cancer.

Adenocarcinoma, Mucinous↗