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Biomedical subjects

T Onodera

Publications and source records attributed to T Onodera.

At least 235 records · Page 13Linked to original sources

A simple technique for repeated blood collection from the tail vein of the rat.

A practical technique was described for collecting blood sample periodically from a conscious rat. Blood obtained from a tail vein, warmed for 10 seconds in water bath (at 50 degrees C), by inserting of a 22 G needle from which the adapter was cut off. Using this method, the influence of phlebotomy on hematologic parameters was determined. This technique was simple, easy, and reliable, and required no special skill and equipment.

Animals↗

[Clinico-biochemical study of experimental renal injuries in rats. 3. Relations between serum half-life of phenolsulfonphthalein and renal injuries].

The serum half-life of PSP(PSP t/2) was determined in normal and nephropathy rats by repeated blood collection under an unanesthetized condition to estimate its usefulness as a renal functional parameter. In normal rats, the serum disappearance curve of PSP (5 mg/kg) could be resolved into two exponential components, and the mean PSP t/2 in the second component was 12 min (n=100). About 71% of the PSP loaded was excreted in urine and 19% in bile. A single subcutaneous injection of HgCl2 delayed the serum disappearance of PSP and simultaneously decreased its urinary excretion and increased its biliary excretion. The serum protein binding ratio of PSP became higher when the serum concentration of PSP was decreased, while it became lower when the serum albumin level was decreased. PSP t/2 in rats treated with gentamicin or puromycin amino-nucleoside as well as that in rats given HgCl2 was increased in correlation with changes in common renal functional parameters such as serum urea nitrogen, serum creatinine, urinary protein and morphologic changes of the kidney. Masugi-type nephritis rats showed no change in PSP t/2. Moreover, PSP t/2 was well correlated with the maximal tubular secretion rate of p-amino-hippuric acid. Since PSP t/2 can be determined periodically on the same animal, it is considered to have effective application as a renal functional test in rats, especially for examining tubular secretion.

Animals↗

Virus-induced diabetes mellitus. Glucose abnormalities produced in mice by the six members of the Coxsackie B virus group.

The capacity of Coxsackie B viruses (CBVs) to produce diabetes in mice was studied before and after passage in various cell types. CBVs that had been passaged in monkey kidney cells or in mouse embryo fibroblasts failed to produce abnormal glucose tolerance tests, whereas virus passaged five or more times in the pancreata of mice or in beta-cell cultures produced transient abnormal glucose tolerance tests. Immunofluorescence and histologic studies revealed that passage of CBVs in cultured beta-cells changed the tropism of these viruses from the acinar pancreas to the islets of Langerhans. Although all six CBV serotypes that had been passaged in beta-cell cultures behaved very similarly, substantial variation was observed with the different virus passages and in some experiments, beta-cell damage and the glucose abnormalities were minimal. From these and other experiments, we conclude that the six members of the CBV group have the potential for infecting and damaging pancreatic beta-cells in mice.

Animals↗

[Studies on experimental renal damage in rats. II. beta 2-microglobulin: purification, radioimmunoassay, and urine and serum levels in tubular nephropathy].

Beta 2-Microglobulin (beta 2-M) was purified from the urine of rats treated with cephaloridine by a combination of ammonium sulfate precipitation, gel chromatography, ion exchange chromatography, zone electrophoresis, and isoelectric focusing. The protein thus obtained was identified as beta 2-M by its molecular weight, electrophoretic mobility, and amino acid composition and was confirmed as a single protein through polyacrylamide gel electrophoresis, Ouchterlony immunodiffusion analyses, and immunoelectrophoresis using rabbit anti-rat beta 2-M sera. A radioimmunoassay was developed for the measurement of serum and urine beta 2-M levels. In rats given gentamicin (20 or 80 mg/kg/day, s.c.) for 10 days, serum beta 2-M was increased simultaneously with changes in common renal function parameters such as serum urea nitrogen, creatinine, and urinary protein. Urinary beta 2-M was elevated from the early stage of nephropathy and correlated with renal morphological change, indicating that urinary beta 2-M can be used as a sensitive and valuable index of renal tubular damage.

Acute Kidney Injury↗

Abnormalities of immunoregulatory T cell subsets in patients with insulin-dependent diabetes mellitus.

Patients with insulin-dependent diabetes mellitus (IDDM) have autoantibodies that react with cells in the islets of Langerhans. To determine whether these patients suffer from a more generalized immunoregulatory disorder, the ratio of phenotypic helper to suppressor cells was evaluated by specific monoclonal antibodies. Our experiments showed that the helper/suppressor cell ratio was significantly increased in patients with IDDM of less of 2 mo duration and then gradually returned to normal. Despite the alteration in the helper/suppressor cell ratio, there was no evidence for polyclonal activation as measured by the number of immunoglobulin-secreting plaque-forming cells in the peripheral blood. There was, however, a significant increase in the number of spontaneous plaque-forming cells in patients suffering from both IDDM and Hashimoto's thyroiditis (HT). Nonetheless, immunoglobulin production after stimulation with pokeweed mitogen was not different in diabetics with or without HT when compared to normal controls. These findings suggest that subtle changes in the immunoregulatory system occur during the early stages of IDDM.

Adolescent↗

[Studies on experimental renal damage in rats. I. Analysis of urinary alkaline phosphatase (author's transl)].

The experiment was undertaken to make a discrimination between glomerulonephritis (GN, Masugi-type) and tubular damage (TD, cephaloridine-induced) in rats by means of urinary alkaline phosphatase (AlP). Urinary AlP concentrations were increased 13 times in GN rats amd 8 times in TD rats, in comparison with the corresponding controls. Cellulose acetate plate electrophoresis before and after neuraminidase digestion revealed that urinary AlP from GN rats migrated similarly to serum and intestinal AlP, while the mobility of urinary AlP from TD rats resembled that of the kidney. The sensitivity of urinary AlP from GN to the inhibitors, L-phenylalanine and urea, was almost equivalent to that of intestinal AlP, and the sensitivity of urinary AlP from TD rats was similar to that from kidney AlP. Histochemically, AlP activity in the kidney appeared normal in GN rats, but it was markedly decreased in TD rats. Those results suggest that the urinary AlP from GN rats is identical to serum AlP originating from intestines, i.e., a selective increase in glomerular permeability in disturbed glomerular filtration occurs. On the other hand, urinary AlP from TD rats originated mainly from the kidney due to the disquamation in the proximal convoluted tubular epithelia. Thus the properties of urinary AlP are important for estimating the site of renal damage.

Alkaline Phosphatase↗

[Multimodal treatment of unresectable pancreatic cancer including intra-operative radiotherapy].

A multimodal treatment was consisted of intraoperative radiation, external radiation, by-pass operation, chemotherapy and total parenteral nutrition if necessary to cover decreased oral-intake. Thirty-three cases were subjected to this therapy for 6 years. The stage of the tumors varied from a localized tumor in the pancreas to a huge tumor with multiple metastases, though the latter abandoned recently to be contraindication to this therapy. At laparotomy, a high energy electron beam was irradiated to the tumor with a dosage of 3,000 rad using a 20Me V Betatron. The tumor was carefully prepared in order to avoid irradiating the duodenum and stomach. Choledochojejunostomy and gastrojejunostomy were performed in almost all of patients with cancer of head of pancreas. In some patients, external radiation was added with a dosage of 3,000 rad by lineacX-ray. After radiotherapy, chemotherapy employing 5-FU or FT-207 was continued including. The survival time after this therapy was varied mainly according to the stages of the tumor. In patients with multiple metastasis to the liver or peritoneal dissemination, no remarkable effects were obtained by this therapy. On the other hand, among 14 patients with localized tumor in the pancreas, 7 survived more than one year and the mean survival time of treated patients was never shorter than that of patients who received resection of the tumor. Most of the treated patients could spend at home until their condition became critical, because by-pass operation could overcome jaundice or the duodenal stenosis and intraoperative radiation could palliate the pain of cancer of pancreas. Tumor effect of intraoperative radiation was confirmed by both of the second laparotomy for twice intraoperative radiation and laparotomy.

Drug Therapy, Combination↗

Virus-induced diabetes mellitus. XX. Polyendocrinopathy and autoimmunity.

Mice infected with reovirus type 1 developed transient diabetes and a runting syndrome. The diabetes was characterized by hyperglycemia, abnormal glucose tolerance tests, and hypoinsulinemia. Inflammatory cells and viral antigens were found in the islets of Langerhans, and virus particles were seen in alpha, beta, and delta cells. The runting syndrome consisted of retarded growth, oily hair, alopecia, and steatorrhea. Inflammatory cells and viral antigens were found in the anterior, but not posterior pituitary. Electron microscopy revealed virus particles in growth hormone (GH)-producing cells and radioimmunoassay showed that the concentration of GH in the blood was decreased. Examination of sera from infected mice revealed autoantibodies that, by immunofluorescence, reacted with cytoplasmic antigens in the islets of Langerhans, anterior pituitary, and gastric mucosa of uninfected mice. Absorption studies and enzyme-linked immunosorbent assays designed to identify the reactive antigens showed that some of the autoantibodies were directed against insulin and others against GH. Reovirus type 3, in contrast to reovirus type 1, did not induce autoantibodies to GH. By use of recombinant viruses, the segment of the reovirus genome responsible for the induction of autoantibodies to GH was identified. Virus containing the S1 gene segment from reovirus type 1, which codes for the sigma 1 polypeptide (i.e., hemagglutinin), infected cells in the anterior pituitary and induced autoantibodies to GH, whereas virus containing the S1 gene segment from reovirus type 3 failed to infect cells in the anterior pituitary and did not induce autoantibodies to GH. We conclude that reovirus type 1 infection can lead to polyendocrinopathy and autoimmunity and that the S1 gene segment is required for the induction of autoantibodies to GH.

Animals↗

Infection of cultured human pancreatic B cells with reovirus type 3.

The capacity of reovirus type 3 to infect insulin-producing B cells was studied in human pancreatic cell cultures. Antibody to reovirus was labelled with fluorescein isothiocyanate and antibody to insulin was labelled with tetramethyl rhodamine isothiocyanate. By using a double-labelled immunofluorescent antibody technique, it was shown that only about 6% of the insulin-containing human B cells in culture became infected when inoculated with unpassaged reovirus type 3. However, by repeated passage of the virus in human pancreatic B cell cultures, the percentage of infected B cells increased to 27%, and the virus titre in cultures rose from 8.0 X 19(4) pfu/ml in the first passage, to 4.9 X 10(6) pfu/ml in the 5th passage. As measured by radioimmunoassay, the intracellular immunoreactive insulin began to decrease at 24 h after infection. This decrease roughly paralleled the increase in virus titre. In contrast, there was relatively little change in immunoreactive insulin in cultures inoculated with unpassaged reovirus type 3. These studies show that the ability of reovirus type 3 to infect human B cells is enhanced by serial passage in human pancreatic cell cultures and that the infection resulted in the destruction of B cells and release of insulin.

Cells, Cultured↗