PubMed Health⌕ Search

Biomedical subjects

M Namba

Publications and source records attributed to M Namba.

At least 271 records · Page 15Linked to original sources

Effects of subchronic treatment of methamphetamine haloperidol on the rat brain levels of GABA, glutamate and aspartate.

Centrally active amino acids (GABA, glutamate, aspartate) were assayed enzyme-fluorometrically in five brain regions of the rat after a 16-day administration of methamphetamine (2.5 mg/kg, i.p.) and haloperidol (2.5 mg/kg, i.p.), or both agents together. Methamphetamine caused no statistically-significant changes in the GABA contents in any brain areas, a significant decrease in the glutamate content of the striatum, hippocampus and midbrain and an increase in the aspartate content of the hypothalamus. Haloperidol treatment resulted in no changes in the GABA content, a significant decrease in the glutamate content of the striatum and a significant increase in the aspartate content in the frontal cortex. The treatment with both agents caused a significant decrease in the GABA content of the hypothalamus. The combined administration normalized a lowering of the glutamate levels in the striatum caused by methamphetamine and haloperidol, respectively, and increased the level of aspartate in the hypothalamus caused by methamphetamine and in the frontal cortex caused by haloperidol.

Animals↗

Differential growth requirements of serum factors (bovine serum albumin and low density lipoprotein) for normal and transformed human cells in a serum-free culture.

Serum-free culture is a useful method for identifying the growth requirements of normal cells of human origin and comparing them to the requirements of transformed human cells. We examined differential growth requirements of serum factors (bovine serum albumin (BSA) and low density lipoprotein (LDL) on normal (HEL), Co-60 gamma ray-transformed (CT-1) and 4-nitroquinoline 1-oxide-transformed (SUSM-1) human fibroblast cells in the absence of serum. A decreased requirement for serum was closely related to a decreased requirement for BSA in both types of transformed cells. The growth rate and saturation density of HEL and CT-1 cells grown in serum-free medium supplemented with the optimal concentrations of BSA were almost equal to the rates of cells grown in serum-supplemented medium. When BSA alone was added to the serum-free medium it did not support the continuous growth of SUSM-1 cells because of cellular detachment. An addition of LDL to serum-free cultures not only promoted the moderate growth of HEL cells, it promoted the continuous growth of SUSM-1 cells as well. In contrast, LDL was not required for the optimal growth of CT-1 cells. Transformed human cells specifically had reduced quantitative and qualitative growth requirements for one or more serum factors.

Blood↗

Prevalence of diabetic retinopathy and distribution of its severity among patients of a university clinic of diabetes in Osaka.

We have been following longitudinal changes of diabetic retinopathy by periodic fundoscopy in patients at our out-patient clinic for diabetes mellitus. In this study, we reviewed the prevalence of diabetic retinopathy and the distribution of its severities. Funduscopic examinations for retinopathy were performed on 242 patients. They ranged in age from 13 to 84 years (52.9 +/- 0.9, mean +/- s.e.). Duration of diabetes ranged from 1 to 31 years (10.7 +/- 0.4). Forty patients were treated with diet alone, 112 with oral hypoglycemic agents and 90 with insulin administration. No retinopathy was found in 83 patients (34%), background retinopathy in 113 (47%), preproliferative retinopathy in 24 (10%) and proliferative retinopathy in 17 (7%). Five patients (2%) were blind. Twenty-seven patients (60%) of 45 with a less than 5-year duration of diabetes were apparently without retinopathy, while the incidence of proliferative retinopathy increased in proportion to the duration. Fasting plasma glucose and glycosylated hemoglobin levels were higher in the patients with proliferative retinopathy than in any other group. All of the blind patients had a long history of untreated diabetes. Whether diabetic control assessed by glycosylated hemoglobin influences the progression of retinopathy could not be demonstrated by a 2-year observation. Further analysis based on a longer duration is needed in this respect.

Adolescent↗

[Potentiation of the cytotoxic effects of various anticancer drugs by interferon on human neoplastic cells (HeLa) in culture].

Potentiation of the cytotoxic effects of various anticancer agents by interferon on human malignant cells was examined in culture. The human neoplastic cells used were HeLa cells derived from uterine cervical cancer. The interferon was produced in human diploid fibroblasts treated with Poly I:C. Anticancer drugs examined were as follows; antibiotics (aclacinomycin, actinomycin D, adriamycin, cycloheximide, mitomycin C, peplomycin, puromycin), antimetabolites (cytosine arabinoside, 5-fluorouracil, 6-mercaptopurine, methotrexate), alkylating agents (ACNU, melphalan), and others (cisplatin, hydroxyurea, vincristine). The cytotoxic effects were determined by colony formation. Our results demonstrated that interferon potentiated significantly the cytotoxic effects of peplomycin, aclacinomycin, cisplatin, 5-fluorouracil, and adriamycin on HeLa cells. The present results indicate that a combined administration of interferon and these drugs may be effective in the treatment of human cancers.

Aclarubicin↗

Immunocytochemical demonstration of rabbit ribonuclease and phospholipase A2 by the peroxidase-antiperoxidase technique in professional phagocytes (pulmonary alveolar macrophages and granulocytic and mononuclear peritoneal exudate cells) and in glycol methacrylate sections of dermal tuberculous (BCG) lesions.

Acid-acting (pH 6-7) (presumably lysosomal) ribonuclease and neutral-acting (pH 7-8) calcium-dependent phospholipase A2 (presumably the enzyme releasing arachidonic acid from membrane phospholipids) were demonstrated by the peroxidase-antiperoxidase (PAP) immunocytochemical technique in rabbit professional phagocytes: pulmonary alveolar macrophages (AM), oil-induced peritoneal exudate macrophages (M phi) and glycogen-induced peritoneal exudate polymorphonuclear granulocytes (PMN). All three cell types stained positively with antisera to purified rabbit lung RNase and purified rabbit granulocyte phospholipase A2. The RNase and phospholipase A2 were also demonstrated by the PAP technique in the activated macrophages and granulocytes present in tissue sections of tuberculous (BCG) lesions. The intensity of staining of these two enzymes in individual macrophages did not change appreciably as the BCG lesions developed and regressed, but there were more macrophages rich in both enzymes when the lesions reached their peak size at 21 days. When the anti-RNase serum was fractionated by immunoabsorbent chromatography, the anti-delta RNase serum fraction stained exudate M phi and PMN better than AM; and the anti-beta RNase fraction stained AM better than M phi and PMN. Similar to isolated phagocytes, tissue granulocytes stained best with the anti-delta fraction; and activated tissue macrophages stained best with the anti-beta fraction. Thus, macrophages and granulocytes contain two types of RNase, beta and delta; and the beta RNase is associated with macrophage activation.

Animals↗

B-cell differentiation antigen expressed on a human myeloma cell line (KMM-1).

KMM-1 is a human multiple myeloma cell line previously shown to express plasma cell phenotypes. Hybridomas against this cell line were produced by fusing spleen cells from hyperimmunized BALB/c mice with X63-Ag8-653 mouse myeloma cells. One monoclonal antibody derived from this fusion, termed 33-3, reacted with all the B-cell stages except the pre-B-cell stage. Both myeloma cells from patients and those from KMM-1 cells were reactive at the same maximum dilution of this antibody. No reactivity was seen with cells of T-lymphocyte origin, platelets, red blood cells, monocytes or granulocytes. The 33-3 antibody was unable to detect any specific marker distinguishing cultured myeloma cells from those that could not be cultured in vitro.

Animals↗

Establishment and characterization of a human myeloma cell line (KMM-1).

A new cell line (KMM-1) was established from a subcutaneous plasmacytoma of a 62-year-old male with multiple myeloma. Immunological studies indicated that cultured cells were derived from the same clone of myeloma cells in vivo: smeared cells were stained with fluorescein-conjugated globulin of antisera monospecific to lambda-chain, and lambda-chains in the cell extracts and in culture media were identical to the Bence-Jones protein found in the patient's urine. The cell line grew in suspension with prominent nucleoli and rough endoplasmic reticulum. Cells had the karyotype of 47, X, -Y, Iq+, -2, +t(1:2) (cen:cen), +7, 12q+, 14q+, +mar and carried no Epstein-Barr virus-determined nuclear antigen. Surface markers were as follows; E rosette (-), IgG Fc receptor (-), C3 receptor (-), S-Ig (+), TdT (-), asialo-GM1 (-). The reasons for the successful establishment of the myeloma cell line are discussed.

Bence Jones Protein↗

Analysis of therapeutic effect in experimental chemoimmunotherapy for rat ascites tumor.

The lyophilized, squalene-treated Nocardia rubra cell wall skeleton (N-CWS) was confirmed to produce tumoricidal peritoneal macrophages resulting in inhibition of tumor growth when injected locally into the syngeneic ascites fibrosarcoma, AMC 60 in ACI/N rats. Furthermore, N-CWS was found to augment therapeutic effect when administered repeatedly after a single local injection of mitomycin-C (MMC). To analyze the effects, various in vitro cytolysis assays were performed using N-CWS-activated peritoneal macrophages. When tumor target cells were exposed in vitro to MMC, the resulting cytolysis in the presence of N-CWS-activated macrophages was similar to cytolysis of intact target cells. On the other hand, when N-CWS-activated macrophages were exposed to MMC, the tumoricidal activity was lost significantly, depending on exposure to MMC. When tumor target cells and N-CWS-activated macrophages were simultaneously exposed to MMC, tumor-cell cytolysis was strikingly depressed. In the final experiment, combined injection of MMC and N-CWS into the ascites tumor resulted in remarkable increases not only in peritoneal exudate cell number, but also in in vitro tumoricidal activity of peritoneal macrophages as compared to those induced by either agent alone. In addition, the production of tumoricidal macrophages by IP injection of MMC alone was also noticeable, as described previously. These results possibly indicate the involvement of macrophage activation in induction of therapeutic effect in chemoimmunotherapy.

Adjuvants, Immunologic↗

In vitro tumor cell killing by peritoneal macrophages from mitomycin C-treated rats.

The local cellular response induced by intraperitoneal injection of mitomycin C was examined in terms of cell-mediated cytotoxicity for tumor cells. An in vitro cytolysis assay involving 125I-iododeoxyuridine-labeled tumor target cells revealed that treatment of normal ACI/N rats (200 g) with a single intraperitoneal injection of mitomycin C (50, 100, or 200 micrograms) induced tumoricidal macrophages in the peritoneal cavity. The tumoricidal activity was dependent on the dose of mitomycin C injected and it was detectable as early as 1 day after the intraperitoneal injection of mitomycin C. In addition to the increased tumoricidal activity, the functional activities of the peritoneal macrophages were found to be increased with respect both to uptake of 2-deoxy-D-glucose and to phagocytosis of latex beads. Additional experiments excluded the possibility that the tumor cell cytolysis was the result of direct cytotoxicity by mitomycin C that might have been incorporated in the peritoneal macrophages or of nutrient depletion in the medium during the cytolysis assay. Furthermore, endotoxin contamination of the mitomycin C, which might have produced the activated macrophages, was not detected. The mechanism by which mitomycin C injected intraperitoneally induced the tumoricidal macrophages locally remains uncertain; however, it is possible also in clinical situations.

Animals↗

Abnormal platelet aggregation response in Huntington's disease.

Platelet aggregation response to epinephrine, dopamine, serotonin, adenosine diphosphate, arachidonic acid, and collagen was examined in seven patients with Huntington's disease and nine of their relatives. All patients, except for two cases that were in terminal states, showed enhanced response to all the stimulants, especially to dopamine and epinephrine. The platelet aggregation response in many relatives also deviated from the normal limit. The relationship between platelet aggregation abnormality in Huntington's disease and the pathophysiology of the disease was discussed from the view of a generalized membrane defect hypothesis in Huntington's disease, and of disturbed cathecholamine metabolism, both in the CNS and periphery. A possibility that platelet aggregation response examination will be a useful screening test of offspring at risk was proposed.

Adenosine Diphosphate↗

Effects of feeder layers made of human, mouse, hamster, and rat cells on the cloning efficiency of transformed human cells.

The effect of feeder layers on cloning efficiency of transformed human cells was investigated. Embryonic human skin or lung fibroblasts; adult human skin fibroblasts; early passage cells from embryos of mouse, rat, and hamster; established mouse cell lines; 3T3 and 10T1/2 were used as feeder layers after they were lethally exposed to Co-60 gamma-rays at 3,000 rad. As test cells to study the effect of feeder layers on cloning efficiency, WI-38 CT 1 cells transformed in vitro by Co-60 gamma-rays and HGC cells cultured from a human gastric cancer were used. The effect of feeder layers on the cloning efficiency of the test cells was dependent on cell density of feeder layer cells, sources of the feeder layer cells, and kinds of test cells. An optimal density of feeder cells produced cloning efficiencies 3 to 15 times higher than in cultures without a feeder layer. Generally, high density of cells in feeder layers decreased the cloning efficiency of the test cells, presumably owing to contact inhibition of growth and depletion of essential nutrients by the feeder layer cells. Regarding the effect of the feeder layers made of human fibroblasts, there were no significant differences in population doubling levels; tissue origins of fibroblasts, or fibroblasts derived from normal individuals, patients with cancer, or with a genetically high familial incidence of cancer, hereditary adenomatosis of the colon and rectum.

Animals↗

Plasma glutamate decarboxylase activity in neuropsychiatry.

Plasma glutamate decarboxylase (GAD) activity was measured in patients with endogenous psychoses and neurologic diseases. Unmedicated schizophrenic patients showed no difference in plasma GAD levels compared to controls. Administration of neuroleptics together with anticholinergic agents increased plasma GAD activity in schizophrenic patients. Compared to controls, patients with major depression and bipolar illness showed significantly lower GAD activity. No effect of antidepressants and minor tranquilizers on plasma GAD activity was found. Relatively lower GAD activity was shown in neurotic patients. The enzyme activity in plasma of patients with Huntington's chorea (HC) was lower than control levels. The plasma GAD concentrations correlated with cerebrospinal fluid concentrations in five HC patients.

Adolescent↗

Effect of epidermal growth factor on collagen formation in liver-derived epithelial clone cells.

Biochemical and morphological studies were made on the effect of epidermal growth factor (EGF), isolated from male mouse submandibular gland, on collagen formation in clone RLC-18(4) epithelial cells from rat liver. EGF did not affect the number of these cells. EGF in the range of 0.5-500 ng/ml caused a dose-dependent increase in the content of hydroxyproline. It also increased the content of acidic glycosaminoglycans (AGAG), which are thought to be closely related to the formation of collagen fibers, and increased the activity of glutamine glucose-6-phosphate aminotransferase, an enzyme for AGAG synthesis but not that of N-acetyl-beta-glucosaminidase, an enzyme for AGAG degradation. It has no significant effect on the protein content of the cells. Studies on the effect of actinomycin D indicated that EGF may enhance de novo synthesis of hydroxyproline in liver epithelial cells and also that of glutamine glucose-6-phosphate aminotransferase, thus increasing the AGAG content of the cells. Antibody to EGF largely blocked collagen formation in the cells, even in the absence of EGF, indicating that EGF or EGF-like substances in the serum may affect collagen formation. In rat liver fibroblasts, EGF had little effect on collagen formation. These results show that EGF may act as a regulatory factor in collagen formation in liver epithelial cells, but not liver mesenchymal cells, in vitro.

Animals↗

Various phenotypes of diabetes mellitus at ultimate outcome of acutely developed diabetic state induced by viral infection.

For 4 to 8 years we followed up 3 diabetic patients in whom the onset of diabetes seemed to be closely related to the well-documented Epstein-Barr virus infection (Case 1) or Coxsackie B4 virus infection (Case 2, 3). Although all developed acute ketosis-prone diabetes in the convalescent stage of the viral infections, the subsequent clinical courses were quite different from each other. Case 1 has remained consistently insulin-dependent and associated with positive islet cell antibody, gastric parietal cell antibody, thyroglobulin hemoagglutinating antibody and thyroidal microsomal hemoagglutinating antibody. Case 2 restored normal glucose tolerance. Case 3 has become noninsulin-dependent diabetes mellitus after a 6 year interval. Thus, it is reasonably presumed that virus could be responsible for the occurrence of different phenotypes of diabetes.

Acute Disease↗

Combined effects of 5-fluorouracil and interferon on proliferation of human neoplastic cells in culture.

The growth inhibitory effects of the combination of 5-fluorouracil (5-FU) and human fibroblast interferon on human neoplastic cell lines and normal human fibroblasts were examined. The neoplastic cell lines used were HeLa (cervical carcinoma), MCF-7 (mammary carcinoma), WI-38 CT-1 (embryonic lung fibroblasts transformed in culture by 60Co gamma-ray irradiation), KMM-1 (myeloma), and Raji (Burkitt's lymphoma). The normal human cell line used was WI-38. The growth inhibitory effects were determined by measuring colony formation for HeLa, MCF-7, WI-38 CT-1, and WI-38 cells, and by measuring cell growth for KMM-1 and Raji cells. Each cell line showed different sensitivities to 5-FU or interferon. The combination of 5-FU and interferon showed synergistic inhibitory effects on the growth of HeLa, WI-38 CT-1, KMM-1, and Raji cells. Neither synergistic nor additive growth inhibitory effects of the combination of 5-FU and interferon were observed in MCF-7 and WI-38 cells.

Animals↗

[Combined effects of 5-fluorouracil and interferon on proliferation of human neoplastic cells in culture].

Potentiation of the cytotoxic effects of 5-fluorouracil (5-FU) by interferon on human tumor cells was examined. The human neoplastic cell lines used were HeLa (uterine cervical cancer), MCF-7 (mammary cancer), WI-38 CT-1 (embryonic lung fibroblasts transformed in culture by Co-60 gamma-ray irradiation), KMM-1 (myeloma), and Raji (Burkitt's lymphoma). As a normal human cell strain, WI-38 (embryonic lung fibroblasts) was used. The cytotoxic effects were determined by colony formation. Each cell line was different in sensitivity to interferon or 5-FU. Interferon potentiated synergistically the cytotoxic effects of 5-FU on HeLa, WI-38 CT-1, and KMM-1 cells. In the case of Raji cells, the cytotoxic effects of the combination of interferon and 5-FU were additive. Neither synergistic nor additive lethal effects of the combination of the two agents were observed in MCF-7 and WI-38 cells. The present results indicate a possibility that a combined treatment with interferon and 5-FU may be effective in certain types of human cancers.

Cell Division↗