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Biomedical subjects

M Namba

Publications and source records attributed to M Namba.

At least 253 records · Page 14Linked to original sources

Potentiation of cytotoxic effects of 5-fluorouracil by inosiplex on cancer cells.

The antitumor effect of 5-fluorouracil (5-FU) was significantly enhanced by inosiplex which has been developed as a drug possessing antiviral activity. The enhancement of antitumor effect of 5-FU was demonstrated by experiments both in vitro and in vivo, viz. depression of the colony formation rate in cultures of HeLa cells (an established cell line of human cervical carcinoma), and prolongation of the survival of mice bearing transplanted Ehrlich ascites tumor of murine mammary carcinoma origin. The HeLa cell colony formation was synergistically decreased in the presence of 0.5-2.0 micrograms/ml of 5-FU combined with 100 micrograms/ml of inosiplex. Inosiplex did not cause any appreciable inhibition of cell growth at this concentration when added alone to the culture. The mean duration of survival of tumor-bearing mice was 18.2, 20.3, 31.9 and 47.1 days in the control group and groups receiving inosiplex, 5-FU, or a combination of 5-FU and inosiplex, respectively; hence significantly prolonged in the combined therapy regimen group as compared with the control and the 5-FU treated group (P less than 0.01).

Animals↗

Decreased response of epinephrine and norepinephrine to insulin-induced hypoglycemia in diabetic autonomic neuropathy.

The responses of epinephrine, norepinephrine and other counter-regulatory hormones to insulin-induced hypoglycemia were investigated in 5 diabetics who showed signs of autonomic neuropathy, in 7 age-matched diabetics without autonomic neuropathy and in 7 healthy subjects. The presence of autonomic neuropathy was evaluated by decreased beat-to-beat variation in heat rates during hyperventilation or orthostatic hypotension. Catecholamines were determined by a totally automated plasma catecholamine analyzing system using a two-column system of high performance liquid chromatography. Plasma epinephrine and norepinephrine responses to hypoglycemia in diabetics with autonomic neuropathy were significantly lower than those in diabetics without autonomic neuropathy. Plasma glucagon response in diabetics was apparently attenuated compared to normal controls and there was no significant difference in glucagon response between the two patient groups. Other counter-regulatory hormone responses did not differ among the three groups. The data demonstrate that the responses of plasma epinephrine and norepinephrine to insulin-induced hypoglycemia are impaired in diabetics with autonomic neuropathy.

Adult↗

Abnormal phosphatidylinositol-cycle of platelet membrane in schizophrenia--a preliminary study.

Phosphatidylinositol (PI)-cycle in the platelet membrane was examined in eight untreated patients with psychotic symptoms. A defect of PI-cycle in the transformation from 1,2-diacylglycerol into phosphatidic acid was found in three patients, who were diagnosed as having Schizophrenic Disorders or Schizophreniform Disorder according to the DSM-III criteria. Two out of the three patients were reexamined while undergoing neuroleptic medication, and they showed the same abnormality in PI-cycle. Further studies were required to determine the nature of the abnormality in PI-cycle in the platelets of schizophrenics.

Adolescent↗

Comparison of standard tissue culture, tissue culture plus staining, and direct staining for detection of genital herpes simplex virus infection.

Genital herpes simplex virus infection in women was studied by using conventional tissue culture (TC) virus isolation compared with short-term (24-h) TC on Lab-Tek chamber slides followed by fluorescent-antibody (FA) staining. Three different staining techniques were used after TC: (i) staining with biotin-avidin (TC-BA/FA), (ii) direct FA (TC-FA), and (iii) indirect FA. The TC-BA/FA method showed complete correlation with the TC method. The TC-FA method showed no false-positive results but 31.5% false-negative results compared with the TC method. In contrast, the TC-indirect FA method showed 11.9% false-positive results and 11.7% false-negative results. The direct staining of specimens by the biotin-avidin technique (direct BA/FA) without prior tissue culture showed 37.7% false-positive results and 11.1% false-negative results. The TC-BA/FA technique thus was as sensitive as, but more rapid than, the TC method. The quality of fluorescence was far superior in TC-BA/FA staining as compared with TC-FA or TC-indirect FA procedures. The TC-BA/FA appears to be a valuable technique in laboratory diagnosis of genital herpes infections, especially in clinical situations requiring rapid detection of the virus.

Cells, Cultured↗

Rapid detection of herpes simplex virus in clinical specimens by use of a capture biotin-streptavidin enzyme-linked immunosorbent assay.

A sensitive enzyme-linked immunosorbent capture assay with biotin and streptavidin (capture B/SA ELISA) was developed to detect herpes simplex virus (HSV) antigen. Rabbit anti-HSV antibody (immunoglobulin G fraction) was coated on flat-bottom, irradiated, 96-well polystyrene microtiter plates and served to capture HSV antigen. Clinical specimens from patients with genital herpes were added. Biotin-linked rabbit anti-HSV immunoglobulin G was used as the second antibody. The antigen-antibody complex was detected with alkaline phosphatase-conjugated streptavidin, which linked to the biotin. With clinical specimens, the test had a sensitivity of 95.6% and a specificity of 91.4% when compared with the tissue culture method. The presence of HSV antigen in specimens devoid of infectivity was confirmed by blocking the reaction with unlabeled rabbit and human antibody to HSV. The level of antigen detected by the capture B/SA ELISA did not necessarily correlate with the infectivity titer of the specimens. HSV antigens could be detected by the capture B/SA ELISA when the virus infectivity was destroyed at 37 degrees C, by UV irradiation, or by Triton X-100 treatment, but not when hypochlorite treatment was used. Greater sensitivity was obtained when HSV-1- and HSV-2-specific antibody reagents were used simultaneously in each test. The capture B/SA ELISA provides a relatively rapid method (4.5 h) which is quite sensitive and specific when compared with other non-tissue culture, direct assay methods.

Antigens, Viral↗

Responses of catecholamines and other counterregulatory hormones to insulin-induced hypoglycemia in totally pancreatectomized patients.

Responses of glucagon, catecholamines, and other counterregulatory hormones to insulin-induced hypoglycemia were evaluated in five totally pancreatectomized patients and six normal subjects. In pancreatectomized patients, plasma glucagon, probably of gastric origin, did not change significantly during hypoglycemia. The responses of epinephrine and norepinephrine were delayed but adequate compared with those in normal subjects. The responses of cortisol and GH were almost as great as those in normal subjects. However, plasma glucose levels did not recover from hypoglycemia normally in these patients. These results suggest that glucagon responses are essential to recover from hypoglycemia and that neither epinephrine nor norepinephrine plays a crucial role in the recovery from acute insulin-induced hypoglycemia in totally pancreatectomized patients.

Adult↗

[Potentiation of cytotoxic effects of 5-fluorouracil by inosiplex on cancer cells].

Inosiplex, a 3:1 molarcomplex of N, N-dimethylamino-2-propanol-p-acetamidobenzoate and inosine, which has been reported to exhibit antiviral activity in vitro and in vivo, enhanced cytotoxic effects of 5-fluorouracil (5-FU). Effects of inosiplex on the potentiation of cytotoxicity of 5-FU were investigated in vitro and in vivo. In vitro studies demonstrated that cytotoxic effects of 5-FU on cloning efficiency of HeLa cells were prominently enhanced by inosiplex, while inosiplex alone showed no cytotoxicity at the concentrations examined. Further, the survival time of mice intraperitoneally inoculated with Ehrlich ascites tumor cells was investigated. The mean survival time of mice treated with the combination of 5-FU and inosiplex significantly prolonged as compared with that of control animals or mice treated with inosiplex alone or 5-FU alone. Since inosiplex has been clinically studied as an antiviral agent and proved to be harmless to humans, the present results indicate that a combined administration of 5-FU and inosiplex may be effective in the treatment of human cancers.

Animals↗

Establishment of two chick embryo fibroblastic cell lines.

Chicken helper factor (chf)-negative chick embryo cells (CEC) were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cultured at 41 degrees in a CO2-incubator and are currently in the 400th passage (over 4 years). They were designated as CHCC-OU1. They pile up, and form colonies in soft agar, but do not produce tumors either in the syngeneic chicken or in nude mice. Chf-negative CEC without MNNG treatment were maintained in the same way and are currently in the 350th passage (over 3.5 years). They were designated as SPCC-OU1. They appear normal and form no colony in soft agar. Both cell lines produce avian endogenous leukosis virus of subgroup E.

Animals↗

Establishment and characterization of a human colon carcinoma cell line (KMS-4) from a patient with hereditary adenomatosis of the colon and rectum.

A human colon carcinoma cell line was established from a metastatic lymph node of a patient with hereditary adenomatosis of the colon and rectum (ACR). Cells of this line, designated KMS-4, have been continuously propagated in culture during the past 24 months. The cells growing on the surface of culture dishes showed epithelial features, and, when inoculated into athymic nude mice, produced adenocarcinomas with a morphology similar to that of the original tumor. Electron micrographs showed that the cultured cells have desmosomes and numerous surface microvilli typical of colon epithelium. Chromosomal analysis revealed the cell line to be of human origin with a diploid mode of chromosome number, but the karyotypes examined were all abnormal. Most of the metaphases commonly had such abnormalities as 7p+, 12p+, +13, +16 and 17p+, accompanied by loss of chromosome No. 19 and/or 20, and, interestingly, all the metaphases contained 7p+ and +13. The cells had a log phase doubling time of 48 to 72 h. The cloning efficiency of the cells was 0.06% in the soft agar medium. Neither 12-O-tetradecanoylphorbol-13-acetate nor bile acids enhanced cell proliferation. The cells abundantly secreted CEA protein into the culture medium (700 ng/ml/106 cells during a 48 h period). The present colon carcinoma cell line derived from a genetically defined individual with ACR should prove useful for research in human oncology or genetics.

Adenocarcinoma↗

Decreased level of beta-endorphin-like immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

beta-Endorphin-like immunoreactivity in cerebrospinal fluid(CSF) was observed to decrease in patients with Huntington's disease and dementia due to brain vascular disease. The greatest decrease was seen in patients with presenile and senile dementia of Alzheimer type(SDAT). The immunoreactivity significantly correlated with psychological functions when examined using a dementia rating scale (r=0.51, p less than 0.01, for all dementia, r=0.65, p less than 0.02, for only SDAT). These results suggest that a B-endorphin-like substance may be related in the pathophysiology of dementia.

Adult↗

Glucose dependent stimulation by prostaglandin D2 of glucagon and insulin in perfused rat pancreas.

Effects of prostaglandin D2 on pancreatic islet function in perfused rat pancreas were examined in comparison with those of prostaglandin E2, which has hitherto been suggested to be a modifier of pancreatic hormone release. In the presence of 2.8 mM glucose, only glucagon release was strongly stimulated by 14 microM of prostaglandin D2, while release of both glucagon and insulin was augmented by 14 microM of prostaglandin E2. When the glucose concentration was elevated to 11.2 mM, insulin release was accelerated by 14 microM of prostaglandin D2 but there was no effect upon glucagon release. Again, release of both glucagon and insulin was augmented by 14 microM of prostaglandin E2 in the presence of 11.2 mM of glucose. The regulation of glucagon and insulin release through prostaglandin D2 is apparently adapted to glycemic changes, and may be a physiological modulator of pancreatic islet function.

Animals↗

Platelet aggregation response in schizophrenia and prostaglandin E1.

Platelet aggregation response to various stimulants was examined in 18 unmedicated schizophrenic patients, 13 medicated patients, and 13 control subjects. Platelet aggregation response to epinephrine decreased only in unmedicated schizophrenic patients. Clinical improvement in seven patients after neuroleptic medication was significantly correlated with an increase in platelet aggregation response to arachidonic acid, and nonsignificantly to epinephrine, dopamine, and serotonin. The inhibitory effect of prostaglandin E1 on platelet aggregation response to adenosine diphosphate was investigated in seven unmedicated schizophrenic patients, six medicated patients, and eight controls. The inhibitory effect of prostaglandin E1 on platelet aggregation response to adenosine diphosphate was significantly reduced in all unmedicated schizophrenic patients. Neuroleptic medication had some effect in normalizing aberrant sensitivity to prostaglandin E1 in those patients, although acute medication induced an adverse reaction in the controls.

Adenosine Diphosphate↗

Inhibition of pancreatic exocrine secretion and augmentation of the release of gut glucagon-like immunoreactive materials by intraileal administration of bile in the dog.

The effect of intraileal instillation of bile, a stimulant of gut glucagon-like immunoreactive materials (gut GLI), on secretin-stimulated pancreatic secretion was examined in anesthetized dogs. Intraileal bile significantly inhibited the flow rate of secretin-stimulated pancreatic secretion. The inhibition of pancreatic secretion was accompanied by an elevation of plasma concentration of gut GLI. Taking the inhibitory effect of glucagon on pancreatic exocrine secretion into consideration, it could be reasonably postulated that gut GLI may be a mediator of bile-induced ileal inhibition of pancreatic exocrine function.

Animals↗

Modulation by prostaglandin D2 of glucagon and insulin secretion in the perfused rat pancreas.

Effects of prostaglandin (PG) D2 on insulin and glucagon secretion from perfused rat pancreas were examined. In the presence of 2.8 mM glucose, only glucagon release was strongly stimulated by 14 microM of PGD2. When the glucose concentration was elevated to 11.2 mM, insulin release was accelerated by 14 microM of PGD2 but there was no effect upon glucagon release. Both glucagon and insulin releases induced by 19 mM arginine with PGD2 were not different from those without PGD2 in the presence of 2.8 mM glucose. But in the presence of 11.2 mM glucose, glucagon release induced by 19 mM arginine was augmented by 14 microM PGD2. Since the distribution of PGD2 has been reported to be in neuroendocrine organs, these results suggest that PGD2 is a possible candidate as a modulator in the neural control of endocrine pancreas.

Animals↗

In vitro studies on potentiation of cytotoxic effects of anticancer drugs by interferon on a human neoplastic cell line (HeLa).

Experiments were performed to ascertain whether the antitumor effect of various anticancer drugs might be enhanced by interferon, using cultures of HeLa cells originating from a human carcinoma of the uterine cervix. The effects of drugs were assessed by counting cell colonies formed in culture. The drugs studied included 4 metabolic antagonists: cytosine arabinoside (Ara-C), 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP) and methotrexate (MTX), 7 antibiotics: aclacinomycin (ACM), adriamycin (ADM), actinomycin D (ACD), cycloheximide, mitomycin C (MMC), peplomycin (PEP) and puromycin; 2 alkylating agents: nimustine hydrochloride (ACNU) and melphalan, and 3 other drugs, vincristine (VCR), cisplatin (CDDP) and hydroxyurea (HU). Interferon was a preparation of the beta-type produced by human fibroblasts. A specific additive or synergistic potentiation of the cytotoxic effect by concomitant application of interferon was observed with PEP, ACNU, ACM, CDDP, 5-FU and ADM; the drug concentration given a 50% inhibition of cell growth was reduced by one-half or more in cultures with the combination of interferon and these drugs. The treatment of cells with interferon alone caused only 10-30% inhibition of cell proliferation.

Alkylating Agents↗

Interferon potentiates cytotoxic effects of 5-fluorouracil on cell proliferation of established human cell lines originating from neoplastic tissues.

A potentiation of the cytotoxic effects of 5-fluorouracil (5-FU) on human tumor cells by interferon 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). The normal human cell strain used was WI-38 (normal human lung fibroblasts). The cytotoxic effects were determined by colony formation for HeLa, MCF-7, WI-38 CT-1 and WI-38 cells, and by cell growth for KMM-1 and Raji cells. 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 2 agents were observed in MCF-7 and WI-38 cells. The present results indicate a possibility that interferon and 5-FU can mutally reduce the amount of the other needed to treat cancer patients.

Cell Line↗

Effect of intraluminal bile or bile acids on release of gut glucagon-like immunoreactive materials in the dog.

The true biological role of gut glucagon-like immunoreactive materials (gut GLI) is still unknown, although the stimulatory effect of intraluminal nutrients on the secretion of gut GLI has been described. The present authors, using the canine intestinal loop prepared from the terminal portion of the ileum, investigated how gut GLI would respond to digestive juice or its components. When bladder bile collected from another dog and diluted to 10% in saline was instilled into canine ileal loop, gut GLI in a branch of regional mesenteric vein was elevated significantly. Cholic acid suspended in saline (0.25 g/50 ml) also stimulated gut GLI secretion in the similar pattern to that of bile administration. On the other hand, 154 mM NaHCO3 which is a major inorganic component of pancreatic juice did not affect the venous level of gut GLI.

Animals↗