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Biomedical subjects

M Namba

Publications and source records attributed to M Namba.

At least 217 records · Page 12Linked to original sources
PubMed1988

Glucagon-like peptide-1 (7-36 amide): a potent glucagonostatic and insulinotropic hormone.

Glucagon-like peptide-1 (GLP-1) (1-37) and the fraction derived from it, GLP-1 (7-36 amide), are peptides encoded by the preproglucagon gene and possibly co-secreted with enteroglucagon. When added at a 25-nM concentration, GLP-1 (7-36 amide) decreased the release of glucagon from the perfused rat pancreas from 68.5 +/- 9.0 pg/ml to 41.5 +/- 11.5 pg/ml at 2 min in the presence of 11.2 mM glucose (P less than 0.01), and from 196.0 +/- 32.5 pg/ml to 87.0 +/- 23.5 pg/ml at 5 min in the presence of 2.8 mM glucose (P less than 0.05). Insulin levels increased from 12.6 +/- 3.0 microU/ml to 48.9 +/- 14.0 microU/ml at 10 min in the presence of 11.2 mM glucose (P less than 0.05) and from 2.0 +/- 0.4 microU/ml to 8.2 +/- 2.3 microU/ml at 2 min in the presence of 2.8 mM glucose (P less than 0.05). Glucagon and insulin release were not affected significantly by GLP-1 (1-37), irrespective of glucose concentration. We suggest that GLP-1 (7-36 amide) rather than enteroglucagon may be the true physiologic gut hormone and that it may act as 'incretin' in the enteroinsular axis. We suggest further that the glucagonostatic and insulinotropic activities of this peptide are unique and might be important in islet-cell function.

Animals↗
PubMed1988

Trophic effect of glucagon-(1-21)-peptide on the isolated rat ileal mucosal cells.

The trophic effect of glucagon-(1-21)-peptide on rat ileal epithelial cells was studied in vitro. Glucagon-(1-21)-peptide stimulated [3H]thymidine incorporation of mucosal cells significantly in a dose-dependent manner. Then glucagon-related peptides which have common sequences with glucagon-(1-21)-peptide were also tested. The biological potencies to augment [3H]-thymidine uptake were closely related with their amino-acid residues of N-terminal region. The result suggests that the N-terminal amino-acid sequence of glucagon molecule plays an important role in intestinal cell growth.

Amino Acid Sequence↗
PubMed1988

Multi-step neoplastic transformation of normal human fibroblasts by Co-60 gamma rays and Ha-ras oncogenes.

As reported previously (Namba et al., 1985; Namba, 1985), normal human fibroblasts were transformed into immortal cells with abnormal karyotypes by Co-60 gamma-ray irradiation. These immortally transformed cells (KMST-6) showed no clonability in soft agar and were not tumorigenic. However, by treatment with Ha-ras oncogenes derived from a human lung carcinoma or Harvey murine sarcoma virus, the KMST-6 cells acquired elevated clonability in soft agar and transplantability in nude mice. All the tumors produced grew progressively without showing regression and killed the mice. The tumors were also serially transplantable into other mice. The Ha-ras oncogene alone did not convert normal human fibroblasts into either immortal or tumorigenic cells. Our current data suggest that gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to chromosome aberrations and immortality, and the Ha-ras oncogene played a role in the progression of the immortally transformed cell population to a neoplastic one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.

Cell Line↗
PubMed1988

Exaggerated insulin secretory response in patients with insulinomas to midaglizole, a drug with alpha 2-adrenergic blocking activity.

Midaglizole is a new alpha 2-adrenergic blocking agent which increases insulin release from normal pancreatic islets. We studied its effect in four patients with insulinomas. In three patients oral administration of 150 mg of midaglizole caused a large increase in serum insulin and a corresponding decrease in plasma glucose. The magnitude of the response cannot exclude the possibility that midaglizole has direct beta cell stimulatory activity. Two of the three patients had operations, and their insulin responses to midaglizole became normal after removing the tumours. In contrast, midaglizole did not stimulate insulin secretion in the fourth patient. A midaglizole stimulation test might be useful in screening patients with insulinomas.

Adenoma, Islet Cell↗
PubMed1988

Fibroblasts of two patients with trisomy 18 show 1.5-fold increase in peptidase A activity over normal human diploid fibroblasts.

Peptidase A (Pep A) activity assigned to chromosome 18q23 was biochemically examined in fibroblasts cultured from two patients with trisomy 18 and in fibroblasts derived from normal individuals. The trisomy 18 fibroblasts showed approximately a 1.5-fold increase in Pep A activity over that of the control fibroblasts. Agar gel electrophoretic analysis revealed no detectable differences in the electrophoretic mobility and isoenzyme patterns of Pep A between the trisomy 18 fibroblasts and normal ones. The present results show the trisomy 18 fibroblasts to be suitable for study of the gene dosage effect of Pep A.

Aspartic Acid Endopeptidases↗
PubMed1988

Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and minute virus of mice.

Morphologically altered and established human fibroblasts, obtained either by 60Co gamma irradiation, treatment with the carcinogen 4-nitroquinoline 1-oxide, or simian virus 40 (SV40) infection, were compared with their normal finite-life parental strains for susceptibility to the autonomous parvoviruses H-1 virus and the prototype strain of minute virus of mice (MVMp). All transformed cells suffered greater virus-induced killing than their untransformed progenitors. The cytotoxic effect of H-1 virus was more severe than that of MVMp. Moreover, the level of viral DNA replication was much (10- to 85-fold) enhanced in the transformants compared with their untransformed parent cells. Thus, in this system, cell transformation appears to correlate with an increase in both DNA amplification and cytotoxicity of the parvoviruses. However, the accumulation of parvovirus DNA in the transformants was not always accompanied by the production of infectious virus. Like in vitro-transformed fibroblasts, a fibrosarcoma-derived cell line was sensitive to the killing effect of both H-1 virus and MVMp and amplified viral DNA to high extents. The results indicate that oncogenic transformation can be included among cellular states which modulate permissiveness to parvoviruses under defined growth conditions.

4-Nitroquinoline-1-oxide↗
PubMed1987

Monoclonal antibodies against human oral squamous cell carcinoma reacting with keratin proteins.

Two mouse monoclonal antibodies (MoAbs), B10 and 1H5, were generated by fusing mouse myeloma NS-1 cells with spleen cells from a BALB/c mouse immunized with Ueda-1 cells derived from human squamous cell carcinoma (SCC) of the floor of the mouth. Immunohistochemical analysis revealed that these MoAbs recognize the filamentous components of cytoplasm which were protein in nature. While the pattern of antigen distribution in various cell lines was not cell-type specific, reactivity of these antibodies with tissue sections was informative. MoAb 1H5 was preferentially reactive with well-differentiated squamous cell carcinoma, however, reaction with adenocarcinoma was observed infrequently. This antibody also preferentially reacted with the spinous layer of normal stratified squamous epithelium. MoAb B10, however, was reactive with nonepithelial tissues as well as with epithelial ones, and its level of binding bore no relationship to the grade of histologic malignancy. SDS-PAGE and Western blotting analysis, using cytokeratin extracts of Ueda-1 cells and human epidermis, demonstrated that MoAb B10 reacted with a wide range of keratin proteins of 65-67K, 58K, 56.5K, 56K, 52K, 50K, 48K, 45K, 40K, 38K, 36K, and 34K molecular weight (MW), while MoAb 1H5 reacted with keratin proteins of 65-67K, 58K, 56.5K, 56K, 52K, 48K, and 34K MW. These results suggest that MoAb 1H5 may recognize keratin subfamilies related to squamous differentiation, whereas MoAb B10 recognizes a wide range of keratin proteins, and may even react with other kinds of intermediate filament proteins (IFPs).

Antibodies, Monoclonal↗
PubMed1987

Presenile dementia combined with amyotrophy: a review of 34 Japanese cases.

Thirty-four Japanese cases exhibiting presenile dementia combined with amyotrophy were reviewed with four case reports. The clinical feature of dementia was generally unspecific and could not be clearly diagnosed as Pick's disease or Alzheimer's disease. But most of these patients did not exhibit manifest visual agnosia or apraxia suggesting 'posterior dementia'. Brain CTs showed mild diffuse atrophy with non-circumscribed fronto-temporal accentuation. PSD (periodic synchronous discharge on EEG) as seen in Creutzfeldt-Jakob disease (CJD) was not noted in any of these cases. Although individual neurological findings were not contradictory to amyotrophy lateral sclerosis (ALS), the clinicopathologic findings, on the whole, could be regarded as indicative of an atypical spinal progressive muscular atrophy. The brain pathology lacked specific changes. A mild to moderate degree of glial proliferation, subcortical gliosis and a moderate spongy state of the upper cortical layers were seen mainly in the fronto-temporal area. Nigral degeneration was observed in half of the cases. No Pick's cells, Pick's balls, Alzheimer's neurofibrillary changes or senile plaques were observed except in two cases, in whom it could be regarded as physiological. Brain weight was lighter than that of normal Japanese but heavier than that of Pick's disease, Alzheimer's disease or CJD. The brain pathology was similar to that of progressive subcortical gliosis. We have concluded that the disease under discussion might be a new disease entity.

Amyotrophic Lateral Sclerosis↗
PubMed1987

Comparison of major cytoskeletons among normal human fibroblasts, immortal human fibroblasts transformed by exposure to Co-60 gamma rays, and the latter cells made tumorigenic by treatment with Harvey murine sarcoma virus.

Immortally transformed human fibroblasts in general acquire an epithelial shape, while normal human fibroblasts demonstrate a spindle-shaped feature. In order to investigate this difference, three types of major cytoskeletal elements, namely, F-actin, tubulin, and vimentin of immortal human fibroblasts were morphologically compared with those of normal human fibroblasts. As a result, a significant difference was observed in the distribution and in the number of F-actin fibers between immortal and normal fibroblasts. The cells of three immortally transformed fibroblast lines, KMST-6, WI-38 VA-13, and SUSM-1, showed a striking reduction in the number, and an altered pattern of organization, of actin fibers. On the other hand, in the normal fibroblasts, actin fibers ran parallel to each other along the long axis of the cells. Tubulin and vimentin showed no significant difference between the immortal and normal cells. Our present data show that the morphological changes seen in the immortally transformed cells are due to the disorganization and the decrease in number of actin fibers. Interestingly, both the immortal cells (KMST-6), which were not tumorigenic, and the Harvey murine sarcoma virus-transformed KMST-6 cells, which were tumorigenic and demonstrated an enhanced expression of the ras gene, revealed an overall similarity in the organization pattern and the number of actin fibers. These findings seem to indicate that the immortally transformed cells have already acquired some cancer characteristics.

Actins↗
PubMed1987

Hyaluronate synthetase inhibition by normal and transformed human fibroblasts during growth reduction.

To establish the relation of glycosaminoglycan synthesis to cell proliferation, we investigated the synthesis of individual glycosaminoglycan species by intact cells and in a cell-free system, using normal and transformed human fibroblasts under differing culture conditions. Reducing serum concentration brought about a marked decline in the synthesis of hyaluronate (HA) as well as cell proliferation on both normal and transformed cells. Both HA synthesis and proliferation decreased with increasing cell densities markedly (in inverse proportion to cell density) in normal cells but gradually in transformed cells. This noticeable congruity of the changes in HA synthesis and proliferation indicates that the change in HA synthesis is related primarily to cell proliferation rather than to cell density or cellular transformation. Examination of HA synthesis in a cell-free system demonstrated that the activity of HA synthetase also fluctuated in conjunction with cell proliferation. Furthermore, growth-reduced cells (except crowded transformed cells) inhibited cell-free HA synthesis and this inhibition was induced coincidentally with a decrease in both HA synthetase activity and proliferation. These findings suggest that the change in HA synthesis is significant in the regulation of cell proliferation.

Cell Division↗
PubMed1987

Typing of herpes simplex virus by capture biotin-streptavidin enzyme-linked immunosorbent assay and comparison with restriction endonuclease analysis and immunofluorescence method using monoclonal antibodies.

A sensitive enzyme-linked immunosorbent capture assay using biotin and streptavidin (capture B/SA ELISA) was developed using type-specific monoclonal antibodies for typing of herpes simplex virus. Rabbit anti-herpes simplex virus immunoglobulin G was used as the capturing antibody, and biotin-linked type-1-specific mouse monoclonal antibody or rabbit type-1- or type-2-specific polyclonal antibody served as the detecting antibody. The captured antigen was detected by an ELISA with alkaline phosphatase-conjugated streptavidin, which reacted with biotin molecules on the detector antibody. The capture B/SA ELISA was compared with other methods for efficiency and reliability in typing. Results obtained by restriction endonuclease digestion of the radiolabeled viral genome were used to determine the type (1 or 2) of clinical isolates. These results were then used as a reference for determining the accuracy of the capture B/SA ELISA, as well as that of the immunofluorescence method, both of which are easily adaptable for use in the clinical laboratory. The three methods were in perfect agreement. It was determined that both the capture B/SA ELISA and the immunofluorescence method using monoclonal antibodies provided typing results with 100% specificity and 100% sensitivity and thus were accurate and reliable. However, the ELISA was the method of choice because of its simplicity, rapidity, and use of nonradioisotopic reagents.

Antibodies, Monoclonal↗
PubMed1987

[Potentiation of the cytotoxic effects of anticancer drugs on human genitourinary neoplastic cells by recombinant gamma-interferon].

Experiments were performed to ascertain whether or not the cytotoxic effects of various anticancer drugs on five human genitourinary malignant cell lines would be enhanced by recombinant gamma-type interferon. The cells used were as follows: HeLa cells from a uterine cervix cancer, HT-1376 and EJ cells from bladder cancers, ACHN cells from a renal cancer, and PC-3 cells from a prostatic cancer. The effects of the drugs were studied by colony formation assay. The following drugs were used: two metabolic antagonists. cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), three antibiotics: adriamycin (ADM), mitomycin C (MMC) and peplomycin (PEP), two alkylating agents: nimustine hydrochloride (ACNU) and melphalan, one vinca alkaloid: vincristine (VCR) and one other drug: cisplatin (CDDP). Interferon used was a preparation of recombinant gamma-type interferon. PEP showed synergistically enhanced cytotoxic effects on HeLa, EJ, HT-1376, and ACHN cells by concomitant application with gamma-IFN. Synergistic cytotoxicity was also detected against HeLa, EJ and ACHN by combined treatment with ADM and gamma-IFN. A similar enhanced cytotoxicity was demonstrated in HT-1376 and PC-3 by 5-FU treatment with gamma-IFN. MMC showed enhanced cytotoxicity only against ACHN cells in the presence of gamma-IFN. The cytotoxic effects of PEP on cells were increased by lower concentrations of gamma-IFN compared with those of other drugs. DNA, RNA and protein synthesis were examined in HeLa cells following combined exposure to PEP and gamma-IFN. The combined therapy was found to produce a specific decrease in DNA synthesis, while yielding no significant inhibition of intracellular RNA and protein synthesis.

Antineoplastic Agents↗
PubMed1986

Multistep process of neoplastic transformation of normal human fibroblasts by 60Co gamma rays and Harvey sarcoma viruses.

As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma-ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST-6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha-MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha-MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha-MSV-transformed KMST-6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma-ray-transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha-MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.

Animals↗
PubMed1986

Inhibition of pentagastrin-stimulated gastric acid secretion by intraileal administration of bile and elevation of plasma concentrations of gut glucagon-like immunoreactivity in anesthetized dogs.

The effects of intraileal administration of bile on gastric acid secretion stimulated by a submaximal dose of intravenous pentagastrin infusion and on plasma concentrations of gut glucagon-like immunoreactivity (gut GLI) were studied in anesthetized dogs. Gastric acid secretion was measured for a 2-h period at 15-min intervals before and after intraluminal instillation of test solutions. 100 ml of canine bladder bile diluted to 10% in saline evoked a significant inhibition (20%) of gastric acid secretion. The inhibition of gastric acid secretion was accompanied by an elevation of plasma concentration of gut GLI, whereas saline instillation (in controls) caused no responses. Although the inhibition of gastric acid secretion and the elevation of plasma gut GLI are parallel phenomena, gut GLI can be reasonably postulated as one of the candidate mediators of bile-induced inhibition of gastric acid secretion, since its structurally related peptides, pancreatic glucagon, glicentin and oxyntomodulin have been reported as inhibitors of gastric acid secretion.

Animals↗
PubMed1986

Morphological changes in rat striatal boutons after chronic methamphetamine and haloperidol treatment.

Dopaminergic (DA) synaptic boutons were identified in rat striatum with an electron microscopic histochemical method. In rats which developed behavioral hypersensitivity after treatment with methamphetamine (MAP) for about 2 weeks, significantly fewer DA boutons were found. This effect was specific to DA boutons without mitochondria and was not seen in boutons with mitochondria. The density of granular synaptic vesicles in DA boutons, however, did not change significantly. These morphological changes would represent a high capability of nerve cells to reorganize synaptic connections under altered chemical environments, but they could not be related uniquely to behavioral hypersensitivity, as similar effects were observed in rats treated with haloperidol which did not develop behavioral hypersensitivity. Peculiarly, the effects of MAP treatment on both behavior and DA boutons were prevented by combined administration of haloperidol.

Animals↗