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Biomedical subjects

A Miwa

Publications and source records attributed to A Miwa.

At least 145 records · Page 8Linked to original sources
PubMed1991

Spider toxin and the glutamate receptors.

A neurotoxin (JSTX) was isolated from the venom of spider (Nephila clavata). JSTX blocked both the excitatory postsynaptic (EPSPs) and glutamate-induced potentials in lobster neuromuscular synapse and squid giant synapse. In mammalian central nervous system, JSTX blocked the EPSPs in CA1 pyramidal neurons resulting from stimulation of Schaffer collateral/commissure input. Pharmacological investigation showed that JSTX preferentially suppressed quisqualate/kainate receptor subtypes but was much less effective on NMDA receptor. Using synthesized spider toxins we studied the structure-activity relationship and found that the 2,4 dihydroxyphenylacetyl asparagine in the toxin structure was responsible for suppressive action, while the remaining part containing a polyamine was related to the agonist binding site with the polycationic part enhancing the toxic activity. Labeling of synthesized JSTX was used for histochemical as well as biochemical studies. Using autoradiography, 125I-JSTX-3 was found to bind at the lobster neuromuscular synapse. Histochemical study utilizing the interaction of biotinylated JSTX-3 with avidin showed specific binding of the toxin in rat cerebellum and hippocampus. JSTX-3-binding protein was purified from rat brain by affinity chromatography. SDS-PAGE of the affinity purified protein showed at least 4 bands ranging from 40 to 70 kDa.

Animals↗
PubMed1991

Small cell carcinoma of the stomach: a clinicopathologic study of 17 cases.

Of 17 cases of small cell carcinoma of the stomach, three were early and 14 were advanced. Grossly, the tumors were mostly polypoid at the early stage, and as they advanced, deep ulcerations developed. Histologically, only one tumor was "oat cell type," and the other 16 were "intermediate cell type." With regard to tumor components, five were "pure" tumor, and 12 were "composite" admixing glandular and/or squamous differentiation. Argyrophil cells were seen in eight tumors. Immunohistochemically positive cells for chromogranin, neuron-specific enolase, and keratin were seen in 12, 10, and 7 tumors, respectively. Carcinoembryonic antigen was negative in the small cell component of most tumors as opposed to strong positivity in the glandular component. Electron-dense core granules were evident in seven of nine tumors examined. These findings suggest that histologic variety is quite characteristic of the small cell carcinomas of the stomach, and this type of carcinoma takes an aggressive clinical course like its counterparts in other organs.

Adenocarcinoma↗
PubMed1991

Long-term bone marrow failure accompanied by skin pigmentation.

A rare case of long-term bone marrow failure with skin pigmentation is presented. The patient was a female with a long history of anemia and skin pigmentation since childhood, although she had no malformations nor chromosomal abnormalities. Hematological improvement has been maintained by the administration of prednisolone. This case may differ from other disorders known as congenital aplastic anemia.

Addison Disease↗
PubMed1990

Hepatocellular carcinoma in primary biliary cirrhosis: an autopsy study.

A survey of Japanese autopsy cases of primary biliary cirrhosis disclosed that hepatocellular carcinoma is apparently becoming a better recognized complication of the advanced stage of primary biliary cirrhosis. Six autopsy cases (five women and one man) of primary biliary cirrhosis associated with hepatocellular carcinoma were obtained from several Japanese institutions and examined. All cases were in an established cirrhotic stage of primary biliary cirrhosis. Hepatocellular carcinoma was incidentally found at autopsy in four cases and, in these, the carcinomas were small in size and number. The other two cases showed advanced hepatocellular carcinoma and one case showed extrahepatic metastasis. Histologically, all cases showed well-differentiated hepatocellular carcinomas. Fatty changes or bile plugs were frequently seen within the tumors. Mallory body clusters and focal deposition of copper-binding protein were consistently found in cirrhotic liver tissues and also in the carcinoma tissues of almost all cases. The presence of atypical adenomatous hyperplasia in the peripheries of some carcinomas suggested that hepatocellular carcinoma in primary biliary cirrhosis may evolve through multiple steps.

Carcinoma, Hepatocellular↗
PubMed1990

G protein is coupled to presynaptic glutamate and GABA receptors in lobster neuromuscular synapse.

1. We have examined the effects of L-glutamate and gamma-aminobutyric acid (GABA) on the presynaptic membrane of spiny lobster by the use of intra-axonal recording near the nerve terminals. 2. Application of glutamate to the synaptic region produced hyperpolarization in the presynaptic membrane but depolarization in the postsynaptic membrane. The presynaptic glutamate potential (PGP) is generated by an activation of K+ channels, as evidenced by its dependence on external K+ concentration. 3. The PGP was not affected by a spider toxin (JSTX), which blocks the postsynaptic glutamate receptor. By contrast, pertussis toxin (IAP) effectively blocked the PGP without affecting the resting conductance channels or action potentials in the presynaptic membrane. 4. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a hydrolysis-resistant analogue of GTP, blocked the PGP, suggesting the involvement of a G protein in the generation of K+ current. 5. Application of GABA induced depolarization or hyperpolarization in the presynaptic axon depending on the resting membrane potential. By reducing external Cl-, GABA-induced hyperpolarizations were converted to depolarizations, indicating that they are mainly mediated by Cl-. 6. In contrast to GABA, baclofen consistently induced hyperpolarization in low Cl- solution as well as in normal solution. Baclofen-induced hyperpolarization was blocked by IAP, indicating the mediation of G protein. 7. These results suggest that the presynaptic membrane of lobster neuromuscular synapse has entirely different types of amino-acid receptors from those in the postsynaptic membrane. Both the excitatory and the inhibitory axonal membrane have glutamate ("glutamateB") and GABAB receptors, which activate K+ channels via G protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Clinical study on heterogeneity of chronic myelomonocytic leukemia].

We examined fourteen patients with chronic myelomonocytic leukemia (CMMoL) according to the following staging criteria at diagnosis; Group A: bone marrow (BM) blast less than 5% (eight cases), Group B; BM blast more than 5% and less than 30% (five cases), Group C; BM blast more than 30% (one case). Compared with Group A, Group B patients have much more peripheral blood leukocyte, granulocyte and monocyte counts, LDH level, and serum and urine lysozyme levels. Two of the five Group B cases transformed to acute leukemia (BC) within one and a half year, and other three patients died of infection and hemorrhage within a year. On the contrary, three of the eight Group A patients survived four years, and transformation to acute leukemia occurred in only one case after four years. Autopsy revealed multiple organ infiltration of monocytoid granulocytes on the patients with advanced stage and more bone marrow blasts. Two cases have coexistence of myeloproliferative disorders, one with essential thrombocythemia, and another with myelofibrosis, which, later, transformed to acute leukemia. And a Group C patient transformed to chronic phase with chemotherapy, and maintained the state for six years, but at the end stage, mature monocytes increased and pancytopenia developed. These findings indicate the heterogeneity of CMMoL in respect of the disease stage and the coexistence of other myeloproliferative disorders.

Aged↗
PubMed1990

[Long survival of a patient presented with blastic crisis of chronic myelomonocytic leukemia].

A 77-year-old man was diagnosed as having acute myelomonocytic leukemia (M4) with increased ringed sideroblasts in the bone marrow (BM) in October, 1979. Complete remission was achieved and ringed sideroblasts disappeared after two courses of CMP (cytarabine, 6-mercaptopurine, prednisolone) therapy. Following remission, there was no increase of blasts during the course of the disease, but monocytosis and dysmyelopoiesis persisted for about seven years. The monocytosis was controlled by 6-mercaptopurine. In June, 1986, however, monocytosis in peripheral blood (PB) and BM developed again, and there was severe pancytopenia and reappearance of ringed sideroblasts without increase of blasts. The patient died of pneumonia on September, 1986. Postmortem examination revealed hypercellular marrow with a few blasts, leukemic cell infiltration into spleen, liver and lymph nodes, ad lung cancer. His clinical and hematological features after remission of acute leukemia accorded with those of CMMoL. The dysmyelopoiesis observed in this case in not induced by anti-leukemic agents, but originated from the same clone as the initial AMMoL, and his disease was thought to be CMMoL converted from blastic crisis to chronic phase.

Aged↗
PubMed1989

The role of peroxisomal fatty acyl-CoA beta-oxidation in bile acid biosynthesis.

The physiological role of the peroxisomal fatty acyl-CoA beta-oxidizing system (FAOS) is not yet established. We speculated that there might be a relationship between peroxisomal degradation of long-chain fatty acids in the liver and the biosynthesis of bile acids. This was investigated using [1-14C]butyric acid and [1-14C]lignoceric acid as substrates of FAOS in mitochondria and peroxisomes, respectively. The incorporation of [14C]lignoceric acid into primary bile acids was approximately four times higher than that of [14C]butyric acid (in terms of C-2 units). The pools of these two fatty acids in the liver were exceedingly small. The incorporations of radioactivity into the primary bile acids were strongly inhibited by administration of aminotriazole, which is a specific inhibitor of peroxisomal FAOS in vivo [F. Hashimoto and H. Hayashi (1987) Biochim. Biophys. Acta 921, 142-150]. Aminotriazole inhibited preferentially the formation of cholate, the major primary bile acid, from both [14C]lignoceric acid and [14C]butyric acid, rather than the formation of chenodeoxycholate. The former inhibition was about 70% and the latter was approximately 40-50%. In view of reports that cholate is biosynthesized from endogenous cholesterol, the above results indicate that peroxisomal FAOS may have an anabolic function, supplying acetyl CoA for bile acid biosynthesis.

Acyl Coenzyme A↗
PubMed1989

Effects of a spider toxin (JSTX) on hippocampal CA1 neurons in vitro.

The effect of a toxin (JSTX) obtained from Nephila clavata (Joro spider) on the CA1 pyramidal neurons of the hippocampus was studied using slice preparations. JSTX blocked the excitatory postsynaptic potentials (EPSPs) in the pyramidal neuron evoked by Schaffer collateral stimulation but was without effect on the antidromic action potentials or on the resting conductance. Depolarization induced by ionophoretic application of glutamate was readily suppressed by JSTX but aspartate-induced depolarization was much less sensitive to the toxin. Among preferential agonists activating 3 receptor subtypes for excitatory amino acids, quisqualate responses were most effectively suppressed by JSTX. Kainate responses were similarly suppressed but in some cells higher concentration of the toxin was needed to block the responses. N-methyl-D-aspartate (NMDA) responses were the least sensitive to JSTX but they were suppressed by +/- 2-amino-5-phosphonovaleric acid (APV). Long term potentiation (LTP) once it had taken place was not completely inhibited by APV. In the presence of JSTX, however, LTP was blocked and tetanic stimuli produced only a short-lived potentiation. In Mg2+ free solution, an orthodromic stimulation evoked repetitive spike responses which were superimposed on the depolarization following the initial spike. APV suppressed the depolarization and associated spikes leaving an orthodromic response which was sensitive to JSTX. The results suggest that JSTX blocks EPSPs in CA1 pyramidal neurons which are mediated by non-NMDA type receptors.

Action Potentials↗
PubMed1989

Scirrhous carcinoma of the stomach: a clinical and pathological study of 106 surgical cases.

Clinical and pathological characteristics of scirrhous carcinoma of the stomach were studied in 106 cases treated by gastrectomy between 1973 and 1983. The male to female ratio was 0.58. The percentage of scirrhous carcinomas to all gastric carcinomas resected in the same period was three times higher in females than males. The age distribution of the patients suggested that there were two peaks in the forties and sixties in the male, and in the thirties and fifties in the female. The incidence of scirrhous carcinoma in all types of gastric carcinoma was significantly higher in the twenties, thirties and forties compared to the lowest incidence in the seventies. In the female group the primary lesion had a tendency to be adjacent to the fundic gland area and to avoid intestinal metaplasia. In the male the opposite was recognized. Cancer nests with single cells or only several cells were common in this type of carcinoma. These findings suggest that there might be two biologically different scirrhous carcinomas both in the male and the female, the appearance of single carcinoma cells might be favored by female sex hormones and young ages, and not only the original gastric mucosa but also mucosa with intestinal metaplasia could be precursors of single carcinoma cells.

Adenocarcinoma, Scirrhous↗
PubMed1989

Comparative study of amino acid composition in an extract from hornet venom sacs: high content of neuroactive amino acids in Vespa.

The amino acid compositions of extracts from the venom sacs of Vespa mandarinia, V. xanthoptera, V. tropica, V. analis and Vespula lewisi were analyzed. omega-Amino acids, which are inhibitory neurotransmitters, such as gamma-amino-n-butyric acid, taurine, beta-alanine and glycine, were predominant components in Vespa, but a minor component in Vespula. Glutamic acid, an aminergic excitatory neurotransmitter, was present in large quantities. Leucine, an insect autotoxin, was detected. Arginine was found in all the venoms and glutamine was also abundant. Tryptophan and histidine, precursors of serotonin and histamine, respectively, were also found. Thus, neuroactive amino acids that may exert inhibitory effects on insects neuronal axons and neuromuscular junctions were present in large amounts, and may facilitate paralysis of insect prey.

Amino Acids↗
PubMed1989

Zinc ion enhances the blocking potency of synthetic analogs of spider toxin (JSTX) on the glutamate receptor.

The effect of synthetic spider toxin analogs containing aza-crown in combination with zinc and copper was studied on the lobster neuromuscular synapse. The suppressive action of N4-type spider toxin analog (N4) on excitatory postsynaptic potentials (EPSPs) was markedly enhanced in the presence of 10(-5)-10(-4) M Zn2+. Cu2+ (10(-4) M) also had a potentiating effect on the suppression of EPSPs by N4 but to a lesser degree than Zn2+. While N6-type spider toxin analog (N6) suppressed EPSPs more effectively than N4, additional suppression was not pronounced in the presence of Zn2+ or Cu2+. The results suggest that chelatable divalent metal ions play an important role in the blocking mechanism of glutamate receptor by the spider toxin.

Action Potentials↗
PubMed1989

Effects of the in vivo administration of recombinant human granulocyte colony-stimulating factor following cytotoxic chemotherapy on granulocytic precursors in patients with malignant lymphoma.

We examined the effects of the in vivo administration of recombinant granulocyte colony-stimulating factor (rhG-CSF) on granulocytic precursors in the bone marrow of 4 patients with malignant lymphoma who received chemotherapy. Patients were treated with rhG-CSF at doses of 100-800 micrograms/m2/day intravenously for 14 days only in the first course of chemotherapy (G-CSF course) followed by the second course of chemotherapy without rhG-CSF which was used as a control course. In the G-CSF course, white blood cell counts (WBCs) demonstrated a biphasic response consisting of a first peak observed within a few days after the initiation of rhG-CSF administration, and a second peak observed on the last day of rhG-CSF injection or the day after. In the second peak, the incidence of granulocyte-macrophage colony-forming units (CFU-GM) in mononucleated bone marrow cells did not change significantly after treatment with rhG-CSF as compared with a control. However, since the number of nucleated cells in the bone marrow increased, the absolute number of CFU-GM in the bone marrow increased. The number of mature and immature granulocytes in the bone marrow increased. These findings suggest that G-CSF stimulates the proliferation and differentiation of granulocytic precursors in the bone marrow in granulocytopenic patients who received cytotoxic drugs and causes mature granulocytes to be released from the bone marrow.

Adult↗
PubMed1989

[Coma, hyperviscosity syndrome, hyperammonemia and myelofibrosis in a patient with IgG, lambda type multiple myeloma].

A 63-year-old man was admitted to our hospital with tremor and somnolence, followed soon by coma. Anemia and retinal bleeding were observed. The blood smear exhibited rouleaux formation and leukoerythroblastosis. A bone marrow aspiration resulted in dry tap. The biopsy specimens revealed remarkable infiltration of myeloma cells with fibrosis. The M-component of IgG-lambda type and hyper-ammonemia were detected in the serum. Liver and renal functions, however, were within normal range. His consciousness recovered after plasmapheresis. Two courses of VMCP (vincristine, melphalan, carboquone and prednisolone) did not affect the paraproteinemia. Five courses of VAD (vincristine, adriamycin and dexamethasone) could lower the level of IgG. He died of pneumonia. The plasma of some patients with multiple myeloma may contain unidentified factors which increase the plasma ammonia.

Ammonia↗
PubMed1989

[Multivariate analysis of prognostic factors influencing survival in chronic myelogenous leukemia].

Prognostic significance of disease features obtained at the time of initial diagnosis was analyzed in 90 patients with chronic myelogenous leukemia (CML) in chronic phase. Median survival of this population was 45.9 months. Univariate analysis revealed that splenomegaly, bone marrow basophils, bone marrow blasts, peripheral blood blasts, and bone marrow eosinophils were significant prognostic factors for survival, and that peripheral blood leukocytes counts, hemoglobin concentration, performance status, age and lymphadenopathy were factors with border line significance. There were multiple interrelationship among these disease features. Multivariate regression analysis identified that age, hemoglobin concentration, and bone marrow blasts were independent primarily significant prognostic factors for survival. The Cox model generated with three variables of age, hemoglobin concentration, and percent blasts in bone marrow provided a useful representation of risk status in the population. A hazard function derived from the patients population segregated patients into three groups with significantly different survival patterns: A lower risk group, an intermediate group and a high risk group of patients with median survival of 57.8, 49.8 and 38.4 months respectively. Survival after CML blast crisis was short and overall median survival of 54 patients with CML blast crisis was 6.4 months. A sole prognostic factor for survival in blast crisis identified by multivariate analysis was blast cell type at CML blast crisis and patients with lymphoid phenotype had a good prognosis with median survival of 9.8 months. Median survival of myeloid crisis was 4.2 months. No other disease features were identified as significant prognostic factors in the present patient population.

Adult↗
PubMed1989

Carcinoid tumors of the gallbladder with adenocarcinomatous differentiation: a morphologic and immunohistochemical study.

Two patients with gallbladder carcinoid tumors with adenocarcinomatous differentiation were examined. In both cases, the tumor contained argyrophilic granules and alcian blue-positive mucin. One contained argentaffin granules and the other showed PAS-positive mucin. Numerous membrane-bound electron-dense neurosecretory granules were demonstrated by ultrastructural study. Immunohistochemistry applied for the tumors clarified the epithelial, hormonal, and metaplastic character. Epithelial tumor markers, i.e., carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA), were positive in these tumors. The neuroendocrine nature was demonstrated by positive results of chromogranin A and neuron-specific enolase (NSE). Hormonal activities were not confirmed in the tumor cells. These results suggested that carcinoid tumors in the gallbladder have a multidirectional differentiation represented by a morphological continuum ranging from carcinoid to adenocarcinoma.

Adenocarcinoma↗
PubMed1989

[Successful CYVADIC combination chemotherapy of metastatic pulmonary lesions involving a mediastinal leiomyosarcoma--a case report].

Discussed is a 34-year-old man who hospitalized for manifesting the superior vena cava syndrome. Chest radiograph and chest CT scan revealed a gross tumor shadow in the superior mediastinum and a tiny shadow in the right lung. Superior vena cavography showed intimal stenosis, irregularities, and stiffness of the superior vena cava. Thus, radiotherapy applied to primary lesion of the mediastinum was provided to relieve his complaints. One year later, predominant metastatic pulmonary lesions and skin lesions developed. Light and electron microscopic findings of a biopsied specimen of the skin lesion were consistent with leiomyosarcoma. CYVADIC combination chemotherapy reduced the pulmonary metastatic lesions dramatically. The literature of mediastinal leiomyosarcoma is reviewed and the origin of this tumor is discussed.

Adult↗