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Biomedical subjects

N Murayama

Publications and source records attributed to N Murayama.

At least 109 records · Page 6Linked to original sources
PubMed1992

Increase of migration of cultured endothelial cells by angiotensin-converting enzyme inhibitor derived from tuna muscle.

The influence of angiotensin-converting enzyme (ACE) inhibitory octapeptide derived from tuna muscle (tuna AI) on the bovine aorta endothelial cell (BAEC) migration was investigated, as compared with captopril. BAEC migration was quantitated 6 d after release from contact inhibition by a teflon fence assay. The culture grown in the presence of tuna AI (1 and 10 microM) clearly exhibited an increase in migration, compared with the control. The media collected from tuna AI (1 and 10 microM)-stimulated BAECs significantly exhibited the interleukin (IL) -1 activity that was detected by the thymocyte costimulation assay with phytohemagglutinin. Although tuna AI was a weaker ACE inhibitor than captopril, the increasing effect of tuna AI on the migration and the IL-1 generation in BAECs was slightly greater than that of captopril. In quiescent BAECs, tuna AI (1 microM) apparently induced c-myc and platelet derived growth factor (PDGF) A-chain messenger ribonucleic acid (mRNA) expressions within 30 min, which persisted for 6 h. In contrast, captopril induced a very low expression of c-myc mRNA, and had no relation to PDGF A-chain mRNA expression. These results suggest that the increase of BAEC migration by tuna AI, unlike captopril, is likely related to the induction or activation of IL-1, and c-myc and PDGF mRNAs, in addition to the inhibition of the conversion of endogenous angiotensin I to angiotensin II.

Amino Acid Sequence↗
PubMed1992

Inhibitory effect of bis(2-aminohexyl) disulfide and bis(2-amino-3-phenylpropyl) disulfide on several mouse inflammations.

The anti-inflammatory profile of the analogues of bis(2-aminopropyl) disulfide dihydrochloride with butyl (compd. II) and phenyl (compd. III) instead of the methyl group was studied in several mouse models related to phagocyte functions. The test samples were administered 2-3 h before the inflammatory stimulation or the peak of inflammation. Subcutaneously administered, compds. II and III significantly inhibited serotonin-induced paw edema in a dose-dependent manner (50% inhibitory dose values: 10 and 5 mg/kg, respectively), when orally administered at 25 mg/kg, these compounds were significantly effective, but their potencies were weaker. Neither compound had any irritant activity when administered at a dose of 12.5 micrograms/5 microliters/paw into the paw. In a sheep red blood cells (SRBC)-induced delayed-type hypersensitivity (DTH) reaction model, compd. II (25 mg/kg, s.c.) significantly inhibited the DTH responses when administered at two different times in relation to the time of challenge. However, there was only slight inhibition by compd. III (25 mg/kg, s.c.) on paw edema formation when administered 14 h after secondary immune response. In a model of experimental acute hepatic failure induced by successive injections of Propionibacterium acnes and lipopolysaccharide, both compounds increased mouse survived, compared with the control mice, and kept the serum levels of components involved in hepatic failure to nearly normal levels. These results demonstrate that compds. II and III possess an inhibitory effect on inflammation related to phagocytes.

Amines↗
PubMed1992

Studies on thermophile products. V. Immunosuppressive profile in vitro of Bacillus stearothermophilus component, Fr.5-B.

The immunosuppressive profile of Bacillus stearothermophilus UK563 component, Fr.5-B, is presented in in vitro studies. Fr.5-B (0.1-1000 ng/ml), provided it was added at the initiation of mixed leukocyte reaction (MLR), inhibited dose-dependently the incorporation of tritiated thymidine ([3H]TdR) into mouse spleen cells and human peripheral blood lymphocytes. Even the addition of Fr.5-B 48 h after the onset of culture suppressed mouse MLR, unlike cyclosporin A (CYA). Fr.5-B significantly inhibited cytotoxic T lymphocyte generation determined by [3H]TdR-release micro-cytotoxicity assay by using mouse mastocytoma P815 as targets. Moreover, this component decreased dose-dependently the expression of class II major histocompatibility molecules (Ia) on mouse peritoneal macrophages induced by concanavalin A supernatant. The present results revealed the unique immunosuppressive property of Fr.5-B which was different from that of CYA.

Animals↗
PubMed1992

Inhibitory effects of bis(2-aminohexyl)disulfide and its analogues on polymorphonuclear leukocyte functions in vitro.

Water soluble analogues of the anti-inflammatory compound, bis(2-aminopropyl)disulfide dihydrochloride (compd. I) with a butyl (II), phenyl (III), benzyl (IV) or pyrrolidinyl group (V) instead of the methyl group were synthesized, and their effects on the functions of cells related to inflammation were studied in vitro. Compounds II, III and IV showed much higher inhibitory activity than compd. I on formyl Met-Leu-Phe (FMLP)-induced O2(-)-generation of polymorphonuclear leukocytes (PMNs) and platelet aggregation. Compound II showed the strongest activity among the compounds (IC50 values: 2.6 microM). The inhibition of O2(-)-generation of PMNs by compd. II was the most effective when FMLP was used as a stimulant rather than when phorbol myristate acetate, A-23187 and opsonized zymosan were used. However, compd. II was not an O2(-)-scavenger. Compounds II, III and IV significantly inhibited a series of activation processes in PMNs, chemotaxis, phagocytosis and lysosomal enzyme release at doses ranging from 10 to 100 microM. Under these doses, compds II, III and IV did not affect the histamine release from mast cells or the hemolysis of erythrocytes. These results strongly suggest that the anti-inflammatory action caused by compd. II and its analogues was at least partly due to inhibition of several functions of PMNs and platelets.

Amines↗
PubMed1992

[Metabolic abnormalities of amino acids in patients with alcoholic liver damage].

The metabolic abnormality of amino acids in patients with alcoholic liver damage is discussed. The abnormalities are variable according to the degree of hepatic damage, the amount of alcohol consumption, and the intake of amino acids. In general, the plasma concentration of branched-chain amino acids, aromatic amino acids and alpha-amino-n-butyric acid increases, whereas that of hydroxy amino acids, alanine and proline decreases, in alcoholics with liver damage. Serum gamma-glutamyltranspeptidase activity increases with the increase of alcohol consumption. This increase is accentuated by lowered carbohydrate intake at the time of alcohol ingestion. A nutritional survey among healthy male subjects revealed that the intake of cereals decreases with increasing amount of alcohol consumption, a finding which suggests that the intake of some amino acids may be altered by drinking habit.

Amino Acids↗
PubMed1992

Effect of repeated oral doses of a novel immunosuppressive macrolide lactone on hepatic mixed-function oxidase system in the rat. Comparative study with ciclosporin.

Effect of pretreatment of rats with FK506((-)-(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-allyl-1,14- dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3methoxycyclohexyl]-1- methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0(4.9)]octacos-18-ene-2,3,10,16-tetrone hydrate, CAS 104987-11-3) on microsomal cytochrome P-450 system and oxidations of the administered drug and other model substrates were studied and compared with those of a pharmacologically related drug, ciclosporin (cyclosporin A). Oral treatment of male Sprague-Dawley rats with FK506 (0.4, 2 or 10 mg/kg/d) for 7 days did not decrease microsomal content of total cytochrome P-450 in livers, but rather increased the content in groups with the dose of 0.4 or 10 mg/kg to the levels of 126-130% of the control. Microsomal NADPH-cytochrome c reductase activities were decreased up to 67% of the control with the increasing dose of FK506 and to 62% in a group treated orally with cyclosporin A (25 mg/kg/d for 7 days), although another microsomal electron-transport component, cytochrome b5, was rather increased in all the treated groups. Treatment with FK506 or cyclosporin A did not reduce but slightly increased microsomal activities of aniline hydroxylation, p-nitroanisole O-demethylation and O-ethoxyresorufin O-deethylation. Microsomal depropylation of 7-propoxycoumarin, a typical P-450IIIA-substrate, was also not reduced in all dose groups of FK506, while it was decreased by the treatment with 25 mg/kg cyclosporin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Flow-injection analysis for malondialdehyde in plasma with the thiobarbituric acid reaction.

A simple, precise, and rapid method to measure plasma malondialdehyde (MDA) was developed by use of solvent extraction--flow-injection analysis. The reagent solution, containing thiobarbituric acid (TBA), 5 g/L in 100 mL/L phosphoric acid, and extraction solvent (methylisobutyl ketone, MIBK) were propelled with a double-plunger micropump at a flow rate of 0.3 mL/min, and 20 microL of sample was introduced into the reagent stream. After TBA-MDA reactant was extracted into MIBK, the organic phase was continuously separated by a successive phase-separation system equipped with two phase separators, and the absorbance of the TBA-MDA reactant was measured at 532 nm. This approach resulted in excellent sensitivity, a CV of < 1.5%, a good correlation with the conventional manual method, and a sampling frequency of 7 samples/h, suggesting that this semiautomated method is suitable for measuring plasma MDA.

Animals↗
PubMed1992

[Drinking-related changes in dietary intake in 2165 male adults--with special reference to carbohydrate, protein and fat].

A food intake-frequency survey using a 7-day weighted inventory questionnaire was conducted among 2165 healthy men aged from 18 to 85 living in Nagano Prefecture. The effect of ethanol consumption on the intake of 12 different groups of food (cereals, potatoes, sugar, confectioneries, fruit, vegetables, soybean and its products, eggs, milk and dairy products, fish, meat, and oils), on the intake of macronutrients (carbohydrate, protein and fat), on the total energy intake including and excluding energy from ethanol, and on the energy percentage from carbohydrate, protein and fat, were analyzed. As ethanol consumption increased, the intake of cereals and confectioneries was found to markedly decrease, and that of potatoes, sugar, fruit, vegetables, milk and dairy products, and oils to decrease to a lesser extent. In contrast, the intake of meat increased with increasing ethanol consumption. The intake of carbohydrate, vegetable protein and fat decreased with increase in ethanol consumption in the following order: carbohydrate greater than vegetable protein = vegetable fat. As ethanol consumption increased, total energy intake including energy from ethanol increased, but the energy excluding ethanol decreased. The energy percentage contributed by carbohydrate, vegetable protein, and vegetable and animal fat decreased with increase of ethanol consumption: the extent of the decrease was most prominent in energy from carbohydrate, followed by vegetable fat, animal fat and vegetable protein in decreasing order. These results suggest that people have a tendency to consume less carbohydrate, especially cereals, when increasing ethanol consumption.

Adult↗
PubMed1992

[A quantitative analysis of ataxia in the upper limbs].

By using a transparent digitizer and a personal computer, we tried a quantitative analysis of ataxia in the upper limbs. A total of 25 upper extremities of 13 patients with spino-cerebellar degeneration (SCD) and 140 upper extremities of 70 normal volunteers were tested by two types of tasks. One was the free speed trace of a circle presented on the display (free circle), and the other was the pursuit of a target moving on a circle at a fixed speed (pursuit circle). The digitizer was put on a color display stabilized horizontally. For 1024 points with a 25 msec sampling time, the trajectory of the stylus pen was transmitted to the computer in real time. Circle diameters of 3 cm and 6 cm were selected. The target rounded the circle at a speed of 6 or 3 times per 1024 points. The mean velocity (MV), mean acceleration (MA), and MA/MV ratio were calculated for the extent of one circle period. And the coefficient of variation (CV) of the shifted distance in each sampling time and the power spectrum by Fast Fourier Transform (FFT) to the acceleration wave were calculated for the total input data. In the free circles, the MV and logarithm of MA varied widely and showed positive correlations. In contrast, those of the pursuit circles converged narrowly near the values of the target. On the other hand, in the SCD group, many patients could not draw the small free circle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Clinical significance of CD7-positive stem cell leukemia. A distinct subtype of mixed lineage leukemia.

Ten leukemia cases with mixed phenotype were investigated in terms of clinical characteristics and cellular origin. Three patients were infants and six patients were older children. Six of them had a high leukocyte count and a mediastinal mass was found in three cases. All but one showed hepatosplenomegaly and/or lymphoadenopathy. In spite of intensive chemotherapy, most of them responded poorly. Cytochemical analysis of their leukemic cells revealed a low percentage of positivity for myeloperoxidase reactivity (less than 25%) in two cases and electron microscopic platelet peroxidase reactivity was found in one of three analyzed cases. Phenotypically, these cells all expressed CD7, and other T-lineage-associated, B-lineage-associated, and/or myeloid-associated antigens were also detected to some extent. In addition, three cases expressed CD41 and one case expressed CD56. The T-cell receptor (TCR) genes and immunoglobulin gene were in the germline configuration in seven cases. In three rearranged cases, two showed only the TCR-delta gene rearrangement, and one had both TCR-gamma and delta gene rearrangements. Cell culture studies with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) revealed differentiation to the T-lineage in two cases and to a myeloid lineage in one case. Megakaryocytic differentiation was detected in two cases in culture without TPA. These results suggest that the cells from these cases arose from stem cells capable of both lymphoid and nonlymphoid differentiation. Although the cells were heterogeneous with regard to their potency of differentiation, they have similar clinical characteristics. Because of poor prognosis, it is important to identify this type of leukemia, and allogenic or autologous bone marrow transplantation should be considered.

Acute Disease↗
PubMed1991

Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency.

Familial deficiency of lecithin:cholesterol acyltransferase (LCAT) is an autosomal recessive disorder characterised by abnormalities of all plasma lipoprotein classes and by abnormal deposition of unesterified cholesterol in tissues. To elucidate the molecular basis of the disease, the LCAT genes of three unrelated Japanese patients were amplified by means of the polymerase chain reaction. Direct sequencing of the amplified fragments covering all exons and junctions showed that the patients are homozygotes for separate gene mutations. In one patient a 3 bp insertion, which should cause a substantial change in the enzyme structure, was found in exon 4; he had near absence of LCAT mass and activity. Two separate missense mutations were identified in exon 6 of the other two patients, who produced functionally defective enzymes that differed widely in specific activity. The replacement of asparagine228 with positively charged lysine completely abolished enzyme activity, whereas the other, conservative, aminoacid substitution (methionine293----isoleucine) gave rise to a partially defective enzyme. These results show that distinct mutations cause differences in plasma LCAT activity and LCAT mass, ultimately leading to differential phenotypic expression of familial LCAT deficiency.

Adult↗
PubMed1991

Differential development of cortical taste areas in granular and dysgranular insular cortices in rats.

Recordings were made from taste neurons in granular and dysgranular areas of the insular cortex of anesthetized SD-rats from the age of 4 days to over 90 days (adults). Almost all of the taste neurons were detected in the dysgranular area prior to weaning, but the number in the granular area increased with age and exceeded the number in the dysgranular area after the age of 50 days. In the dysgranular area, most taste neurons, irrespective of the postnatal age, were located at layer 5. However, in the granular area they were found at a deeper layer, with the advance in age; e.g. layer 2-3 at 14-20 days to layer 5 in adults. Thus, taste afferents in granular and dysgranular areas of the insular cortex differ with advance in age.

Aging↗
PubMed1991

Monoclonal nature of transient abnormal myelopoiesis in Down's syndrome.

Neonates with Down's syndrome occasionally show an excess of blasts in their peripheral blood. This disorder spontaneously resolves within several months and is called transient abnormal myelopoiesis (TAM) or transient myeloproliferative disorder. It has been uncertain whether the excess of blasts in TAM is a result of a clonal proliferation or a polyclonal reactive condition. The clonality of cells in females can be examined by analysis of the methylation patterns of the X chromosomes of proliferating cells using restriction fragment length polymorphism (RFLP). Using this strategy, we studied three females with Down's syndrome accompanied by TAM who showed heterozygosity in RFLP of either the hypoxanthine phosphoribosyltransferase or phosphoglycerate kinase gene. Analysis of the methylation patterns of these genes demonstrated a clonal nature for blasts in three patients. Thus, TAM is a clonal proliferative disorder. In addition, lymphocytes with a normal appearance contained in analyzed samples from these patients also showed a monoclonal pattern, suggesting that TAM may be a disorder of multipotent stem cells.

Bone Marrow↗
PubMed1991

Subcellular distribution of thyroxine 5'-monodeiodinase activity in rabbit kidney.

Thyroxine 5'-monodeiodinase is located in the proximal tubules of the rabbit kidney. To estimate the subcellular distribution of 5'-monodeiodinase activity, we prepared subcellular fractions, a basolateral membrane fraction and a brush border membrane fraction, from kidneys of Japanese white rabbits. Each fraction (0.5 mg protein) was incubated at 37 degrees C for 60 min with 0.5 micrograms T4 in the presence of 5 mM DTT. The T3 generated in the reaction mixture was extracted with cold ethanol and measured by RIA. For analysis of propylthiouracil-insensitive thyroxine 5'-monodeiodinase, we examined its kinetic behavior at nanomolar concentrations of the substrate, T4, in the presence of 100 microM propylthiouracil. In order of decreasing activity, basolateral membrane, microsomal fraction, mitochondrial fraction, cytosolic fraction, brush border membrane and nuclear fraction were capable of converting T4 to T3. Upon addition of 10(-5) M propylthiouracil to the reaction mixture, 5'-monodeiodinase activities of basolateral membrane and brush border membrane were inhibited by more than 90%, but that of microsomes was inhibited by only about 50%. In addition, kinetic analysis of microsomal 5'-monodeiodinase activity at nanomolar T4 concentrations in the presence of 10(-4) M propylthiouracil suggested on apparent Km of 3.8 nmol. These results indicate that there is high-Km 5'-monodeiodinase activity (PTU-sensitive) in the basolateral and brush border membranes and also high-Km and low-Km 5'-monodeiodinase (PTU-insensitive) in the microsomes of rabbit kidney.

Animals↗
PubMed1991

Cellular mechanism of lithium-induced nephrogenic diabetes insipidus in rats.

One of the mechanisms by which Li evokes polyuria is thought to be impairment of arginine vasopressin (AVP)-sensitive adenylate cyclase (AdC) in cells of the renal collecting duct. To investigate how AdC is influenced by chronic administration of Li, we created nephrogenic diabetes insipidus (NDI) in rats and microdissected the medullary collecting tubule from both control and NDI rats. In the NDI group, the 10(-6) M AVP-stimulated cAMP contents failed to increase completely, and the levels were significantly lower than that of the control group (10.4 +/- 1.4 vs. 48.4 +/- 4.7 fmol/mm, P less than 0.001). Pretreatment with pertussis toxin (PT), an inhibitor of inhibitory G protein (Gi), did not affect the basal cAMP levels in both groups, although it increased AVP-stimulated cAMP production in the NDI group in a dose- and time-dependent manner. AVP-stimulated cAMP production with over 100 ng/ml PT in the NDI group reached the levels observed in the control group. Incubation with cholera toxin, an agonist of stimulatory G protein (Gs), increased the cAMP content in the two groups to almost equal levels. To exclude the possibility that prostaglandin E2 (PGE2) is involved in the cellular mechanism of Li-induced NDI, the effect of indomethacin (Indo) on PT action was examined. However, Indo (10(-5) M) did not influence either the basal or AVP-dependent cAMP contents. From these results it is suggested that Li impairs AVP-sensitive AdC not through inhibition of Gs but through activation of Gi and that PGE2 may not be involved in the cellular pathogenesis of NDI at least in the rat at the step of cAMP formation.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Change of external urethral sphincter function in prostatic patients.

External urethral function was urodynamically examined in 13 patients with benign prostatic hypertrophy (BPH) associated with chronic urinary retention and in 5 volunteers. Prevoiding drop in external urethral sphincter pressure was noted in all the volunteers, whereas it was not found in 6 of the 13 cases of BPH. Bladder neck opening pressure was higher in these 6 cases (p less than 0.05). After administration of phentolamine, prevoiding drop was noted in 5 of these 6 cases, and bladder neck opening pressure decreased so much that there was no significant intergroup difference. The above results mean that the increase in alpha-adrenergic receptors makes the prostate, which has been already hypertrophied, less elastic, inhibiting external urinary sphincter function.

Aged↗
PubMed1991

Isolation of a new antitumor substance from Bacillus stearothermophilus.

A new antitumor substance, BS-1, was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563 by ethylacetate extraction and HPLC. BS-1 inhibited the proliferation of mouse macrophage-like cells, P388-D1 (IC50: 4 micrograms/ml) and mouse mastocytoma, P-815 (IC50: 0.6 microgram/ml), but not that of Balb/c 3T3.

Animals↗