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Biomedical subjects

S Yoshimoto

Publications and source records attributed to S Yoshimoto.

At least 19 recordsLinked to original sources

Effect of chromium administration on glucose tolerance in stroke-prone spontaneously hypertensive rats with streptozotocin-induced diabetes.

The present study was conducted to assess the effect of chromium (Cr) administration on glucose tolerance in insulin-dependent diabetes that accompanies hypertension. Four rat groups were used: stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) with and without streptozotocin (SZ, 40 mg/kg)-induced diabetes. Each group of rats was subdivided to the Cr-dose group and the control group. The Cr-dose group, which was intraperitoneally administered Cr solution (20 micrograms trivalent chromium/kg body weight/d for 4 weeks), and the control group (saline) were studied for plasma glucose and plasma insulin during intraperitoneal glucose tolerance test (IPGTT) and insulin action by isolated adipocytes. For diabetic SHRSP showing the highest plasma glucose and lowest plasma insulin among the four groups, Cr administration led to the greatest reduction in plasma glucose without a significant effect on plasma insulin during IPGTT. For each diabetic WKY and normal SHRSP and WKY, those given Cr showed lower levels of plasma glucose with lower levels of plasma insulin than the controls. For diabetic SHRSP, glucose uptake by isolated adipocytes in the Cr-dose group was higher than that in the control group. This effect of Cr administration involved enhancement of insulin responsiveness and sensitivity, attributed to enhanced affinity of the insulin receptor. A similar tendency was observed for diabetic WKY. However, for normal SHRSP and WKY, the increase in glucose uptake due to Cr administration coincided only with enhanced insulin responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Decrease in plasma GLP-1 immunoreactivity in starved rats.

To determine whether starvation affects the metabolism of glucagon-like peptide-1 (GLP-1), we measured the plasma levels of proglucagon-derived peptides and the biosynthesis and posttranslational processing of proglucagon in groups of six rats starved for 1, 3 and 5 days. The plasma levels of GLP-1 immunoreactivity (GLP-1 IR) and glucagon-like immunoreactivity (GLI) decreased during starvation reaching 79 and 56% of the respective control values by day 5 (P less than 0.05 and less than 0.01 vs control). The same is true of the plasma IRI level. The ileal contents of GLP-1 IR and GLI were 50.8 +/- 3.8 pmol/g wet weight and 161.8 +/- 13.2 pmol/g wet weight, respectively, on day 5 of starvation, which were significantly lower (P less than 0.01) than the respective values of 94.8 +/- 16.6 pmol/g wet weight and 262.7 +/- 28.1 pmol/g wet weight in control rats. However, the pancreatic contents of proglucagon-derived peptides tended to increase during starvation, although their increases were not statistically significant. No significant change in the posttranslational processing of proglucagon was detected during starvation. The decrease in the ileal proglucagon-derived peptides content was not associated with a decrease in intestinal proglucagon mRNA transcripts. These results suggested that decreased synthesis of proglucagon-derived peptides by the intestine was largely responsible for the reductions in their circulating levels in starved rats.

Analysis of Variance

[A study of factors affecting the concentration of serum lipid peroxide in the elderly inhabitants in a rural area].

Among 16 male (mean age of 66.6 years) and 51 female (mean age of 65.3 years) inhabitants of a rural area, the concentration of serum lipid peroxide measured as malondialdehyde (MDA) by Yagi's method was analyzed by physicochemical and food intake items. The MDA level in serum showed a peak of 6.2 nmol/ml at fifties years old in females and showed constant values of 4.6 and 6.1 nmol/ml for females and males, respectively, in those aged 60 more. The MDA level significantly correlated positively to total- or LDL-cholesterol level and urinary K/Cr, thus MDA level seemed to be a risk factor of arteriosclerosis. Fruit intake significantly positively correlated to MDA level in male. The MDA level showed a significantly higher level in the group with both higher total-cholesterol and urinary K/Cr levels, than in the other groups. It is suggested that a high intake of potassium increases the MDA level in the group with higher total-cholesterol level.

Aged

[A case of pulmonary atypical mycobacteriosis complicated with aplastic anemia, treated with surgical resection and postoperative sparfloxacin].

A few weeks after treatment with INH, RFP and SM, severe aplastic anemia developed in a 49-year-old man with pulmonary atypical mycobacteriosis due to M. kansasii. All drugs were discontinued immediately after bone marrow examination revealed severely hypoplastic marrow, but pancytopenia continued for several months. Although M. kansasii was sensitive to other drugs including CS and TH, these two drugs were also discontinued because of their respective psychiatric and hepatic adverse effects. Ofloxacin (OFLX), to which M. kansasii was sensitive, was administered without clinical improvement and complete resistance to OFLX developed after several months treatment. Right upper and middle lobectomy and S6 partial lobectomy was performed, and postoperative sparfloxacin (SPFX) administration resulted in cure of the disease. Drug sensitivity testing revealed that the organism had acquired resistance to OFLX, but was still sensitive to SPFX. Thus, SPFX appears to be an useful drug for the treatment of atypical mycobacteriosis.

Anemia, Aplastic

[Secondary sideroblastic anemia caused by long term administration of anti-tuberculous agents including isoniazid].

A 54 year-old man, who had been treated for several years with isoniazid, was transferred to our hospital because of intractable pulmonary tuberculosis. He was given several anti-tuberculous agents including INH, CS and/or PZA for a long period of time without improvement of the pulmonary tuberculosis. After 7 years' treatment with INH, hypochromic microcytic anemia developed. Parenteral administration of iron preparation failed to improve the anemia. The bone marrow findings revealed erythroid hyperplasia and a few erythroblasts showed megaloblastic change. The bone marrow iron staining revealed increased sideroblasts of which 88% were ringed-form. INH was then discontinued and pyridoxal phosphate was administered with rapid complete improvement of the anemia. INH is well known as a causative agent for acquired secondary sideroblastic anemia, however only one case of INH-induced sideroblastic anemia has been reported in Japan. This is the second reported Japanese case of INH-induced secondary sideroblastic anemia, which appears to be a very rare condition because of genetically determined rapid acetylation of INH in Japanese.

Anemia, Sideroblastic

[Post-gastrectomized vitamin B12 deficient anemia with marked leukoerythroblastosis and ringed sideroblasts].

A 77 year-old man, who had received total gastrectomy and splenectomy 11 years ago for gastric cancer was transferred to our hospital because of severe macrocytic anemia. He had been treated with vitamin B1, B2, C and iron preparations for several weeks. Ten days before admission numbness developed in his legs. On physical examination he appeared severely anemic. Laboratory findings revealed severe macrocytic anemia with poikilocytosis, anisocytosis, polychromasia, red cell fragmentation, Howell-Jolly bodies, Cabot rings and marked erythroblastosis (421/100 WBC). Hypersegmented neutrophils and immature granulocytes were also seen in the blood. The bone marrow picture showed marked erythroid hyperplasia, but erythroblasts revealed only slight megaloblastic changes. On bone marrow iron staining all erythroblasts were classified as type III sideroblasts and 15% of them were ringed-form. Serum vitamin B12 was low (44 pg/ml). Methylcobalamin given intramuscularly led to the rapid improvement of all hematological abnormalities including leukoerythroblastosis. Two weeks after vitamin B12 administration, ringed sideroblasts could no longer be detected in the bone marrow. Post-gastrectomy vitamin B12 deficiency anemias combined with erythroblastosis and ringed sideroblasts is a rare condition. Splenectomy is thought to play an important role in the pathogenesis of these conditions.

Aged

Potentiating effect of NH4Cl on vasoconstriction in rat aorta.

The effect on the vasocontractile response of pretreatment with NH4Cl at a concentration (10 mM) that made almost no change in the resting tension was investigated using aortic strips from rats. NH4Cl pretreatment for 10 min significantly potentiated strip contractions induced by KCl (less than or equal to 30 mM), BAY K 8644 (0.1 microM) and phenylephrine (0.01 microM). This potentiating action of NH4Cl was eliminated in presence of nifedipine (1 microM). KCl (14.7 mM)-stimulated 45Ca uptake in rat aorta was significantly potentiated by pretreatment with NH4Cl (10 mM) for 10 min, but this NH4Cl effect was also eliminated in the presence of nifedipine. These results suggest that NH4Cl potentiates contractions induced by KCl and agonists in rat aorta by facilitating calcium influx through the nifedipine-sensitive calcium channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

The role of cerebral microvessel endothelium in regulation of cerebral blood flow through production of endothelin-1.

We have previously reported the production of endothelin-1 (ET-1) by the cerebral microvessel endothelia and suggested an important role of ET-1 and microvessel endothelia in the regulation of local blood flow within the brain. In the present study, radioimmunoassay of ET-1 revealed that ET-1, produced by cultured cerebral microvessel endothelia grown on a filter, is released mainly to the basal side (corresponding to the basement membrane side), not to the apical side (corresponding to the vascular lumen side). This might indicate that ET-1 constricts arterioles locally at the same place where it is produced by endothelia. The present results also show that cultured cerebral microvessel endothelia produce less ET-1 under low oxygen pressure and that they produce more ET-1 under low carbon dioxide pressure. Taken together, our results may suggest that the negative feedback regulation of cerebral blood flow through oxygen and carbon dioxide pressure is mediated by ET-1 produced locally by cerebral microvessel endothelia.

Capillaries

Effect of carbon dioxide and oxygen on endothelin production by cultured porcine cerebral endothelial cells.

We have previously reported the production of endothelin, a potent vasoconstrictor peptide, by porcine cerebral microvessel endothelia and suggested its important role in the regulation of local blood flow within the brain. In our present study, radioimmunoassay with anti-porcine endothelin antiserum revealed that endothelin, produced by cerebral microvessel endothelia grown on a filter, is released mainly to the basement membrane side, not the vascular lumen side. This finding suggests that endothelin constricts arterioles locally where it is produced by endothelia. We also found that cerebral microvessel endothelia produce less endothelin under low oxygen pressure and more endothelin under low carbon dioxide pressure. Our results suggest that endothelin has a role in the regulation of cerebral blood flow in response to oxygen and carbon dioxide pressure.

Animals

Effects of physical exercise and cold stimulation on serum testosterone level in men.

The concentrations of testosterone (TS) and other related hormones in serum were examined before and after physical exercise with a bicycle ergometer (90 Watts, 20 min.) and a cold water stimulation in 32 19-year-old males. While exercising, the serum TS level significantly increased by 20.8% (p less than 0.05), the luteinizing hormone (LH) level by 3.6% (p less than 0.05) and noradrenaline (NA) level by 140.0% (p less than 0.01). During cold water stimulation, TS decreased by 10.0%, LH increased by 22.1% and NA decreased by 23.8%. Based on changes in hormone levels within the individual during the loads. there was a significant positive correlation coefficient (r) between TS and LH, and between TS and NA, with r (TS-LH) = 0.399 (p less than 0.05) and r (TS-NA) = 0.481 (p less than 0.05) for physical exercise, while r (TS-LH) = 0.403 (p less than 0.05) and r (TS-NA) = 0.431 (p less than 0.05) for cold water stimulation, respectively. These results suggest that physical exercise increases TS level in serum by increasing LH and NA levels, but these tendencies were not found with cold water stimulation.

Adult

[A case of rush dust (IGUSA-SENDO) pneumoconiosis with a large conglomerate mass shadow].

A 61-year-old woman, who had engaged in "tatami" mat production for 20 years, showed a gradually increasing large conglomerate mass shadow associated with small irregular opacities on chest X-ray film. Transbronchial lung biopsy revealed findings consistent with pneumoconiosis, with no suggestion of pulmonary tuberculosis or lung cancer. After 6 years' observation, right upper lobectomy was performed because the mass shadow was still increasing in size. Histological examination revealed a well-defined large mass composed of numerous macrophages containing abundant silicate minerals and fibroblasts proliferating in storiform fashion. No evidence of tuberculosis or malignancy has ever been detected. These findings are compatible with the previously reported pathological findings of "IGUSA-SENDO" pneumoconiosis; however, PR4 type "IGUSA-SENDO" pneumoconiosis has never been previously reported. This is the first reported case of PR4 type "IGUSA-SENDO" pneumoconiosis.

Female

[In vitro activities of newly developed quinolones, fleroxacin, lomefloxacin and sparfloxacin against Mycobacterium tuberculosis].

In vitro antituberculous activities of three newly developed quinolones, fleroxacin (FLRX, AM-833), lomefloxacin (LFLX) and sparfloxacin (SPFX, AT-4140) were evaluated in comparison to that of ofloxacin (OFLX) using M. tuberculosis strains isolated from patients and the Ogawa egg medium. SPFX was apparently more active than OFLX, but both FLRX and LFLX were less active. SPFX inhibited completely the growth of all 20 strains of M. tuberculosis isolated from patients who were not previously treated with OFLX in a concentration of 1.25 micrograms/ml. However, this agent inhibited the growth of only 4 strains (28.6%) of 14 OFLX-resistant M. tuberculosis in a concentration of 1.25 micrograms/ml, suggesting a partial cross-resistance between SPFX and OFLX.

Anti-Infective Agents

Cerebral microvessel endothelium is producing endothelin.

Endothelin, a potent vasoconstrictor peptide, was recently isolated from the supernatant of the cultured endothelia of the porcine aorta and is now supposed to be the most likely candidate for the endothelium-derived contractile factor (EDCF), which is responsible for the endothelium-dependent vasoconstriction by various stimuli. In this study, the production of endothelin by the endothelia of porcine cerebral microvessels was revealed by the Northern blot analysis with porcine endothelin cDNA probe and the enzyme-linked immunosorbent assay (ELISA) with anti-porcine endothelin antibody. Our results raise the possibility that the endothelia of cerebral microvessels regulate the local blood flow within the brain through the production of endothelin.

Animals

Structural characterization of the isoenzymatic forms of human myeloperoxidase: evaluation of the iron-containing prosthetic group.

Myeloperoxidase (MPO) from human neutrophils has been purified and found to exist in three isoenzymatic forms, resolved by ion exchange chromatography. In addition to differences in subunit size and cellular compartmentalization of the isoenzymes, differences have been reported in their activity and susceptibility to inhibition. The structural basis of these isoenzymes is unclear; we attempted to further define their functional characteristics and structural identity. First, we measured respective enzymatic activity using a panel of substrates; MPO I was found to have lower activity with some substrates (pyrogallol, guaiacol, potassium iodide [KI]), but similar activity to the other isoenzymes with 4-aminoantipyrine. These studies confirm that MPO I is enzymatically distinct from MPO II and MPO III. Next, we examined the structural basis of these differences by evaluating the iron-containing prosthetic group in each form using electron paramagnetic resonance (EPR) and determination of the pyridine hemochrome. No significant difference between the isoenzymes was noted in these parameters, suggesting that the prosthetic group is the same in each protein. The cause for any difference in enzymatic activity must lie then in variations extrinsic to the heme, and based on previous studies of the gene and protein analysis, the posttranslational modification of MPO must account for these isoenzymatic species.

Electron Spin Resonance Spectroscopy

Effect of age on contractile response to angiotensin II in rat aorta.

The effects of aging on contractile response to angiotensin II and tachyphylaxis to it were investigated using aortic strips from rats aged 1.5, 4 and 22 months. Whether the endothelium was present or not, the contractile response to angiotensin II was greater and tachyphylaxis to it was less in 1.5-month-old rats than in 4- and 22-month-old rats. The differences between 4- and 22-month-old rats were not significant. Removal of the endothelium enhanced angiotensin II-induced maximal contraction and depressed the tachyphylaxis, these endothelial effects being greater in 4- rather than in 1.5-month-old rats. When the contractile force of angiotensin II was adjusted to a similar level for 1.5- and 4-month-old rats, the endothelial effect on the tachyphylaxis was greater in the 4-month-old rats, but no significant difference was noted in the endothelial effect on the contractile force. These results suggest that during growth, the contractile response of rat aorta to angiotensin II decreases while the endothelial effect on it increases.

Acetylcholine

Relation of serum and erythrocyte magnesium levels to blood pressure and a family history of hypertension. A follow-up study in Japanese children, 12-14 years old.

Serum and erythrocyte magnesium concentrations (S-Mg, E-Mg) were measured in 122 junior high school students followed up for two years from 12 to 14 years of age, and the relationship to blood pressure and a family history of hypertension were investigated. The subjects who had high S-Mg and E-Mg levels at the first examination two years prior tended to show high levels after this follow-up. There were significant positive correlations between two intraindividual values of S-Mg and E-Mg. A similar tendency was found for blood pressure. Tracking phenomena were observed with these measures. The subjects who had high E-Mg levels at the first examination showed no blood pressure elevation during the two-year period. The subjects with a family history of hypertension [FH(+)] showed a higher degree of blood pressure rise during two years than those with no family history [FH(-)], with a significant difference in systolic blood pressure at the age of 14. E-Mg tended to be lower in the FH(+) group than in the FH(-) group with a significant difference in 14-year-old girls. These results suggest that a hereditary predisposition to hypertension is related to magnesium metabolism and that intracellular magnesium deficiency may influence blood pressure elevation in the FH(+) children.

Adolescent

Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops.

The structure-activity relationship of sugars inducing secretion of glucagon-like peptide-1 from the gut was examined using intestinal loops prepared from the terminal portion of the ileum of dogs. The plasma glucagon-like peptide-1 concentration in a mesenteric vein draining only the looped region of the intestine was increased after infusion of 139 mmol/l solutions of D-glucose, D-galactose, D-glucuronic acid, 3-0-methyl-D-glucose, maltose, sucrose or maltitol into the intestinal lumen, but not after infusion of solutions of D-fructose, D-fucose, D-mannose, D-xylose or lactose. The increases in plasma glucagon-like peptide-1 concentration correlated with the corresponding increases in glucagon-like immunoreactivity induced by these sugars. The plasma glucose level of the regional mesenteric vein increased significantly from the basal level after instillation of D-glucose, but not after instillation of other sugars. It is suggested that cells of the gut have a glucose sensor for release of products of the glucagon gene and that this sensor has specific steric requirements. The sugars that induced glucagon-like peptide-1 release share the molecular features of electron density near C(6), an equatorial hydroxyl at C(2), and an axial hydroxyl at C(1), which could account for their recognition by the glucose sensor to initiate the releases of glucagon-like peptide-1 and glucagon-like immunoreactivity.

3-O-Methylglucose