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Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 865 records · Page 48Linked to original sources
PubMed1993

Hepatic vagal amino acid sensors modulate amino acid induced insulin and glucagon secretion in the rat.

To clarify the physiological role of vagal amino acid sensors in the liver, the effect of hepatic vagotomy and/or celiac vagotomy (sectioning of the hepatic branch and/or the celiac branches of the vagus nerve) on the secretion of insulin and glucagon after intraperitoneal injection of neutral (L-alanine, L-leucine, and L-phenylalanine), acidic (L-glutamate), or nonmetabolized (cycloleucine) acids, was examined in rats. Hepatic vagotomy enhanced both plasma glucose and glucagon concentrations after intraperitoneal injection of alanine more than those in sham-vagotomized (control) rats, while after intraperitoneal injection of leucine, hepatic vagotomy decreased plasma glucose concentrations and enhanced plasma insulin concentrations more than in control animals. These effects, following both alanine and leucine administration, were blocked by celiac vagotomy. Glutamate, phenylalanine, and cycloleucine stimulation in hepatic-vagotomized rats caused no significant differences in plasma glucose, insulin, or glucagon levels as compared to those in sham-vagotomized rats. Celiac vagotomy alone did not affect plasma glucose, insulin, or glucagon concentrations after stimulation by these five amino acids. The physiological role of alanine and leucine sensors may be to prevent amino acid-induced exaggerated pancreatic hormone secretion and to maintain blood glucose homeostasis, while glutamate, phenylalanine, and cycloleucine have no effect on this pancreatic neuroendocrine system.

Amino Acids↗
PubMed1993

Acute and chronic effects of VMH lesions on circadian rhythms in food intake and metabolites.

In the dynamic phase, 3 weeks after surgery, food intake increased especially during the latter part of the light cycle in VMH-lesioned rats, and the difference between light and dark cycles disappeared. The rhythms of serum insulin, glucose, and triglyceride disappeared. Concentrations of glucose during the light cycle were lower than those of sham-operated rats, although concentrations of triglyceride and insulin were higher than those of sham-operated rats at all times. In the static phase, 12 weeks after surgery, the difference of food intake between light and dark cycle appeared in VMH-lesioned rats, but the loss of rhythmicity for serum glucose, insulin, and triglyceride remained. Concentrations of glucose except early light phase and concentrations of triglyceride and insulin at all times were higher than those of sham-operated rats. VMH lesions thus abolished circadian rhythmicity in serum insulin, glucose, and triglyceride for a long period; however, the disturbed rhythmicity of food intake was reversible.

Animals↗
PubMed1993

Cigarette smoking during pregnancy lowers aromatase cytochrome P-450 in the human placenta.

To clarify whether cigarette smoking during pregnancy causes an organic alteration in placental estrogen producing ability, we determined the catalytic activity of aromatase by the tritiated water assay, and tissue level of aromatase cytochrome P-450 (P-450arom) by the specific enzyme-linked immunosorbent assay, in placental samples from nonsmokers and smokers. As pregnancy progressed, both aromatase activity and P-450arom concentration increased in placentas from nonsmokers and smokers. However, the gradient of the increase was significantly less in heavy smokers (> or = 20 cigarettes a day) than in normal and moderate smokers (< 20 cigarettes a day). At term, the mean aromatase activity and P-450arom concentration in placentas from heavy smokers were significantly lower than in nonsmokers and moderate smokers, while aromatase activity per P-450arom (turnover rate) and the mean placental weight were comparable among the three groups. In contrast, the ratio of aryl hydrocarbon hydroxylase activity to aromatase activity was higher in placentas from heavy smokers. Immunohistochemical studies showed that P-450arom was localized in the cytoplasm of syncytiotrophoblasts of chorionic villi in placentas from both nonsmokers and smokers. These results suggest that the induction of placental P-450arom during gestation is suppressed by maternal smoking, resulting in a reduction in estrogen producing ability, while placental xenobiotic P-450 is induced.

Aromatase↗
PubMed1993

Higher white blood cell counts and band forms in newborns delivered vaginally compared with those delivered by cesarean section.

The authors retrospectively reviewed complete blood counts in the medical records of all babies admitted to a normal newborn nursery from January through December 1989. The subjects consisted of 326 babies who were delivered vaginally (VgD) and 138 who were delivered by Cesarean section (CS). All blood samples were drawn by warmed or unwarmed heel sticks or by venipuncture. The subject's age at the time of blood drawing was similar in both VgD and CS groups (13.4 vs. 13.9 hours, P = 0.51). The number of total leukocytes, neutrophils, band forms, and platelets was significantly higher in VgD newborns than in CS newborns. The mean and standard error of the mean for each of these blood counts (each per microliter) were 23.9 x 10(9) +/- 0.33 versus 21.1 x 10(9) +/- 0.6, 14.6 x 10(9) +/- 0.26 versus 12.8 x 10(9) +/- 0.39, 1.18 x 10(9) +/- 0.08 versus 0.82 x 10(9) +/- 0.08, and 304 x 10(9) +/- 4.1 versus 286 x 10(9) +/- 0.6, respectively (P values for the first three comparisons were all less than 0.005). However, there was no difference between the two groups with regard to hemoglobin, hematocrit, and absolute number of lymphocytes, eosinophils, basophils, and monocytes (P > 0.5). It was speculated that the higher leukocyte, neutrophil, and band counts in VgD babies are the consequences of physical stress and periodic hypoxia, which are more frequent and prolonged with VgD compared with CS delivery. The authors suggest that the mode of delivery should be considered when interpreting blood counts in neonates.

Cesarean Section↗
PubMed1993

Biotin-containing intranuclear inclusions in endometrial glands during gestation and puerperium.

Intranuclear inclusions sometimes are observed in endometrial glands, especially during puerperium, and superficially they resemble those from herpesvirus-infected cells. To study the significance of the inclusions, endometrial and placental tissue from 215 subjects, including 69 pregnancy-associated samples, were examined. With screening by peroxidase-labeled avidin alone, followed by the peroxidase reaction, only pregnancy-related endometrium (in 32 cases) demonstrated reactivity in the intranuclear inclusions. These intranuclear inclusions demonstrated positive immunostaining for biotin using the peroxidase-antiperoxidase method in all but six cases, whereas there was no reaction for Herpes simplex in any of the cases. The endometrial tissues of the 32 cases were obtained from the 16th gestational week to the 37th postpartum day. Although the histogenesis of these intranuclear inclusions has not been clarified, they should not be mistaken for those in endometrial cells infected by herpesvirus because of intranuclear biotin and a false-positive histochemical reaction in the avidin-biotin-peroxidase complex method.

Biotin↗
PubMed1993

Site-specific DNA damage and 8-hydroxydeoxyguanosine formation by hydroxylamine and 4-hydroxyaminoquinoline 1-oxide in the presence of Cu(II): role of active oxygen species.

Mutagenic hydroxylamine (NH2OH) and 4-hydroxyamino-quinoline 1-oxide (4-HAQO), a carcinogenic metabolite of 4-nitroquinoline 1-oxide (4-NQO), cleaved isolated DNA in the presence of Cu(II), but not in the presence of Mn(II), Mn(III), Fe(II) or Fe(III). The Cu(II)-mediated DNA damage by NH2OH was inhibited by catalase and bathocuproine, a Cu(I)-specific chelator, but not by scavengers of hydroxyl free radical. With the Cu(II)-mediated DNA damage by 4-HAQO, similar scavenger effects were observed. It is suggested that free .OH is not the main active species causing the DNA damage in both the cases. The predominant cleavage sites were thymine residues, especially the thymine residue of 5'-GTC-3' sequence. Since the cleavage pattern was similar to that induced by Cu(I) plus H2O2 but not to that induced by Cu(II) plus H2O2, it is speculated that the copper-oxygen complex derived from the reaction of H2O2 with Cu(I) participates in the DNA damage. 8-Hydroxydeoxyguanosine (8-OH-dG) residues were efficiently formed in calf thymus DNA treated with NH2OH plus Cu(II) or 4-HAQO plus Cu(II). The role of Cu(II)-mediated DNA damage and 8-OH-dG formation in the genotoxicity of NH2OH, 4-HAQO and 4-NQO is discussed.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1993

Hydrolysis of micellar diheptanoylphosphatidylcholine catalyzed by bovine pancreatic phospholipase A2: kinetic characterization of group I and II enzymes.

Initial velocity data for the hydrolysis of micellar 1,2-diheptanoyl-sn-glycero-3-phosphorylcholine (diC7PC) catalyzed by bovine pancreatic PLA2 (Group I) were analyzed using the Michaelis-Menten equation. The Km value for the micellar substrate was found to be independent of Ca2+ concentration, as was the Km value for the monodispersed substrate. The pH dependence curve of Km in the presence of saturating amounts of Ca2+ showed two transitions reflecting large pK shifts of two ionizable groups from 5.0 to 5.45 and from 9.5 to 10.25, whereas the Km value for the monodispersed substrate was independent of pH [Fujii et al. (1991) J. Biochem. 110, 1008-1015]. The pH dependence curve of kcat showed three transitions, indicating the participation of three ionizable groups with pK values of 5.45, 8.4, and 10.25. Deprotonation of the first group and protonation of the third group were found to be essential for catalysis. The respective groups were assigned as the catalytic group His 48, the N-terminal alpha-amino group, and invariant Tyr 52. The present results as well as those for another Group I PLA2 (Naja naja atra) are very different from those for Group II PLA2s (Agkistrodon halys blomhoffii and Trimeresurus flavoviridis), which showed Ca(2+)-dependent substrate binding and no participation of the alpha-amino group in catalysis [Teshima et al. (1989) J. Biochem. 106, 518-527; Nishimura et al. (1992) J. Biochem. 111, 210-218].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Isolation and amino acid sequence of a phospholipase A2 inhibitor from the blood plasma of Agkistrodon blomhoffii siniticus.

Phospholipase A2 inhibitor (PLI) was purified from the blood plasma of Chinese Mamushi, Agkistrodon blomhoffii siniticus, by sequential chromatography on Sephadex G-200, Mono Q, and Blue-Sepharose CL-6B columns. The purified PLI was a glycoprotein with an apparent molecular mass of 75 kDa and was composed of a single subunit with a mass of about 20 kDa. From the results of a cross-linking experiment, the PLI was found to present as a homotrimer of the subunit. The fundamental properties of A. blomhoffii siniticus PLI were very similar to those of Habu Trimeresurus flavoviridis PLI [Kogaki et al. (1989) J. Biochem. 106, 966-971], although the latter was composed of two homologous subunits, PLI-A and PLI-B [Inoue et al. (1991) J. Biol. Chem. 266, 1001-1007]. The amino acid sequence of the subunit of A. blomhoffii siniticus PLI was determined by alignment of the peptides obtained by lysyl endopeptidase digestion or Staphylococcus aureus V8 protease digestion. The subunit was composed of 147 amino acid residues with one residue, Asn103 being N-glycosylated. The molecular weight of its protein portion was calculated to be 16,444 Da. The amino acid sequence of A. blomhoffii siniticus PLI subunit showed about 75% homology to those of T. flavoviridis PLI subunits, and also showed significant homologies to those of the carbohydrate recognition domains of C-type lectins.

Amino Acid Sequence↗
PubMed1993

Age-related changes of DRG neuronal attachment to extracellular matrix proteins in vitro.

Attachment of dorsal root ganglion (DRG) neurones from 3-month-old (young adult) and 24-month-old (aged) mice to the following substrates was evaluated after 6 h in culture: (1) poly-L-lysine (PL), (2) PL + type I collagen (CL-I), (3) PL + type IV collagen (CL-IV), (4) PL + laminin (LM) and (5) PL + fibronectin (FN). In the young adult mice, each substrate coated onto PL, significantly increased the ratio of attachment, compared with PL alone. In the aged mice, CL-I and LM, but not CL-N or FN improved the attachment. There was no difference in cell survival or neurite extension after 48 h in culture between the two groups of mice. These results suggest that ageing causes selective changes of the neuronal cell-surface receptors respective to extracellular matrix proteins such as CL-IV and FN.

Aging↗
PubMed1993

Changes in plasma 5-S-cysteinyldopa concentration in B16 melanoma-bearing mice treated with interferon-beta or dacarbazine.

We have previously shown that the urinary excretion of 5-S-cysteinyldopa (5-S-CD) reflects well the progression of B16 mouse melanoma. We examined the usefulness of plasma concentration of 5-S-CD in following the progression of melanoma and evaluating the efficacy of immuno- and chemotherapeutic agents in the B16 mouse model. Murine interferon-beta (MuINF-beta; 3 x 10(5) U) or dacarbazine (DTIC; 50 mg/kg) was administered once a day for 10 or 5 consecutive days starting 8 days after subcutaneous inoculation of B16 melanoma cells in C57BL/6 mice. Blood samples were collected from the tail vein and tumour volumes were measured every other day until day 24. Levels of 5-S-CD in plasma were determined by high-performance liquid chromatography. Tumours became palpable on day 6-8 and grew exponentially thereafter in the control mice. Tumours in INF-beta-treated mice also grew exponentially, although at a reduced rate. However, the growth of tumours in the DTIC-treated mice was almost suppressed between days 12 and 18. Mean values of tumour volume on day 16 were 1.45, 1.05, and 0.83 cm3 in the control, INF-beta-treated, and DTIC-treated groups, respectively. The plasma concentration of 5-S-CD began to increase on day 8, at much slower rates in the experimental groups than those in the control group. Mean values of plasma 5-S-CD on day 16 were 14.3, 5.9, and 5.6 nmol/l in the control, INF-beta-treated, and DTIC-treated groups; 5-S-CD level on day -2 was 1.8 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Hebephrenia as the most prevalent subtype of schizophrenia in Japan.

The author reviewed the frequency of the hebephrenic subtype compared to the paranoid subtype diagnosis of schizophrenia in Japan, using research papers and statistical reports that have been published during this century. It was found that the reported rates for the hebephrenic subtype ranged from a low of 23% to a high of 68% with the majority falling between 30% and 50%. These rates had not varied significantly over a long period of time or across wide geographical areas. It was discussed that Japanese psychiatrists were so sensitive to the negative symptoms of schizophrenia that they had a broader concept of hebephrenia as compared to other Kraepelian subtypes in schizophrenia.

Ambulatory Care↗
PubMed1993

Antimelanoma activity of chloroquine, an antimalarial agent with high affinity for melanin.

The antimalarial agent chloroquine is known for high affinity for melanin. This 4-aminoquinoline derivative was examined for anti-melanoma activity and uptake into melanoma cells. Chloroquine inhibited growth of cultured melanoma cells; the effect was much greater to a moderately pigmented cell line HMV-II than to a nonpigmented HMV-I. Treatment with chloroquine at a dose of 62 mg/kg i.p. for 12 days prolonged by 71% the life span of mice bearing B16 melanoma, while 24-day treatment at 31 mg/kg resulted in a 81% increase in life span. HMV-II cells showed a two-fold increase in uptake of chloroquine as compared with HMV-I cells. Chloroquine, 24 hr after administration to mice implanted s.c. with B16 melanoma, was selectively accumulated in the pigmented tissues, melanoma and eyes. Other nonpigmented tissues such as the liver, lung, and kidney showed rapid uptake (within 1 hr) and release. These results suggest that chloroquine is toxic to pigmented melanoma cells, the process being partly mediated by binding to melanin.

Animals↗
PubMed1993

Determinants of fasting hypertriglyceridemia in ventromedial hypothalamic obesity in rats.

The present study investigated the mechanism of fasting hypertriglyceridemia in ventromedial hypothalamic (VMH) obesity by measurement of post-heparin plasma lipoprotein lipase (LPL) activity, triglyceride secretion rate (TGSR), and plasma insulin. One week after VMH lesions, when the lesioned rats were gaining weight rapidly (the dynamic phase), they showed normal plasma triglyceride levels with increased plasma LPL activity and TGSR. There was a positive correlation between hyperinsulinemia and elevated plasma LPL activity or TGSR in VMH-lesioned rats, while no correlation was observed in control rats. Ten weeks after VMH lesions, when the rats had become obese and reached a steady-state weight gain (the static phase), they showed hypertriglyceridemia with increased plasma LPL activity and TGSR. There was, again, a positive correlation between hyperinsulinemia and elevated plasma LPL activity or TGSR in VMH-lesioned rats. These results suggest a possible mechanism of fasting hypertriglyceridemia in these rats; in the dynamic phase adipose tissue adequately takes up circulating triglyceride because the tissue has sufficient take-up capacity and hence hypertriglyceridemia does not develop. In the static phase the tissue cannot adequately take up circulating triglyceride because of a limitation of its capacity, resulting in hypertriglycemia despite enhanced triglyceride secretion and increased LPL activity in both phases.

Animals↗
PubMed1993

Acute myocardial infarction without warning: clinical characteristics and significance of preinfarction angina.

We investigated the clinical characteristics of acute myocardial infarction (AMI) not preceded by angina in 256 patients with first AMIs. Complications, including sustained ventricular tachycardia or ventricular fibrillation, pump failure and cardiac rupture, were more frequent in patients with AMI not preceded by angina (group 1, n = 92) than those preceded by angina (group 2, n = 164). The in-hospital mortality rate was higher in group 1 than in group 2. Poor preexisting collateral channels or lack of ischemic preconditioning may be responsible for the poorer outcome in group 1 patients.

Aged↗
PubMed1993

Regressing nevoid nail melanosis in childhood.

The natural course of nail pigmentation was documented in 4 Japanese children. Although initial progression of melanosis concerning size and degree of pigmentation was noted, all cases showed a tendency to fade during the follow-up period. The published cases of nevoid nail melanosis in childhood were reviewed, and we concluded that they were essentially benign. However, should there be any suspicion of malignant changes, punch biopsy is indicated for medico-legal reasons. Management of growing pigmented nail streaks in childhood is one of the most difficult and delicate problems facing dermatologists, as they can be precursors of malignant melanoma. There is a condition of the nail known as longitudinal melanonychia or naevus striae unguis, possibly of nevoid nature. Prevalence rates of nevoid diseases showing pigmentation of the skin vary depending on the ethnic origin. In order to understand the natural course of nail area pigmentation in childhood, we have followed 4 Japanese children with such a condition. We report our observations and review the literature.

Child↗
PubMed1993

Expression of follistatin, an activin-binding protein, in vascular smooth muscle cells and arteriosclerotic lesions.

Activin-A has a mitogenic effect on vascular smooth muscle cells (SMCs) and is produced by monocyte/macrophage lineage cells. Here, we studied the expression of follistatin, an activin-binding protein, in both A10 cells, a rat aortic SMC line, and vascular SMCs derived from adult rat aorta. Follistatin mRNA was detected in these cells by Northern blot analysis. Ligand blot and immunoblot analyses demonstrated that follistatin was produced in the conditioned medium at a higher level by A10 cells than by SMCs. Furthermore, immunostaining and in situ hybridization of the arteriosclerotic lesions showed that follistatin was highly expressed in the diseased artery, where abnormal proliferation of SMCs occurred. We suggest that follistatin is produced by vascular SMCs and is involved in the course of atherogenesis.

Activins↗
PubMed1993

The phenotypic and functional changes of rat Kupffer cells cultured with interleukin-2.

We examined the direct effects of human recombinant interleukin 2 (hrIL-2) in vitro on the phenotypic and the functional changes of rat Kupffer cells (KCs) isolated by collagenase perfusion and differential centrifugation. When KCs were cultured with high concentrations of hrIL-2, marked changes were dose-dependently observed in phenotypic expression, phagocytic activity, and accessory cell function compared to untreated KCs. In the phenotypic changes, approximately 70% of KCs expressed class 2 antigen after 48-hr culture. Moreover, rapid expression of iC3b receptor on KCs was observed after 6 hr culture. KC phagocytic activity of both 0.81- and 2-microns latex particles was increased by incubating with hrIL-2 (10(4) U/ml) as compared to those of untreated KCs. Complement-mediated phagocytosis was more dominant than that of Fc receptor-mediated phagocytosis without hrIL-2 and augmented by increasing concentrations of hrIL-2. Accessory cell function of KCs was greatly augmented by preincubation with hrIL-2 (10(4) U/ml) for 24 hr. In the presence of 10(-6) M of indomethacin or prostaglandin E2, accessory cell function was at a lower level than without. This suppressive effect of indomethacin or prostaglandin E2 was reduced at lower concentrations. These results suggest that the potential ability of hrIL-2-activated KCs is closely associated with the ongoing pathophysiological process in the liver during IL-2 immunotherapy.

Animals↗