Search PubMed⌕ Search

Biomedical subjects

M Kubota

Publications and source records attributed to M Kubota.

At least 289 records · Page 16Linked to original sources
PubMed1995

Asymptomatic hyperglycaemia is associated with increased intimal plus medial thickness of the carotid artery.

Atherosclerotic changes have not been demonstrated directly in asymptomatic hyperglycaemic non-diabetic subjects, although high mortality due to coronary heart disease has been reported. We measured arterial wall thickness non-invasively, in order to directly demonstrate atherosclerosis of the carotid arteries of hyperglycaemic non-diabetic subjects and to evaluate its risk factors. The thicknesses of the intimal plus medial complex (IMT) of the carotid arteries of 112 asymptomatic hyperglycaemic non-diabetic subjects (aged 22-81, 95 males and 17 females) were compared with those of 55 healthy male subjects and 211 non-insulin-dependent NIDDM male diabetic patients. The subjects were subgrouped into impaired glucose-tolerant (IGT) subjects who had a 2-h glycaemic level of more than 7.8 mmol/l, and non-IGT subjects whose 2-h glycaemic levels were within 6.7-7.7 mmol/l. Non-IGT and IGT subjects showed significantly greater IMTs than age-matched healthy males and showed no significant differences compared to age-matched NIDDM patients. Multivariate analysis demonstrated that the risk factors for IMT of non-IGT and IGT subjects were age and systolic blood pressure. According to data on the accumulation of atherogenic risks (hypertension, dyslipidaemia, and smoking), IMT increased linearly in non-IGT and IGT subjects. However, non-IGT and IGT subjects without hyperlipidaemia, hypertension, or smoking risk still had significantly greater IMT than age-matched normal males (1.019 +/- 0.063 vs 0.770 +/- 0.111 mm, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Negative-ion fast atom bombardment tandem mass spectrometry for characterization of sulfated unsaturated disaccharides from heparin and heparan sulfate.

Negative-ion fast atom bombardment tandem mass spectrometry has been used in the characterization of non-, mono-, di- and trisulfated disaccharides from heparin and heparan sulfate. The positional isomers of the sulfate group of monosulfated disaccharides were distinguished from each other by negative-ion fast atom bombardment tandem mass spectra, which provide an easy way of identifying the positional isomers. This fast atom bombardment collision induced dissociation mass spectrometry/mass spectrometry technique was also applied successfully to the characterization of di- and trisulfated disaccharides.

Carbohydrate Sequence↗
PubMed1995

Augmentation by aphidicolin of 1-beta-D-arabinofuranosylcytosine-induced c-jun and NF-kappa B activation in a human myeloid leukemia cell line: correlation with apoptosis.

1-beta-D-arabinofuranosylcytosine (ara-C) (2 microM) can induce apoptosis in a human myeloid leukemia cell line, U937, after 4 h of incubation. Pretreatment of cells with aphidicolin (2 microM) augments ara-C-induced apoptosis, since it was first observed at 0.4 microM ara-C and became more intense at 2 and 10 microM. Although aphidicolin itself had a marginal effect on c-jun expression, it significantly augmented ara-C induced c-jun upregulation by shortening the lag time and lowering ara-C concentrations necessary for the induction of detectable c-jun transcripts. Aphidicolin and ara-C acted synergistically to increase NF-kappa B DNA binding activity as determined by an electrophoretic mobility shift assay. Expression of c-myc was slightly increased through the DNA degradative phase, and was then downregulated. Thus, the activation of NF-kappa B and c-jun expression seems to be well correlated with the potentiation by aphidicolin of ara-C-induced apoptosis.

Antimetabolites, Antineoplastic↗
PubMed1995

Influence of oral sulfonylurea agents on hepatic glucose uptake.

Although the metabolic derangement in the subjects with well-established NIDDM is characterized by both insulin resistance and diminished insulin secretion, the impaired sensitivity to insulin in the target tissues is assumed to represent the primary defect in most NIDDM individuals. Therefore, the therapeutic modality that can augment insulin-mediated glucose metabolism in the target tissues seems rational in the treatment of NIDDM. Glimepiride (HOE490), a newly developed sulfonylurea, has been reported to have a more potent hypoglycemic action than glibenclamide while its ability to stimulate insulin secretion is much weaker. Thus, part of the potent hypoglycemic action of HOE490 has been speculated as being due to an extrapancreatic effect. First we examined the effect of strict glycemic control on insulin resistance seen in NIDDM using euglycemic hyperinsulinemic clamp combined with oral glucose loading (Clamp-OGL) to 9 subjects with NIDDM. After 3 to 4 weeks of intensified insulin therapy, insulin-mediated glucose uptake by the liver significantly increased while peripheral glucose disposal did not change. Secondly we applied Clamp-OGL to 5 subjects with IDDM to study the acute metabolic effect of HOE490 on glucose handlings by the target tissues. Intravenous administration of HOE490 at a rate of 6.0 micrograms/min did not affect hepatic glucose uptake in these subjects. Thus we studied subacute metabolic effect of HOE490 on glucose handlings by the target tissues in 7 normal dogs using euglycemic clamp combined with hepatic venous catheterization technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Insulin resistance in essential hypertensive patients with impaired glucose tolerance.

This study evaluated insulin secretion and insulin sensitivity in 17 non-obese hypertensive patients (aged 45.6 +/- 2.2 years, body mass index 24.0 +/- 0.5 kg/m2, mean +/- S.E.M.) with (n = 8) and without glucose intolerance (n = 9) and compared the results with those of 16 age-matched non-obese normotensive subjects with (n = 7) and without glucose intolerance (n = 9). The hypertensive patients without glucose intolerance showed a significantly lower insulin-mediated glucose disposal and a compensating increase in second-phase insulin secretion compared with normotensives without glucose intolerance. In hypertensives with glucose intolerance, insulin-mediated glucose disposal was significantly lower and second-phase insulin secretion was comparable to that in normotensives without glucose intolerance. After 3 months of angiotensin-converting enzyme (ACE) inhibition with oral administration of delapril, blood pressure was significantly reduced in the hypertensives with glucose intolerance (n = 9). The insulin-mediated glucose disposal significantly (P < 0.01) recovered from 6.0 +/- 0.81 to 8.0 +/- 0.71 mg/kg per min. The second-phase insulin secretion tended to be lower (but not significantly) but insulin clearance increased from 15.4 +/- 0.85 to 19.1 +/- 1.42 ml/min (P < 0.05). These data show that in hypertensive patients without glucose intolerance insulin resistance might compensatorily augment second-phase insulin secretion and lead to hyperinsulinemia. In hypertensives with glucose intolerance, insulin resistance might induce postprandial hyperglycemia, which leads to hyperinsulinemia because of second phase insulin secretion at a level similar to that of normotensives.

Administration, Oral↗
PubMed1995

Somatic cell mutation frequency at the HPRT, T-cell antigen receptor and glycophorin A loci in Cockayne syndrome.

Skin fibroblasts of patients with Cockayne syndrome (CS) are hypersensitive to the lethal or mutagenic effect of ultraviolet light, which may cause genetic instability. Up to now, however, no systematic study of in vivo somatic cell mutation in CS cells has been reported. This article describes our investigation of the mutation frequencies (Mfs) at three different loci, i.e. hypoxanthine-guanine phosphoribosyl transferase (HPRT), T-cell antigen receptor (TCR) and glycophorin A (GPA), in six patients with CS. Mfs at the HPRT and TCR loci were found to be within the normal range as determined in age-matched controls. In the GPA locus of two patients, there was a slight increase, but it was much smaller than that reported in other DNA repair deficient syndromes. The frequency of spontaneous HPRT mutation in Epstein-Barr virus transformed B-lymphoblastoid cells derived from CS patients was similar to that in cells from normal children. The molecular characterization of the representative HPRT mutant T cell clones from CS patients did not show any structural alterations. These results may explain, at least in part, why CS is not associated with predisposition to cancer.

Adolescent↗
PubMed1995

A possible approach to the suppression of side effects induced by PGE1.

Prostaglandin E1 (PGE1) is known to possess various actions in vivo. Of these actions, the contraction of the ileum and inflammation are undesirable side effects. We previously proposed a hypothesis concerning the receptors for human blood platelet aggregation and its inhibition, and the contraction of the ileum and uterus based on a study of structure-activity relationships. If the same principle can be applied to contraction of the ileum and inflammation induced by PGE1, compounds that suppress the side effects of PGE1 can be developed. The antihistamine diphenylpyraline and the anticholinergic atropine antagonized PGE1-induced contraction of the ileum in guinea pigs. Papaverine, which is a smooth muscle relaxant, also acted as an antagonist. Gabexate mesylate (FOY), a non-peptide proteinase inhibitor, inhibits guinea pig ileum contraction induced by PGE1, but epsilon-guanidinocaproic acid (GCA), a metabolite of FOY, does not. Increased microvascular permeability of the abdominal skin in rats induced by the local injection of PGE1 and histamine was suppressed by atropine, papaverine and diphenylpyraline. FOY, not GCA, had a weak inhibitory action. We demonstrate the possibility of suppressing the side effects of PGE1 based on the results obtained in the present and previous studies.

Alprostadil↗
PubMed1995

Interferon-alpha treatment for severe atopic dermatitis.

Patients with both severe atopic dermatitis (AD) and chronic myeloid leukemia, chronic hepatitis B, or chronic hepatitis C were treated with interferon-alpha (IFN-alpha). IFN-alpha treatment improved AD. Moreover, there were also significant decreases in serum IgE and IgG4 levels and in in vitro spontaneous IgE and IgG4 production by patients' mononuclear cells.

Adolescent↗
PubMed1995

Functional differences between activated and normal rat liver macrophages: LPS uptake capacity by flow cytometric analysis in contrast with TNF-alpha release.

Activated liver macrophages are considered to play an important role in the development of liver injuries. Functional differences between activated and normal rat liver macrophages were investigated. In addition, from the therapeutic point of view, the effects of prostaglandin E1, prostaglandin I2 and E3330 ((2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)]-2-nonyl-2-propenoic acid) on the functions of liver macrophages were also determined. Rat liver macrophages were primed by Propionibacterium acnes and activated by a small dose of lipopolysaccharide. Lipopolysaccharide uptake capacity was evaluated quantitatively by flow cytometric analysis. Tumor necrosis factor-alpha activities were measured by bioassay. There were no significant differences in lipopolysaccharide uptake capacity between activated and normal liver macrophages, while activated liver macrophages had a significantly (P < 0.01) higher capacity in the release of tumor necrosis factor-alpha. Prostaglandin E1 and E3330 inhibited tumor necrosis factor-alpha release without suppressing lipopolysaccharide uptake capacity. In this study we have clarified the functional differences between activated and normal liver macrophages. The beneficial effects of prostaglandin E1 and E3330 on the functions of liver macrophages were also demonstrated.

Animals↗
PubMed1995

Carpal tunnel syndrome in patients undergoing CAPD: a collaborative study in 143 centers.

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed carpal tunnel syndrome (CTS) were retrospectively studied in 143 centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and 1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients treated solely with CAPD developed CTS 12-108 months after starting CAPD. The remaining 2 patients who were initially treated with HD for 7-9 years and then switched to CAPD developed this complication 9 years after starting CAPD. All 7 patients were women, ranging in age from 32 to 70 (average 52) years. We detected the presence of amyloid deposits in 2 of 5 specimens and beta 2-microglobulin in 2 of 4 specimens from these patients. It was concluded that CAPD minimizes the emergence of CTS although constant surveillance is necessary to detect CTS in patients during CAPD.

Adult↗
PubMed1995

Ionic lead, but not other ionic metals (Ni2+, Co2+ and Cd2+), suppresses 2-methoxy-4-aminoazobenzene-mediated cytochrome P450IA2 (CYP1A2) induction in rat liver.

Male F344 rats were pretreated with lead nitrate, nickel chloride, cobalt chloride or cadmium chloride, and their effects on the induction of cytochrome P450 (CYP) enzymes, mainly CYP1A2 enzyme, with 2-methoxy-4-aminoazobenzene (2-MeO-AAB) in the livers were comparatively examined by enzymatical, immunochemical, and molecular biological methods. When rats were pretreated with each ionic metal, the total CYP amount in the liver microsomes decreased, as compared with that of rats treated with 2-MeO-AAB alone. However, among the ionic metals used only lead reduced the levels of the mRNA and protein of CYP1A2 induced with 2-MeO-AAB in the rat liver, and decreased the microsomal activity (per CYP) for CYP1A2-mediated mutagenesis. Furthermore, ionic lead, but not other ionic metals, showed an ability to induce a placental form of glutathione S-transferase (GST-P). The level of CYP1A2 induced with 2-MeO-AAB was decreased along with increase in that of the induced GST-P.

Animals↗
PubMed1995

Purification and properties of a novel enzyme, maltooligosyl trehalose synthase, from Arthrobacter sp. Q36.

Arthrobacter sp. Q36 produces a novel enzyme, maltooligosyl trehalose synthase, which catalyzes the conversion of maltooligosaccharide into the non-reducing saccharide, maltooligosyl trehalose (alpha-maltooligosyl alpha-D-glucoside) by intramolecular transglycosylation. The enzyme was purified from a cell-free extract to an electrophoretically homogeneous state by successive column chromatography on Sepabeads FP-DA13, DEAE-Sephadex A-50, Ultrogel AcA44, and Butyl-Toyopearl 650M. The enzyme was specific for maltooligosaccharides except maltose, and catalyzed the conversion to form maltooligosyl trehalose. The Km of the enzyme for maltotetraose, maltopentaose, maltohexaose, and maltoheptaose were 22.9 mM, 8.7 mM, 1.4 mM, and 0.9 mM, respectively. The enzyme had a molecular mass of 81,000 by SDS-polyacrylamide gel electrophoresis and a pI of 4.1 by gel isoelectrofocusing. The N-terminal and C-terminal amino acids of the enzyme were methionine and serine, respectively. The enzyme showed the highest activity at pH 7.0 and 40 degrees C, and was stable from pH 6.0 to 9.5 and up to 40 degrees C. The enzyme activity was inhibited by Hg2+ and Cu2+.

Amino Acid Sequence↗
PubMed1995

Purification and characterization of a novel enzyme, maltooligosyl trehalose trehalohydrolase, from Arthrobacter sp. Q36.

A novel enzyme, maltooligosyl trehalose trehalohydrolase from Arthrobacter sp. Q36 was purified from a cell-free extract to an electrophoretically pure state by successive column chromatography on Sepabeads FP-DA13, Butyl-Toyopearl 650M, DEAE-Toyopearl 650S, and Toyopearl HW-55S. The enzyme specifically catalyzed the hydrolysis of the alpha-1,4-glucosidic linkage that bound the maltooligosyl and trehalose moieties of maltooligosyl trehalose. The Km of the enzyme for maltosyl trehalose, maltotriosyl trehalose, maltotetraosyl trehalose, and maltopentaosyl trehalose was 5.5 mM, 4.6 mM, 7.0 mM, and 4.2 mM, respectively. The enzyme had a molecular mass of 62,000 by SDS-polyacrylamide gel electrophoresis and a pI of 4.1 by gel isoelectrofocusing. The N-terminal amino acid of the enzyme was threonine. The enzyme showed the highest activity at pH 6.5 and 45 degrees C, and was stable from pH 5.0 to 10.0 and up to 45 degrees C. The activity was inhibited by Hg2+, Cu2+, Fe2+, and Zn2+.

Amino Acid Sequence↗
PubMed1995

A case of non-insulin dependent diabetes mellitus with antiinsulin antibody: effect of subcutaneous injection of human recombinant insulin-like growth factor-I.

We saw a 57-yr-old female non-insulin dependent diabetes mellitus (NIDDM) patient with antiinsulin antibody, in whom insulin-like growth factor-I (IGF-I) was shown to be effective as a blood glucose-lowering agent. Due to the presence of the antibody, the patient suffered from postprandial hyperglycemia and frequent hypoglycemia, which were uncontrollable even by multiple insulin injection therapy. In contrast to insulin injection (0.24 IU/kg body wt) which showed a delayed glucose-lowering effect, subcutaneous injection of recombinant human IGF-I (0.05-0.1 mg/kg body wt) caused a quick fall in plasma glucose levels. Prolongation of the glucose-lowering effect of "rapid-acting" insulin frequently caused subsequent hypoglycemia in this patient, but the effect of IGF-I seemed to have disappeared within the first three hours.

Diabetes Mellitus, Type 2↗
PubMed1995

Recurrent Cushing's disease associated with nephrotic syndrome.

A case of recurrent Cushing's disease with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) is presented. Functional pituitary adenoma recurred 6 years after transsphenoidal pituitary adenomectomy. Due to infiltration into the surrounding tissues, transcranial surgery was performed. However, this failed to induce a remission and thus gamma knife therapy was applied. Histopathological evaluation revealed that the glomerular lesions had progressed to a rather advanced stage of MPGN. Although this association could be coincidental, the recurrence of pituitary macroadenoma might be induced by the cessation of steroid treatment for the nephrotic syndrome.

Adult↗