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Biomedical subjects

M Kubota

Publications and source records attributed to M Kubota.

At least 19 recordsLinked to original sources
PubMed1995

A 13-Mer peptide of a brain injury-derived protein supports neuronal survival and rescues neurons from injury caused by glutamate.

Neuronal survival is mediated by several kinds of proteins. Among these, neurotrophic factors play important roles in the nervous system by supporting neuronal activity and survival. It has been suggested recently that certain factors promote neuronal survival in the case of brain injury. To examine this possibility, we purified a novel neurotrophic factor from Gelfoam that was implanted at the site of injury caused in neonatal rats. During amino acid sequence analysis, we found that a fragmental peptide of this neurotrophic protein consisting of 13 amino acids showed neurotrophic activity. This 13-mer peptide promoted survival of septal cholinergic and mesencephalic dopaminergic neurons in culture and rescued hippocampal neurons from injury caused by glutamate in culture. This peptide rescued neurons from cell death caused by glutamate, even when added 4.5 h after glutamate exposure.

Amino Acid Sequence↗
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

n-3 and n-6 fatty acid intake and serum phospholipid fatty acid composition in middle-aged women living in rural and urban areas in Okayama Prefecture.

Dietary fatty acids and serum lipids were evaluated in 68 middle-aged women living in the northern, rural area of Okayama Prefecture, and were compared with the values obtained from 65 urban women from the southern part of this prefecture. A higher level in HDL cholesterol and a lower atherogenic index were observed in the rural women. The percent of energy intake as fat was lower (20.4 +/- 0.8% vs. 23.2 +/- 0.7%) and that of carbohydrate was greater in the rural group. Eicosapentaenoic (EPA, 0.41 +/- 0.04 g/day) and docosahexaenoic acid (DHA, 0.70 +/- 0.08 g/day) intakes were significantly higher in the rural subjects than in the urban group. Significantly higher DHA levels and n-3/n-6 fatty acid ratios in serum total phospholipids were found in rural women in their fifties and the sixties compared to urban women. Dietary linoleic acid (LA) amounts were positively correlated with LA (p < 0.05), and negatively with the EPA (p < 0.05) and DHA (p < 0.01) contents of serum total phospholipids. These results suggest that the traditional Japanese diet, containing little fat but enriched in complex carbohydrates and n-3 fatty acids of marine origin, may be related to the low atherogenic index in this rural area.

Adult↗
PubMed1994

Different effect of thymidine kinase loss on TTP pools; comparison among human leukemia cell lines.

Thymidine kinase (TK)-deficient cells were established from six human leukemia cell lines to evaluate the role of TK in maintaining intracellular TTP pools. The residual TK activities in mutant cells were less than 3% of those of wild-type strains, except for a B-lymphoid cell line, Ball-1 (8.7%). In a promyelocytic leukemia cell line (HL-60), a splenic B cell line (WI-L2) and Ball-1, a mutational loss of TK resulted in a decrease of TTP pools by 80%, 33% and 54%, respectively. On the other hand, in the T cell lines, Molt-3, Molt-4 and CEM, TTP did not show any significant differences between parent and TK-deficient cells. TK-deficient HL-60 cells had, however, comparable levels of dATP, dGTP and dCTP with wild-type cells. An analysis of growth characteristics showed that the decrease of TTP was not due to the change of the cell cycle distribution. These results indicate that TK plays a different role in maintaining TTP pools among human leukemia cell lines.

B-Lymphocytes↗
PubMed1994

Somatic mutations at T-cell antigen receptor and glycophorin A loci in pediatric leukemia patients following chemotherapy: comparison with HPRT locus mutation.

Frequencies of somatic mutations in pediatric patients with leukemia were evaluated following intensive treatment at three different loci: the hypoxanthine-guanine phosphoribosyl transferase (HPRT), T-cell antigen receptor (TCR), and glycophorin A (GPA) gene. Thirty-two children with acute lymphoblastic leukemia (ALL), nine children with acute myelogenous leukemia (AML), and 20 age-matched healthy controls were included in the study of mutant frequencies (Mfs) at the HPRT and TCR loci. Among these patients and controls, individuals with heterozygous MN blood type, i.e., 14 children with ALL, three children with AML, and nine healthy controls, served for the further assessment of variant frequency (Vf) at the GPA locus. In ALL patients, geometric mean Mfs and Vfs at these loci were significantly higher than in healthy controls. The high Mf value at the HPRT locus persisted for up to 8 years after the end of chemotherapy. On the other hand, the Mf values at the TCR locus and Vf values at the GPA locus declined gradually with time. In AML patients, on the other hand, the geometric mean Mf only at the TCR locus was significantly higher than in the controls, albeit to a lesser degree than in ALL patients. These data suggest that anti-cancer therapy induces somatic mutations at various loci and that ALL patients are more susceptible to mutagenic intervention than are AML patients.

Adolescent↗
PubMed1994

Bio-histochemical aspects of integrins (alpha 2 beta 1, alpha 6 beta 1) in invasive mammary carcinomas: an immunohistochemical study.

Immunohistochemical expression of integrins was examined in 39 human invasive mammary carcinomas, of which 34.2% and 43.6% expressed integrins alpha 2 beta 1 and alpha 6 beta 1, respectively. Immuno-electron microscopy clearly demonstrated that the integrins were in the cell membrane of the carcinoma cells. Similar expression of integrin alpha 2 beta 1 or alpha 6 beta 1 in both the intraductal component and invasive portion of the same tumor was seen in 76.9% and 85.7% of cases, respectively. This suggested that invasive carcinoma cells retained their integrin expression after invasion through the basement membrane. Reciprocal expression of integrins alpha 2 beta 1 and alpha 6 beta 1 was seen in 20 cases. Expression of alpha 2 beta 1 was seen significantly less frequently in scirrhous carcinoma than in the more differentiated papillotubular or solid tubular carcinoma (Chi-squared test, P < 0.05). Intraductal components of carcinoma were present more frequently in cases expressing integrin alpha 2 beta 1 than in those that were negative. This suggests the potential usefulness of integrins as clinical parameters in the surgical treatment of mammary carcinoma, since recent trials of conservative treatment for mammary carcinoma have focused on the intraductal spread of the tumor cells.

Antigens, CD↗
PubMed1994

In vivo administration of granulocyte colony-stimulating factor promotes neutrophil survival in vitro.

We recently showed that recombinant human granulocyte-colony stimulating factor (rhG-CSF) maintained the viability of human neutrophils in incubation for up to 72 hours. However, it is not known whether rhG-CSF can enhance neutrophil survival in in vivo situations. To clarify this issue, we investigated neutrophil survival in vitro following in vivo injection of rhG-CSF. Neutrophils were obtained from 4 pediatric patients with malignancies and healthy adult volunteers before and after rhG-CSF administration. Neutrophils obtained before rhG-CSF treatment started to undergo apoptosis after 24 h of incubation. In contrast, the survival of neutrophils drawn after rhG-CSF administration increased by approximately 24 h. Concomitantly, the appearance of typical ladder-like DNA fragmentation was delayed. Such an increase in neutrophil survival was inhibited by co-incubation with either H 7 (10 mumol/l) or H 8 (20 mumol/l), which worked as protein kinase C inhibitors. Although our study did not measure neutrophil survival in vivo directly, it provides us with further evidence that rhG-CSF may function to prolong neutrophil life expectancy in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Diversion of the sign of phototaxis in a Chlamydomonas reinhardtii mutant incorporated with retinal and its analogs.

The blind mutant FN68 of the unicellular flagellate green alga Chlamydomonas reinhardtii is negatively phototactic in the presence of the native chromophore all-trans retinal. In contrast, analog chromophores such as a ring-acyclic retinal and those in which trans/cis isomerization about the C11 = C12 double bond was blocked induced predominantly positive phototaxis in the same strain under the same experimental conditions. These observations can be interpreted by assuming that the negative and the positive phototaxis is mediated distinctively by two rhodopsin species which differ in their affinities with the exogenous chromophores. However, a more reasonable explanation, which requires fewer assumptions, is that the sign of phototaxis depends on a delay in intracellular photosignal transduction. This novel view was deduced directly from the widely accepted hypothesis [1980, Microbiol. Rev. 44, 572-630] on phototaxis mechanisms.

Animals↗
PubMed1992

Nuclear magnetic resonance abnormalities of the cerebral white matter in children with acute lymphoblastic leukemia and malignant lymphoma during and after central nervous system prophylactic treatment with intrathecal methotrexate.

BACKGROUND: A prospective study was conducted to test the feasibility of nuclear magnetic resonance (NMR) imaging in the early diagnosis of treatment-induced leukoencephalopathy. METHODS: The study group included 16 patients with acute lymphoblastic leukemia and 4 patients with malignant lymphoma. All were given intravenous and intrathecal (IT) methotrexate (MTX) for central nervous system prophylaxis. Serial NMR studies were performed before and/or during induction-consolidation cycles. RESULTS: NMR imaging disclosed leukoencephalopathy in 8 of the 20 patients (40%) in the early stages of treatment. In six of the eight, the leukoencephalopathy was resolved after temporary or permanent interruption of IT MTX, and chemotherapy was completed successfully. The other two patients are being treated. Transient neurologic abnormalities developed in two of the eight patients. CONCLUSIONS: The possible causal relationship between leukoencephalopathy and the antimetabolic effects of MTX is discussed. This study clearly shows that NMR imaging is valuable in the early diagnosis and management of treatment-induced leukoencephalopathy.

Adolescent↗
PubMed1992

Insulin resistance in Werner's syndrome.

Insulin resistance in Werner's syndrome (WS) was studied using the glucose clamp technique, and compared with physiologically aged and young subjects. Fasting immuno-reactive insulin (IRI) was increased in patients with Werner's syndrome compared with aged and young subjects. Metabolic clearance rate (MCR) of glucose was decreased in the aged and WS. A rightward shift of the dose-response curves of insulin and MCR of glucose was observed in the aged and WS with a more pronounced shift in the latter. MCR of insulin was also decreased in WS. [125I]insulin binding to erythrocytes was similar in the three groups. These results suggest that insulin resistance associated with WS is due to a post-binding defect manifested by a rightward shift of the dose-response curve of insulin-induced glucose disposal and a decrease in insulin clearance rate.

Adult↗
PubMed1992

Pre-treatment of a human T-lymphoblastoid cell line with L-asparaginase reduces etoposide-induced DNA strand breakage and cytotoxicity.

The effect of L-asparaginase (L-asp) pre-treatment on etoposide-induced DNA strand breakage and cytotoxicity was investigated. In a T-lymphoblastoid cell line, Molt 4, etoposide-induced DNA strand breaks, DNA-protein cross-links and cytotoxicity were reduced by pre-treatment with L-asp for 15 hr, but it did not cause these changes in a promyelocytic-leukemia cell line, HL-60, which is less sensitive than Molt 4 to L-asp. However, pre-treatment of Molt 4 cells with L-asp did not significantly alter the accumulation of [3H]-etoposide. Cell-cycle analyses showed an increase in G1-phase cells, a significant decrease in both S-phase cells and G2/M-phase cells pre-treated with L-asp in Molt 4 cells, but L-asp exposure did not result in any significant changes in HL-60 cells. On the other hand, L-asp pre-treatment did not affect topoisomerase-I (Topo-I) inhibitor, camptothecin (CPT)-induced DNA strand breaks or toxicity in Molt 4 cells. Our data imply that a decrease in S- and G2/M-phase cells following L-asp treatment may explain the reduction of etoposide-induced DNA lesions and cytotoxicity in Molt 4 cells, since topoisomerase-II (Topo-II) content or activity is a function of cellular proliferation status.

Asparaginase↗
PubMed1992

Large deletion of androsterone UDP-glucuronosyltransferase gene in the inherited deficient strain of Wistar rats.

LA Wistar rats have a deficiency of androsterone UDP-glucuronosyltransferase (UDPGT) and are present in Wistar rat colonies around the world. In order to clarify the molecular mechanism of the deficiency, androsterone UDPGT cDNA clone, pGT2 was isolated from rat liver cDNA library and was digested with restriction enzymes to afford three probes for Northern and Southern blot analyses in HA (normal), heterozygous LA and LA Wistar rats. In Northern blot analysis, androsterone UDPGT mRNA was totally absent in LA Wistar rat liver. Southern blot analysis suggested a large deletion of androsterone UDPGT gene in the rats. Genomic DNA amplifications with synthetic primers which have nucleotide sequences corresponding to the 5'-region of androsterone UDPGT cDNA, suggested that androsterone UDPGT gene has exon 1 with a length of some 700 bp and that this exon is deleted in LA Wistar rats. Based on these lines of evidence, it is concluded that the large portion of androsterone UDPGT gene is deleted in LA Wistar rats, which results in the absence of androsterone UDPGT mRNA and consequently the corresponding enzyme protein.

Animals↗
PubMed1992

In vitro release of glutamate and aspartate from zebra finch song control nuclei.

The release of glutamate and aspartate from a song control nucleus, the robust nucleus of the archistriatum (RA) of the zebra finch was examined in slice preparations. The RA received inputs from two other song control nuclei, the high vocal center (HVc) and the lateral magnocellular nucleus of the anterior neostriatum (1MAN). The fibers that innervated the RA from either the HVc or the 1MAN caused calcium-dependent release of glutamate and aspartate after electrical stimulation. It is likely that synapses of the RA from the HVc and the 1MAN utilize glutamate or aspartate as a neurotransmitter.

Animals↗
PubMed1992

Diagnosis and surgical treatment of five cases of triple shunt (ASD + VSD + PDA).

Five patients with triple shunt (atrial septal defect, ventricular septal defect, and patent ductus arteriosus) were treated surgically during the past twelve years (1978-1989). They developed severe cardiac and respiratory failure in the neonatal period and/or in early infancy. Simultaneous repair of the triple shunt was performed, but initially two patients suffering severe cardiac failure were lost immediately after operation. The following three patients were operated on relatively soon after establishing a definitive diagnosis and a successful outcome was able to be achieved. Repeated evaluation of the patient with echocardiography was necessary for diagnosis. Early primary operation is, therefore, considered to be the treatment of choice after confirming the diagnosis.

Cardiac Catheterization↗
PubMed1992

Urinary excretion of 3,4-dimethylhippuric acid in workers exposed to 1,2,4-trimethylbenzene.

The urinary excretion of 3,4-dimethylhippuric acid (34DMHA), a 1,2,4-trimethylbenzene (124TMB) metabolite, was investigated in workers exposed to 124TMB vapor. The time-weighted average of exposure to 124TMB was determined with a diffusive sampler. For biological monitoring of exposure, urine samples were collected from individual workers and analyzed for metabolites by high-pressure liquid chromatography. The concentration of urinary 34DMHA had a positive correlation with the level of exposure to 124TMB (r = 0.72). The data suggest that 34DMHA is one of the useful indicators for biological monitoring of 124TMB exposure.

Air Pollutants, Occupational↗
PubMed1992

A case of neurofibromatosis associated with clitoral enlargement and hypertension.

We report a case of clitoral and renovascular involvement of neurofibromatosis resulting in an enlarged phallus with juvenile hypertension. The patient was successfully treated by removal of the clitoral tumor and nephrectomy. This is the first of 15 reported cases with clitoral involvement, that showed concurrent renovascular hypertension.

Child↗