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Biomedical subjects

Y Ohkubo

Publications and source records attributed to Y Ohkubo.

At least 55 records · Page 3Linked to original sources
PubMed1999

Associations of the angiotensinogen gene (M235T, T174M) and the angiotensin I-converting enzyme gene (I/D) with blood pressure in Japanese workers.

Blood pressure may be influenced by several polymorphisms associated with hypertension, such as the angiotensinogen gene (M235T, T174M) and the angiotensin I-converting enzyme gene (I/D). We investigated the associations of these polymorphisms with blood pressure and components of the renin-angiotensin system in Japanese workers. Additionally, we examined whether the polymorphisms were independently associated with blood pressure when other factors were taken into consideration in a general linear model. The study population, which was entirely Japanese, consisted of 196 male subjects. Subjects were selected from workers who received a company health examination. Systolic blood pressure of the M235T MM genotype was significantly higher than that of the MT genotype. Diastolic blood pressure of the M235T MM genotype was significantly higher than that of the MT or TT genotypes. Serum ACE activity of the ACE II genotype was significantly lower than that of the ID or DD genotypes. Multivariate analysis using a general linear model, including age and body mass index, demonstrated that the M235T MM genotype was one of the independent factors affecting blood pressure. The present study demonstrated that the M235T MM genotype was independently associated with systolic blood pressure and diastolic blood pressure in Japanese male workers.

Adult↗
PubMed1999

Redox control of Epstein-Barr virus replication by human thioredoxin/ATL-derived factor: differential regulation of lytic and latent infection.

Human thioredoxin (hTRX)/adult T-cell leukemia (ATL)-derived factor (ADF) was originally reported as an interleukin-2 (IL-2) receptor-alpha-inducing factor produced by human T-cell lymphotropic virus-1-positive (HTLV-1+) cell lines. Growing evidence indicates that hTRX/ADF plays important roles in cellular responses against oxidative stress and is involved in a variety of cellular functions. A high level of hTRX/ADF expression is also observed in other human virus-infected cell lines including those of Epstein-Barr virus (EBV) and human papillomavirus. In this report, we analyzed the effect of hTRX/ADF on lytic amplification and persistent replication of EBV as a model for lytic versus latent phase of viral replication in host cells. Addition of hTRX/ADF clearly suppressed lytic replication of EBV in Raji cells and B95-8 cells induced to the lytic phase of 12-O-tetradecanoylphorbol-13-acetate (TPA), and it prevented the death of these cells evoked by the lytic induction. In contrast, hTRX/ADF did not have any effect on persistent replication in the latent phase. These data indicated that hTRX/ADF prevents EBV-transformed cells from proceeding into the lytic phase and regulates cohabitation of EBV and its host cells.

Carcinogens↗
PubMed1999

Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection.

The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.

Anti-Bacterial Agents↗
PubMed1999

Possible neural mechanisms involved in footshock stress-induced enhancement of exploratory behavior in mice.

The effect of inescapable footshock stress on open-field activity, as measured by the number of ambulations, was studied in male mice. Ambulations significantly increased after footshock stress, the most significant effect appeared after 20 min-stimulation and the effect decreased as footshock time lengthened. The footshock stress-induced enhancement of ambulation was inhibited by haloperidol (0.2, 0.5 and 1 mg/kg), phentolamine (5 and 10 mg/kg), mianserin (20 mg/kg), atropine (0.5, 1 and 2 mg/kg), naltrexone (10 mg/kg) and MK-801 (0.05, 0.1 and 0.2 mg/kg), but was not influenced by propranolol (5, 10 and 20 mg/kg) or diazepam (1, 2 and 5 mg/kg). Haloperidol (0.5 and 1 mg/kg) and mianserin (5, 10 and 20 mg/kg) also exerted an inhibitory effect on non-stressed normal mice. These results suggest that dopaminergic, alpha-adrenergic, cholinergic, opioidergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission systems are involved in the footshock stress-induced ambulatory activation.

Animals↗
PubMed1999

Reciprocal facilitation of motor evoked potentials immediately before voluntary movements in Parkinson's disease.

Changes of motor evoked potentials (MEPs) from the agonist and antagonist forearm muscles were investigated in 13 patients with Parkinson's disease and age-matched controls, in whom transcranial magnetic stimulation (TCMS) was delivered to the cortical hand motor area immediately before voluntary wrist flexion. MEPs recorded from the agonist muscles, namely the wrist flexors, were gradually facilitated in accordance with a shortening of the interval between TCMS and wrist flexion in both groups. In contrast, MEPs recorded from the antagonist muscles, namely the wrist extensors, were gradually facilitated as the intervals were shortened only in parkinsonian patients. The reciprocal facilitation of the antagonist MEPs was statistically significant when TCMS was delivered within 80 msec before the voluntary movements, suggesting the presence of the same underlying mechanism of symptomatic cocontraction observed in patients with Parkinson's disease.

Adult↗
PubMed1998

Comparative glucoregulatory responses of mice to restraint and footshock stress stimuli.

Effects of two types of stress, restraint and footshock, on plasma glucose level, insulin secretion, and glucose uptake by the liver, heart and femoral muscle were investigated in mice. Plasma glucose level gradually increased and reached maximum at 60 min after the onset of restraint stress, while footshock stress slightly increased plasma glucose level only 15 min after the onset of the stress, and this subsequently decreased significantly. The basal plasma insulin level and glucose-induced insulin secretion significantly decreased during both the stress stimuli. Glucose uptake by the femoral muscle was slightly increased during restraint stress, and was significantly increased during footshock stress. These results suggest that the transient increase in plasma glucose level during the early period of both stress stimuli might be caused by the inhibition of insulin secretion, and subsequent decrease in plasma glucose level during the latter phase of both stress stimuli was probably due to the increase in glucose uptake by the skeletal muscle. The present study confirmed that there was a difference in stress-induced glucoregulatory changes between restraint stress and footshock stress. This difference might be due to the degree of muscle movement during the stress stimuli.

Animals↗
PubMed1998

[The effects of LH-RH agonist alone or with flutamide in the treatment of stage D2 prostate cancer].

We compared the clinical efficacy of treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist alone to combined androgen blockade (CAB) with a LH-RH agonist and fiutamide. A total of 66 stage D2 prostate cancer patients were enrolled from Nov. 1992 to Mar. 1996 (n = 30: LH-RH agonist alone, n = 36 CAB). Serum PSA levels after 3 months of treatment and progression-free survival rates (Kaplan-Meier curves) were compared. Results were statistically evaluated by Wilcoxon's text. There were no differences in PSA levels between LH-RH agonist alone and CAB. Progression-free survival rates were longer in the patients treated CAB compared to LH-RH agonist alone (P = 0.041). Furthermore, in patients with poorly differentiated prostate cancers, longer survival rates were also observed with CAB (P = 0.030). However, there were no differences in high EOD (> or = 2) patients between the two treatments (P = 0.652).

Aged↗
PubMed1998

[A case of xanthogranulomatous pyelonephritis followed by computed tomographic scan].

Since it is difficult to differentiate xanthoglanulomatous pyelonephritis (XGP) from renal cancer, most cases of XGP are diagnosed after nephrectomy. We report a rare case of XGP followed by abdominal computed tomographic (CT) scan. A 65-year-old woman was admitted with high fever. Drip infusion pyelography showed a right renal stone but did not visualize the right kidney. A swollen right kidney was revealed on abdominal CT scan. Diabetes mellitus was detected by blood examinations and XGP was suspected. Conservative therapy with antibiotics was performed, the symptoms disappeared within 2 weeks and the right atrophic kidney was revealed on abdominal CT scan 12 months after onset. Histopathological findings on a renal biopsy specimen obtained 1.5 months after treatment were compatible with XGP. The diagnosis of XGP will become easier by using a combined approach including radiographic findings, physical finding and other data.

Aged↗
PubMed1997

Lysyl-tRNA synthetase from Bacillus stearothermophilus. Formation and isolation of an enzyme-lysyladenylate complex and its analogue.

The formation of an enzyme.lysyladenylate complex was studied with a highly purified lysyl-tRNA synthetase [L-lysine:tRNALYS ligase (AMP-forming); EC 6.1.1.6] from Bacillus stearothermophilus. The apparent dissociation equilibrium constants of the enzyme with L-lysine and ATP in the process of the complex formation were estimated to be 50.9 and 15.5 microM, respectively, at pH 8.0, 30 degrees C, by fluorometric measurement. The isolated enzyme.lysyladenylate complex was relatively stable with a rate constant of decomposition of 1.7 x 10(-5) s-1 at pH 8.5 and 0 degree C. The rate constant of transfer of L-lysine from the complex to Escherichia coli tRNA was 1.2 x 10(-2) S-1 at pH 8.5 and 0 degree C. The effects of replacing L-lysine by several analogues on the complex formation were examined. L-Lysine hydroxamate, a strong inhibitor of the L-lysine dependent ATP-PPi exchange reaction, produced a stable complex with the enzyme and ATP, enzyme.lysinehydroxamate-AMP probably being formed. The binding stoichiometry of the assumed L-lysinehydroxamate-AMP per mol of the dimer enzyme was 1:1.

Adenosine Monophosphate↗
PubMed1997

Spermine modulates calcium flux through the rat erythrocyte membrane.

The uptake of 45Ca by inside-out erythrocyte membrane vesicles (IOV) was dose-dependently inhibited by spermine. A cationic substance, Mg2+, did not affect this inhibitory activity of spermine. Ca(2+)-ATPase activity, however, was not inhibited by spermine at a concentration that could inhibit the uptake of 45Ca by the IOV. The release of 45Ca from IOV was significantly accelerated by spermine. Spermine bound to the surface of the IOV and was removed by treatment with acetic acid. These results suggest that spermine stimulates the release of Ca2+ from the IOV (or uptake of Ca2+ by erythrocytes) via an effect on the outer surface of the IOV (or the inner surface of erythrocytes).

Animals↗
PubMed1996

Hepatocyte growth factor induces transglutaminase activity that negatively regulates the growth signal in primary cultured hepatocytes.

Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of rat hepatocytes with 117 nM hepatocyte growth factor (HGF). In the same manner, putrescine incorporation into proteins of cells occurred in HGF-treated cells but did not in those pretreated with monodansylcadaverine (MDC), a TGase inhibitor, even in the presence of HGF. These results suggest that HGF-induced TGase was active and catalyzed some cross-linkage reaction. Cycloheximide completely blocked the increase in TGase activity induced by HGF, suggesting that HGF stimulated de novo synthesis of TGase within 6 h. Both [35S]methionine incorporation and Northern blotting analyses supported this possibility. Pretreatment of cells with MDC additionally increased HGF-induced DNA synthesis and the ratio of cells in S-phase. Similarly, TGase antisense oligonucleotide inhibited de novo synthesis of TGase, resulting in increase in the ratio of S-phase cells in the presence of HGF. Analyses of cross-linking of HGF to the receptor indicated that the antisense oligonucleotide inhibited the downregulation of HGF receptor subsequent to HGF-addition. These results provide the first evidence for inducibility of de novo synthesis of TGase by HGF and suggest that TGase negatively regulates the growth signal of HGF through the downregulation of receptor.

Animals↗
PubMed1996

Autonomous regulation of proliferation and growth arrest in mouse primordial germ cells studied by mixed and clonal cultures.

In culture, mouse primordial germ cells (PGCs) proliferate and undergo growth arrest with a time course similar to that in vivo. It is unclear whether this behavior is regulated autonomously or by coexisting somatic cells. We performed mixed culture experiments using PGCs from 8.5- and 11.5-d.p.c. embryos and found no interaction between the PGCs and somatic cells at the two stages. Next, we carried out clonal culture of PGCs and examined the proliferation of and morphological change in individual clones. Such clonal culture did not reveal any subpopulation of PGCs with an increased growth rate or less differentiated characteristics, which might have been suggested by formation of the embryonic germ cell lines. Our results suggest that there is an autonomous regulation of growth and cell shape change in PGCs which occur as stochastical events but are not strictly timed by the number of cell divisions.

Animals↗
PubMed1996

Transglutaminase induced by epidermal growth factor negatively regulates the growth signal in primary cultured hepatocytes.

Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of rat hepatocytes with 17 nM epidermal growth factor (EGF). In the same manner, putrescine incorporation into the proteins of cells occurred in EGF-treated cells, but not in those pretreated with monodansylcadaverine (MDC), a TGase inhibitor, even in the presence of EGF. These results suggest that EGF-induced TGase was active and catalysed some cross-linkage reaction. Cycloheximide completely blocked the increase in TGase activity induced by EGF, suggesting that EGF stimulated de novo synthesis of TGase within 6 h. Furthermore, Northern blotting analysis indicated that EGF increased the expression of TGase mRNA. Pretreatment of cells with MDC additionally increased EGF-induced DNA-synthesis and the ratio of cells in S-phase. TGase antisense oligonucleotide inhibited de novo synthesis of TGase, resulting in increases in the ratios of S- and G2/M-phase cells in the presence of EGF. This effect was the result of inhibition of EGF-induced down-regulation of high-affinity receptor expression. These results suggest that the EGF-induced increase in TGase activity is a negative regulator of a growth signal in rat hepatocytes.

Animals↗
PubMed1996

Lysyl-tRNA synthetase from Bacillus stearothermophilus. Purification, and fluorometric and kinetic analysis of the binding of substrates, L-lysine and ATP.

Lysyl-tRNA synthetase [L-lysine:tRNA(Lys)ligase (AMP forming); EC 6.1.1.6] was purified from Bacillus stearothermophilus NCA1503 approximately 1,100-fold to homogeneity in PAGE. The enzyme is a homodimer of M(r) 57,700 x 2. The molar absorption coefficient, epsilon, at 280 nm is 71,600 M-1.cm-1 at pH8.0. Enzyme activity in the tRNA aminoacylation reaction and the ATP-PPi exchange reaction increases up to 50 degrees C at pH 8.0, but is lost completely at 70 degrees C. The pH-optima of the two reactions are 8.3 at 37 degrees C. In the tRNA aminoacylation reaction, the Km values for L-lysine and ATP are 16.4 and 23.2 muM, respectively, and in the ATP-PPi exchange reaction, the Km values for L-lysine and ATP are 23.6 and 65.1 muM, respectively at 37 degrees C, pH 8.0. Interaction of either L-lysine or ATP with the enzyme has been investigated by using as a probe the ligand-induced quenching of protein fluorescence and by equilibrium dialysis. These static analyses, as well as the kinetic analysis of the L-lysine dependent ATP-PPi exchange reaction indicate that the binding mode of L-lysine and ATP to the enzyme is sequential ordered (L-lysine first). The interaction of lysine analogues with the enzyme has also been investigated.

Acylation↗
PubMed1996

[A case report of ileovesical fistula in radiation enteritis].

A 49-year-old female was admitted with chief complaint of fecaluria on March 4th 1993. A radiation therapy had been performed for uterocervical cancer 18 years ago. The small intestine and bladder was detected by DIP- and cystogram simultaneously. It was diagnosed as an ileovesical fistula. A segmental resection of the ileum with partial cystectomy was performed on March 23rd. Histopathologically, the ileum showed a radiation enteritis. Eventually, we diagnosed that this ileovesical fistula was caused by radiation. After operation, an incompletion of suture occurred. So we made an ileostomy secondarily and performed hyperbaric oxygen therapy. The patient was getting well temporarily but died of gastric hemorrhage on May 1st.

Female↗
PubMed1996

FK960 N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action.

With passive avoidance (PA), Morris water maze (WM) and eight-arm radial maze tasks, we evaluated the memory-enhancing action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a compound which we have found through rational drug screening based on our hypothesis that penile erection is a valid predictor of central cholinergic activation. Memory performance in the tasks was impaired in aged (24- to 26-months-old) rats as well as in rats with nucleus basalis magnocellularis lesions. Scopolamine (1 mg/kg i.p.) treatment induced memory impairment in PA and WM; treatment with cysteamine (200 mg/kg s.c.) induced memory impairment in PA but not in WM, whereas fimbria fornix lesioning affected the rats in the opposite manner. FK960 (0.1-10 mg/kg i.p.) ameliorated all the memory impairments except those induced by cysteamine or fimbria fornix lesion, and the dose-response curves were bell shaped with maximal response at 1 to 3.2 mg/kg. The effects of FK960 on the scopolamine-induced memory impairment in the PA and/or WM were abolished by cysteamine (200 mg/kg s.c.), dl-p-chlorophenylalanine methyl ester hydrochloride (150 mg/kg i.p. for 3 days) or raphe lesioning, but not by neonatal 6-hydroxydopamine (35 micrograms/head) treatment. Neurochemical analysis revealed that cysteamine and raphe lesions reduced brain somatostatin and serotonin contents, respectively. The treatment with FK960 (0.32-320 mg/kg p.o.) dose-dependently increased both serotonin and 5-hydroxyindoleacetic acid levels in the brain areas examined and significantly increased hippocampal somatostatin contents at the smaller doses. From these results, we conclude that FK960 ameliorates cognitive dysfunction through an activation of the somatostatinergic-serotonergic link.

Aging↗
PubMed1995

Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.

To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangiopathy is indicated as follows; HbA1c < 6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180 mg/dl.

Albuminuria↗