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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 271 records · Page 15Linked to original sources
PubMed1997

The chemokine repertoire of human dermal microvascular endothelial cells and its regulation by inflammatory cytokines.

Activation of endothelium is a critical event during the initiation of inflammatory processes and is associated with the induction of cell adhesion molecules and cytokines. The latter include chemotactically active cytokines (chemokines) that promote leukocyte diapedesis from the circulation to sites of evolving inflammation. In this study we evaluated the chemokine repertoire of human endothelial cells derived from the skin (HDMECs) and regulation of these chemokines by cytokines. HDMECs and an immortalized human dermal microvascular endothelial cell line, HMEC-1, were investigated for the expression of C-X-C and C-C chemokines at mRNA and protein levels. Upon stimulation with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), both HDMECs and HMEC-1 expressed high levels of IL-8, GRO, and monocyte chemoattractant protein-1 (MCP-1). RANTES was only weakly induced; however, concomitant treatment with TNF-alpha and interferon-gamma (IFN-gamma) led to upregulation of RANTES, indicating a synergy between these two cytokines. The C-X-C chemokine IFN-inducible protein-10 was upregulated by IFN-gamma but not by other cytokines studied. Macrophage inflammatory protein-1alpha and beta, 1-309, and ENA-78 could not be induced. The chemokine repertoires of HDMECs and HMEC-1 were compared to those of human umbilical vein endothelium and found to be rather similar with the important exception that IFN-gamma and IL-4 up-regulated MCP-1 only in macrovascular endothelium. Our data indicate that HDMECs contribute to the dermal cytokine network by selective production of MCP-1, IL-8, GRO, RANTES, and IP-10, which may critically influence the site-specific recruitment of leukocyte subsets.

Cells, Cultured↗
PubMed1997

Synthesis of optically active amino acids from alpha-keto acids with Escherichia coli cells expressing heterologous genes.

We describe a simple method for enzymatic synthesis of L and D amino acids from alpha-keto acids with Escherichia coli cells which express heterologous genes. L-amino acids were produced with thermostable L-amino acid dehydrogenase and formate dehydrogenase (FDH) from alpha-keto acids and ammonium formate with only an intracellular pool of NAD+ for the regeneration of NADH. We constructed plasmids containing, in addition to the FDH gene, the genes for amino acid dehydrogenases, including i.e., leucine dehydrogenase, alanine dehydrogenase, and phenylalanine dehydrogenase. L-Leucine, L-valine, L-norvaline, L-methionine, L-phenylalanine, and L-tyrosine were synthesized with the recombinant E. coli cells with high chemical yields (> 80%) and high optical yields (up to 100% enantiomeric excess). Stereospecific conversion of various alpha-keto acids to D amino acids was also examined with recombinant E. coli cells containing a plasmid coding for the four heterologous genes of the thermostable enzymes D-amino acid aminotransferase, alanine racemase, L-alanine dehydrogenase, and FDH. Optically pure D enantiomers of glutamate and leucine were obtained.

Alanine Dehydrogenase↗
PubMed1997

Airway inflammation induced by recombinant guinea pig tumor necrosis factor-alpha.

We have cloned and expressed recombinant guinea pig tumor necrosis factor-alpha (gpTNF-alpha) and examined its inflammatory activities after tracheal instillation in guinea pigs. A 1,071-bp cDNA, including the region encoding the full-length 234-amino acid gpTNF-alpha protein, was cloned from concanavalin A-stimulated guinea pig splenocytes. The 154-amino acid protein corresponding to secreted gpTNF-alpha was expressed as a fusion protein in Escherichia coli, purified by affinity chromatography, and cleaved to yield a 17-kDa protein. gpTNF-alpha had a cytotoxic effect on WEHI 164 cells and was detected by goat anti-murine tumor necrosis factor-alpha (TNF-alpha) antibody in Western blots. Intratracheal instillation of gpTNF-alpha (50-150 ng) caused pronounced and dose-dependent airway eosinophilia. Incubation of gpTNF-alpha with rabbit anti-murine TNF-alpha sera or heating the gpTNF-alpha before instillation reduced bronchoalveolar lavage (BAL) eosinophils to near control levels. Maximum BAL eosinophilia was observed at 24 h, but eosinophil numbers remained significantly above vehicle-treated animals for 72 h. Hence, gpTNF-alpha elicits a pronounced and protracted eosinophil accumulation in the guinea pig lung.

Amino Acid Sequence↗
PubMed1997

Connexin32 gene expression in rat sciatic nerves and cultured Schwann cells.

A Western blot analysis showed connexin32 (Cx32) to be present in the myelin membrane. Cx32 mRNA rapidly decreased in the distal segments of crushed sciatic nerves and thereafter returned to normal, as did P0 mRNA. Both Cx32 and P0 mRNAs were detectable in cultured Schwann cells and were enhanced by the addition of forskolin. The developmental profile showed that Cx32 mRNA had thus markedly increased by the time that myelination had become most active, and thereafter only slowly increased unlike P0. Cx32 mRNA seems to parallel myelin size, which thus suggests that Cx32 supports myelin maintenance as a gap junction protein that facilitates the intramyelin exchange of small molecules.

Aging↗
PubMed1997

Chromosomal mapping of the gene encoding serotonin N-acetyltransferase to rat chromosome 10q32.3 and mouse chromosome 11E2.

Pineal melatonin is produced during the night. Its nocturnal increase regulates circadian rhythms and the photoperiodic reproductive response. Serotonin is acetylated to N-acetylserotonin by serotonin N-acetyltransferase (SNAT) and then methylated to form melatonin by hydroxyindole-O-methyltransferase (HIOMT). The rhythmicity of melatonin synthesis is regulated by the rhythmic activity of SNAT. Most laboratory mice do not have melatonin because of a genetic defect in the activity of SNAT and/or HIOMT. In a previous study using a recombinant inbred strain, we have found that the locus controlling pineal SNAT activity (Nat4) is located on mouse Chromosome 11. Recently, SNAT has been cloned in the rat. In the present study, the gene encoding SNAT was localized, using a rat cDNA fragment, on rat and mouse chromosomes by direct R-banding fluorescence in situ hybridization (FISH). In addition, using molecular linkage analysis with interspecific backcross mice, a gene encoding SNAT was mapped on a mouse chromosome. The gene encoding SNAT was localized to rat chromosome 10q32.3 and mouse Chromosome 11E2 by FISH. The molecular linkage analysis demonstrated that the gene encoding SNAT maps 1.5 cM distal to D11Mit11. The data suggest that Nat4 encodes SNAT. These chromosomal locations are in a region of conserved linkage homology between the two species.

Animals↗
PubMed1997

Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells.

The effects of beta-adrenoceptor agonists (beta-agonists) on the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) were investigated. The beta-agonists, procaterol, clenbuterol, fenoterol and terbutaline, inhibited TNF-alpha and IL-1 beta production in a concentration-dependent manner, whereas they had no effect on IL-8 production. TNF-alpha production was inhibited more potently than IL-1 beta. Dibutyryl cyclic AMP (dbcAMP) also inhibited the production of TNF-alpha and IL-1 beta, but not IL-8. TNF-alpha production was almost completely inhibited by dbcAMP, whereas IL-1 beta production appeared to be partially refractory even at the highest concentration examined. Both procaterol and theophylline elevated cAMP levels in LPS-stimulated PBMCs, but the effect of procaterol was limited. The inhibition of TNF-alpha and IL-1 beta production by procaterol was additively potentiated with theophylline. dl-Propranolol, a beta-adrenoceptor antagonist, abrogated the inhibition of TNF-alpha and IL-1 beta production by procaterol. These results indicate that beta-agonists inhibit the production of proinflammatory cytokines, such as TNF-alpha and IL-1 beta, by elevating intracellular cAMP levels. These properties of beta-agonists might be beneficial in the treatment of allergic inflammation.

Adrenergic beta-Agonists↗
PubMed1997

Setting Priorities in Occupational Health Research in Vietnam.

To set priorities for occupational health research in Vietnam, the authors developed a questionnaire, using a consensus-conference approach. The questionnaire, which was composed of two parts (five main categories with subgroups), was distributed to 51 specialists in occupational safety and health (OSH) in Vietnam. The responses from 50 persons were analyzed. Among the main categories, the environmental impact of industrial activity was rated the most important, followed by ergonomics and engineering of OSH, incidence/prevalence of work-related diseases and identification of susceptible groups, social impact of industrial activity, and OSH problems of agricultural workers. Among the three problems in the subgroup "environmental impact of industrial activity," individual health effects was considered the most important. These results were evaluated to arrive at an understanding of the actual situation of OSH problems in Vietnam.

Journal Article↗
PubMed1997

Stereospecific formation of (24R,25R)-3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid catalyzed with a peroxisomal bifunctional D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase.

The absolute configuration of 3 alpha,7 alpha,12 alpha, 24-tetrahydroxy-5 beta-cholestan-26-oic acid CoA ester (V-CoA) produced by the incubation of (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid CoA ester (24E-THC-CoA) with D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase (D-bifunctional protein) was investigated. When 24E-THC-CoA was incubated with D-bifunctional protein the formation of only one isomer (24R,25R-isomer) of four possible stereoisomers of V-CoA was observed, which suggested the cis-addition of water to a side chain double bond of 24E-THC-CoA. The dehydration reaction of V-CoA catalyzed by D-bifunctional protein was also observed when (24R,25R)-V-CoA was used as a substrate. The other three isomers (24R,25S-, 24S,25R- and 24S,25S-isomers) were not dehydrated with D-bifunctional protein. These results showed that D-bifunctional protein catalyzes stereospecifically the hydration and dehydration step in bile acid biosynthesis.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Inhibition by hop bract polyphenols of cellular adherence and water-insoluble glucan synthesis of mutans streptococci.

The inhibitory effect of hop bract polyphenols (HBP) on cariogenic streptococci was investigated. It was found that the high molecular weight polyphenol (estimated about 36,000-40,000) inhibited the cellular adherence of Streptococcus mutans MT8148 (serotype C) and Streptococcus sobrinus ATCC 33478 (serotype g) at much small concentrations than the polyphenols extracted from oolong tea or green tea leaves. Furthermore, HBP also inhibited the action of glucosyltransferase, which was involved in the water-insoluble glucan synthesis, but did not suppress the growth and the acid production of the bacteria. These results suggest that HBP would be a candidate to act against dental caries caused by Mutans Streptococci.

Bacterial Adhesion↗
PubMed1997

Association between self-reported stressful feeling by SACL and mortality in a Japanese community.

A cohort study consisting of 4,291 residents of a Japanese community has been conducted since 1987. The associations between stressful feelings measured by Stress Arousal Checklist (SACL) and mortality of all causes and cancer were examined. The relative risks (RRs) for mortality for 7 years for high stressful state (SACL score: 7-17) and moderate stressful state (3-6) subjects compared with low stressful state subjects (0-2) were 1.1 (95% CI = 0.69-1.68), 1.3 (95% CI = 0.85-2.00) for all causes and 1.5 (95% CI = 0.80-2.99), 1.3 (95% CI = 0.67-2.61) for cancer respectively, after being adjusted for sex, age, smoking, drinking, exercise and medical-care use. When each item of the SACL was examined independently, six out of 17 items of SACL which were "not comfortable", "not contented", "not cheerful", "dejected", "nervous", "not pleasant" showed elevated RRs for all causes of mortality with statistical significance (RRs: 1.4, 1.4, 1.7, 1.7, 1.5, 1.5, respectively), after being adjusted for the possible confounding factors stated above. Especially, the adjusted RRs of "not cheerful" and "dejected" for all causes was 1.7 (95% CI = 1.20-2.33), 1.7 (95% CI = 1.17-2.46), respectively. The results suggested that stressful feelings of "not cheerful" and "dejected" might increase mortality.

Adult↗
PubMed1997

[Effect of worksite dental health program on periodontal status--evaluation by CPITN and bleeding on probing at each tooth].

A dental health promotion program which aimed to prevent periodontal disease was carried out at a shipyard in Nagasaki Prefecture. Repeated tooth cleaning instruction and prophylaxis were conducted in order to adopt proper oral hygiene habits. The first 3 months of this program included 'Initial instruction,' and 'Regular instruction' were given every 6 months in following 2 years. The oral examination was carried out before and after Initial instruction, and at each Regular instruction. The effect of this program was evaluated by 2 measures: CPITN and Bleeding on probing. After this program, the rate of teeth with pockets 4 -5 mm deep or deeper (CPITN 3, 4) was decreased. In contrast, the rate of teeth with no sign of periodontal disease (CPITN 0) was increased remarkably: the percentage increased from 8% preinitial instruction to 40% with regular instruction. Both the rate and grade of teeth with bleeding on probing were decreased. These results indicated that this program was helpful in improving the periodontal status. CPITN and Bleeding on probing at each tooth as an evaluation measure made our analysis more detailed.

Health Education, Dental↗
PubMed1997

[A case of severe involvement of the motor neuron system accompanied with cerebellar ataxia].

Here we report a sporadic case of severe involvement of the motor neuron system accompanied with cerebellar ataxia. A 55-year-old Japanese woman was admitted to our hospital because of unstable gait and clumsiness of hands. Since she had prominent ataxia, she was initially diagnosed as late onset cortical cerebellar atrophy (LCCA). However, mild muscular weakness and atrophy were pointed out. Weakness in extremities progressed slowly and she became unable to walk in two years. On the second admission, in addition to cerebellar ataxia, she had moderate to severe muscular weakness and atrophy with fasciculation in extremities. Although she had no sensory impairment, micturitional disturbance nor orthostatic hypotension, she had impaired skin sweating response. MRI imaging revealed moderate cerebellar and brain stem atrophy. Neurophysiological examination revealed upper and lower motor neuron damage. Beta-D-N acetylglucosaminidase activity was normal and SCA1, DRPLA and Machado-Joseph disease were excluded by DNA studies. Combination of motor neuron disease and cerebellar degeneration has been very rare. Only two cases similar to our case were reported before. Our patient had anti GM1-ganglioside antibody in her serum, suggesting that motor neuron disease and cerebellar degeneration may occur with the same pathophysiological mechanism.

Cerebellar Ataxia↗
PubMed1997

Analysis of the inflammatory cytokine network among TNF alpha, IL-1 beta, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis.

We investigated the cytokine network in rabbit lipopolysaccharide (LPS)-induced arthritis, using inhibitors against homologous TNF alpha, IL-1 beta, and IL-8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10 micrograms each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNF alpha and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1 beta and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNF alpha and IL-8, and infiltrating leukocytes were positive for IL-1 beta and IL-1 Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNF alpha and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1 beta was reduced by anti-TNF alpha monoclonal Ab (mAb), IL-1 Ra or anti-IL-8 IgG. Peak concentrations of IL-1Ra were reduced by anti-TNF alpha mAb or anti-IL-8 IgG. Anti-TNF alpha mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti-IL-8 IgG was less than that of anti-TNF alpha mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNF alpha are the most proximal cytokines and induce subsequent production of IL-1 beta and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis.

Animals↗
PubMed1997

[Effects of polychlorinated biphenyls on regenerating myelin of peripheral nerve in rats].

The effects of polychlorinated biphenyls (PCB) on regenerating myelin of the peripheral nerves were investigated in rats. The sciatic nerves were crushed at the mid-thigh level on the last of 32 days of oral administration of PCB. The sciatic nerves were biopsied from the crushed regions at 4, 8 and 12 weeks after crushing. The nerves were fixed in 2.5% glutaraldehyde buffered with 0.1 M sodium cacodylate and embedded in epon 812. The ultrathin sections were analysed by JEOL JEM-1210 with EDAXDX-4. The chloride which was composed of PCB was increased in myeline on 4 weeks after crushing. Freeze fracture study of myelines of sciatic nerves on 8 and 12 weeks after crushing showed an increase of intramembranous particle on 12 weeks and an increase of caveolae on 8 weeks. These results suggest that PCB may affect the plasmamembrane of shwann cell and induce the disturbance of myeline.

Animals↗
PubMed1997

[Elevation of serum creatine kinase in the patients with Kanemi Yusho].

18.9% of the patients with Kanemi Yusho showed an elevation of serum creatine kinase, however, the cause is still unknown. The relation between exercise, dehydration, thyroid hormone and concentration of PCB was studied. Dehydration, hyperexercise and PCB affected the elevation of creatine kinase. No relation between PCB and thyroid hormone or creatine kinase and thyroid hormone was observed. PCB may change the permeability of muscle plasma membrane.

Creatine Kinase↗
PubMed1997

Risk factors for left ventricular hypertrophy in chronic hemodialysis patients.

Left ventricular hypertrophy is reported to be common in chronic hemodialysis patients, and also to increase the risk for mortality in chronic hemodialysis patients. An echocardiographical and clinical study was carried out to investigate the risk factors for left ventricular hypertrophy in 151 non-diabetic chronic hemodialysis patients without valvular diseases or myocardial infarction in two hemodialysis units in Fukuoka, Japan. The left ventricular mass index (LVMI) correlated positively to age, systolic blood pressure and interdialysis weight gain while it correlated negatively to the duration of hemodialysis therapy and hematocrit. Resorting to a multivariate analysis, the LVMI was found to positively correlate to age and the systolic blood pressure while it correlated negatively with the duration of hemodialysis therapy and the hematocrit level. These findings suggest that hypertension and anemia may thus be independent risk factors for left ventricular hypertrophy.

Cross-Sectional Studies↗