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Biomedical subjects

T Oshima

Publications and source records attributed to T Oshima.

At least 37 records · Page 2Linked to original sources
PubMed2001

Non-dipper phenomenon in essential hypertension is related to blunted nocturnal rise and fall of sympatho-vagal nervous activity and progress in retinopathy.

Although the relation between the blunted nocturnal decline in blood pressure and target organ damages is well established, the mechanism underlying these results has not been clarified. We investigated the relationship among heart rate variability, nocturnal change in blood pressure and the severity of cardiac and extracardiac target organ damages caused by essential hypertension. We studied 52 Japanese inpatients with essential hypertension (24 men and 28 women; mean age, 49+/-3 years). After a stabilization period of 1 week, ambulatory blood pressure monitoring (ABPM) and 24-h ECG monitoring were performed and analyzed. The non-dipper subjects were defined as those whose nocturnal decrease of mean BP was < 10% of daytime blood pressure (BP). The sex, age, body mass index. duration of hypertension, and 24-h BP were similar in dipper (n = 34) and non-dipper (n = 18) patients. The left ventricular mass index (LVMI) was significantly higher and the degree of hypertensive retinopathy was significantly worse in the non-dipper patients than that of the dipper patients. In the non-dipper patients, indexes of time-domain analysis such as the sum of differences between adjacent RR intervals (NNDrms), the number of pairs of adjacent RR intervals differing by more than 50 ms in the entire recording (RR 50) were significantly lower than that of the dipper patients. Additionally, as for spectral analysis, daytime low frequency/high frequency (LF/HF) was higher and nighttime high frequency (HF) was lower than that of the dipper patients. Independent predictors were the 24-h mean blood pressure (MBP) for left ventricular hypertrophy (LVH), nighttime systric BP (SBP) for progress in retinopathy and duration of hypertension for proteinuria. In conclusion, decrease in parasympathetic nervous function and increase in sympathetic nervous function may contribute to occurrence of non-dipper phenomenon, as well as progress in retinopathy.

Blood Pressure↗
PubMed2001

Expression of connexin 30 in the developing mouse cochlea.

Mutations in the GJB6 gene encoding connexin 30 (Cx30) can cause dominant forms of nonsyndromic deafness. By studying immunohistochemical localization of Cx30 in the mouse cochlea at different ages from 0 to 30 days after birth, we found that the expression of Cx30 is nearly the same as that of Cx26. These findings suggest that as well as Cx26, Cx30 may also contribute to the generation and maturation of endocochlear potential.

Age Factors↗
PubMed2001

Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function.

OBJECTIVES: The purpose of this study was to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the calcium antagonist amlodipine on endothelial function before and after 2, 4, 8, 12, 24 and 48 weeks of treatment. BACKGROUND: There are limited data on whether and how long endothelial function is improved after initiation of ACE inhibitor treatment and how the grade of endothelial function further progresses after improvement of endothelial dysfunction in patients with essential hypertension. METHODS: The forearm blood flow (FBF) was measured in 25 patients with essential hypertension and in 25 normotensive subjects by using strain-gauge plethysmography during reactive hyperemia (RH) (280 mm Hg for 5 min) and after sublingual administration of nitroglycerin (NTG, 0.3 mg). RESULTS: The FBF of patients with essential hypertension during RH was significantly less than that of normotensive subjects. The increase in FBF after sublingual NTG was similar in both groups. Both imidapril (n = 13) and amlodipine (n = 12) significantly reduced systolic blood pressure and diastolic after eight weeks of treatment from the pretreatment values. Forearm vascular resistance was significantly decreased after two weeks of treatment. Imidapril significantly augmented RH after 12 weeks of treatment from the pretreatment values (31.6 +/- 5.7 to 38.2 +/- 6.0 m/min per 100 ml tissue, p < 0.05), whereas amlodipine did not alter RH for each treatment period. The ability of imidapril to improve RH was maintained throughout the 48-week treatment period. There was no significant difference in RH at 12, 24 and 48 weeks. The increase in FBF after sublingual administration of NTG was similar in all treatment periods for the two groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of RH in hypertensive patients treated with imidapril. CONCLUSIONS: These findings suggest that the ACE inhibitor imidapril augments RH after 12 weeks of treatment in patients with essential hypertension and that this ACE inhibitor-induced augmentation of RH may be due to an increase in NO.

Aged↗
PubMed2001

Occurrence of D-Amino Acids and a pyridoxal 5'-phosphate-dependent aspartate racemase in the acidothermophilic archaeon, Thermoplasma acidophilum.

Free D-amino acid content in some archaea was investigated and D-forms of several amino acids were found in them. In the acidothermophilic archaeon, Thermoplasma acidophilum, the proportion of D-aspartate (D-Asp) to total Asp was as high as 39.7%. Crude extracts of Thermoplasma acidophilum had Asp-specific racemase activity that was pyridoxal 5'-phosphate (PLP)-dependent. The relative insensitivity to a SH-modifying reagent distinguished this activity from those of the PLP-independent Asp racemases found in other hyperthermophilic archaea (Matsumoto, M., et al., J. Bacteriol. 181, 6560-6563 1999). Thus, high levels of d-Asp should be produced by a new type(s) of Asp-specific racemase in Thermoplasma acidophilum, although the function of d-Asp in this archaeon remains unknown.

Alanine↗
PubMed2001

Thermostabilization of a chimeric enzyme by residue substitutions: four amino acid residues in loop regions are responsible for the thermostability of Thermus thermophilus isopropylmalate dehydrogenase.

A chimeric 3-isopropylmalate dehydrogenase, named 2T2M6T, made of parts from an extreme thermophile, Thermus thermophilus, and a mesophile, Bacillus subtilis, was found to be considerably more labile than the T. thermophilus wild-type isopropylmalate dehydrogenase. In order to identify the molecular basis of the thermal stability of the T. thermophilus isopropylmalate dehydrogenase, 11 amino acid residues in the mesophilic portion of the chimera were substituted by the corresponding residues of the T. thermophilus enzyme, and the effects of the side chain substitutions were analyzed by comparing the reaction rate of irreversible heat denaturation and catalytic parameters of the mutant chimeras with those of the original chimera, 2T2M6T. Four single-site mutants were successfully stabilized without any loss of the catalytic function. All these four sites are located in loop regions of the enzyme. Our results strongly suggest the importance of these loop structures to the extreme stability of the T. thermophilus isopropylmalate dehydrogenase.

3-Isopropylmalate Dehydrogenase↗
PubMed2001

A noninvasive measurement of reactive hyperemia that can be used to assess resistance artery endothelial function in humans.

We demonstrated that endothelial function in patients with essential hypertension is impaired by a decrease in nitric oxide production using both reactive hyperemia and acetylcholine infusion methods. This noninvasive method of evaluating reactive hyperemia is a useful alternative to intra-arterial infusions of vasoactive agents in the assessment of resistance vessels' endothelial function in forearm circulation.

Acetylcholine↗
PubMed2001

Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules.

In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances.

Animals↗
PubMed2001

Interferon-gamma and interleukin-10 reciprocally regulate endothelial junction integrity and barrier function.

Inflammatory bowel disease (IBD) is associated with Th1/Th2 cytokine dysregulation, leukocyte extravasation, and tissue edema, but the mechanisms for cytokine-mediated vascular dysfunction are not understood. To investigate how cytokines might control edema in IBD, we determined vascular permeability and IFN-gamma expression in two models of murine colitis: SCID mice reconstituted with CD45RB(high T-lymphocytes (CD45RB(high)/SCID mice), and interleukin-10 gene deficient (IL-10(-/-)) mice. We also investigated the in vitro effects of IFN-gamma and IL-10 on human endothelial solute barrier and junction protein expression. Vascular permeability in CD45RB(high)/SCID and IL-10(-/-) mice was quantified using tissue (131)I-IgG accumulation. The IFN-gamma message was quantified using the ribonuclease protection assay. Endothelial barrier integrity in vitro was measured by transmonolayer electrical resistance, and junctional proteins were examined by immunoblotting and fluorescence microscopy. Both CD45RB(high)/SCID and IL-10(-/-) mice exhibit enhanced colonic microvascular leakage and IFN-gamma message levels compared to their respective controls. In vitro, IFN-gamma also reduced endothelial barrier (monolayer electrical resistance, increased albumin permeability) and reduced tight junction (occludin) expression and staining. These effects were reversed by pretreatment of monolayers with IL-10. Therefore, in vivo IFN-gamma and IL-10 may modulate microvascular leakage in IBD partly by controlling the expression of intestinal endothelial tight junctional proteins.

Animals↗
PubMed2001

Nicorandil accelerates recovery of neuromuscular block caused by vecuronium.

PURPOSE: To examine the effect of nicorandil, a K ATP channel agonist, on neuromuscular block caused by vecuronium in patients anesthetized with nitrous oxide, oxygen, isoflurane, and fentanyl. METHODS: Sixty adult patients were allocated to four groups of 15: nicorandil-post-tetanic count (N-PTC), nicorandil-train-of-four (N-TOF), control-post-tetanic count (C-PTC) or control-train-of-four (C-TOF) group. In the N-PTC and N-TOF groups, 0.1 mg kg nicorandil was given as a bolus followed by an infusion at 1 microg x kg(-1) x min(-1). Two minutes after the bolus, 0.1 mg x kg(-1) vecuronium was administered. In the C-PTC or C-TOF group normal saline was given instead of nicorandil. PTC and TOF responses were measured mechanically using a force displacement transducer. RESULTS: Time from the administration of vecuronium to the onset of neuromuscular block in the N-PTC or N-TOF group did not differ from that in the C-PTC or C-TOF group (241 +/- 33 vs 225 +/- 32 sec, mean +/- SD). Times from vecuronium injection to the return of PTC in the N-PTC and C-PTC groups, and those of T1, T2, T3, and T4 (first, second, third, and fourth stimulation of TOF) in the N-TOF and C-TOF groups did not differ. Recoveries of PTC in the N-PTC and C-PTC groups followed similar time course. T1/control twitch height and TOF ratio (T4/T1) in the N-TOF group were higher than those in the C-TOF group 80-120 min and 100-120 min after administration of vecuronium, respectively. CONCLUSION: Nicorandil accelerates recovery of neuromuscular block caused by vecuronium.

Anesthesia, Inhalation↗
PubMed2001

Selection of stabilized 3-isopropylmalate dehydrogenase of Saccharomyces cerevisiae using the host-vector system of an extreme thermophile, Thermus thermophilus.

A leuB strain of Thermus thermophilus TTY1, was transformed with a plasmid vector that directed expression of 3-isopropylmalate dehydrogenase (IPMDH) of Saccharomyces cerevisiae encoded by the LEU2 gene. The original strain could not grow at 50 degrees C without leucine, probably because of the low stability of S. cerevisiae IPMDH. The mutants that could grow without leucine were selected at 50 degrees, 60 degrees, 62 degrees, 65 degrees, 67 degrees, and 70 degrees C, step by step. All the mutant strains except for one isolated at 50 degrees C accumulated mutations. Mutations were serially accumulated: Glu255Val, Asn43Tyr, Ala62Thr, Asn110Lys, and Alal 12Val, respectively, at each step. The analyses of residual activity after heat treatment and the denaturation profile as monitored by circular dichroism showed that thermal stability was increased with accumulation of the mutations. The kinetic parameters of most mutant enzymes were similar to those of the wild type. However, some mutant enzymes showed a reverse correlation between stability and activity: the enzymes with a large increase in thermal stability showed lower activity. Although the wild-type enzyme is unstable in the absence of glycerol, the stabilizing effect of glycerol was not observed for all the mutant enzymes containing the Glu255Val substitution, which is assumed to be located at the hydrophobic interface between two subunits.

Cloning, Molecular↗
PubMed2001

Effect of obesity on endothelium-dependent, nitric oxide-mediated vasodilation in normotensive individuals and patients with essential hypertension.

The purpose of this study was to determine the interdependent and independent effects of hypertension and obesity on endothelial function in humans. We evaluated the forearm blood flow (FBF) response to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, in 16 lean and 12 obese normotensive individuals and the 18 lean and 15 obese hypertensive patients with no history of smoking, hypercholesterolemia, diabetes mellitus, or renal dysfunction. The FBF was measured using a mercury-filled Silastic strain-gauge plethysmograph. The systolic and diastolic blood pressures (BP) and forearm vascular resistance were significantly greater in hypertensive patients than in the normotensive individuals. Insulin resistance, determined by a homeostatic model assessment (HOMA), was significantly greater in the obese group than in the lean group (3.59 +/- 1.68 v 1.91 +/- 1.12, P < .01). There was no significant difference in the HOMA index between normotensive and hypertensive subjects regardless of weight. The response of FBF to acetylcholine was greatest in lean normotensive individuals and least in obese hypertensive patients (40.5 +/- 8.5 and 10.4 +/- 2.8 mL/min/100 mL of tissue, P < .001 v other groups). The FBF response was similar in obese normotensive individuals and lean hypertensive patients (24.1 +/- 7.9 and 19.3 +/- 3.2 mL/min/100 mL of tissue). The vasodilatory effect of ISDN was similar in all four groups. Multiple regression analysis revealed that the maximal FBF response to acetylcholine correlated independently with age (P = .043), obesity (P = .012), HOMA index (P = .002), and mean BP (P < .001). These findings suggest that obesity and hypertension are independently involved in abnormal endothelium-dependent vasodilation by attenuated nitric oxide production.

Acetylcholine↗
PubMed2001

Poly ADP ribose-polymerase inhibitors prevent the upregulation of ICAM-1 and E-selectin in response to Th1 cytokine stimulation.

We studied the role of poly-ADP-ribose polymerase (PARP) in the mobilization of ICAM-1, VCAM-1, and E-selectin by TNF-alpha and IL-1beta in cultured human endothelial cells. Enzyme linked immunosorbent analysis (ELISA) was used to assess if ICAM-1, VCAM-1, and E-selectin were expressed at the cell surface, and if PARP inhibition (using the selective PARP inhibitor GPI 6150) blocked the induced expression. Endothelial cell adhesion molecule expression was evaluated at 4 and at 24 h after cytokine stimulation. At 4 h ICAM-1 and E-selectin, but not VACM-1, were stimulated by both IL-1beta and TNF-alpha. Blocking PARP via GPI 6150 only affected TNF-alpha induced E-selectin expression at 4 hours. ICAM-1, VCAM-1, and E-selectin expression were all stimulated by both IL-1beta and TNF-alpha in the 24 h assays. PARP inhibition with GPI 6150 blocked the IL-1beta mediated stimulation of both ICAM-1 and E-selectin expression, and blocked TNF-alpha stimulation of ICAM-1 expression at 24 h. These experiments suggest that specific PARP inhibition may provide a novel method of controlling leukocyte dependent inflammation through the reduction of ICAM-1 and E-selectin expression in endothelial cells in response to cytokines.

Benzopyrans↗
PubMed2001

A case of rapid progressive glomerulonephritis with IgA deposits after renal transplantation.

A 46-yr-old Japanese male who underwent a second cadaveric kidney transplantation on 31 October 1996 after suffering Type II diabetic mellitus for 25 yr was admitted to our institute on 23 January 1999, because of colicky abdominal pain and abdominal discomfort. Elevated levels of serum creatinine, severe proteinuria and microscopic haematuria were observed. The allograft biopsy specimen disclosed crescentic glomerulonephritis. Immunofluorescence showed granular deposits of mainly IgA and C3 along glomerular capillary walls and mesangial areas. Electron microscopy showed extensive subepithelial and mesangial electron dense deposits. Rapid and irreversible worsening of graft function led to resumption of haemodialysis on 31 May 1999. We speculated that this case was an atypical form of de novo Henoch-Schönlein purpura nephritis (HSPN) in transplanted kidney because of the histopathological findings of the allograft biopsy and clinical symptoms.

Cadaver↗
PubMed2001

Glucocorticoids and IL-10, but not 6-MP, 5-ASA or sulfasalazine block endothelial expression of MAdCAM-1: implications for inflammatory bowel disease therapy.

BACKGROUND: Enhanced MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the aetiology of inflammatory bowel disease, but little is known about MAdCAM-1: regulation, or how inflammatory bowel disease therapies modulate MAdCAM-1. AIM: To examine how agents currently used to treat inflammatory bowel disease affect MAdCAM-1: induced by tnf-alpha in an in vitro model of inflammatory bowel disease. METHODS: Endothelial monolayers were pretreated with dexamethasone (DEX): 5-aminosalicylic acid (5-ASA), 6-mercaptopurine (6-MP), sulfasalazine or interleukin-10: (IL-10: prior to TNF-alpha (20 ng/mL), and MAdCAM-1: measured by Western blotting, RT-PCR, EMSA and lymphocyte adhesion assays. RESULTS: MAdCAM-1: was induced dose- and time-dependently by TNF-alpha on endothelial cells. Either dexamethasone or IL-10: reduced TNF-alpha-induced MAdCAM-1: protein, mRNA and lymphocyte adhesion. However, neither 5-ASA, sulfasalazine nor 6-MP blocked MAdCAM-1 induction. CONCLUSIONS: Our data indicate that dexamethasone or IL-10 can exert therapeutic activity in inflammatory bowel disease through MAdCAM-1 inhibition. 5-ASA, sulfasalazine and 6-MP, while beneficial in inflammatory bowel disease, do not directly control MAdCAM-1, and are beneficial through inhibition of other inflammatory processes.

Animals↗
PubMed2001

Influence of natural and synthetic compounds on cell surface expression of cell adhesion molecules, ICAM-1 and VCAM-1.

Various natural and synthetic compounds including alkaloids, terpenoids and phenolics were tested for inhibition of the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which are crucial in the regulation of immune response and inflammation. Of 40 compounds tested, two compounds significantly downregulated the expression of VCAM-1 on murine endothelial cells (F-2) and ten compounds that of ICAM-1 on mouse myeloid leukemia cells (M1). Sanguinarine chloride (5) and isoliquiritigenin (13) were capable of lowering the levels of both ICAM-1 and VCAM-1. The structure-activity relationships study on chalcone and flavone derivatives related to 13 suggested that the inhibitory activity of the chalcone derivatives is attributable to the 4-hydroxy group as well as the possible coplanarity between the phenyl ring and the adjacent conjugated ketone.

Alkaloids↗
PubMed2001

Cold adaptation of the thermophilic enzyme 3-isopropylmalate dehydrogenase.

We have performed random mutagenesis coupled with selection to isolate mutant enzymes with high catalytic activities at low temperature from thermophilic 3-isopropylmalate dehydrogenase (IPMDH) originally isolated from Thermus thermophilus. Five cold-adapted mutant IPMDHs with single-amino-acid substitutions were obtained and analyzed. Kinetic analysis revealed that there are two types of cold-adapted mutant IPMDH: k(cat)-improved (improved in k(cat)) and K(m)-improved (improved in k(cat)/K(m)) types. To determine the mechanisms of cold adaptation of these mutants, thermodynamic parameters were estimated and compared with those of the Escherichia coli wild-type IPMDH. The Delta G(m) values for Michaelis intermediate formation of the k(cat)-improved-type enzymes were larger than that of the T. thermophilus wild-type IPMDH and similar to that of the E. coli wild-type IPMDH. The Delta G(m) values of K(m)-improved-type enzymes were smaller than that of the T. thermophilus wild-type IPMDH. Fitting of NAD(+) binding was improved in the K(m)-improved-type enzymes. The two types of cold-adapted mutants employed one of the two strategies of E. coli wild-type IPMDH: relative destabilization of the Michaelis complex in k(cat)-improved-type, and destabilization of the rate-limiting step in K(m)-improved type mutants. Some cold-adapted mutant IPMDHs retained thermostability similar to that of the T. thermophilus wild-type IPMDH.

3-Isopropylmalate Dehydrogenase↗
PubMed2001

Ancestral residues stabilizing 3-isopropylmalate dehydrogenase of an extreme thermophile: experimental evidence supporting the thermophilic common ancestor hypothesis.

Ancestral amino acid residues were inferred for 3-isopropylmalate dehydrogenase (IPMDH), and were introduced into the enzyme of an extreme thermophile, Sulfolobus sp. strain 7. The thermostability of the mutant enzymes was compared with that of the wild type enzyme. At least five of the seven mutants tested showed higher thermal stability than the wild type IPMDH. The results are compatible with the hyperthermophilic universal ancestor hypothesis. The results also provide a new method for designing thermostable enzymes. The method only relies on the first dimensional structures of homologous enzymes that can be obtained from genetic databases.

Circular Dichroism↗