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Biomedical subjects

T Matsuo

Publications and source records attributed to T Matsuo.

At least 253 records · Page 14Linked to original sources

Single transduction in the transcriptional activator CooA containing a heme-based CO sensor: isolation of a dominant positive mutant which is active as the transcriptional activator even in the absence of CO.

We constructed an in vivo reporter system to measure the activity of CooA as the transcriptional activator and showed that the recombinant CooA was active as the transcriptional activator in the presence of CO even in E. coli cells. A dominant positive mutant of CooA, in which Met131 was replaced by Leu, was isolated by a random mutagenesis with this reporter system. The electronic absorption spectra of M131L mutant were identical to those of wild type CooA in oxidized (Fe3+), reduced (Fe2+), and CO-bound (CO-Fe2+) state, indicating that the coordination structure and environment of the heme were not changed by this mutation. Methionine at position 131 was the carboxyl-terminal end of the heme-binding domain of CooA, which would be adjacent to the hinge region connecting the heme-binding domain and the DNA-binding domain.

Bacterial Proteins↗

Inhibition of collagen-induced platelet aggregation by argatroban in patients with acute cerebral infarction.

Platelet aggregation induced by collagen is enhanced in patients with cerebral thrombosis [1], and platelet aggregates and activation products such as beta-thromboglobulin appear in the circulation, particularly during the acute phase [2]. It is known that the presence of activated platelets markedly amplifies thrombin generation by the prothrombinase complex. Platelet aggregation, for which thrombin is the most potent stimulator, is effected by the activation of the thrombin receptor. Activated platelets likely provide the principal surfaces on which intrinsic coagulation factors and prothrombinase assemble in vivo. Moreover, the blood coagulation cascade is simultaneously enhanced during the acute phase of cerebral infarction, resulting in thrombin production and fibrin formation [3]. Cerebral arterial thrombosis is thought to be initiated by rupture of atherosclerotic plaque. Platelets adhere to the constituents of the plaque, and platelet aggregation and the formation of thrombin occur rapidly. The presence of activated platelets involving thrombin generation in cerebral infarction remains to be further clarified. The present study in patients with acute cerebral infarction was undertaken to determine whether argatroban, a direct thrombin inhibitor, is effective in inhibiting collagen-induced platelet aggregation. It is well known that argatroban inhibits not only thrombin cleavage of fibrinogen with a Ki of 19 nM, but also thrombin-mediated platelet activation with a Ki of 40 nM [4]. We evaluated whether the sensitivity of platelets to collagen is increased in the presence of a trace amount of thrombin associated on platelets, at a concentration that does not induce platelet aggregation in acute cerebral infarction. The study also measured the inhibitory effect, if any, of the addition of argatroban during platelet hyperactivation induced by collagen.

Acute Disease↗

Identification and characterization of a retinoic acid-regulated human homologue of the unc-33-like phosphoprotein gene (hUlip) from neuroblastoma cells.

A cDNA, 7G1, was isolated from retinoic acid (RA) differentiated neuroblastoma cells whose expression was high in human fetal brain and spinal cord mRNA but undetectable in adult brain or non-neuronal tissues. Sequence analysis indicates that 7G1 is homologous to the Caenorhabditis elegans gene unc-33. A 5.5-kilobase pair full-length cDNA from a human fetal brain cDNA library contains an 1710-base pair open reading frame. Because the predicted 570 amino acid sequence of 7G1 shares 98% identity with the murine Ulip gene product, an unc-33-like-phosphoprotein, we refer to 7G1 as the human Ulip (hUlip). hUlip is also similar to the bacterial enzyme D-hydantoinase and the recently described vertebrate gene products CRMP62, TOAD-64, CRMP1, CRMP2, and mUNC. RA stimulates an increase in hUlip mRNA that is transcriptionally regulated. RA stimulates an increase in polypeptides of 58, 60, 65, and 70 kDa with the 58- and 65-kDa species being dephosphorylated forms of the 60- and 70-kDa species. This study presents a model in which to study the regulation and expression of the hUlip gene, a member of an emerging family of molecules that potentially mediates signals involved in axonal outgrowth.

Adult↗

Species-specific B-cell epitope on the C-terminal region of the alpha antigen from Mycobacterium scrofulaceum.

In the amino acid (AA) sequences of alpha antigen from mycobacteria, C-terminal regions were variable among a variety of mycobacterial species though the N-terminal regions were relatively conserved. These regions may possess some species-specific antigenic determinants of the alpha antigen from Mycobacterium scrofulaceum (S-alpha). AAs288-300 of S-alpha fused to beta-galactosidase was reactive with the antisera raised against S-alpha. The same fused peptide did not react with the antisera raised against the alpha antigen from Mycobacterium avium (A-alpha) and Mycobacterium bovis BCG (B-alpha). B-cell epitope mapping then was performed focusing on the C-terminal region of S-alpha using the synthetic peptides. Their reactivities with antisera raised against the alpha antigens of three different mycobacterial species were assessed by ELISA. AAs279-286 were a cross-reactive common immunodominant region among three mycobacterial species. This region may be one of the cross-reactive common epitopes in mycobacterial species. And AAs291-300 were reactive only with the antisera raised against S-alpha. This region may possess a species-specific epitope.

Amino Acid Sequence↗

Characterization of the transcriptional initiation regions of genes for the major secreted protein antigens 85C and MPB51 of Mycobacterium bovis BCG.

The component of mycobacterial 85 complex (85A, 85B, and 85C) and MPB51 are very important from immunological, biochemical, and antimycobacterial points of view. In this study, the transcriptional properties of genes encoding three components of 85 complex and MPB51 from BCG were analysed. The authors' analyses revealed that genes for 85A and MPB51 were transcribed as a single unit despite the one operon-like structure and these four genes were probably under a different regulatory control. These findings may help to understand the immunological and physiological roles of these antigens.

Amino Acid Sequence↗

Hanshin-Awaji earthquake as a trigger for acute myocardial infarction.

On Jan. 17, 1995, the Hanshin-Awaji district was struck by the most destructive earthquake ever to occur in Japan. It is commonly believed that acute emotional stress such as that caused by an earthquake can trigger acute myocardial infarction (AMI). The objective of this study was to evaluate the effect of the quake stress on the onset of AMI in our district. The number of patients with AMI during the first 4 weeks after the quake increased by about 3.5-fold. The mean age of patients was 72.5 +/- 2.8 years, and the proportion of women (53%) was significantly greater than in the preceding years. The proportion of patients without prodromal angina pectoris was 53%. The mean post-traumatic stress disorder reaction index score (n = 14) was 40.1 +/- 4.1, which indicates a severe stress level. The mean score in the women (45.9 +/- 4.7; n = 7) was significantly higher than that in the men (34.3 +/- 6.4; n = 7). We concluded that after an earthquake, severe emotional stress can trigger AMI, more often than normal in women.

Aged↗

Cataract and aqueous flare levels in patients with atopic dermatitis.

PURPOSE: To determine whether cataract in patients with atopic dermatitis is associated with higher levels of aqueous flare or cells. METHODS: In a prospective study, 35 consecutive patients examined during a 6-month period at the atopic dermatitis service in a university hospital underwent standardized ophthalmologic evaluations including the quantitative measurement of aqueous flare and cells by a laser flare-cell meter. RESULTS: Seven patients had bilateral cataract with anterior or posterior subcapsular opacities, or both; one patient had similar cataract in one eye and no cataract in the opposite eye; and 27 patients had no cataract in either eye. Fifteen eyes with cataract showed significantly higher levels of aqueous flare (2.1 to 33.9 photon counts per millisecond with a median of 18.0) compared with 55 eyes without cataract (2.4 to 16.0 photon counts per millisecond with a median of 9.2; Mann-Whitney U test, P = .0008). The association of cataract with higher levels of aqueous flare remained significant when only one eye (the right eye) of each patient was chosen for statistical analysis (P = .0024). CONCLUSION: Higher levels of aqueous flare caused by the breakdown of blood-aqueous barrier may contribute to the formation of cataract in patients with atopic dermatitis.

Adolescent↗

Brain beta-adrenergic receptor binding in rats with obesity induced by a beef tallow diet.

We have previously reported that compared with safflower oil diet, feeding a beef tallow diet leads to a greater accumulation of body fat by reducing sympathetic activities. The present study examined the effects of dietary fats consisting of different fatty acids on alpha1- and beta-adrenergic receptor binding in the hypothalamus and cerebral cortex. Male Sprague-Dawley rats were meal-fed isoenergetic diets based on safflower oil (rich in n-6 polyunsaturated fatty acids) or beef tallow (rich in saturated fatty acids) for 8 weeks. Binding affinities of the beta-adrenergic receptor in the hypothalamus and cortex were significantly lower in the beef tallow diet group, but those of the alpha1-receptor did not differ between the two groups. The polyunsaturated to saturated fatty acid (P/S) ratio and fluidities of plasma membranes in the hypothalamus and cortex were lower in the beef tallow diet group than in the safflower oil diet group. These results suggest that the beef tallow diet decreases membrane fluidity by altering the fatty acid composition of plasma membranes in the hypothalamus and cerebral cortex of rat. Consequently, beta-adrenergic receptor binding affinities in the brain were lower in rats fed the beef tallow diet than in rats fed the safflower oil diet. We recognized that there is possible link between the membrane fluidity and the changes in affinity of beta-adrenoceptors in rat brain.

Animals↗

Bilateral iridocyclitis with retinal capillaritis in juveniles.

PURPOSE: The authors present clinical features of 18 juvenile patients with a new type of uveitis termed bilateral iridocyclitis with retinal capillaritis (BIRC). METHODS: The authors reviewed medical records of 18 consecutive patients who showed bilateral iridocyclitis with retinal capillary leakage but no systemic manifestations during an 11-year period from January 1985 to December 1995. RESULTS: Twelve of the 18 patients were female and the age at onset ranged from 9 to 17 years old. All patients had many cells in the anterior chamber and anterior vitreous, together with mutton fat keratic precipitates. Fluorescein angiography showed leakage from the optic disc and retinal capillaries, mainly in the midperiphery, which corresponded to retinal cloudiness. Macular edema was minimal, and all patients maintained good vision. The inflammation responded well topical, oral, and intravenous administration of corticosteroids, the choice of which was based on the extent of retinal inflammation. Human leukocyte antigen (HLA)-DR6 and HLA-Cw7 were associated significantly with the presence of BIRC (chi square test, P < 0.0001). CONCLUSIONS: Bilateral retinal capillaritis affecting capillaries in various areas of the retina and overlying retinal cloudiness with no distinct lesions are unique to these patients. Fluorescein angiography is essential for diagnosis of BIRC.

Acute Disease↗

Limitation of dietary copper and zinc decreases superoxide dismutase activity in the onion fly, Delia antiqua.

Larvae of the onion fly, Delia antiqua, have lower superoxide dismutase (SOD) activity when they are fed a defined synthetic diet that contains no copper or zinc. SOD activity was rapidly recovered when these larvae were fed onion bulbs. Addition of copper and zinc to the synthetic diet also led to the recovery of SOD activity. Results of an immunoblotting analysis using anti-D. antiqua CuZnSOD mouse monoclonal antibody suggest that this alteration of SOD activity is dependent on the amount of CuZnSOD.

Animals↗

Earthquake-induced potentiation of acute risk factors in hypertensive elderly patients: possible triggering of cardiovascular events after a major earthquake.

OBJECTIVES: We sought to investigate the potentiation of acute risk factors after the Hanshin-Awaji earthquake (7.2 on the Richter scale). BACKGROUND: The frequency of cardiovascular events increases just after a major earthquake, but the causative factors have not been fully investigated. METHODS: We studied the changes in cardiovascular risk factors in 42 elderly outpatients with well-controlled hypertension living near the epicenter (Awaji-Hokudan districts) 7 to 14 days after the earthquake when the major felt-aftershocks persisted. They all experienced the highest stress grading of 6 (catastrophic stress) according to the DSM-III-R. To study the hemostatic profile and endothelial cell state, we measured the blood pressure (BP), hematocrit and lipid profiles as well as fibrinogen, a marker of fibrin turnover (D-dimer), fibrinolytic factors (plasmin-alpha2-plasmin inhibitor complex [PIC], tissue-type plasminogen activator [t-PA] antigen and t-PA inhibitor [PAI] activity) and an endothelial cell-derived marker (von Willebrand factor [vWF]). RESULTS: Systolic and diastolic blood pressures and other variables increased after the earthquake. Before and after the earthquake, the median (25th to 75th percentiles) systolic BP was 152 (range 142 to 164) and 170 mm Hg (range 161 to 178), respectively (p < 0.0001), and the diastolic BP was 83 (range 79 to 88) and 91 mm Hg (range 84 to 96), respectively (p < 0.0001). Of blood viscosity determinants, hematocrit was 38.1% (range 40.7% to 35.9%) and 39.7% (range 42.9% to 38.3%), respectively (p < 0.001), and fibrinogen 316 (range 272 to 360) and 335 mg/dl (range 307 to 391), respectively (p < 0.05). Von Willebrand factor was 128% (range 74% to 148%) and 148% (range 100% to 178%), respectively (p < 0.01); D-dimer was 410 (range 285 to 633) and 560 ng/ml (range 391 to 888), respectively (p < 0.0001); and PIC was 0.74 (range 0.58 to 0.91) and 0.75 microg/ml (range 0.58 to 1.1), respectively (p < 0.05). In contrast, lipid profiles did not change after the quake. When the patients were classified into the high stress and moderate stress groups according to the degrees of damage to their house and injury to family members, the levels of fibrinogen, vWF, PIC and t-PA antigen were increased only in the former group, whereas BP, hematocrit and D-dimer levels were increased in both groups. These abnormalities of acute risk factors, except for vWF, were transient and decreased to prequake levels by 4 to 6 months after the quake. CONCLUSIONS: Earthquake-induced stress seems to induce transient increases in BP, blood viscosity determinants and fibrin turnover and to prolong endothelial cell stimulation. The potentiation of these acute risk factors might contribute to the occurrence of cardiovascular events just after a major earthquake in elderly subjects with hypertension.

Aged↗

Suppressing effects of S-methyl methanethiosulfonate and diphenyl disulfide on mitomycin C-induced somatic mutation and recombination in Drosophila melanogaster and micronuclei in mice.

S-Methyl methanethiosulfonate (MMTS) and diphenyl disulfide (DPDS) are temporary enzyme-sulfhydryl blocking agents. They are naturally occurring phytoalexin-like and synthetic substances known to be very potent bio-antimutagens in Escherichia coli B/r WP2. In the present paper, the suppressing effects of MMTS on mitomycin C (MMC)-induced mutant wing spots in the somatic mutation and recombination test (SMART) of Drosophila melanogaster, and of MMTS and DPDS on MMC-induced micronucleated peripheral reticulocytes are described. MMTS consistently reduced the numbers of MMC-induced small single, large single and twin spots per wing at a dose of 10-1000 micrograms/vial, in a dose-dependent manner. MMTS reduced the number of twin spots per wing on the spontaneous mutation at the dose of 1000 micrograms/vial. MMTS and DPDS dose-dependently reduced the frequencies of MMC-induced micronucleated peripheral reticulocytes at a dose of 10-40, and 3-100 micrograms/kg, respectively. Our results confirmed that enzyme-sulfhydryl blocking agents, such as MMTS and DPDS, are effective antimutagens in vivo too.

Animals↗

Development of argatroban, a direct thrombin inhibitor, and its clinical application.

Argatroban, a direct thrombin inhibitor, is used clinically because of its safe and effective antithrombotic action. This drug of low molecular weight shows reversible inhibition of thrombin irrespective of whether thrombin is fibrin-bound or soluble. Optimal anticoagulant effects can easily be attained by monitoring with the activated partial thromboplastin time or whole-blood activated clotting time when a therapeutic range of argatroban equivalent to that of heparin is used. The antithrombotic action is simply detected with a chromogenic substrate assay. The clinical use of the drug in Japan was approved for the treatment of chronic peripheral arterial obstructive disease and acute ischemic stroke. For coronary artery disease in patients with deficiency of antithrombin activities attributable to either antithrombin III or heparin cofactor II deficiency, argatroban is effective as an anticoagulant. Acute coronary occlusion during and after percutaneous transluminal coronary angioplasty can be treated by argatroban as an alternative to heparin. The presence of platelets activated by a trace amount of thrombin is evidenced by modified methods of platelet aggregometry in acute ischemic stroke. Therefore, argatroban can render the platelets insensitive against the platelet hyperaggregation enhanced by thrombin.

Anticoagulants↗

Pharmacokinetics of carboplatin and etoposide in a haemodialysis patient with Merkel-cell carcinoma.

We present a Merkel-cell carcinoma patient with chronic renal failure requiring haemodialysis and evaluate the pharmacokinetics of carboplatin and etoposide during haemodialysis. The area under the concentration-time curve of carboplatin was increased by prolonging the interval between administration and haemodialysis. However, that of etoposide was not changed. Carboplatin showed good membrane permeability in haemodialysis, while etoposide showed no permeability. In conclusion, the pharmacokinetics of carboplatin could be controlled by haemodialysis and the interval between chemotherapy and haemodialysis. However, the pharmacokinetics of etoposide were not affected.

Aged↗

Early onset of immunological heparin-induced thrombocytopenia in acute myocardial infarction.

We studied five patients who developed a decrease in platelet count of more than 30000 x 10(6)/l within 24 h of heparin treatment and direct percutaneous transluminal coronary angioplasty and/or intracoronary thrombolytic therapy among 38 consecutive patients with acute myocardial infarction (AMI). Anti-platelet factor 4 (PF4)-heparin complex antibodies were detected in the sera of these five patients, although they had never previously been exposed to heparin. These patients might have had specific antibodies before heparin treatment. PF4 might be released from activated platelets and bind to endogenous heparin-like molecules, and antibodies with cross-reactivity to the PF4-heparin complex may have been generated by the endogenous complex before the first heparin treatment. We conclude that it is worthwhile to check the platelet count and screen for anti-PF4-heparin complex antibody in advance to prevent thrombotic complications due to heparin treatment in patients with AMI.

Acute Disease↗

Factor VII R353Q polymorphism and lacunar stroke in Japanese hypertensive patients and normotensive controls.

Elevated plasma factor VII (FVII) levels are reported to be associated with cardiovascular disease in both Caucasians and Japanese. Recent reports indicate that individuals with the FVII 353Q allele have decreased plasma FVII levels. Thus, we investigated the association between lacunar stroke and the FVII R353Q polymorphism in 137 hypertensive patients with silent or overt lacunar stroke (stroke group), 83 non-stroke hypertensives without any lacunae detected by magnetic resonance imaging (non-stroke group), and 97 normotensive control subjects matched for age, sex, and smoking status recruited at an annual health examination (normotensive control group). The frequency of the FVII 353Q allele was 0.057 in the normotensive control group, 0.051 in the non-stroke group and 0.061 in the stroke group. These frequencies, as well as genotype distribution, were not significantly different from each other, even when we subclassified the ischemic group into silent (n = 54) and clinically overt (n = 64) lacunar stroke subgroups. These results suggest that the FVII 353Q allele is not an important genetic determinant for cerebrovascular disease in Japanese individuals.

Adult↗