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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

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

Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C.

Cigarette smoking has been shown to cause endothelial dysfunction. To examine the effects of vitamin C and cigarette smoking on endothelium-dependent vasodilation, we measured the lumen diameter and flow velocity of the brachial arteries at rest, during reactive hyperemia following transient arterial occlusion, and after sublingual nitroglycerin (0.3 mg) in smokers (n = 20) and nonsmokers (n = 20) with high-resolution ultrasound after infusion of saline or saline plus vitamin C (10 mg/min for 20 min). We also performed the same study in smokers (n = 15) before and 10 min after cigarette smoking. In addition, we measured the serum levels of vitamin C and the plasma levels of thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation. The smokers had lower vitamin C levels, higher TBARS levels, and showed impairment of flow-dependent vasodilation (5.3 +/- 1.9 vs. 9.2 +/- 1.5%, P < 0.0001) compared with nonsmokers. Vitamin C administration improved the impairment of flow-dependent vasodilation (5.3 +/- 1.9 to 9.0 +/- 3.2%, P < 0.001) and decreased TBARS in smokers but not in nonsmokers. Furthermore, cigarette smoking acutely worsened the impairment of flow-dependent vasodilation (5.4 +/- 1.8 to 1.5 +/- 1.3%, P < 0.01) and increased TBARS. We conclude that 1) endothelium-dependent vasodilation in the brachial arteries is impaired in smokers and this impairment is improved by vitamin C administration in association with a decrease in TBARS and 2) cigarette smoking produces acute impairment of endothelium-dependent vasodilation in smokers in association with an increase in TBARS.

Adult↗
PubMed1997

Differential effects of extracellular Mg2+ on thrombin-induced and capacitative Ca2+ entry in human coronary arterial endothelial cells.

Receptor-mediated and capacitative Ca2+ entry are the primary Ca2+ entry pathways in endothelial cells (ECs). The mechanisms for Ca2+ entry via these pathways have not been fully elucidated. In this study, the effect of low and high external Mg2+ concentrations on these Ca2+ entry pathways was examined in human coronary arterial ECs. External Mg2+ concentration did not affect cytosolic free Mg2+ concentration. After exposure to thrombin in Ca(2+)-free medium, addition of Ca2+ to the medium caused a rise in cytosolic free Ca2+ concentration ([Ca2+]i), indicating thrombin-induced Ca2+ influx. Thrombin-induced Ca2+ influx was inhibited by not only low but also high external Mg2+ concentrations. After depletion of endoplasmic Ca2+ stores by thapsigargin, addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating capacitative Ca2+ entry. Capacitative entry was found to be accelerated by low external Mg2+ and inhibited by high external Mg2+ concentration. Results suggest that receptor-mediated Ca2+ influx requires external Mg2+ but is inhibited by increased external Mg2+ concentrations and that capacitative Ca2+ entry is reduced by external Mg2+ in human coronary arterial ECs.

Calcium↗
PubMed1997

Relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension.

The infusion of L-arginine induces the production of nitric oxide and stimulates the immediate secretion of insulin. To examine the relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension, we evaluated the renal and insulin responses to L-arginine, 500 mg/kg infused intravenously over 30 minutes, in 23 patients with mild essential hypertension who were neither obese nor diabetic and in 20 normotensive control subjects. We found no difference between the two groups in blood glucose or insulin in the fasting condition. The renovascular relaxation induced by L-arginine was significantly less in patients with essential hypertension than in normotensive control subjects. The increase in plasma cyclic GMP in response to L-arginine was lower in hypertensive patients than in normotensive subjects. Although the serum concentrations of glucose in response to L-arginine were similar in the two groups, the serum insulin response of the essential hypertensives was significantly higher than that of the normotensive subjects. In all subjects, the peak cyclic GMP response to L-arginine was significantly correlated with the peak delta glucose/ delta insulin ratio response to L-arginine (r = .69, P < .001). Findings suggested that an impairment of endothelium-dependent renal vascular relaxation and a reduced sensitivity to insulin are present in patients with essential hypertension. A link may be present between the abnormality of the L-arginine/nitric oxide/cyclic GMP pathway and insulin resistance in patients with essential hypertension.

Arginine↗
PubMed1997

Nitric oxide in the rat spinal cord in Freund's adjuvant-induced hyperalgesia.

To elucidate the involvement of nitric oxide in spinal nociceptive processing, the correlation of thermal withdrawal latency with nitric oxide synthase-stained neurons in the rat lumbar dorsal horn was analyzed after adjuvant-induced inflammation. From 4 hr through 5 days after subcutaneous injection of complete Freund's adjuvant into the hind paw, a marked thermal hyperalgesia was observed for heat stimulus applied to the affected region. NADPH-diaphorase- and nitric oxide synthase-positive neurons increased significantly in the superficial layers of the dorsal horn ipsilateral to the inflamed hind paw at day 3 of adjuvant-induced inflammation. No change in NADPH-diaphorase-positive neurons was observed at 1 hr and 1 day of adjuvant-induced inflammation. The intravenous administration of N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg), an inhibitor of nitric oxide synthase, significantly blocked the adjuvant-induced thermal hyperalgesia at day 3 of inflammation, but not at day 1; and it had no effect in non-inflamed rats. This anti-hyperalgesic effect of L-NAME at day 3 of inflammation was reversed by the prior administration of L-arginine (600 mg/kg, i.p.), a substrate of nitric oxide synthase. These data suggest that nitric oxide producing neurons in the spinal dorsal horn are involved in maintaining and facilitating the hyperalgesia associated with chronic nociception.

Animals↗
PubMed1997

Practical role of genetic profiling and preservation stock of human tumour xenograft lines as a tool in animal experiments for antitumour drug evaluation.

Human tumour xenografts (HTXs) are a useful tool for animal experiments especially for evaluation of new antitumour drugs. We have been establishing HTXs, and have developed tumour chemosensitivity panels for new drug evaluation using them. With regard to quality control (problems in changes into mouse-type tumours and/or artificial cross-contamination among tumour lines), we studied genetic profiling, and effects of long-term passaging on tumour properties such as growth and chemosensitivities, and we discuss the use of cryopreservation stock of HTXs and periodic replacement in order to maintain reproducibility of the experimental results. We examined isozyme markers and DNA fingerprinting to identify species and individuality of the tumours, respectively. Growth curves and sensitivities to antitumour drugs were examined using HTXs with different passaging in nude mice. Among the tumours we maintained, five human tumours were found to have changed to mouse origin from their isozyme markers and were excluded. We identified the individuality of tumours which we used for the chemosensitivity panels by DNA fingerprinting, and their properties were stable for long-term passaging in nude mice. However, growth speed and chemosensitivities to drugs were altered with long-term passaging, although DNA fingerprint analysis did not show any obvious changes with passaging. Genetic profiling, such as isozyme markers and DNA fingerprinting, is useful to identify individuality of experimental HTXs, and tumours should be renewed periodically even when there are no signs of artificial contamination when they are used in experiments which require continuous reproducibility of experimental results.

Animals↗
PubMed1997

Restriction of dietary sodium may enhance nitric oxide production in rats.

To clarify the precise relationship between sodium and nitric oxide (NO), we studied the effects of altered sodium intake on NO production. Male Wistar rats were maintained on a low-sodium (0.2% NaCl), normal-sodium (2% NaCl), or high-sodium (8% NaCl) diet for 10 days or 8 weeks; 24-h urine was collected at those times for assay of nitrate ion (NO3-), a stable metabolite of NO, and of cyclic GMP. Urinary excretion of NO3- and cyclic GMP was increased on the 10th day in the low-sodium group, as compared with the normal- and high-sodium groups. The urinary excretion of cyclic GMP was increased at the 8th week, and NO3- showed a tendency to increase in the low-sodium group, as compared with the high-sodium group. An up-regulation of NO production may explain, at least in part, the antihypertensive effect of sodium restriction.

Animals↗
PubMed1997

Coexistence of an autonomously functioning thyroid nodule in a patient with Graves' disease: an unusual presentation of Marine-Lenhart syndrome.

A 44-year-old woman developed hyperthyroidism due to the coexistence of Graves' disease and an autonomously functioning thyroid nodule (AFTN). Anti-thyrotropin receptor antibody (TRAb) was strongly positive (83.2%), and a thyroid scan initially showed diffuse uptake of Tc-99m pertechnatate in both lobes and further increased uptake in accordance with the right lobe nodule. The nodule in the right lobe was histologically diagnosed as thyroid follicular adenoma. After she was maintained in a euthyroid state by treatment with Methymazole (MMI), thyroid uptake of Tc-99m in the nodule became lower and was slightly suppressed by T3 administrations probably due to its dependence on TSH. Subtotal thyroidectomy was performed and she subsequently became euthyroid with negative TBII activity. It is concluded that she had a coexisting functioning nodule with Graves' disease (Marine-Lenhart syndrome) and that the nodule changed from hot to cool along with the anti-thyroid treatment, unlike usual cases of this syndrome showing a cold nodule on the initial imaging under the hyperthyroid state. Repeated Tc-99m pertechnatate thyroid scans were helpful in evaluating the reaction of MMI and TSH in both lesions separately in the present case.

Adenoma↗
PubMed1997

Chemotherapeutic profiles of human tumors implanted in SCID mice showing appreciable inconsistencies with those in nude mice.

Sensitivities to antitumor drugs of human tumor xenografts (HTXs) implanted in C.B-17-scid and in BALB/cA-nu were compared to examine whether genetic backgrounds of immune deficiency of the host mice influenced the chemotherapeutic profiles of implanted tumors. In a total of 25 pairs of corresponding experiments with each host mouse strain (5 HTXs x 5 drug treatment groups), we obtained consistent results in 23 (92.0%) experiments consisting of 10 which were both significantly effective and 13 which were both ineffective, although the remaining two (8.0%) experiments showed inconsistent results. A human T-cell lymphoma cell line, LM-2-JCK, implanted in nude mice, was resistant to treatment with 65 mg/kg of cyclophosphamide, but this tumor showed sensitivity to the same treatment when implanted in either SCID mice or mice with a recombination activating gene 2 defect [BALB/cA-TgH (Rag2)], suggesting that the genetic immune background of the host mouse should not be overlooked as a factor affecting tumors.

Animals↗
PubMed1997

Quarantine for contaminated pathogens in transplantable human tumors or infections in tumor bearing mice.

To quarantine human tumor samples for transplantation into immune deficient mice or tumor xenograft lines established and introduced from other institutions, we performed isolated implantation and passaging of tumors in a vinyl isolator, and microbiological examinations of sentinel mice kept together with tumor bearing mice. We examined 105 pairs of sentinel mice used to quarantine 907 tumors, and found six cases of contamination or infection with Staphylococcus aureus, 20 cases with Pseudomonas aeruginosa and one case with mouse hepatitis virus (MHV). It was, however, possible that Mycoplasma pulmonis contamination was overlooked because the microbe had been isolated from tumors passaged after quarantine, even though the results of the quarantine of these tumors showed no sign of pathogens. Direct culture of tumors for the microbe was recommended to improve the quarantine system.

Animals↗
PubMed1997

Cardiovascular regulation by L-arginine in the brain of rats: role of the brain renin-angiotensin system and nitric oxide.

The effect of brain L-arginine on arterial pressure was investigated by injecting L- or D-arginine into the cerebral ventricles of male Wistar rats that were anesthetized with urethane. Intracerebroventricular (I.C.V.) injection of 1 micromol L-arginine reduced the arterial pressure and the abdominal sympathetic nervous activity (SNA), whereas the injection of 10 micromol L-arginine induced a transient pressor response and reduced both the heart rate and SNA. Although I.C.V. injection of 1 micromol D-arginine had no effect on cardiovascular function or SNA, injection of 10 micromol of this enantiomer elicited a transient pressor response, similar to that induced by 10 micromol L-arginine, followed by a persistent increase in arterial pressure and a corresponding increase in SNA. I.C.V. pretreatment with the nitric oxide synthase inhibitor N(G)-monomethyl L-arginine abolished the vasodepressor response and reduced the inhibition of SNA induced by I.C.V. injection of 1 micromol L-arginine; such pretreatment increased the arterial pressure, heart rate, and SNA measured 30 min after I.C.V. injection of 10 micromol L-arginine. I.C.V. pretreatment with the angiotensin II type 1 receptor antagonist CV-11974 inhibited the pressor response to 10 micromol L-arginine and the first phase of the pressor response to 10 micromol D-arginine. Intravenous pretreatment with the alpha1-adrenoceptor blocker bunazosin hydrochloride abolished the pressor response to 10 micromol L-arginine and both phases of the pressor response to 10 micromol D-arginine. Brain L-arginine thus appears to exert pressor actions through stimulation of the brain renin-angiotensin system and peripheral SNA. However, these actions may be attenuated by L-arginine-derived nitric oxide.

Animals↗
PubMed1997

Sudden death due to diabetic coma in insulin-department diabetes mellitus: an autopsy report.

Sudden death caused by the acute onset of diabetic coma is reported. A 15-year-old female had been suffering from insulin-dependent diabetes mellitus for the prior 8 years and had a fever and vomiting for the past few days. On the 4th day, after the onset of fever and vomiting, she died suddenly, and was autopsied to clarify the cause of death. Macroscopic examination revealed that the pancreas was atrophic (40 g) whereas the liver was markedly enlarged (2,740 g). Histological findings were: 1) The islets of Langerhans were decreased in size and number. They were not positive for aldehyde-fuchsin staining, 2) There were severe fatty changes in the liver cells. The retained blood in the left ventricle was analyzed: glucose, 1,016 mg/dl; acetone, 345 mg/l; acetoacetate, 5.91 mmol/l: D-3-hydroxybutyrate, 4.17 mmol/l; hemoglobin A1c, 10.2%; fructosamine, 416 mumol/l; total serum cholesterol, 220 mg/dl; triglycerides, 205 mg/dl; free fatty acid, 8.0 mEq/l; urea nitrogen, 40 mg/dl. Although the biochemical estimation of the glucose and ketone levels in post-mortem body fluids was recognized as being unreliable, many of these values were far elevated in comparison with those of normal individuals. Thus, we concluded that the cause of death was diabetic ketoacidosis. We also discuss the diagnostic problems of postmortem blood chemistry.

Adolescent↗
PubMed1997

[Application of urinary free dopamine as a marker of renal function, and comparison with other renal marker].

Urinary free dopamine (U-f-DA) is derived from renal DA synthesized in the renal proximal tubules, and plays an important role for diuresis and natriuresis. We were previously reported that U-f-DA was the superior marker of renal function as compared with ordinary methods including alpha 1-microglobulin (U-alpha 1 MG), beta 2-microglobulin (U-beta 2 MG) and N-acetyl-beta-D-glucosaminidase (U-NAG) in spot urine samples. U-f-DA can be used as index for the evaluation of renal transplantation. In order to evaluate the clinical usefulness of U-f-DA as a marker of renal function, we investigated as follows; firstly, the age related changes of U-f-DA in healthy out-patients, secondly, the correlation between U-f-DA and creatinine clearance (CCr), serum creatinine (S-Cr) in in-patients, and thirdly, the chronological changes of U-f-DA, U-alpha 1 MG, U-beta 2 MG, CCr and S-Cr in patients with chronic renal failure before and after renal transplantation. There is no age-related changes in U-f-DA from patients with 3 years to 88 years old. U-f-DA was positively correlated with CCr and negatively correlated with S-Cr. There are parallel changes of U-f-DA and CCr in increasing direction, on the other hand, parallel changes of U-alpha 1 MG, U-beta 2 MG and S-Cr in decreasing direction after renal transplantation. In patients with post renal transplantation who were not well controlled, S-Cr increased gradually with the decreasing level of U-f-DA. These results suggest that the measurement of U-f-DA in spot urine samples is useful marker for evaluation of the renal function and can be used an index of viability of the transplanted kidney.

Adolescent↗
PubMed1997

[Serum hepatocyte growth factor as a possible indicator of vascular lesions].

To investigate the possible involvement of hepatocyte growth factor (HGF) with vascular lesions, we studied the relationship between serum HGF concentrations and the grades of retinal arteriosclerosis, coronary atherosclerosis, and the proliferative changes in the retina of diabetic subjects. Individuals with more advanced grades of arteriosclerotic change showed higher serum HGF values (grade 0, 0.056 +/- 0.004ng/ml; grade 1, 0.132 +/- 0.026ng/ml; grade 2-3, 0.271 +/- 0.023ng/ml). The serum HGF concentration was increased (p < 0.05) in subjects with double- (0.323 +/- 0.037ng/ml) or triple-(0.345 +/- 0.027ng/ml) vessel coronary heart diseases, as compared to that in subjects with single-vessel coronary heart disease (0.191 +/- 0.027ng/ml). Serum HGF in diabetics without retinopathy was lower than that in nondiabetic subjects (0.041 +/- 0.003ng/ml vs 0.080 +/- 0.010ng/ml, p < 0.05), but did not differ from other diabetic subjects with background retinopathy (0.058 +/- 0.007ng/ml) or preproliferative retinopathy (0.048 +/- 0.010ng/ml). Serum HGF was increased in proliferative retinopathy without photocoagulation (0.138 +/- 0.035ng/ml, p < 0.01), but not with photocoagulation (0.040 +/- 0.008ng/ml). Increased serum HGF may be involved in the pathogenesis of arteriosclerosis/atherosclerosis or retinal neovascularization, and measurement of serum HGF may be a useful test to predict the presence of these vascular lesions.

Arteriosclerosis↗
PubMed1997

[Sleeve lobectomy for tuberculous bronchial stenosis: a case report].

We describe a patient with tuberculous bronchial stenosis who was subjected to bronchoplasty. The patient was a 33-year-old man who had stenosis of the left main bronchus. Because the lesion was associated with bronchomalacia, previous balloon dilatation therapy had failed. At thoracotomy, the left upper lobe was found not to be saved for the tuberculous lesion. Although there were many inflamed nodules in the left lower lobe due to repeated episodes of pneumonia, we decided to save it using bronchoplasty expecting its respiratory functional recovery. He ran uneventful course postoperatively and his lung function improved. We conclude that bronchoplasty may prove effective for patients with tuberculous bronchial stenosis associated with bronchomalacia; and thus, to avoid pneumonectomy, bronchoplasty should be attempted even if the reconstructed lung is mildly inflamed.

Adult↗