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Biomedical subjects

J Shimizu

Publications and source records attributed to J Shimizu.

At least 55 records · Page 3Linked to original sources
PubMed2000

Augmentation of somato-sympathetic reflex in the ischemic hindlimb of anesthetized rats.

Activities of the visceral sympathetic nerve increase with noxious mechanical stimulation. This study investigated the effects of noxious mechanical stimulation of hindlimb on arterial blood pressure, heart rate (HR) and renal sympathetic nerve activities (RNA) in anesthetized rats intact or under ischemic conditions. This study utilized two methods of noxious mechanical stimulation. One was pinching of the hindpaw; the other, strangulation of the ankle joint. Twenty-three male Wistar rats were used in the experiment. Pinching and strangulation of the intact hindlimb caused an increase in RNA. The increased RNA was greater during strangulation than during pinch stimulation (p < 0.0001). In the ischemic hindlimb produced by occlusion of the left common iliac artery, pinching and strangulation caused a further increase in RNA (p < 0.0001). Arterial blood pressure and HR significantly increased during strangulation with ischemic condition (p < 0.05). These results suggest that the reflex effects of somatosensory input on RNA were augmented in the ischemic hindlimb.

Analysis of Variance↗
PubMed2000

Radio frequency transmyocardial revascularization enhances angiogenesis and causes myocardial denervation in canine model.

BACKGROUND AND OBJECTIVE: Transmyocardial revascularization (TMR) relieves angina and improves exercise tolerance in patients. Angiogenesis and myocardial denervation have been proposed as factors contributing to these benefits. To test whether radio frequency transmyocardial revascularization (RF-TMR) enhances angiogenesis and causes myocardial denervation. STUDY DESIGN/MATERIALS AND METHODS: RF-TMR channels were created in 12 dogs which survived up to 4 weeks. Bromodeoxyuridine was administered subcutaneously to mark proliferating cells as an assay of angiogenesis. Western blot analysis of tyrosine hydroxylase and blood pressure response to topical bradykinin were used as indices of myocardial denervation. RESULTS: RF-TMR increased local vascularity by an average of 50%, whereas the rate of vascular cell proliferation was tripled over that of the untreated region. Changes in mean arterial pressure with bradykinin and tyrosine hydroxylase content were significantly decreased in RF-TMR regions as compared with normal myocardium in the same hearts. CONCLUSION: RF-TMR enhances angiogenesis and causes myocardial denervation in canine myocardium as with laser TMR.

Animals↗
PubMed2000

Clinicopathological and biological assessment of lung cancers with pleural dissemination.

BACKGROUND: This study provides the surgical outcome of lung cancer patients with pleural dissemination, with the assessment of the clinicopathological and biological prognostic factors. METHODS: Forty-three patients who underwent operations were studied. Vascular endothelial growth factor (VEGF) and autocrine motility factor receptor (AMFR/gp78) expression was immunohistochemically evaluated. RESULTS: In total, the overall 3 and 5-year survival rates were 31.4% and 13.1%, respectively. The patients who underwent the pleuropneumonectomy had a worse outcome than those who underwent limited operations (pleurectomy plus parenchymal resections were less than pneumonectomy). VEGF and AMFR/gp78 were highly expressed in primary tumors. Among the patients who underwent limited operations, pathological types other than adenocarcinoma and high expression of VEGF were significantly associated with a worse outcome. The pathological type was the only characteristic to retain a significant independent prognostic impact on overall survival. CONCLUSIONS: The results imply the validation of limited operation for lung cancer with pleural dissemination for the local control. High frequency of VEGF and AMFR/gp78 expression conform to the interpretation that patients with pleural dissemination have a high-risk of systemic disease.

Adenocarcinoma↗
PubMed2000

Dietary docosahexaenoic acid can alter the surface expression of CD4 and CD8 on T cells in peripheral blood.

The effect of dietary docosahexaenoic acid (DHA) on T cell states in peripheral blood was investigated. Weanling male C57Bl/6N mice were kept on one of three 10% fat diets containing various amounts of DHA and linoleic acid for 4 weeks. Changing the concentration of dietary DHA did not alter the proportion of T cells expressing CD4 or CD8. However, increasing the concentration of dietary DHA lowered the expression of CD4 and CD8 on the cell surface. The decreased expression of these surface molecules involved in T cell proliferation has serious implications in the role of DHA as an immunosuppressant.

Animals↗
PubMed2000

Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation.

A CD4(+) T cell subpopulation defined by the expression levels of a particular cell surface molecule (e.g. CD5, CD45RB, CD25, CD62L or CD38) bears an autoimmune-preventive activity in various animal models. Here we show that the expression of CD25 is highly specific, when compared with other molecules, in delineating the autoimmune-preventive immunoregulatory CD4(+) T cell population. Furthermore, although CD25 is an activation marker for T cells, the following findings indicate that immunoregulatory CD25(+)CD4(+) T cells are functionally distinct from activated or anergy-induced T cells derived from CD25(-)CD4(+) T cells. First, the former are autoimmune-preventive in vivo, naturally unresponsive (anergic) to TCR stimulation in vitro and, upon TCR stimulation, able to suppress the activation/proliferation of other T cells, whereas the latter scarcely exhibit the in vivo autoimmune-preventive activity or the in vitro suppressive activity. Second, such activated or anergy-induced CD25(-) spleen cells produce various autoimmune diseases when transferred to syngeneic athymic nude mice, whereas similarly treated normal spleen cells, which include CD25(+)CD4(+) T cells, do not. Third, upon polyclonal T cell stimulation, CD25(+)CD4(+) T cells express CD25 at higher levels and more persistently than CD25(-)CD4(+) T cell-derived activated T cells; moreover, when the stimulation is ceased, the former revert to the original levels of CD25 expression, whereas the latter lose the expression. These results collectively indicate that naturally anergic and suppressive CD25(+)CD4(+) T cells present in normal naive mice are functionally and phenotypically stable, distinct from other T cells, and play a key role in maintaining immunologic self-tolerance.

Animals↗
PubMed2000

Energy-wasteful total Ca(2+) handling underlies increased O(2) cost of contractility in canine stunned heart.

Postischemic myocardial stunning halved left ventricular contractility [end-systolic maximum elastance (E(max))] and doubled the O(2) cost of E(max) in excised cross-circulated canine heart. We hypothesized that this increased O(2) cost derived from energy-wasteful myocardial Ca(2+) handling consisting of a decreased internal Ca(2+) recirculation, some futile Ca(2+) cycling, and a depressed Ca(2+) reactivity of E(max). We first calculated the internal Ca(2+) recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation. Stunning significantly accelerated the decay and decreased RF from 0.63 to 0. 43 on average. We then combined the decreased RF with the halved E(max) and its doubled O(2) cost and analyzed total Ca(2+) handling using our recently developed integrative method. We found a decreased total Ca(2+) transport and a considerable shift of the relation between futile Ca(2+) cycling and Ca(2+) reactivity in an energy-wasteful direction in the stunned heart. These changes in total Ca(2+) handling reasonably account for the doubled O(2) cost of E(max) in stunning, supporting the hypothesis.

Animals↗
PubMed2000

Postextrasystolic contractile decay always contains exponential and alternans components in canine heart.

In isolated, blood-perfused canine hearts, postextrasystolic potentiation (PESP) decays monotonically after a noncompensatory pause following a spontaneous extrasystole (ES). The monotonic PESP decay yields myocardial internal Ca(2+) recirculation fraction (RF). We have found that after a compensatory pause (CP), PESP decays in alternans, consisting of an exponential and a sinusoidal decay component. We have proposed that this exponential component also yields RF. In the present study, we examined the reliability of this alternative method by widely changing the ES coupling interval (ESI), CP, and heart rate in the canine excised, cross-circulated left ventricle. We found that all PESP decays consisted of the sum of an exponential and a sinusoidal decay component of variable magnitudes whether a CP existed or not. Their decay constants as well as the calculated RF were independent of the ESI and CP. This confirmed the utility of our alternative RF determination method regardless of the ESI, CP, and heart rate. Direct experimental evidence of Ca(2+) dynamics supportive of this alternative method, however, remains to be obtained.

Animals↗
PubMed2000

Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats.

The aim of this study was to estimate the contributions of dietary n-3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n-6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n-3 PUFA (n-3 diet) and the other an n-6 PUFA (n-6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor alpha in the rats fed the n-3 diet, compared with rats fed the n-6 diet. NK cell activity was reduced by consumption of the n-3 diet. This study suggests that consumption of n-3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.

Animals↗
PubMed2000

Defect in cell wall integrity of the yeast saccharomyces cerevisiae caused by a mutation of the GDP-mannose pyrophosphorylase gene VIG9.

The Saccharomyces cerevisiae VIG9 gene encodes GDP-mannose pyrophosphorylase, which synthesizes GDP-mannose from GTP and mannose-1-phosphate. Although the null mutant was lethal, the vig9 mutants so far obtained showed no growth defect but immature protein glycosylation and drug hypersensitivity. During our search for cell-wall mutants, we found a novel temperature-sensitive mutant, JS30, which required an osmotic stabilizer for viability. JS30 excreted cell surface proteins in the medium without any indication of cell lysis. Although conventional genetic analysis using mating was impossible, by detailed characterization of JS30 including an in vitro enzyme assay and nucleotide sequencing, we found the defect of JS30 was due to a mutation in the VIG9 gene. These results indicated a critical role of GDP-mannose in maintenance of cell-wall integrity.

Cell Wall↗
PubMed2000

Rapidly progressive polymyositis with elevated antiacetylcholine receptor antibody activity.

We report a 51-year-old woman with polymyositis accompanied by a high titer of antiacetylcholine receptor antibody. The patient presented with weakness of grip strength followed by rapidly progressive dyspnea, which required mechanical ventilation. She was treated with a glucocorticoid and came off the respirator one week later. Antiacetylcholine receptor antibody activity was elevated in the acute phase and decreased during recovery, although other signs of myasthenia gravis were negative. This patient suggested that in cases of rapidly progressive bulbar palsy and limb muscle weakness, it is necessary to include polymyositis associated with elevated antiacetylcholine receptor antibody activity in the differential diagnosis.

Anti-Inflammatory Agents↗
PubMed2000

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle.

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.

Animals↗
PubMed2000

Effective arterial elastance of irregular beats during atrial fibrillation in canine left ventricle.

Effective arterial elastance (E(a)) was originally defined as the end-systolic pressure (ESP)/stroke volume (SV) ratio of the left ventricle (LV). E(a) combined with LV contractility (E(max)), E(a)/E(max), proved to be powerful in analyzing the ventriculo-arterial coupling of normal and failing hearts in regular beats. However, E(a) sensitively changes with LV E(max), preload, and afterload widely changing among irregular beats. This has discouraged the use of E(a) during arrhythmia. However, we hypothesized that E(a) could serve as the effective afterload (not always arterial) elastance against ventricular ejection under arrhythmia. We tested this hypothesis by analyzing beat-to-beat changes in E(a) of irregular beats during electrically induced atrial fibrillation (AF) in normal canine in situ hearts. We newly found that during AF in each heart: 1) E(a) changed widely among irregular beats and became markedly high in weak beats with small SVs; 2) E(a) and E(a)/E(max) distributed non-normally with large skewness but 1/E(a) distributed more normally; 3) 1/E(a) correlated closely with end-diastolic volume, E(max) and preceding beat intervals; and 4) the reciprocal of mean 1/E(a) closely correlated with mean ESP/mean SV. These results support our hypothesis that E(a) can serve as the effective afterload elastance against ventricular ejection on a per-beat basis during AF. E(a)/E(max) can also quantify the ventriculo-afterload (not arterial) coupling on a per-beat basis. This study, however, warns that mean E(a) and mean E(a)/E(max) of irregular beats cannot necessarily represent their averages during AF.

Animals↗
PubMed2000

Acute inflammatory demyelination in reperfusion nerve injury.

We investigated the pathological appearance of acute inflammation and its role in the development of demyelination in reperfused rat sciatic, tibial, and peroneal nerves after a 5-hour period of near-complete ischemia. Polymorphonuclear neutrophil migration was seen early in the endoneurial lesion. After 18 hours of reperfusion, there was maximal intercellular adhesion molecule-1 expression on endoneurial vessels, and polymorphonuclear neutrophil accumulation was then prominent, reaching a peak 24 hours after reperfusion. Endoneurial mononuclear macrophages increased nearly fourfold after 48 to 72 hours of reperfusion. Macrophages were observed invading Schwann cells and myelin lamellae with associated demyelination. Thus, this study provides evidence of macrophage-associated demyelination after reperfusion similar to that seen in inflammatory neuropathies.

Acute Disease↗