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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 379 records · Page 21Linked to original sources

Cellular immunity in hemodialysis patients: a quantitative analysis of immune cell subsets by flow cytometry.

Immune cell subsets, when measured by two-color flow cytometry in a population of 129 hemodialysis patients, showed significant variance from normal values. Lymphopenia, decreased absolute counts, and altered percentage values of immune cells were found. Increased proportions of CD3+, T cell receptor (TCR) alpha beta + cells and CD4+ T lymphocytes were present. An abnormally high percentage of a subset of activated TCR alpha beta + cells (alpha beta + DR+) was also seen in hemodialysis patients. The proportion of B lymphocytes was found to be significantly lower as compared with controls. Relative values for TCR gamma delta+cells, both for activated (gamma delta + DR+) and nonactivated (gamma delta + DR-) subsets, as well as for CD8+ lymphocytes and natural killer cells did not vary from those of normal controls. Also, the CD4+/CD8+ ratio showed no significant change. Analysis of absolute counts of the investigated immune cell populations revealed significantly decreased numbers for the majority of subsets, as a result of the preexisting lymphocytopenia, characteristic of end-stage renal disease. We conclude that profound quantitative alterations of immune cells, including TCR+T cells subsets, exist in hemodialysis patients. These account, at least in part, for the immune dysregulation associated with chronic renal failure.

B-Lymphocyte Subsets↗

Influence of a high salt diet on glomerular injury and the preventive effects of amiloride in adriamycin nephropathy.

The effects of a high salt diet on glomerular hypertrophy and sclerosis were examined in a focal glomerular sclerosis rat model. Sprague-Dawley rats were injected twice with Adriamycin (ADR, 2.5 mg/kg body weight) and then divided into 3 groups: (1) ADR rats fed a 1% sodium chloride (NaCI) diet (control ADR rats); (2) ADR rats fed an 8% NaC1 diet (ADR-NaC1 group), and (3) ADR rats fed a 10% sodium bicarbonate (NaHCO3) diet (the ADR-NaHCO3 group), and were then observed for 8 weeks. There were no differences in the blood pressure levels between the control ADR and ADR-NaC1 groups. The urinary protein excretion was significantly less in the ADR-NaC1 and ADR-NaHCO3 groups than in the control ADR group. However, a progressive increase in the blood urea nitrogen and serum creatinine associated with extensive glomerular sclerosis and hypertrophy was only observed in the ADR-NaC1 group. An increase in the glomerular diameter preceded the development of glomerulosclerosis in this group. Furthermore, a daily administration of amiloride, a Na+/H+ exchanger inhibitor, to the ADR-NaC1 rats prevented the development of glomerular hypertrophy and sclerosis. These results therefore suggest that the aggravated effect of a high salt diet on glomerular sclerosis may be related to glomerular hypertrophy which is associated with the stimulation of the Na+/H+ exchanger.

Amiloride↗

Effect of maternal diabetes on longevity in offspring of spontaneously hypertensive rats.

We studied the effect of maternal diabetes induced by neonatal streptozotocin treatment on the longevity of the male offspring in spontaneously hypertensive rats (SHR). Maternal diabetes significantly decreased the survival in the offspring as compared with the control (p < 0.01). Mean age at death was 14.9 +/- 0.6 months in the offspring from the diabetic dams and 17.9 +/- 1.1 months in that from the control. The life span was significantly correlated with the birth weight (rs = 0.55, p = 0.009). These findings suggest that a diabetic pregnancy may accelerate an age-related degenerative process of the offspring in SHR.

Animals↗

Impaired maze learning and cerebral glucose utilization in aged hypertensive rats.

To elucidate the effects of prolonged hypertension on brain function during aging, we examined learning of an eight-arm radial maze task and local cerebral glucose utilization in young-adult (3 to 4 months old) and aged (16 to 17 months old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Young-adult SHR learned the task more slowly than young-adult WKY, but cerebral glucose utilization, measured by the [14C]2-deoxyglucose method in 24 brain structures, was not significantly different in the two groups. The aged SHR and WKY exhibited impaired learning ability. Cerebral glucose utilization was reduced (13% to 23%) in six regions in aged WKY and in 12 regions in aged SHR compared with values in the respective young-adult groups. Furthermore, the aged SHR showed a greater disturbance of learning acquisition and more profound reduction of cerebral glucose utilization in five regions than the aged WKY. In SHR, hypometabolism, indicated by a decrease in glucose utilization in 15 brain structures including the cerebral cortex, hippocampus, and visual system, was significantly correlated with impaired learning acquisition, indicated by an increase in total error choices. These findings show that (1) hypertension per se does not impair maze learning or cerebral glucose utilization in young-adult rats, and (2) brain function is impaired during aging and prolonged hypertension is an additional factor facilitating brain dysfunction associated with neuronal hypoactivities, resulting in behavioral deterioration including learning disability. Thus, early control of hypertension seems important for preventing or reducing brain dysfunction in senescence.

Aging↗

Can transcranial Doppler really detect reduced cerebral perfusion states?

BACKGROUND AND PURPOSE: This study was designed to determine whether transcranial Doppler ultrasonography (TCD) may detect reduced perfusion states of the brain in patients with hypertension or diabetes mellitus with suspected cerebral atherosclerosis and arteriolosclerosis. METHODS: We determined blood flow velocity with TCD in the middle cerebral artery and cerebrovascular vasodilator responses to carbon dioxide in 22 patients with or without carotid artery occlusive disease and minor stroke; we compared the results with the measurements of cerebral blood flow and oxygen metabolism by positron emission tomography (PET). RESULTS: Blood flow velocity measured by TCD correlated with ipsilateral cerebral blood flow measured by PET in frontal, temporal, and striatal regions and throughout the entire hemisphere (P < .05 to P < .005). Relative changes in blood flow velocity and calculated cerebrovascular resistance tested by carbon dioxide inhalation both correlated closely with regional mean transit time (calculated as the ratio of cerebral blood volume divided by cerebral blood flow) in frontal, striatal, temporal, parietal, and occipital regions and also in the entire hemisphere (P < .05 to P < .0001). TCD variables did not correlate with hemispheric measurements of oxygen metabolism by PET. CONCLUSIONS: Although TCD is not useful in assessing impairments of cerebral metabolism, it is useful for detecting abnormalities of cerebral hemodynamics among patients with risk factors for cerebrovascular disease.

Adult↗

The impact of alcohol and hypertension on stroke incidence in a general Japanese population. The Hisayama Study.

BACKGROUND AND PURPOSE: The relationship between alcohol intake and stroke has been inconsistent in previous studies. We examined the separate and combined effects of drinking habits and hypertension on stroke incidence in a prospective survey of a general Japanese population. METHODS: A total of 1621 stroke-free Hisayama residents aged 40 years or older were classified by their alcohol intake into nondrinkers, light drinkers (< 34 g of ethanol per day), and heavy drinkers (> or = 34 g of ethanol per day) and followed up prospectively for 26 years from 1961. RESULTS: During the follow-up period, cerebral infarction developed in 244 subjects and cerebral hemorrhage in 60. For men, the incidence of cerebral hemorrhage increased significantly with rising alcohol consumption. In contrast, the incidence of cerebral infarction was slightly lower in light drinkers than in nondrinkers, while it increased significantly in heavy drinkers compared with light drinkers. Female drinkers had a lower incidence of cerebral infarction but a slightly higher incidence of cerebral hemorrhage than nondrinkers, as did male light drinkers. Among the hypertensive subjects, the age- and sex-adjusted relative risk of cerebral hemorrhage was significantly elevated in heavy drinkers versus abstainers (3.13; 95% confidence interval [CI], 1.08 to 9.10), but the increase was not significant for light drinkers. In contrast, the relative risk did not significantly increase for normotensive light and heavy drinkers. Compared with hypertensive light drinkers, the relative risk of cerebral infarction significantly increased in hypertensive heavy drinkers (1.96; 95% CI, 1.08 to 3.57) but remained unchanged in normotensive heavy drinkers. Significant associations between alcohol intake and stroke were substantially the same even after controlling for other risk factors in multivariate analysis. CONCLUSIONS: Among hypertensive individuals, heavy alcohol consumption leads to a significant increase in the risk of cerebral hemorrhage, suggesting a synergistic effect of alcohol and hypertension, while light alcohol consumption significantly reduces the risk of cerebral infarction.

Adult↗

Silent cerebral infarction in a community-based autopsy series in Japan. The Hisayama Study.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the prevalence and characteristics of silent cerebral infarction in a population-based consecutive autopsy series of residents of Hisayama, Kyushu, Japan. METHODS: Autopsy records, cerebral pathological findings, and clinical charts of 966 Hisayama residents recorded during the 26 years from 1961 to 1987 were examined (autopsy rate, 82.4%). The subjects were divided into three groups: those with both clinically apparent strokes and pathologically verified cerebral infarcts (stroke group), those having pathological evidence of cerebral infarction in the brain but without clinical stroke episodes (silent infarction group), and those with neither infarction nor stroke episode (noninfarction group). Risk factors and brain pathology in the three groups were compared. RESULTS: Silent cerebral infarction was found in 12.9% of the 966 subjects who had undergone autopsy, and its frequency increased with age. The subjects with silent infarcts were older, had higher systolic or diastolic blood pressure, and had atrial fibrillation more frequently than subjects in the noninfarction group. There were no significant differences in the locations of infarcts between the stroke and silent infarction groups, although infarcts tended to be located in the deeper area of the brain in the latter. The number and size of infarcts were smaller in the silent infarction group than in the stroke group. CONCLUSIONS: Diastolic blood pressure and atrial fibrillation appear to be strong predictors of silent cerebral infarction in the Japanese general population. Stroke becomes clinically apparent as infarct volume increases.

Adult↗

Impact of thalamic hematoma on six-month mortality and motor and cognitive functional outcome.

BACKGROUND AND PURPOSE: In this study we examined the functional outcome of thalamic hemorrhage after 6 months as it related to neurological and computed tomographic (CT) findings in 104 patients. METHODS: Level of consciousness was determined on admission. Extension and volume of hematoma were examined with CT within 3 days. After 6 months, motor function was evaluated using hemiplegic staging by the scale of Brunnström, and cognition was assessed by the Hasegawa dementia rating scale administered in Japanese. RESULTS: Twelve patients (12%) died from stroke after 6 +/- 6 days (mean +/- SD), which correlated with volume of hematomas (P < .001), levels of consciousness (P < .005), and miosis (P < .01). Six patients (6%) died from systemic complications after 23 +/- 18 days, which correlated with age (P < .05). Initially, 88 patients (85%) had hemiparesis; which persisted in 78 (75%) patients (18 deaths and 60 survivors). After 6 months, the Brunnström scale scores were lower in patients with hematomas extending to the internal capsule (P < .01) than in those with hematomas localized within the thalamus, and scores were lowest in patients with hematomas extending to the midbrain or putamen (P < .01). Motor function was well correlated with the extension and volume of hematomas (P < .001) and with the consciousness level (P < .001). Activities of daily living were correlated with hematoma extension and advanced age. Cognitive impairment was correlated with disturbance of consciousness (P < .01) and ventricular extension of the hematoma (P < .05) in 80 nonaphasic patients. CONCLUSIONS: The extension and volume of hematomas, indicating direct cerebral damage, are useful indicators of mortality from thalamic hemorrhage, motor functional outcome, and level of activities of daily living after 6 months. The disturbance of consciousness and ventricular extension of the hematoma, suggesting diffuse brain damage, could be predictors of cognitive function.

Activities of Daily Living↗

Effect of administration and withdrawal of doxazosin on ambulatory blood pressure in patients with essential hypertension.

The effect of both administration and withdrawal of doxazosin on patients with essential hypertension was evaluated by twenty-four-hour ambulatory blood pressure (BP) monitoring. Six hypertensive men were treated with doxazosin starting at 1 mg/day, and the dosage was titrated at weekly intervals up to a maximum of 8 mg/day. The twenty-four-hour BP profile was monitored noninvasively before treatment, in the fourth week of treatment, and on days 2 and 7 after the discontinuation of doxazosin. The average twenty-four-hour systolic and diastolic BPs (SBP and DBP) were lowered by doxazosin treatment and returned to the pretreatment levels within two days of doxazosin withdrawal. Doxazosin treatment produced a significant decrease in the daytime SBP and DBP but not in the nighttime BP values. The daytime BP decrease was no longer detected on days 2 and 7 after drug withdrawal. The twenty-four-hour pulse rate was not influenced by either doxazosin administration or discontinuation. The plasma norepinephrine concentration and plasma renin activity were increased by doxazosin treatment and were decreased by drug withdrawal. There was no rebound hypertension following doxazosin withdrawal. Thus, the present study using twenty-four-hour BP monitoring showed that doxazosin treatment reduced the daytime BP in patients with essential hypertension and that this reduction was abolished within two days after doxazosin discontinuation.

Adult↗

Brain infarction developed in hypertensive and normotensive patients during hospitalization--hemodynamic factors.

To determine the effects of changes in blood pressure (BP) on the development of ischemic stroke, 17 patients who developed acute brain infarction during hospitalization were analyzed in relation to the vascular risk factors such as hypertension, previous stroke, diabetes mellitus, and hyperlipidemia. Their BPs were retrospectively referred to the onset of stroke. The average values of mean arterial blood pressure (MABP) on admission were 137 mmHg in hypertensive patients (HT; n = 9) and 101 mmHg in normotensives (NT; n = 8). HT patients received antihypertensive treatment after admission and MABP decreased by 22 mmHg (14%) prior to the ictus (three to sixty-five days after admission). MABP in NT patients remained constant before the attack (-1.4 mmHg, four to one hundred ten days after admission). Similarly, MABP decreased by 17 mmHg (four to ninety-three days) before the ictus in patients with previous stroke (n = 9), whereas it changed only a little in patients without history of stroke (n = 8). BP in each group elevated immediately after the stroke and gradually decreased to 90% of the resting level after two weeks. An excessive reduction of BP may induce brain infarction in HT or chronic stroke patients or cause it to recur.

Acute Disease↗

Cerebral blood flow and metabolism in hypertensive patients with cerebral infarction.

The authors investigated, by positron emission tomography, the effect of long-standing hypertension on cerebral blood flow (CBF) and oxygen metabolism in patients with chronic atherothrombotic brain infarction. In the nonbrain infarct (non-BI) group (n = 13, mean age: sixty-two years), the regional CBF (rCBF) was decreased significantly with a rise in the mean arterial blood pressure (MABP) in the cerebral cortexes (r = -0.575) and the deep gray matter (r = -0.451), whereas the regional cerebral metabolic rate for oxygen (rCMRO2) remained unchanged. In the brain infarct (BI) group (n = 22, mean age: fifty-eight years), however, the rCBF as well as the rCMRO2 were reduced even in the normotensive patients and thus did not correlate with the MABP. These results suggest that long-standing hypertension per se causes a reduction in the rCBF but not in the oxygen metabolism with a compensatory increase in the oxygen extraction fraction. On the other hand, patients with brain infarction, even normotensives, show a diffuse decrease in cerebral circulation and metabolism, which is probably due to the more severe sclerotic changes that take place in the cerebral vessels.

Blood Pressure↗

A randomized trial of E5510 versus aspirin in patients with transient ischemic attacks. The Japanese E5510 TIA study-1 (JETS-1) Group.

In a randomized double-blind trial, the Study Group compared the efficacy of E5510, a novel antiplatelet agent, and aspirin in preventing the recurrence of transient ischemic attacks (TIA). In total, 227 patients who suffered from TIA in the twelve weeks prior to the study were enrolled. They were randomly allocated to three treatment groups, ie, 71 patients in the E5510 4 mg group, 77 patients in the E5510 2 mg group, and 79 patients in the aspirin 324 mg group, and were treated for twelve to twenty-four weeks. The incidence of recurrent TIA or stroke was 21.5% in the aspirin group and was significantly lower in the E5510 groups, being 8.5% in the 4 mg group (P < 0.05) and 11.7% in the 2 mg group (P < 0.05). Adverse events were observed in 5 cases in the 4 mg group, in 8 cases in the 2 mg group, and in 10 cases in the aspirin group, but none of them were serious. Since safety was judged to be comparable among the three groups, E5510 appears to be an antiplatelet agent for the treatment of TIA with a clinical benefit over aspirin.

Aged↗

Human T-lymphotropic virus type I-associated uveitis in patients with Graves' disease treated with methylmercaptoimidazole.

Human T-lymphotropic virus type I (HTLV-I) is responsible for a certain form of uveitis [HTLV-I-associated uveitis (HAU)]. A previous history of Graves' disease has been reported in 9-17% of the patients with HAU. In this study, the prevalence of patients with either HTLV-I antibody or uveitis was evaluated in 819 consecutive patients with thyroid disorders between 1991 and 1992. Serum HTLV-I antibody was found in 25 of 392 patients with Graves' disease, 19 of 257 with chronic thyroiditis, and 3 of 170 with nodular goiter. Five of 25 HTLV-I-positive patients with Graves' disease developed HAU. All of these 5 patients had been treated with methylmercaptoimidazole (MMI). Within a few months before the onset of uveitis, 3 patients were hyperthyroid, and 2 were hypothyroid. In 2 of 5 patients, an exacerbation of uveitis occurred soon after the readministration of MMI for the relapse of hyperthyroidism. None of the 367 HTLV-I negative patients with Graves' disease nor 22 HTLV-I-positive patients with chronic thyroiditis or nodular goiter developed uveitis. It was therefore suggested that Graves' disease, thyroid dysfunction and/or MMI administration might be related to the development of HAU.

Adult↗

Cerebral blood flow and brain function in hypertension.

In mild hypertensive patients, regional cerebral blood flow, measured by positron emission tomography, was reduced in the frontal cortex and basal ganglia compared with normotensive patients. In moderate to severe hypertensive patients, cerebral oxygen metabolism was diminished, although the patients were neurologically intact. In elderly hypertensives, white matter vascular lesions on brain imaging were more frequent and cognitive function was impaired, compared with age-matched normotensives. In nontreated spontaneously hypertensive rats (SHR), local cerebral blood flow was decreased in the cortex and thalamus, compared with normotensive rats (NTR). Spatial memory and learning in maze tests were more impaired in aged SHR than in old NTR or young SHR. This impairment was related to decreased cerebral glucose utilization in the medial septal nucleus, hippocampus, and other regions of the brain. Reduced cerebral blood flow, increased media thickness of the cerebral arteries and impaired cognitive function in SHR were improved by long-term antihypertensive treatment. In humans as well as animals, long-standing hypertension per se leads to reductions in cerebral blood flow, metabolism, and cognitive function, each of which possibly may be improved by controlling hypertension with long-term antihypertensive treatment.

Animals↗

Effects of intra-arterial infusion of insulin on forearm vasoreactivity in hypertensive humans.

We previously demonstrated that intra-arterial infusion of insulin attenuates vasoreactivity to phenylephrine and angiotensin II in the forearm of normotensive humans, which suggests that the pressor effects of insulin via sympathetic activation may be offset in peripheral arteries. In the present study, we investigated the effects of insulin on vasoreactivity in hypertensive humans. Seven male patients with essential hypertension (age, 26 +/- 2 yr; blood pressure, 159 +/- 4/103 +/- 4 mmHg; mean +/- SEM) were studied. We measured forearm blood flow by a strain gauge plethysmograph while infusing phenylephrine (1, 4, 12 nmol/min) and angiotensin II (5, 10, 20 pmol/min) locally into the brachial artery before and during simultaneous intra-arterial infusion of human insulin (0.15 mU/kg/min). Forearm vascular resistance was calculated from directly measured arterial pressure and forearm blood flow. Intra-arterial infusion of insulin raised the local plasma insulin level without changing the blood glucose level, basal forearm blood flow, or forearm vascular resistance. Phenylephrine and angiotensin II increased forearm vascular resistance dose-dependently before and during insulin infusion. In contrast to the previous results in normotensive subjects, locally infused insulin did not attenuate vasoconstrictive responses to phenylephrine and angiotensin II in patients with essential hypertension. These results suggest that the balance between the pressor and depressor effects of insulin might be altered in favor of a pressor effect in patients with hypertension.

Blood Glucose↗

Acute spontaneous hemorrhagic degeneration of the thyroid nodule with subacute thyroiditis-like symptoms and laboratory findings.

Seventeen consecutive patients (3 men and 14 women, aged 14-75 years) with a hemorrhagic degeneration of the thyroid nodule, which was confirmed by both ultrasonography and either reddish or brown fluid evacuated by fine-needle aspiration, were classified as either acute type with an episode of abrupt painful swelling of the thyroid (n = 4), or chronic type in which a painless thyroid nodule was incidentally found (n = 13). One of the four acute type patients demonstrated subacute thyroiditis-like symptoms and laboratory findings including transient painful thyrotoxicosis associated with high serum levels of thyroid hormones and thyroglobulin (Tg), a suppressed serum TSH level, a low thyroidal radioactive iodine uptake (RAIU), and accelerated erythrocyte sedimentation rate (ESR). In the other three acute type patients the serum level of Tg increased markedly, the serum thyroid hormones level increased in one, the thyroidal RAIU was low in two, and the ESR was accelerated in one. In the thirteen chronic type patients, the serum levels of the thyroid hormones and the thyroidal RAIU were within the normal range, and few inflammatory signs were observed. These findings suggest that acute hemorrhagic degeneration of the thyroid nodule may thus cause transient subacute thyroiditis-like symptoms and laboratory findings.

Acute Disease↗

Sulfamethizole absorption test for the assessment of gastric emptying. Comparison with scintigraphic method.

BACKGROUND: To investigate whether the sulfamethizole absorption test can be applied for the assessment of gastric emptying, we measured comparatively plasma sulfamethizole concentration and gastric emptying as determined by scintigraphy in 15 subjects. METHODS: After the ingestion of a solid-liquid meal that contained sulfamethizole and radioisotope (technetium-99m-labeled diethylenetriaminepentaacetic acid), the plasma sulfamethizole concentrations were measured every 15 to 60 min up to 180 min. The initial emptying time (duration after ingestion until 10% reduction in radioactivity of the stomach) and the exponential curve in the cumulative reduction of radioactivity were used as indicators of gastric emptying. RESULTS: The initial emptying time was significantly correlated with the sulfamethizole concentration at 15 min after ingestion (r = -0.64, p < 0.05). A close correlation was observed between the rate of decrease in radioactivity and sulfamethizole concentration at 60 min after ingestion (r = 0.80, p < 0.001). CONCLUSIONS: The sulfamethizole absorption test can be used for the evaluation of gastric motility. Two points of measurement, 15 and 60 min after ingestion, are sufficient to demonstrate the initial and subsequent gastric emptying.

Female↗