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Biomedical subjects

M Shimazaki

Publications and source records attributed to M Shimazaki.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Renal sodium handling and renal dopaminergic activity in overweight normotensive subjects].

Recently, we reported that the blunted natriuretic ability related to an attenuation of renal dopaminergic activity might play an important role in the hypertensive mechanisms of overweight patients with essential hypertension. On the other hand, the interrelationships between obesity, blood pressure and renal sodium handling in normotensives (NT) have not been clear. The purpose of the present study is to reveal the role of renal dopaminergic activity on renal sodium handling in overweight NT. The study consisted of 52 hospitalized NT receiving a regular diet containing 200mEq of sodium, 75mEq of potassium, 2400kcal/day, who were divided into two groups of 31 non-obese (NNT) and 21 obese (ONT) subjects. NNT was categorized as the body mass index (BMI) less than, and ONT as the BMI equal to or more than, 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance. During the clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa) and of inorganic phosphorus (FEP) and urinary excretion of free dopamine (uDA) were determined. There were no significant differences in age, HR, Ccr or UNaV between the two groups. Higher MAP and lower FENa) were observed in ONT than in NNT, but the differences in these parameters were not statistically significant. However, FENa in ONT was significantly lower than in MAP-and Ccr-matched NNT. In addition, FENa correlated negatively with BMI in ONT, unlike in NNT. MAP was correlated positively with FENa, and a similar tendency was found between MAP and FEP in NNT, but not in ONT. On the other hand, there was no significant correlation between BMI and uDA in either NNT or ONT. This result was different from our previous data in patients with essential hypertension (EHT) in which BMI correlated with uDA positively in non-obese EHT and negatively in obese EHT. These findings suggest that blunted natriuretic ability may exist in ONT, and the role of renal dopaminergic activity related to the attenuated natriuretic ability in ONT may be less important than in obese EHT.

Adult↗
PubMed1991

Reduced retinoid content in hepatocellular carcinoma with special reference to alcohol consumption.

Although alcohol is known to enhance hepatocarcinogenesis, the mechanism of this action remains to be explained. To test the hypothesis that ethanol depletes the liver of antitumor promoters such as retinoid, we measured the retinoid concentration in hepatocellular carcinoma tissues and noncancerous surrounding liver tissues in humans known to have a history of alcohol consumption. By high-performance liquid chromatography, the retinoid contents of 29 surgically resected hepatocellular carcinoma specimens and their noncancerous surrounding tissues were measured. Retinoid contents were decreased in both the cancerous and the surrounding noncancerous liver tissues of patients with a high intake of alcohol. The levels correlated inversely with the estimated cumulative lifetime ethanol consumption. The decrease in the retinoid content of hepatic parenchymal cells paralleled that in stellate cells. When compared with the surrounding liver tissues, the cancerous liver tissues were in the state of retinoid deficiency. In summary, alcohol abuse may help promote the hepatocarcinogenesis in man by depleting the liver of the antitumor promoter, retinoid.

Adult↗
PubMed1991

[The coefficient of variation of RR intervals (CVRR) on electrocardiogram in patients with essential hypertension with reference to aging, hemodynamics and sympatho-adrenomedullary function].

To evaluate the significance of parasympathetic nerve activity in essential hypertension, we measured the coefficients of variation of RR intervals (CVRR) on electrocardiogram and examined the relationships between CVRR and aging, hemodynamics and sympatho-adrenomedullary function in normotensive subjects (NT) and in patients with essential hypertension (EHT). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA), plasma adrenaline concentration (pAd) and CVRR resting in a supine position were simultaneously measured in 37 NT (33.8 +/- 2.0 years) and 47 mild-to-moderate EHT (51.3 +/- 1.5 years). In both NT and EHT, significantly negative correlations between CVRR and age (NT: r = -0.54, p less than 0.001, EHT: r = -0.41, p less than 0.005) were observed, however, CVRR correlated with neither MAP, HR nor pAd. CVRR tended to correlate negatively with pNA (r = -0.27, p less than 0.1) in NT, unlike in EHT. The mean value of CVRR in EHT (n = 10, age: 38.3 +/- 1.6 years, CVRR: 3.61 +/- 0.37%) was significantly (p less than 0.005) lower than in age-matched NT (n = 10, age: 38.3 +/- 2.5 years, CVRR: 5.76 +/- 0.45%). These results indicate that the parasympathetic tone suggested by CVRR may be related to aging and sympathetic nerve activity, and that parasympathetic function might be impaired in EHT.

Adolescent↗
PubMed1991

[Shy-Drager syndrome: its autonomic function, alpha 2 receptor density and mechanism of postprandial hypotension].

The autonomic function, platelet alpha 2 receptor (alpha 2R) density, and mechanism of postprandial hypotension were examined in a 58-year-old man with Shy-Drager syndrome (SDS). His chief complaints were orthostatic syncope and impotence. His blood pressure was kept within normal limits in a supine position, but severe hypotension and fainting occurred when he assumed an upright posture. There were diminished sweating response to warm stress, abnormal pupil reactions to drugs, lack of blood pressure elevation at phase IV during the Valsalva maneuver, and a lack of pressor response to hyperventilation and cold stress. The plasma norepinephrine levels (pNE) were very low in a supine position at rest and in a head-up tilt position. Severe blood pressure fall (hypotension) associated with a lack of pNE elevation occurred during an oral glucose tolerance test (oGTT). Platelet alpha 2R density increased and the pressor response to infused norepinephrine (NE-R) was pronounced. The heart rate response to injected atropine was clearly attenuated. The coefficient of the R-R interval variation in the ECG (CVRR), which may reflect parasympathetic activity, was markedly low at rest. In addition, a decrease in a head-up tilt position and increase during oGTT also resolved. These results indicate that a dysfunction of the parasympathetic and sympathetic nervous systems and the up-regulation in the alpha 2R system that leads to an increase in alpha 2R density in SDS are involved in this disease and that the mechanism of postprandial hypotension in SDS may be different from that in normal elderly subjects.

Atropine↗
PubMed1991

[Correlations between the coefficient of variation of RR intervals and sympathetic nerve activity following superior tilting in normotensive subjects and in patients with essential hypertension].

The relationship between changes in sympathetic nerve activity and those in parasympathetic tone with a change in position was investigated in patients with essential hypertension using the coefficient of variation of RR intervals on electrocardiograms (CVRR). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA) and CVRR were measured in a supine position at rest and 20 min after having the head tilted 60 degrees superiorly in 10 normotensives (NT: 51.9 +/- 3.0 yrs) and 7 essential hypertensive patients (EHT: 51.0 +/- 2.8 yrs). After changing the position, CVRR decreased significantly in the NT, but not in the EHT; whereas, significant increases of both HR and pNA without significant changes in MAP were shown in both groups. A significant negative correlation between percentage changes in CVRR (% delta CVRR) and pNA (% delta pNA) were observed in the NT, but not in the EHT. However, there was no relationship of % delta CVRR to % delta MAP or to % delta HR in either group. It was suggested from the changes in CVRR that suppression of the parasympathetic tone, which occurs in the NT group corresponding to sympathetic augmentation to present a decrease in blood pressure with a change in position, may be impaired in the EHT group.

Blood Pressure↗
PubMed1990

Time course of changes in phenotypes of cultured tumor-infiltrating lymphocytes isolated from human colorectal cancer.

A study was conducted to investigate the time course of changes in phenotypes of cultured tumor-infiltrating lymphocytes (TIL) isolated from 5 patients with colorectal cancer. Following initial incubation with protein phytohemagglutinin (PHA-P, final concentration 0.1 w/v%), one of the inducers of interleukin-2 (IL-2) receptor, and recombinant interleukin-2 (rIL-2, 1000U/ml) for 3 days, TIL was further cultured with rIL-2 alone for another 46 to 79 days. Phenotypes of cultured TIL were analyzed by a two color flow-cytometry. The following results were obtained: 1) Yields of TIL isolated from cancerous tissues were 1.0 x 10(6) to 1.6 x 10(6) cells/g wet weight, and TIL grew 31 to 3700 folds in the entire period of culture. These growth rates were significantly higher than those obtained by the conventional method of culture with rIL-2 alone (1 to 720 folds). 2) The population of cytotoxic T cells (CD8(+), CD11(-)) reached the maximum (92%, median value) at 5 weeks of culture, and thereafter gradually decreased to 61% at 9 and 10 weeks. In contrast, the population of activated natural killer cells (CD16(+) and Leu7 (+) or (-)) remained below 4% for the entire period of culture. 3) Maximum enhancement of specific cytotoxic activities of cultured TIL was observed during 3 to 4 weeks in culture, using K562 cells as well as Daudi cells as target cells. In conclusion, addition of PHA-P seems to beneficially affect the growth rate of TIL in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Effects of thyroid hormone and actinomycin D on phosphate uptake of brush-border membrane vesicles from kidney of rachitic rats.

It is generally accepted that 3,5,3'-triiodothyronine (T3) is responsible for most of the known physiological actions of thyroid hormone. Our new rachitogenic diets, deficient in both vitamin D and iodine and low in phosphorus (1.13% calcium and 0.14% phosphorus), induced typical rachitic changes in rats. To know the possible role of T3 on bone and phosphate (Pi) metabolism and its related biochemical and molecular mechanism, weanling male Wistar rats were fed this diet for 28 days, and then treated with 6 micrograms/100g BW of T3 and/or 60 micrograms/100g BW of actinomycin D intraperitoneally. After 2 hours of treatment, renal brush-border membrane vesicles (BBMV) were prepared according to the calcium precipitation method, and their Na(+)-dependent Pi uptake was analyzed by Lineweaver-Burk plots. Km value was not significantly altered by all these treatments. In contrast, Vmax value as a Pi uptake index was significantly increased in T3-treated rats compared with rachitic control. This increase was evident as less as 2 hr after T3 administration, so it was assumed that T3 stimulated the Pi uptake not by mediation of the de novo protein synthesis. However this increase was suppressed by administration of actinomycin D, and then this result suggests that the antirachitic effect of T3 is mediated by somehow de novo protein synthesis. After all, T3 acting as an antirachitic agent, the most likely possibility is that T3 provides favorable conditions for mineralization of bone by improving Pi transport in various types of cells, even under rachitogenic condition, at least of hypophosphatemic type, and correction of phosphate metabolism may be the most essential prerequisite for cure of this type of rickets.

Animals↗
PubMed1990

Reverse triiodothyronine nuclear binding in rat brain.

Reverse triiodothyronine (rT3) had been believed biologically inactive, but recently we demonstrated nuclear binding sites for rT3 in human placenta. In this study we examined rT3 binding sites in rat brain. Male Wistar normal rats aged 2, 4 and 9 weeks were killed and the brain was removed for rT3 binding assay. In another series, male Wistar rats weighing about 40g were divided into two groups: group 1 (rickets group), kept on our original rachitogenic diet and group 2, kept on standard diet. After 28 days on either diet they were killed and the brain was removed for assay. Cerebral nuclear protein was extracted with 0.4M KCl buffer. In normal 2 week-old rats specific binding sites for rT3 were detected in all parts of the brain, but at 7 weeks of age the density of the binding sites was decreased and at 9 weeks it is almost 0. Scatchard analysis performed in rachitic rats showed a curvilinear pattern, suggesting two sets of receptors existing in brain tissue; in cerebral cortex one with a association constant (Ka) of 1.07 X 10(8)M-1 and a limited capacity (Bmax) of 0.75 X 10(-15) moles/mg tissue and the other with Ka = 4.93 X 10(6), Bmax = 12.1 X 10(-15), and in thalamus including hypothalamus, one with Ka = 1.00 X 10(8), Bmax = 1.00 X 10(-15) and the other with Ka = 4.57 X 10(6) and Bmax = 18.6 X 10(-15).

Animals↗
PubMed1989

Attenuated renal production of dopamine in patients with low renin essential hypertension.

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

Adolescent↗
PubMed1989

Immunohistochemical localization of two types of carbonic anhydrase isozymes in oncocytoma and oncocytic epithelial cells.

An immunohistochemical study was performed on the localization of carbonic anhydrase isozymes I and II (CA I and CA II, respectively) in oncocytoma and oncocytic epithelial cells. Tumors examined were those deserved to be called oncocytomas such as Warthin's tumor, Hürthle cell tumor of the thyroid gland and renal oncocytoma. In addition, the same immunostaining was done on several pathologic lesions, accompanying moderate number of cells similar in tinctorial character to oncocytes, such as some type of adenoma of the thyroid gland, endometrial hyperplasia, endometriosis and so on. Specific antibodies against CA I and CA II prepared from human erythrocytes were converted into Fab' fragment and labeled with horseradish peroxidase. In each tissue sample, the majority of oncocytes or oncocytic epithelial cells showed a tendency to exhibit an immunostaining reaction for CA I and II intenser than that of adjacent original normal epithelium from which they might derive. To the authors' knowledge, no reports have been appeared on biological relevance of an increased activities of carbonic anhydrase in conjunction with a large number of mitochondria appearing in such oncocytic cells. In the present study, it is revealed that the immunoreactivities of CA isozymes increased in oncocytes as the number of mitochondria increased, suggesting that oncocytes have a high level of carbonic anhydrase for catalyzing the hydration of an increased amount of carbon dioxide generated chiefly via oxidative metabolism by mitochondria, the number of which is notably increased compensatorily for their deficient coupling of oxidative phosphorylation or other metabolic anomaly.

Adenoma↗
PubMed1989

[A high risk group of hepatocellular carcinoma in man, with special reference to its clinical significance for the screening of early liver cancer. Gifu Study Group for Early Liver Cancer].

A high risk group of hepatocellular carcinoma (HCC) was statistically established using multiple regression analysis of 331 cases with liver cirrhosis (LC), in which 78 cases later developed HCC. Highly contributing factors to hepatocarcinogenesis were found to be positive HBsAg, age, drinking history, sex (male), history of blood transfusion, history of acute hepatitis (or jaundice) and elevated plasma levels of alpha-fetoprotein. A prospective study was initiated in April, 1985 employing another 122 LC patients to clinically evaluate the significance of the high risk group of HCC. 28 cases with small HCC (less than 3 cm in diameter) were newly found: 4 with chronic hepatitis and 24 with LC, among whom 22 developed from the high risk group (sensitivity 92%, specificity 44%). Three year survival rate of 28 cases thus found was 56%, and causes of death of 9 fatal patients were 4 cancer death, 4 hepatic failure and 1 gastrointestinal bleeding. In conclusion, the high risk group is valuable for the screening of early liver cancers, and treatments of hepatic failure as well as of HCC itself are important to improve the prognosis of HCC patients thus diagnosed.

Carcinoma, Hepatocellular↗
PubMed1989

Pulmonary embolization-induced thymus hyperplasia in rabbits.

The effects of pulmonary embolization on the thymus glands of rabbits were studied morphologically, morphometrically and immunohistochemically. Pulmonary embolization was induced by an intravenous injection of 0.4 ml of Sephadex bead suspension (particle size; 150 to 300 microns, about 2,000 per ml). Both mean weight and volume of the thymus of rabbits killed at 2 weeks after embolization, were about 1.5 times more than those in control animals treated with physiologic saline. Histological examinations showed enlargement of the cortex and medulla of the thymus, and the embolized Sephadex beads in the branches of pulmonary arteries of the lung. The area ratios of medulla/cortex, in the embolization group and in control, were not significantly different. The cells with immunohistochemically positive staining of anti-nuclear antigen of monoclonal antibody of Ki-67, were found in both portions of the medulla and cortex. These data suggest that pulmonary embolization in the rabbit induces true thymic hyperplasia. An intravenous injection of India ink into the right highest intercostal artery revealed the distribution of bronchial arteries, which send the branches to the right lobe of the thymus. In 2 out of 4 animals killed 2 weeks after pulmonary embolization, the left lobe of the thymus as well as the right were stained with the injected ink. As it is known that pulmonary vascular obstruction caused a marked increase in the bronchial blood flow, these data suggest that the thymus blood supply from the bronchial arteries increases in the conditions of pulmonary embolization, which might contribute to thymus hyperplasia.

Animals↗
PubMed1989

Nuclear binding sites for reverse triiodothyronine in human placenta.

It has been generally believed that reverse triiodothyronine (reverse T3, rT3) is biologically inactive. Nevertheless the serum rT3 level is very high in fetal life, when the serum calcium level is higher than in the maternal. For this hypercalcemia in fetal life, there is no convincing evidence that any major calcium regulating hormone is responsible. And the assumption that rT3 may be concerned in active transport of calcium at placenta could be suggested. In this study nuclear protein was isolated from human placenta by extraction with 0.4M KCl buffer and binding studies utilizing radioactive rT3 were carried out. Scatchard analysis presented a curvilinear pattern, suggesting two classes of receptors: One with a association constant (Ka) of 1.14 X 10(8) M-1 and a limited capacity (Bmax) of 32.0 X 10(-15) mol/100 micrograms DNA and the other with Ka = 4.34 X 10(6) and Bmax = 454 X 10(-15). Its relative affinities for several thyroid hormone analogues were calculated. If the affinity for rT3 was assigned l, that for triiodothyronine would be 1/40, thyroxine: 1/63, Triiodothyroacetic acid: 1/18. Sulfhydryl agents affecting these binding characteristics were also studied. The Ka was not substantially changed but the Bmax was notably decreased by dithiothreitol (43%) and 2-mercaptoethanol (26%). In liver nuclei, the binding characteristics of rT3 receptor were analyzed for comparison. In this case only a single class of low affinity-high capacity rT3 binding site with a Ka of 6.69 X 10(6) was detected, a finding which was apparently different from those in placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1988

Running-wheel avoidance learning in rats (Rattus norvegicus): effects of contingencies and comparisons of different strains.

In Experiment 1, we showed that active- and passive-avoidance responding in a running wheel was learned because of the avoidance contingency. In Experiment 2, strain differences among four commercially bred rats were assessed in an active-avoidance paradigm. Wistar, Donryu, and Fischer rats learned faster than Sprague-Dawleys. In Experiment 3, learning in a multiple active/passive avoidance schedule was examined, and both components of this task were learned. This multiple schedule was used to investigate strain differences in selectively bred rats in Experiments 4 and 5. Tsukuba low-emotional (TLE) rats responded more than Tsukuba high-emotional (THE) rats in both components. However, discrimination of passive components was better in THE than in TLE rats. Syracuse high-avoidance rats were superior in the active component, whereas Syracuse low-avoidance rats showed superior performance in the passive component.

Animals↗
PubMed1988

The effect of ouabain on pressor responses to infused noradrenaline in patients with essential hypertension.

The relationship between changes in the pressor response to infused noradrenaline induced by intravenous injection of ouabain, an Na+,K+-ATPase inhibitor, and plasma renin activity and plasma ionized calcium was examined in 16 normotensive subjects and in 16 patients with essential hypertension. These patients were divided into 11 normal-renin and five low-renin essential hypertensives. The pressor response was significantly greater in low-renin hypertensives than in normotensives and normal-renin hypertensives. Following the injection of ouabain, the pressor response was significantly increased with no change in basal levels of blood pressure, plasma noradrenaline concentration, plasma calcium and plasma parathyroid hormone in both normotensives and essential hypertensives. The pressor response to noradrenaline was negatively correlated with levels of plasma noradrenaline and calcium after the injection of ouabain as well as before the injection in normotensives and essential hypertensives. The regression line between the pressor response and that of plasma noradrenaline or plasma calcium was significantly shifted towards a higher pressor response in normotensives, but not in essential hypertensives. The changes in the pressor response to noradrenaline induced by the injection of ouabain was significantly smaller in essential hypertensives, particularly in low-renin hypertensives, compared with normotensives. These results suggest that: (1) ouabain increases the pressor response to noradrenaline; (2) this increase is related to calcium metabolism; (3) endogenous Na+,K+-ATPase inhibitor(s) might be elevated in essential hypertensives; and (4) an increase in endogenous Na+,K+-ATPase inhibitor might, therefore contribute to an enhanced noradrenaline response in essential hypertensives, particularly in low-renin hypertensives.

Blood Pressure↗