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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 361 records · Page 20Linked to original sources

Changes in cytosolic 3,5,3'-tri-iodo-L-thyronine (T3) binding activity during administration of L-thyroxine to thyroidectomized rats: cytosolic T3-binding protein and its activator act as intracellular regulators for nuclear T3 binding.

Changes in the amount of cytosolic 3,5,3'-tri-iodo-L-thyronine (T3)-binding protein (CTBP) and its activator during administration of L-thyroxine (T4) to thyroidectomized rats were investigated. Thyroidectomy decreased the amount of CTBP in the kidney, whereas the activator was not significantly modified by thyroidectomy. The activator was increased by administration of T4 to thyroidectomized rats. The amount of CTBP was also increased by administration of T4. The activator increased the maximal binding capacity (MBC) without changes in the affinity constant for T3 binding in CTBP. A T4-induced increase in MBC in cytosol inhibited nuclear T3 binding in vitro by competition of T3 binding between CTBP and the nuclear receptor. These results suggest that thyroid hormone increases the capacity for cytosolic T3 binding through increasing the amount of CTBP and its activator, and that these increases play a role in regulating the amount of T3 that binds to its nuclear receptor.

Animals↗

[Age related changes in the walking cycle during fastest walking in healthy male subjects].

Velocity, step length and walking rate during fastest walking were measured together with maximum torque (MVC) in the left knee extension for 81 healthy males with aged from 22 to 79 years. Velocity and step length showed an accelerated decline from the sixties, while walking rate decreased with age linearly. Multiple regression analysis with age, height, weight and MVC as independent variables and velocity, step length and walking rate as dependent variables indicated that (1) walking velocity was significantly related to age, MCV and weight, (2) step length to MVC and weight, and (3) walking rate to age.

Adult↗

[A case of systemic lupus erythematosus with neurological manifestations as initial symptoms].

According to the past reports, neuropsychiatric manifestations have been seen in 10-75% of patients with systemic lupus erythematosus and are second only to renal involvement as a cause of death. The clinical feature is multiple. And cerebrovascular diseases due to systemic lupus erythematosus are detected in 3-16% of the neuropsychiatric manifestations. Occlusion of the intracranial major arteries is less frequently found in other cerebrovascular diseases. And central nervous system involvement usually occurs at some intermediate or terminal stage of systemic lupus erythematosus, so is rarely regarded as one of the initial symptoms. We studied the case of a patient with systemic lupus erythematosus with occlusion of the right middle cerebral artery indicated by angitis and 'string of beads' appearance of the right internal carotid artery indicated by fibromuscular dysplasia. The patient was a 38 year old female and began to feel weakness in the left hand and developed mild-left hemiparesis due to infarction of right temporo-parieto-occipital lesion which was revealed by CT scan. Carotid angiograph showed irregularity at the right middle cerebral artery and 'string of beads' appearance of the right internal carotid artery. Gradually neurological manifestations improved, but a facial 'butterfly' rash, palmar erythema and polyarthritis were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Medial gastrocnemius motor nucleus in the rat: age-related changes in the number and size of motoneurons.

The age-related alterations in the number and size of alpha- and gamma-motoneurons were studied in the medial gastrocnemius (MG) motor nuclei in rats at four ages: young (5 months), middle aged (10-13 months), old (26 months), and very old (31 months). Small volumes (0.1-0.5 microliter) of 40% horseradish peroxidase (HRP) solution were injected into the cut MG nerve bilaterally by using glass micropipettes and a pressure injection system. The number, position, and soma size (average soma diameter) of MG motoneurons were determined by using photographic maps of each TMB-stained section. The total number of myelinated axons was counted in seven MG nerves from the same animals. The average soma diameters in each MG nucleus were distributed bimodally; cells with average diameter greater than 21.0-24.0 micron were presumed to be alpha-motoneurons and those with smaller diameters were presumed to be gamma. The mean number of presumed alpha-motoneurons was significantly less in the old and very old groups as compared with the young and middle-aged. In contrast, the number of presumed gamma-motoneurons was the same across age groups. The mean average soma diameter of both alpha- and gamma-motoneurons was smaller in the old animals. The apparent decrease in the total number of labeled motoneurons in old animals was also reflected in a decrease in myelinated axon counts. We conclude that there is a significant decrease in the absolute numbers of motoneurons in rats aged 26 months and older, with most of the decrease occurring among the larger alpha-motoneurons.

Aging↗

Characteristic difficulty in rhythmic movement with aging and its relation to Parkinson's disease.

A total of 137 healthy participants aged from 20 to 79 years, including 59 over 60 years, were examined using a finger-tapping test. The test requested the participant to respond synchronously with the right middle finger to a periodic sound train with frequencies of 1, 2, 3, 4, and 5 Hz (cycles/sec). Difficulty keeping the rhythmic movement at a given rate was found to be a characteristic of aging. For the participants over 30 years, the mean rate of tapping deviated towards a faster rate for the stimulus frequency at 4 or 5 Hz (hastened tap, HT). The percentage of the participants who exhibited HT increased with decade of age; 0(20s), 11(30s), 13(40s), 17(50s), 30(60s) and 29(70s). HT in aging appears similar to hastened tapping which is typically observed in patients with Parkinson's disease and may be related to extrapyramidal dysfunction. Hastened tapping in the elderly supports the hypothesis that Parkinson's disease is a model for premature aging, suggesting that HT in aging represents an extrapyramidal motor dysfunction due to the neuroanatomical and neurochemical changes in the nigro-striatal system of the aging brain.

Adult↗

Effect of thyroid hormone on the protein inhibitors for Ca2+-dependent proteinase in brain: evidence for the induction by thyroidectomy of irreversible changes in immature rats.

The effects of thyroid hormone on the levels of protein inhibitors for Ca2+-dependent proteinase were studied in rat brain. Four different inhibitory proteins (I, II, III, and IV) were isolated from immature (7-day-old) rat brain. The molecular weights of these inhibitory proteins, which were estimated by gel-exclusion chromatography on Sephacryl S-200 column, were approximately 280,000 (I), 70,000 (II), 50,000 (III), and 35,000 (IV). All of these inhibitory proteins were decreased by thyroidectomy. Four-day T4 administration (100 micrograms/kg daily) to thyroidectomized-immature animals restored proteins I, II, and IV. However, protein III was not recovered with the same treatment of the rats. In mature rats (40-day-old), four different inhibitory proteins were identified in the brain. The molecular weights were identical to those obtained in immature rat brain. As observed in immature rats, all of these inhibitory proteins were decreased by thyroidectomy. In contrast to the results obtained in immature animals, however, inhibitory protein III, as well as I, II, and IV, was restored by T4 administration (100 micrograms/kg daily) to thyroidectomized mature rats. The results suggested that thyroid hormone increases protein inhibitors for Ca2+-dependent proteinase in brain, and that irreversible decrease in one of the inhibitors is induced by thyroid hormone deficiency in immature animals. The phenomenon may be related to the neonatal hypothyroidism-induced irreversible damage to the central nervous system in patients with cretinism.

Aging↗

Selective alterations of insulin actions by glucagon in isolated rat epididymal adipocytes.

Previously we demonstrated that glucagon inhibits high affinity insulin binding without influence on low affinity binding in rat adipocytes in vitro. In this study we investigated the effects of glucagon on insulin actions in adipocytes in vitro. Glucagon modified neither glucose oxidation nor lipogenesis stimulated by insulin. The antilipolytic action of insulin was decreased by preincubation of the cells with glucagon. Glucose transport enhanced by insulin was diminished by preincubation of the cells with glucagon. The decrease in antilipolysis was a lowering of the maximal response to insulin, whereas the decrease in glucose transport was a lowering of the sensitivity to insulin. These results suggested that glucagon does not necessarily inhibit all of the insulin actions, and that the mechanism of insulin stimulation of glucose transport, which is supposed to be mediated by glucagon-sensitive insulin receptor, is different from those of insulin-induced antilipolysis, glucose oxidation, and lipogenesis.

3-O-Methylglucose↗

Conformational transition of thyroid hormone receptor upon hormone binding: demonstration by aqueous two-phase partitioning.

An aqueous two-phase partitioning study of partially purified nuclear thyroid hormone receptor from rat liver was performed. Stability of 3,5,3'-tri-iodo-L-thyronine (T3)-receptor complex and T3-binding activity in the presence of dextran or polyethylene glycol were assessed in order to determine the amount of occupied or unoccupied receptors in each phase. Partition coefficients were calculated as the ratio of receptor concentration in the upper polyethylene glycol-rich phase H2O and that in the lower dextran-rich phase H2O. The partition coefficient was a sensitive function of the salt at pH above 6.1 and below 5.1. The salt had no effect on the partition coefficient at pH around 5.6. These results suggest that the isoelectric point of the thyroid hormone receptor is about 5.6, confirming previous determinations using isoelectric focusing. The partition coefficient of the receptor decreased upon T3 binding, regardless of the salt composition. In contrast, the partition coefficient of thyroxine-binding globulin increased upon T3 binding. Free T3 preferentially partitioned into the upper polyethylene glycol-rich phase and gave a partition coefficient higher than 1.0. These results strongly suggest that the decrease in the partition coefficient of the receptor upon hormone binding reflects conformational changes or changes in electrostatic properties of the receptor upon hormone binding. Such an alteration may be involved in biological activation of the receptor upon hormone binding.

Animals↗

Plasma levels and renal clearance of two isomers of dopamine sulfate in patients with essential hypertension.

Two isomers of dopamine sulfate, dopamine 3-O-sulfate(3-O-S) and dopamine 4-O-sulfate(4-O-S), in the plasma and urine of patients with essential hypertension and normotensive controls were measured by HPLC-fluorometry. The plasma level of 3-O-S was significantly higher in patients with essential hypertension than in normotensive controls (20.9 +/- 2.2 pmol/ml and 16.3 +/- 1.4 pmol/ml respectively, p less than 0.05) and the plasma levels of 4-O-S were slightly increased in hypertensive patients. The plasma level of 3-O-S was correlated with the serum level of creatinine in both normotensives and hypertensives. In hypertensives, the plasma level of 3-O-S was also correlated with that of noradrenaline. However the creatinine clearances were similar in the two groups, the urinary clearance of 3-O-S was slightly lower in patients with essential hypertension than in normotensive controls. These data indicate that the plasma level of 3-O-S is elevated in essential hypertension because of the abnormality in dopaminergic metabolism and renal disturbance in its excretion.

Creatinine↗

[Effective anticancer agents and the advance of surgical technics in tumors].

Functions and cosmetic features are markedly damaged by extensive or standard operation. Furthermore, high-risk cancers with poor prognosis have been considered to be strong candidates for intensive care since early times. Pediatric solid tumors and sarcomas of the bone soft tissue are included in these cases. Although the enlargement of surgical invasion directly corresponds to the improvement of radicalness in many cases, ultra-enlargement does not always reflect ultra-radicalness, rather resulting in acute exacerbation due to the spreading of cancer cells. Because an extent of cancer is sometimes estimated to be larger than its actual area, useless and dangerous extensive operation may be undertaken. The development of effective drugs and the advance of irradiation techniques contribute to the improvement of surgical results in combination with the advance of operative techniques.

Antineoplastic Agents↗

Changes in plasma lipids and uric acid with sodium loading and sodium depletion in patients with essential hypertension.

The short-term effects of manipulating dietary salt intake on plasma levels of cholesterol, lipoproteins and uric acid were studied in two groups of patient with essential hypertension. With dietary salt restriction in 8 patients (10 g to 2 g salt/day for five days), plasma total cholesterol, esterified cholesterol, beta-lipoprotein, low density lipoprotein and uric acid rose significantly. With salt repletion (2 g salt/day to 20 g/day for five days) in 17 patients, plasma total cholesterol, esterified cholesterol, beta-lipoprotein, low density lipoprotein and uric acid fell significantly. Total/HDL cholesterol ratio increased significantly with salt restriction and decreased significantly with repletion. However, very low density lipoprotein, HDL-cholesterol, triglyceride, phospholipid, chylomicron and non-esterified fatty acid were not influenced by the changes in salt intake. These results indicate that the severe restriction of dietary salt raises plasma cholesterol and uric acid levels in patients with essential hypertension in the short term.

Blood Pressure↗

Effects of oral and intravenous administrations of dopamine and L-dopa on plasma levels of two isomers of dopamine sulfate in man.

The levels of two isomers of dopamine sulfate, dopamine-3-O-sulfate (DA3S) and dopamine-4-O-sulfate (DA4S), in human plasma were measured by HPLC-fluorometry. The basal plasma levels of DA3S and DA4S in the early morning were 13.8 +/- 1.9 and 3.2 +/- 0.5 pmoles/ml, respectively (means +/- S.E.M.). Oral administrations of dopamine (50 mg/body) and 1-dihydroxyphenylalanine (L-DOPA, 250 mg/body) increased the plasma levels of these dopamine sulfates almost 100-fold to 1807 +/- 266 and 1674 +/- 195 pmoles/ml of DA3S, and 466 +/- 83 and 321 +/- 76 pmoles/ml of DA4S. Intravenous dopamine infusion (5 micrograms/kg/min for 30 min) markedly increased the plasma free dopamine concentration, as expected, but increased the levels of DA3S and DA4S only slightly to 110 +/- 32 and 25 +/- 9 pmoles/ml, respectively. In contrast, intravenous L-DOPA (25 mg/body) resulted in a slight increase of free dopamine followed by marked increases of DA3S and DA4S to 691 +/- 219 and 139 +/- 40 pmoles/ml, respectively. These data indicate that O-sulfation of dopamine, especially 3-O-sulfation, is the main pathway for metabolism of intravenously and orally administered L-DOPA and orally ingested dopamine. This sulfation is suggested to occur in the gut wall.

Administration, Oral↗

Effect of thyroid hormone on peroxisomal flavin enzymes in rat liver and kidney.

The effect of thyroid hormone on peroxisomal enzyme activity was studied in thyroidectomized- and T4-administered-thyroidectomized rats. In liver, the activities of isozyme A of L-alpha-hydroxyacid oxidase, D-amino acid oxidase, urate oxidase and catalase were decreased by thyroidectomy, and the diminished enzyme activities were restored by T4 administration to rats. These modifications induced by thyroidectomy or by T4 administration, however, were prominent only in immature animals (20-day-old rats). Although the changes in-alpha-hydroxyacid oxidase and D-amino acid oxidase activities, induced by thyroidectomy or by T4 administration, were also observed in 40-day-old rats, those in urate oxidase and catalase activities were not significant in 40-day-old rats. Acyl CoA oxidase activity was not affected by thyroidectomy or by T4 administration in either 20- or 40-day-old rats. In the kidney, isozyme B of L-alpha-hydroxyacid oxidase activity was reduced by thyroidectomy and the diminished enzyme activity was restored by T4 administration in both 20- and 40-day-old rats. D-Amino acid oxidase and catalase activities in kidney, however, were not significantly modified by thyroidectomy or by T4 administration in either 20- or 40-day-old rats. The results suggest that thyroid hormone can modify the peroxisomal enzyme activity, which is prominent in immature animals.

Alcohol Oxidoreductases↗

Evidence for the presence of active and inactive forms of cytosolic triiodothyronine binding protein in rat kidney: cooperative action of Ca2+ in NADPH activation.

The effect of NADPH and Ca2+ on 3, 5, 3'-L-triiodothyronine (T3) binding to cytosolic T3 binding protein (CTBP) in rat kidney was investigated in vitro. Extraction of rat kidney cytosol with 10% charcoal at 4 degrees C for 30 min. inactivated specific T3 binding. The decreased T3 binding activity in extracted cytosol could be restored by adding NADPH or Ca2+ to the incubation medium. Each substance increased the capacity for T3 without changes in the affinity for T3. The T3 binding was maximally increased by 25 microM NADPH or by 1.0 mM Ca2+ in the presence of 0.1 mM EDTA. The increase in T3 binding, induced by 25 microM NADPH, was enhanced by adding 0.2-1.0 mM Ca2+ in a concentration dependent-manner. The increase in T3 binding, induced by 1.0 mM Ca2+, was also enhanced by adding 3.125-25.0 microM NADPH. The NADPH-induced increase in T3 binding capacity was amplified by Ca2+ in a multiplicative manner. The results suggested that Ca2+ cooperatively augmented an NADPH function in cytosolic T3 binding.

Animals↗

Changes in plasma atrial natriuretic polypeptide concentration during head-out water immersion and saline infusion in normal men.

The physiological mechanism regulating secretion of human atrial natriuretic polypeptide (hANP) was examined by measuring plasma hANP by a specific radioimmunoassay during head-out total body water immersion (WI) and saline infusion in normal men. Seven healthy men were immersed in water for 1 hour, 6 normal men and women were given an infusion of 1 liter of normal saline over 1 hour and 8 normal men were given a similar infusion over 2 hours. During WI, the urinary volume (UV) and urinary Na excretion (UNaV) increased significantly, and the plasma hANP level increased significantly from 246 +/- 12 (mean +/- SE) pg/ml to 392 +/- 32 pg/ml after 35 +/- 5 min, but returned to the basal level after 90 min. The increase in hANP level was correlated with an increased UNaV between 30 to 60 min during WI. The plasma norepinephrine, renin activity, aldosterone and cortisol levels also decreased during WI. Saline infusion caused variable increases in the hANP level: the mean peak values of hANP and times of the peaks from the start of saline infusion were respectively 305 +/- 30 pg/ml after 30 +/- 3 min of infusion at a rate of 1L/1 hr and 285 +/- 25 pg/ml after 69 +/- 15 min of infusion at a rate of 1L/2 hrs. The time of the peak of plasma hANP during infusion at 1L/2 hrs was significantly longer than the peaks for WI or an infusion of saline at 1L/1 hr. Moreover, the peak hANP level was significantly smaller during either condition of saline infusion than during water immersion. These results indicate that i) acute central hypervolemia caused by WI increases hANP secretion, and this increase may participate in natriuresis during WI, and ii) saline infusion causes an increase in plasma hANP of variable magnitude, the increase being more rapid for a more rapid infusion of saline. This suggests that hANP is released into the circulation by acute volume expansion and plays a physiologically important role in maintaining blood volume homeostasis in man.

Adult↗

[The influences of neurotransmitters on the traumatic unconsciousness, immediate convulsion and mortality in the experimental mice model].

In order to clearing the influence of neurotransmitters in concussive unconsciousness, immediate convulsion and mortality, the following experiments were performed. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 gm dropped from a height of 20 cm on to the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in 66% and death in 30% of animals. The severity of consciousness disturbance was evaluated by two parameters; (1) time interval required for the recovery of righting reflex (RR) and (2) time interval for the recovery of spontaneous movement (SM). Agonist or antagonist of various neurotransmitters was given intraperitoneally 0.5 or 2 hours before injury. The following results were obtained although some of them were statistically not significant. Physostigmine shortened both RR (p less than 0.1) and SM (p less than 0.01), whereas scopolamine did not change these intervals. Atropine sulfate shortened both of them. Nevertheless, atropine methylbromide, which dose not pass through blood-brain-barrier, also had same effects. Methamphetamine shortened both RR (p less than 0.1) and SM (p less than 0.05), whereas haloperidol prolonged these intervals. 5-HTP shortened RR (p less than 0.05), but prolonged SM (p less than 0.1). Methysergide shortened both RR (p less than 0.05) and SM (p less than 0.01). Convulsive seizure was suppressed by physostigmine (p less than 0.01) or 5-HTP (p less than 0.20). These results suggested that suppression of dopaminergic and cholinergic systems, and/or activation of serotonergic system contribute to concussive unconsciousness.

Animals↗

The effect of reduced alcohol consumption on blood pressure: a randomised, controlled, single blind study.

A randomised, controlled, single blind trial was conducted in office workers with mild hypertension (systolic blood pressure (SBP) 140 to 180 mmHg, diastolic blood pressure (DBP) 90 to 110 mmHg) to determine the effect of decreasing alcohol consumption. After a baseline examination, 50 male volunteers aged 30 to 59 were randomised to two groups. Group A were told to abstain from or reduce alcohol consumption for two weeks, while group B were instructed to maintain their usual alcohol consumption. Complete records were obtained on 49 subjects. The daily alcohol consumption of groups A and B at baseline was similar, i.e. 71.9 ml and 72.5 ml of ethanol, respectively, and changed to 16.1 ml and 62.9 ml, respectively, during the experiment. After two weeks, group A were asked to resume their normal consumption whilst group B were asked to reduce or abstain (phase II). However in view of a treatment period interaction, statistical analysis was confined to phase I. During phase I, group A, whose alcohol consumption had reduced, showed decreases of 5.8 and 7.1 mmHg in SBP during the the first and second weeks, respectively. In group B, these decreases were only 0.6 and 1.9 mmHg, respectively. The difference between the falls in SBP in groups A and B was significant (P = 0.005) as judged by analysis of variance. The DBP also decreased, but there was no significant difference between the decreases in the two groups. Changes in gamma-glutamyl-transpeptidase, a biochemical marker of alcohol consumption, from the initial values to the end of phase I were significantly different in groups A and B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗