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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 1,045 records · Page 58Linked to original sources

Effects of intracellular ATP on calcium current in freshly dispersed single cells of guinea-pig portal vein.

In smooth muscle cells freshly dispersed from the guinea-pig portal vein, inward currents were recorded with the whole-cell clamp method in the presence of 2.4 mM Ca2+ under the condition in which outward K+ currents were suppressed and the effects of ATP in patch pipettes were studied. There was a large variation of the rate of current decay, the half-decay time ranging from 20 to 80 ms, but it was difficult to demonstrate clearly the presence of fast (T-type) and slow (L-type) Ca2+ channels based on threshold, the effects of changing holding potential, and of nicardipine, a dihydropyridine Ca2+ channel blocker. Intrapipette ATP had a weak potentiating effect on inward current, but did not seem to influence the correlation between peak current amplitude and current configuration. Cyanide (0.5 mM) reduced inward currents, particularly when ATP concentration was low and only limited recovery was observed. It was concluded that the amplitude and the rate of current decay of inward currents are not only determined by intracellular ATP, but also significantly influenced by some other factor, such as that involved in 'run-down' of Ca2+ currents.

Action Potentials↗

Creutzfeldt-Jakob disease with congophilic kuru plaques: CT and pathological findings of the cerebral white matter.

In a patient whose Creutzfeldt-Jakob disease with congophilic kuru plaques that was proved at necropsy, the early brain CT showed low-density areas in the cerebral white matter before cortical atrophy and ventricular enlargement became apparent. Subsequently, there occurred diffuse white matter lucency and severe brain atrophy. At necropsy, there was severe white matter destruction which was more prominent than cortical neuronal loss. Serial CT scans were of great value for demonstrating the early and predominant changes in the cerebral white matter.

Animals↗

Intracellular Ca2+ concentration and pHi during metabolic inhibition.

To study the changes in intracellular Ca2+ concentration ([Ca2+]i) and pH (pHi) during metabolic inhibition, rat ventricular myocytes were dual loaded with the acetoxymethyl esters of fura-2 (fura-2/AM) and 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF/AM) and perfused with 2 mM sodium cyanide (NaCN). The percent of rod-shaped cells was 30% of the control after 30 min NaCN in the absence of glucose. [Ca2+]i increased from 82 +/- 8 to 151 +/- 25 (SE) nM (P less than 0.05) when cells were shortened, and to 421 +/- 106 nM (P less than 0.05) when cells were rounded. There was a positive relationship between pCai and pHi (r = 0.425, P less than 0.01). When 50 mM glucose was added during NaCN, there were no significant changes in [Ca2+]i and the percent of rod-shaped cells after 30 min. The pHi of rod-shaped cells, however, decreased to 6.95 +/- 0.03 (P less than 0.01). Although the acidic solution (70% O2-30% CO2) decreased pHi to 6.90 +/- 0.05 (P less than 0.01), there were no changes in the cell shape or [Ca2+]i. The addition of NaCN for 30 min decreased the rod-shaped cells to 18% of the control. Mild acidosis did not cause the changes in cell shape or [Ca2+]i. There was also no protection of the NaCN-induced changes in cell shape by intracellular acidosis. It is likely that the changes in cell shape during metabolic inhibition were related to the depletion of metabolic energy and the increase in [Ca2+]i.

Analysis of Variance↗

Suppressed serum and urine levels of indoxyl sulfate by oral sorbent in experimental uremic rats.

In uremic patients, the serum concentration of indoxyl sulfate is markedly increased. To determine if oral sorbent (AST-120) suppresses the endogenous synthesis of indoxyl sulfate, it was administered to experimental uremic rats, and the serum concentration and urinary excretion of indoxyl sulfate were quantified by high-performance liquid chromatography. Oral sorbent decreased both the serum concentration and urinary excretion of indoxyl sulfate, suggesting that there was suppression of the endogenous synthesis of indoxyl sulfate by the oral sorbent. Oral sorbent did not decrease the serum concentration and urinary excretion of hippuric acid, but it did alleviate the deterioration of renal function in the experimental uremic rats.

Adsorption↗

Neutrophil chemotactic factors in the respiratory tract of patients with chronic airway diseases or idiopathic pulmonary fibrosis.

This study was designed to clarify the contributions of specific neutrophil chemotactic factors (NCF) in neutrophil accumulation in the human respiratory tract associated with various diseases. The activity and characteristics of the NCF in the bronchoalveolar lavage (BAL) fluid and culture media of alveolar macrophages obtained from normal volunteers, control patients, patients with chronic airway diseases (CAD) and patients with idiopathic pulmonary fibrosis (IPF) were examined. The BAL fluid from normal volunteers contained NCF comparable with the chemotactic factors interleukin-8 (IL-8) and leukotriene B4 (LTB4). Analysis of the biochemical characteristics of NCF released from alveolar macrophages suggests that they are derived from alveolar macrophages. The NCF activities in BAL fluids from patients with CAD and IPF were higher than those in BAL fluids from normal volunteers and control patients. Biochemical analysis demonstrated that several kinds of NCF, including those derived from the complement component C5 and alveolar macrophages, were present in the BAL fluid from patients with CAD and respiratory infections. The especially marked increase of C5-derived NCF indicate their importance in neutrophil accumulation in the respiratory tract of patients with CAD. Alveolar macrophages released different types of NCF after different lengths of culture periods (4 h and 24 h). Alveolar macrophages from patients with IPF released larger amounts of NCF than alveolar macrophages from normal volunteers, indicating the importance of alveolar-macrophage-derived NCF as well as C5-derived NCF in neutrophil accumulation in the respiratory tract of patients with IPF. These results suggest that various types of NCF increase in response to different disease states of the respiratory tract and serve to regulate the accumulation of neutrophils.

Adult↗

Nicotine-sensitive paresis.

Immediately after a patient with myoclonus epilepsy smoked a nicotine-containing cigarette, tetraparesis and hyperreflexia with ankle clonus developed, but disappeared within several minutes. During paresis, the H-reflex size of the soleus muscle increased, EEG showed more slow waves than before smoking, and the cerebral perfusion increased around the motor cortex as shown by single photon emission CT. A similar effect occurred when the patient chewed nicotine gum, and smoking a cigarette with a high nicotine content induced severe positive and negative myoclonus after the development of tetraparesis. Administration of the C6-type nicotinic antagonist mecamylamine not only countered the smoking effect, but ameliorated the spontaneous positive and negative myoclonus. Mecamylamine may prove useful for the treatment of positive and negative myoclonus in myoclonus epilepsy.

Adult↗

Three types of membranous ATPase on rat liver lysosomes.

At least three types of vanadate-insensitive membranous ATPase were identified on rat liver lysosomes: bafilomycin A1-sensitive Mg(2+)-ATPase (H(+)-ATPase), N-ethylmaleimide (NEM)-sensitive but bafilomycin A1-insensitive Mg(2+)-ATPase (ATPase I), and NEM-insensitive Ca2+/Mg(2+)-ATPase (ATPase II). They showed different sensitivity to chemicals and ions with apparent molecular masses of 700-800, 500-650, and 360 kDa, respectively. Of these membranous ATPases, H(+)-ATPase seemed to constitute only one tenth of the ATPase activity on rat liver lysosomes and to be the only ATPase that exposed its active site to the cytoplasmic side of the lysosomal membranes.

Adenosine Triphosphatases↗

New bronchodilators. II. 3H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel 3-substituted imidazo[4,5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4,5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen-induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5-position were more tolerant of the activity than those at the 3-position. 5-Ethyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo.

Animals↗

Effects of aminotriazole treatment on biosyntheses of primary bile acids in vivo.

The influence of aminotriazole treatment on primary bile acid biosynthesis was studied in detail. After administration of aminotriazole to rats, bile was collected for 8 h. The content of chenodeoxycholic acid in the bile was increased to 144% of the control by aminotriazole treatment, but that of cholic acid was decreased to 48.4%. In another experiment, [4-14C]cholesterol was injected into rats immediately after aminotriazole treatment, and then bile was collected. The content of radioactive chenodeoxycholic acid in the bile was significantly increased to 130% of the control, but that of radioactive cholic acid was unchanged. In a similar experiment with [2-14C]mevalonate, the content of radioactive chenodeoxycholic acid in the bile was hardly changed by aminotriazole treatment, but that of radioactive cholic acid was greatly decreased to 41.2% of the control. Aminotriazole treatment did not affect the ratios of tauroconjugate to glycoconjugate of the two bile acids. Thus, aminotriazole treatment affects the syntheses of not only cholesterol (F. Hashimoto, C. Sugimoto and H. Hayashi, Chem. Pharm. Bull., 38, 2532 (1990); F. Hashimoto and H. Hayashi, Biochim. Biophys. Acta, 1086, 115 (1991)) but also primary bile acids in vivo. Namely, aminotriazole treatment activated biosynthesis of chenodeoxycholic acid from exogenous cholesterol, but did not affect that of cholic acid. Aminotriazole hardly affected the synthesis of chenodeoxycholic acid through endogenous cholesterol (from mevalonate), but inhibited that of cholic acid.

Amitrole↗

Role of left atrial booster pump function in a worsening course of congestive heart failure.

We evaluated changes in left ventricular (LV) preload and the Doppler-derived transmitral late to early diastolic peak velocity ratio (A/E ratio) during the exercise in 27 patients with ischemic heart disease. After the exercise, A/E ratio decreased in 16 patients with a remarkable elevation in LV preload, and increased in 11 with a mild elevation. Further, Doppler transmitral flow in conjunction with pulmonary venous flow and hemodynamic parameters were analyzed in 11 dogs during a worsening course of heart failure induced by dextran infusion. The relationship of A/E ratio to LV end-diastolic pressure showed a quadratic curve concave to the pressure axis. A/E ratio, an index expressing left atrial (LA) contribution to LV filling, returned to that seen before volume loading under the condition of cardiac dysfunction. Pulmonary venous reflux fraction determined as the ratio of peak velocity of pulmonary venous reflux during LA systole to the sum of systolic and diastolic peak velocities of pulmonary venous antegrade flow, did not increase here. In this situation, blood could not be ejected from the left atrium into the left ventricle and even into the pulmonary veins during LA contraction. Finally, LV filling was not compensated by the left atrium, and LA booster pump function itself was deteriorated.

Aged↗

Characterization of the triphenyltin-induced increase in intracellular Ca2+ of mouse thymocytes: comparison with the action of A23187.

The properties of triphenyltin (TPT) in increasing intracellular Ca2+ ([Ca2+]i) of thymocytes was studied, in comparison with those of A23187, by the use of fluorescent dyes to monitor membrane potential and [Ca2+]i. Both 1 microM TPT and 30 nM A23187 increased the [Ca2+]i associated with the hyperpolarization mediated by Ca(2+)-dependent K+ conductance. The time course for the TPT-induced increase in the [Ca2+]i was much slower than that of A23187. When the external Ca2+ ([Ca2+]o) was removed, TPT produced a slight, but persistent, increase in the [Ca2+]i while A23187 caused only a transient increase in the [Ca2+]i. Reintroduction of Ca2+ to the external solution produced an increase in [Ca2+]i in both cases. Therefore, these results suggested that the increase in the [Ca2+]i of thymocytes induced by TPT and A23187 was dependent on the presence of [Ca2+]o and an intracellular Ca store. The potency of TPT in increasing the [Ca2+]i was greater than those of diphenyltin and monophenyltin, suggesting an involvement of the lipophilic property of organotins in increasing [Ca2+]i. The TPT-induced increase in the [Ca2+]i may be partly responsible for the toxicity of TPT on organs and/or organ systems.

Animals↗

Prorenin-renin axis in synovial fluid in patients with rheumatoid arthritis and osteoarthritis.

This study was undertaken 1) to determine whether or not renin is present in synovial fluid in patients with rheumatoid arthritis and osteoarthritis, and, if present, 2) to investigate whether it is synthesized in synovial fluid, or it is only transported from the circulation into the synovial cavity. The active renin concentration (indirect) was measured with angiotensin I radioimmunoassay kits. Inactive renin was converted into active renin with Sepharose-bound trypsin. Both active and inactive forms of renin were found in synovial fluid. They were significantly higher in patients with rheumatoid arthritis (n = 9) than in those with osteoarthritis (n = 16). In plasma, the concentration of inactive renin was significantly higher (P less than 0.001) in the former. Albumin, transferrin, alpha 2-macroglobulin, ceruloplasmin and immunoglobulins G and M were also found in synovial fluid. In each disease, a plot of the log ratio of synovial fluid to the serum concentration against the log molecular weight of each protein gave an approximately straight line curve, suggesting that these proteins are derived from the circulation and are transported into the synovial cavity. In contrast, the ratio of synovial fluid to plasma concentrations of active renin was significantly higher than that predicted on the basis of the above-mentioned interrelationships in both diseases, whereas the ratio of inactive renin was significantly lower. These findings suggest that 1) inactive and active renin are filtered into the synovial fluid from the circulation, and that 2) inactive renin is converted into the active form in the fluid.

Aged↗

Left ventricular performance at rest and during exercise in patients with dual-chamber pacemakers.

In 13 patients with an implanted dual-chamber atrioventricular (AV) demand pacemaker, left ventricular performance was elicited by pacing mode manipulation for study using gated cardiac pool scintigraphy at rest and during exercise. There was no significant difference between DDD and VVI at 70 and 90 beats/min with respect to cardiac output, peak ejection rate or peak filling rate. At 110 beats/min, the cardiac output was greater with DDD as compared to VVI. The peak filling rate was also significantly greater with DDD as compared to VVI (DDD: 3.6 vs VVI: 2.8 EDV/s, p less than 0.05). During exercise the cardiac output was greater with DDD as compared to VVI at the same rate. The peak filling rate during exercise was significantly greater with DDD as compared to VVI (DDD: 3.0 vs VVI: 2.5 EDV/s, p less than 0.01). We conclude that DDD is more beneficial than VVI in maintaining cardiac performance during exercise.

Adult↗

Crossover trial comparison of enalapril maleate and trichlormethiazide in the treatment of essential hypertension: emphasis on the quality of life.

Enalapril and trichlormethiazide were compared with respect to effects on the quality of life in a crossover study of 36 patients with hypertension. Multiple-choice 34-item questionnaires with three possible answers (severe, mild and none) per question were used to assess symptoms and mood. Twenty patients were initially given enalapril and 16 were initially given trichlormethiazide. There was no significant difference in the antihypertensive efficacy of the 2 drugs. Treatment with enalapril resulted in significant improvement in 11 of the 34 items, and a tendency for another 4 items to improve. Treatment with trichlormethiazide resulted in significant improvement in only 5 items and a tendency to improve in 2. When enalapril and trichlormethiazide were compared, significantly greater improvement in 2 items and a tendency toward greater improvement in 4 items was seen with enalapril treatment. Thus, enalapril was found to be more efficacious than trichlormethiazide with respect to quality of life in patients with hypertension.

Aged↗

Properties of active magnesium flux across the small intestine of the guinea pig.

Steady-state net flux of Mg2+ was measured in everted preparations of guinea pig jejunum and ileum, and effects of anoxia, Na+ and Ca2+ concentration, ouabain, and Ca2+ channel blockers were examined. Uphill Mg2+ flux in the mucosal-to-serosal direction was seen in both intestinal segments, with the flux value being 1.5 times greater in the ileum than in the jejenum. The Mg2+ flux was 1.7 times greater than the net Ca2+ flux under the same experimental conditions. The Mg2+ flux was strongly dependent on oxygen and the presence of Na+ in the medium; both anoxia and total replacement of Na+ inhibited the flux by 90-100%. Also, ouabain added to the serosal side, and verapamil or D600 added to the mucosal side, inhibited the flux by about 90%. Inhibitory effects of both ouabain and Na(+)-free conditions were much greater for the Mg2+ flux than for the Ca2+ flux. A stepwise increase in Mg2+ concentration in a Na(+)-free mucosal solution caused a stepwise elevation of the mucosal negativity. The relative elevation of the evoked potential in response to Mg2+ concentration possessed saturable and linearly increasing components. Only the saturable component was found to be dependent on oxygen and sensitive to ouabain. Under the influence of ouabain and verapamil, the generation of the Mg(2+)-evoked potential was greatly inhibited. These findings suggest that Mg2+ is actively absorbed by the jejunum and ileum of the guinea pig, and that active transcellular transport involves a verapamil-sensitive entry step and Na(+)-dependent or ouabain-sensitive exit process which differs from Ca2+ extrusion mechanisms.

Animals↗

[Affected siblings with Alzheimer's disease had missense mutation of codon 717 in amyloid precursor protein gene].

Using reverse genetic techniques, the gene responsible for familial Alzheimer's disease (FAD) is one of the clues to identify the pathogenesis of Alzheimer's disease (AD). Recently a missense mutation in the APP (amyloid precursor protein) gene (generally this mutation was called APP717) was detected in 2 Caucasian AD families and the same mutation was found in 3 Japanese AD families. We experienced brother's cases who were diagnosed as AD. Both of them and one normal person of the next generation had APP717. The first symptom of the elder brother (case 1) was forgetfulness at 52 years old, then dementia was advanced. In his clinical course there were characteristic findings such as the mirror sign, pseudodialog and jargon which has been rarely described in the Japanese literature. Finally he died of pneumonia at 57 years old. He was diagnosed as AD pathologically and physical findings of brain CT, SPECT (single photon emission computed tomography) and EEG supported this diagnosis clinically. The first symptom of the younger brother (case 2) was also forgetfulness at 45 years old, then severe dementia was advanced, at last he died of pneumonia at age 53 old. On the other hand the mother of the brothers died of severe dementia, so it was suspected that brothers died of severe dementia, so it was suspected that she had had AD. The clinical courses and pathological findings were thought to be typical of AD, namely there were no significant differences in comparison with other cases of FAD and sporadic AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

[Detection and identification of pathogenic bacteria by polymerase chain reaction with primers from DNA sequence of ribosomal RNA].

Applicability of the polymerase chain reaction method for identification of pathogenic bacteria was examined with the primers synthesized from the ribosomal RNA gene sequence containing both homologous and species-specific regions of bacterial species from Mycoplasma to Mycobacteria. Two out of the nine sets of promoters prepared, each covering about 650 nucleotides spanning from 16S RNA to 23S RNA regions, produced the corresponding DNA fragments from all the strains tested, and another set did so from all species but Mycoplasma. This method enabled one to detect and identify E. coli in a sample containing 2 x 10(2) CFU. The restriction enzyme patterns of the PCR products obtained with Hae-III, Hha-I, Mbo-I, Msp-I, Rsa-I and Taq-I were so characteristic as to differentiate one species from another. Ten strains of E. coli showed identical restriction patterns and 10 of S. aureus also showed identical patterns indicating that the restriction pattern is species-specific. The method may be applicable to detection and identification of a certain species bacteria which are suspected to be consealed in water or food samples, or clinical specimens, especially when the consealed bacterial genus or species can not be predicted.

Base Sequence↗