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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 1,027 records · Page 57Linked to original sources

The effectual level of ursodeoxycholic acid in therapy for non-advanced chronic cholestasis is fifty percent of total serum bile acids.

Ursodeoxycholic acid therapy (600 mg/day) was evaluated in twelve patients with non-advanced chronic cholestasis. Within four months, ursodeoxycholic acid replaced more than 50% of total bile acids in 8 patients and the reduction of serum gamma-glutamyltranspeptidase, alkaline phosphatase and transaminases averaged 30% or more. The serum levels of chenodeoxycholic acid depend on those of ursodeoxycholic acid, but are not related to those of biochemical parameters. Drug therapy was continued in three poor responders for 2-3 four-month periods. In one case an increase of the serum proportion of ursodeoxycholic acid was associated with a reduction in biochemical parameters. The other two cases had high serum levels of chenodeoxycholic acid and/or cholic acid throughout the entire course of treatment. While the treatment of chronic cholestasis requires an effectual serum proportion of ursodeoxycholic acid, it is important to distinguish endogenous persistent hyper-bile-acidemia from ursodeoxycholic acid-related acidemia.

Adult↗

Generation of plasma kinin by three types of protease isolated from Porphyromonas gingivalis 381.

Three types of protease (A, B and C) isolated from the culture supernatant of Porphyromonas gingivalis 381 had peculiar activities on kinin generation from high molecular-weight kininogen in vitro. Protease C released bradykinin from the kininogen in a reaction mixture containing 2 mM dithiothreitol, but A and B did not. However, the activity of degrading bradykinin was much stronger in protease A and B than in C. These findings suggest that only protease C shows plasma kallikrein activity.

Bradykinin↗

The complete amino acid sequence of the follitropin beta-subunit of the bullfrog, Rana catesbeiana.

The amino acid sequence of the bullfrog, Rana catesbeiana, follitropin beta-subunit has been determined by sequencing the intact protein (residues 1-39) and peptides originated by lysyl endopeptidase and pepsin. Twelve cysteine residues and two sugar chain binding sites at Asn-5 and Asn-22 are positional identities with bullfrog and mammalian beta-subunits. The bullfrog FSH beta-subunit is composed of 107 amino acid residues with a molecular mass of 11,782 Da, including the six cystine bridges and excepting the sugar chain. The bullfrog FSH beta-subunit has approximately 60% sequence identity with that of mammals and 40% with the fish gonadotropin beta-subunit. Conserved sequences among mammals (residue numbers 33-55 and 66-71) extensively differed from those of the bullfrog.

Amino Acid Sequence↗

Characteristic findings on the standard 12-lead ECG in patients with the fasciculoventricular Mahaim fiber.

Standard 12-lead electrocardiograms with a Q wave in lead V1 were obtained from 32 subjects without organic cardiac disease and analyzed for features that might characterize an abnormal atrioventricular conduction through the fasciculoventricular Mahaim fiber. Following an infusion of ajmaline, the Q wave in V1 vanished abruptly and changed to an rS pattern in the 12 ajmaline responders. Discriminant analysis was performed to distinguish the ajmaline responders from the others. The explanatory variables were number of precordial leads with the abnormal Q wave, existence of the septal q waves, existence of the slurring of the Q wave in V1, existence of clockwise rotation, and existence of high voltage (RV5 + SV1 > 3.5 mV). Three variables, the absence of the septal q waves, the presence of the slurring, and the absence of clockwise rotation, were found to predict a positive response to ajmaline (discriminant probability = 77%). These findings associated with the Q wave in V1 suggest that the fasciculoventricular fiber may be present.

Adolescent↗

Relationship of QRST isointegral maps during simulated left bundle branch block to impairment of left ventricular function due to myocardial infarction.

The clinical usefulness of QRST isointegral maps for assessing left ventricular (LV) dysfunction due to myocardial infarction (MI) in patients with MI in the setting of simulated left bundle branch block (LBBB) was investigated. Isointegral maps were recorded during sinus rhythm and right ventricular pacing, which simulated LBBB, in 62 patients with MI and 26 patients without MI. An abnormal decrease in the QRST value in the isointegral map was assessed by the difference map that indicated a "-2 SD area" where the QRST integral value was less than the normal range (mean - 2 SD) calculated from 608 normal individuals. The isointegral maps during the two activation sequences were similar in patients with and without MI (r = 0.87 and 0.92, respectively). The sum of QRST integral values less than the normal range (sigma DM) during simulated LBBB correlated significantly with the asynergy index, derived from left ventriculographic data (r = 0.81, p < 0.01). LV dysfunction (asynergy index > or = 2) was diagnosed in simulated LBBB with a sensitivity of 81%, specificity of 77%, and diagnostic accuracy of 80% when the criterion that LV dysfunction is present if the number of lead points in the -2 SD area exceeds 4, and a sensitivity of 71%, specificity of 81%, and diagnostic accuracy of 74% if sigma DM exceeds 200 mVms was used. The findings demonstrate that isointegral maps may be useful in assessing LV dysfunction due to MI in patients with MI and LBBB in addition to detecting the presence and site of MI in these patients.

Adult↗

Small differences among body surface and epicardial QRST integral maps recorded during normal activation and experimentally simulated left bundle branch block or preexcitation in canine hearts.

QRST integral maps were constructed from 87-lead body surface electrocardiograms (ECGs) and from 45-lead epicardial electrograms during artificial pacing, which simulated left bundle branch block (LBBB) and Wolff-Parkinson-White syndrome in 12 dogs. Although the ECGs and electrograms differed in configuration for each conduction model, the body surface and the epicardial QRST integral maps showed only small differences. Correlation coefficients (r) and root mean square differences (rms) were calculated to assess quantitatively the similarities in the QRST integral maps among the different conduction models. Mean r values between the normal conduction and the left bundle branch block models were 0.95 in the body surface maps and 0.89 in the epicardial maps. Mean r values between the normal conduction and the Wolff-Parkinson-White ECG models were 0.97 in the body surface maps and 0.91 in the epicardial maps, and rms values were small enough. The small differences were also verified by the difference maps and by paired t tests. QRST integral maps on the epicardium and on the body surface were largely independent of altered activation sequences in both the left bundle branch block and the Wolff-Parkinson-White ECG models.

Animals↗

Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition.

To investigate the role of Ca2+ metabolism and pH in diabetic cardiomyopathy, intracellular Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) of isolated myocytes were measured simultaneously using fura-2 and BCECF. We used diabetic (D.M.) rats at 8 weeks after the injection of streptozotocin (45 mg/kg, i.v.). (1) [Ca2+]i of D.M. myocytes was lower than that of controls (53 +/- 3 and 75 +/- 5 nM, mean +/- S.E., P less than 0.01). There was no difference in pHi (7.06 +/- 0.02 in D. M., 7.07 +/- 0.02 in control). There was no difference in the percentage of non-rounded cells at 30 min after the perfusion of glucose-free solution which contained 2 mM sodium cyanide (NaCN) between D.M. and controls (53% and 52%). When cells were rounded, the value of [Ca2+]i was significantly lower in D.M. myocytes than that in controls (172 +/- 21 and 421 +/- 106 nM, P less than 0.05). (2) When the cells were shortened or rounded in the high [Ca2+]o solution (24.5 mM), [Ca2+]i of D.M. rats was significantly lower than that of control rats. (3) The percentage of non-rounded cells at 30 min after the perfusion of NaCN increased in controls by 50 mM glucose (95%, P less than 0.01), but not in D.M. (47%). Insulin (25 mU/ml) and glucose (15 mM) increased the percentage of non-rounded cells in D.M. after 30 min perfusion with NaCN (88%, P less than 0.01 v.s. 53% without glucose nor insulin). It is suggested that there are disturbances of Ca2+ metabolism in D.M. myocytes, and that there is a close relation between cell injury and glucose utilization during metabolic inhibition.

Animals↗

Gastric carcinoma cells with endocrine differentiation show no evidence of proliferation.

The proliferative activity of gastric cancer cells with endocrine features was evaluated in five cases by means of a double-immunostaining procedure. The endocrine cells were recognized by a monoclonal antibody to chromogranin A (CGA) and the proliferative activity by a monoclonal antibody to proliferating cell nuclear antigen (PCNA). With the use of two different chromogens it was easy to determine whether CGA was located in the cytoplasm and whether PCNA was located in the nucleus of the same section. The CGA-positive endocrine cells of the normal gastric antral mucosa could be readily distinguished from the PCNA-positive cells scattered in the mucosal neck zones. Over 1,000 CGA-positive cancer cells were counted per case. A few cells (average, less than 1.0%) exhibited faint nuclear staining with anti-PCNA; in no instance was unequivocal PCNA reactivity demonstrable in the gastric cancer cells with endocrine differentiation. By contrast, the PCNA reaction was positive in one fourth to one third of the other cancer cells. These observations suggest that gastric cancer cells with endocrine features are differentiated and do not participate in the cell cycle.

Cell Division↗

A neuropathological study of a case of the Prader-Willi syndrome with an interstitial deletion of the proximal long arm of chromosome 15.

An autopsy case, a 6-month-old girl, with an interstitial deletion of the long arm of chromosome 15;del(15)(q11.1q12) was reported. Muscle hypotonia, poor sucking and intermittent ocular deviation were noticed soon after birth. She also exhibited external features peculiar to the Prader-Willi syndrome (PWS). The muscle hypotonia persisted and head control was not achieved. She died at the age of 6 months due to bronchopneumonia. G-banding analysis of prometaphase chromosomes revealed a deletion of chromosome 15. Bronchopneumonia of the lungs and fatty metamorphosis of the liver were found. Neuropathological anomalies recognized were; disturbed undulating structures, resembling cortical micropolygyria and pachygyria, in the dentate nucleus and the inferior olivary nucleus, grumose degeneration of the nerve cells in the dentate nucleus, and heterotopia of middle-sized neurons in the cerebellar white matter. No abnormalities were observed in the hypothalamus-pituitary system. In some autopsy cases of PWS, cerebellar lesions have been reported. These might be related to the muscle hypotonia in PWS.

Brain↗

An electron microscopic study of glomeruli in Japanese patients with non-insulin dependent diabetes mellitus.

Renal biopsy specimens of 29 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined by quantitative electron microscopic morphometry. In NIDDM the relative increase of percent total mesangium and mesangial capillary surface density (S/Vb) and the relative decrease of peripheral capillary surface density (S/Va) were compared with disease controls. However, mesangial-GBM-epithelial surface density (S/Vc) was not different between both groups. These results suggest that the increased mesangial matrix expands directly towards the capillary lumen as well as along the inner surface of GBM, and narrows the capillary lumen and filtration surface. The duration of diabetes mellitus (DM) did not correlate with all morphological parameters. The mesangial expansion correlated with urinary protein excretion and decreased creatinine clearance (CCr). GBM thickening correlated with proteinuria, but not with CCr. The degree of these morphological changes could be the indicators of hypertension of NIDDM patients. Areas of thin GBM were occasionally noticed in glomeruli which revealed thick GBM extensively, although the mechanism of GBM thinning is not known at the present time.

Adult↗

Determinants of left ventricular filling dynamics: alteration in the Doppler-derived transmitral filling profile with progressive impairment of cardiac function in a dog preparation.

To clarify the factors determining transmitral filling, left ventricular and atrial pressures (LVP and LAP) and Doppler-derived diastolic indices were analysed in six anaesthetized dogs at various right atrial pacing rates during dextran infusion. The relationship of the late to early diastolic peak velocity ratio (A/E ratio) to end-diastolic LVP (LVEDP) showed a quadratic curve concave to the LVEDP axis in five animals (r2 = 0.320-0.588). An elevation in LVEDP up to 25 mmHg accompanied an increase in A/E ratio (ascending limb), and further LVEDP elevation caused its inverse decline (descending limb). Multiple regression analysis indicated that A/E ratio correlated positively with maximal LVP, a-wave LAP and heart rate, and negatively with v-wave LAP in both limbs. The time constant of isovolumic LVP decline, which was prolonged as LVEDP was elevated, was a positive correlate of A/E ratio in the ascending limb, but lost its influence on A/E ratio in the descending limb. An elevation in v-wave LAP must have masked the expected effect of left ventricular relaxation abnormality on A/E ratio in this limb. Thus, the transmitral filling profile did not alter unidirectionally, but returned to that seen before volume loading, with a simultaneous progressive impairment of cardiac function.

Animals↗

Site of attachment of mercuribenzoate in crystals of an actin:DNase I complex.

Crystals of a complex of chicken gizzard G-actin and DNase I were soaked in a solution of radioactive 4-hydroxymercuribenzoate (MB). The soaked crystals, which contained 0.93 mol of MB per mol of G-actin, were dissolved in "G-buffer" and digested with trypsin, and the resulting peptides were fractionated by thin-layer chromatography. The MB is exchangeable between peptides that contain cysteine residues, but the data obtained here suggested that MB attached to the cysteine residue at the 373rd position of the G-actin molecule.

Actins↗

Further studies on aspartate aminotransferase of thermophilic methanogens by analysis of general properties, bound cofactors, and subunit structures.

Aspartate aminotransferase (AspAT) [EC 2.6.1.1] of thermophilic methanogen was further characterized with the enzyme from Methanobacterium thermoautotrophicum strain FTF-INRA as well as M. thermoformicicum strain SF-4. AspAT of strain FTF-INRA was similar in the amino donor specificity to the enzyme of M. thermoformicicum strain SF-4, in that it was active on L-cysteine and L-cysteine sulfinate in addition to L-glutamate and L-aspartate. The enzymes gave similar absorption spectra having maxima at around 326 and 415 nm with no pH-dependent shift but were found to contain 1 mol of tightly bound pyridoxal 5'-phosphate (PLP) per subunit. Reconstitution of each apoenzyme with added PLP resulted in partial recovery of the original enzymatic activity, suggesting a significant conformational change of the active site region upon removal of the cofactor. Polyacrylamide gel electrophoresis (PAGE) and gel filtration analyses revealed a tetrameric structure (180 kDa) of identical subunits with a molecular mass of 43 kDa for each of these enzymes. Electric current was found to affect the interaction or affinity of each subunit, promoting dissociation of the native enzyme into the monomeric form. Alkaline treatment was effective only for dissociation of the enzyme from strain SF-4. They were distinguishable by the more rapid reassociation of the monomer to the native aggregated form in the enzyme of strain FTF-INRA.

Aspartate Aminotransferases↗

A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice.

5'-Deoxy-5-fluorouridine (5'-DFUR) is one of the oral fluoropyrimidines widely used in the treatment of gastric, colorectal and breast cancers in Japan. 5'-DFUR is converted to 5-fluorouracil by pyrimidine nucleoside phosphorylase in the tumor. 5'-DFUR has toxic effects on the intestine and may cause severe diarrhea. Trimethoxybenzoyl-5'deoxy-5-fluorocytidine (Ro09-1390) is a prodrug of 5'-DFUR, which was developed to reduce the intestinal toxicity of 5'-DFUR. The present study was designed to assess the antitumor activity and spectrum of Ro09-1390, and to compare its efficacy with that of 5'-DFUR. Six digestive organ cancer xenograft lines (two gastric, one esophageal, one colorectal, one gall bladder and one bile duct cancers) were s.c. transplanted into nude mice. The agents were orally administered daily for 14 days at doses of 0.08-0.64 mmol/kg (1-8 times the maximal clinical dose of 5'-DFUR). Both 5'-DFUR and Ro09-1390 significantly inhibited the growth of two gastric cancer lines, and the IC50's for Ro09-1390 in both lines were lower than the respective values for 5'-DFUR. The esophageal, colorectal, gall bladder and bile duct cancer lines, however, were resistant to both agents. 5'-DFUR at 0.64 mmol/kg significantly inhibited the growth of these cancers, but with high mortality, and most mice receiving this dose died within 14 days after the start of therapy, suffering from severe diarrhea and body weight loss. Ro09-1390 at the same dose resulted in low mortality, but evidenced similarly low antitumor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Disaccharide analysis of the skin glycosaminoglycans in systemic sclerosis.

The disaccharides constituting chondroitinase-digestible glycosaminoglycan (GAG) in the skin lesions of patients with systemic sclerosis were determined using high-performance liquid chromatography (HPLC). In scleroderma there was an increase in the amount of delta Di-4S(DS), the main disaccharide unit of dermatan sulphate, and a decrease in delta Di-HA, the disaccharide unit of hyaluronic acid, as compared with normal skin from a similar site. The distribution pattern of the main disaccharides constituting chondroitin sulphate and dermatan sulphate in scleroderma differed from that in scars or scleredema.

Adult↗

Survey of a receptor protein in human erythrocytes for hemagglutinin of Porphyromonas gingivalis.

The purpose of this study is to survey a receptor protein in human erythrocyte membrane for the hemagglutinin (HA) of Porphyromonas gingivalis. Human erythrocytes were modified by either chymotrypsin or P. gingivalis HA along with the disappearance of their hemagglutinating ability and the removal of the band 3 protein. By preparative electrophoresis, this protein was isolated and purified from human erythrocytes. The purified protein showed strong inhibitory activity for hemagglutination and the binding to P. gingivalis cells, whose binding sites were calculated to be approximately 9000, suggesting its binding to the active site of HA. Hemagglutinin purified from P. gingivalis by affinity absorption to sheep erythrocyte ghosts possessed strong trypsin-like activity, and both the HA and the enzyme activities were inhibited by arginine. Specific modification of arginyl residues in human erythrocytes by phenylglyoxal diminished the hemagglutinating ability. From the similarity of the inhibition profile and possible active sites between HA and the trypsin-like protease, it is suggested that hemagglutination may occur as a result of the primary reaction of the enzyme (protease) and the substrate. These results suggest that band 3 may be a key protein in human erythrocyte membrane for HA from P. gingivalis and its binding sites may be arginyl residues of the protein.

Aminopeptidases↗

Comparisons of the effects of ryanodine on catecholamine secretion evoked by caffeine and acetylcholine in perfused adrenal glands of the guinea-pig.

1. The effect of ryanodine on catecholamine secretion induced by caffeine and muscarinic receptor activation was investigated in perfused adrenal glands of the guinea-pig. 2. Caffeine (40 mM) caused only a small increase in catecholamine secretion during perfusion with standard Locke solution. Caffeine-induced catecholamine secretion was markedly enhanced after removal of CaCl2 together with replacement of NaCl with sucrose. 3. In the absence of CaCl2 and NaCl, 50 microM ryanodine had no effect on the resting catecholamine secretion. Caffeine (40 mM) administered 15 min after treatment with ryanodine caused an increase in catecholamine secretion similar to that prior to application of ryanodine, but failed to have any effect thereafter. Combined application of ryanodine and caffeine also prevented catecholamine secretion induced by caffeine applied subsequently. 4. Catecholamine secretion induced by 100 microM acetylcholine (ACh) was only partially inhibited after treatment with ryanodine plus caffeine under Ca(2+)-free, Na(+)-deficient conditions. 5. Preferential influence of ryanodine on the response to caffeine was also confirmed in catecholamine secretion evoked by paired stimuli with caffeine and ACh alternately, during perfusion with either Ca(2+)-free Locke or sucrose-substituted solutions. 6. These results indicate that caffeine increases catecholamine secretion by mobilizing Ca2+ from intracellular Ca2+ stores through ryanodine-sensitive mechanisms in guinea-pig adrenal chromaffin cells. Ca2+ stores sensitive to caffeine and muscarinic receptor activation may not overlap entirely.

Acetylcholine↗