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Biomedical subjects

H Yasuda

Publications and source records attributed to H Yasuda.

At least 433 records · Page 24Linked to original sources

Calpain is activated by beta-adrenergic receptor stimulation under hypoxic myocardial cell injury.

This study was undertaken to investigate the correlation between hypoxic cell injury and protease activity, as well as the effects of alpha 1-, and beta-adrenergic blocking agents and calcium antagonists during hypoxia. Cell death during hypoxia rose to 80% after 6h. Calpain activity increased to 4 units during hypoxia, much higher than the 0.7 units seen in aerobic condition at 6h. This activity was markedly inhibited by calpain-specific inhibitor I (n-acetyl-leucyle-leucyle-norleucinal). alpha 1-adrenergic blocking agents did not affect calpain activity and cell death under hypoxia. On the other hand, beta-adrenergic blocking agents and calcium antagonists suppressed the calpain activity and decreased cell death during hypoxia. These beta-adrenergic blocking agents and calcium antagonists also inhibited intracellular calcium-influx during hypoxia. These results suggest the beta-adrenergic receptor stimulation activates adenylate cyclase activity and enhances calcium-influx during hypoxia. The elevated intracellular calcium concentration then stimulates calpain activity under hypoxia. These results prove that beta-adrenergic blocking agents and calcium antagonists prevent protein degradation during hypoxic cell injury.

Adrenergic beta-Antagonists↗

Age-related alterations in adenylyl cyclase system of rat hearts.

Cardiac membranes from 26-, 52- and 104-week-old Wistar rats were used to investigate the age-related alterations in the beta-adrenergic receptor-adenylyl cyclase system. The densities and affinities of beta-adrenoceptors did not change with aging. There were no significant changes in the total amount of stimulatory G-protein (Gs), and in Gs activity measured in a reconstitution assay using human platelet membranes. The major isoform of Gs alpha, however, changed from a 45,000 to 52,000 dalton peptide with aging. The total amount of pertussis toxin substrates (Gi2 and Go) decreased significantly with aging. This finding was supported by the fact that pertussis toxin-induced potentiation of adenylyl cyclase activity was markedly reduced in the aged group. The activity of catalytic protein assessed by forskolin-stimulated adenylyl cyclase activity was decreased at 104 weeks. On the other hand, GTP analogue-stimulated adenylyl cyclase activity was significantly potentiated in the same group. These results suggest that the decreased sensitivity to catecholamines observed in aged hearts is mainly due to a dysfunction of catalytic protein, and that decreased Gi activity partially compensates for this catalytic dysfunction.

Adenosine Diphosphate↗

Effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine on the vasoactive effects of endothelin-3.

To clarify the mechanisms underlying the vasoactive effects of endothelin-3 (ET-3), we examined the effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine (L-NMMA) on the perfusion pressures of isolated rat mesenteric arteries infused with ET-3. ET-3 at 10(-15)-10(-8) M elicited significant vasodilations in a dose-related manner, in which 10(-9) and 10(-8) M ET-3 caused biphasic pressure changes involving a transient dilation and subsequent vasoconstriction. Five micromolar indomethacin did not affect the vasodilations and vasoconstrictions induced by ET-3. In endothelium-denuded arteries, 10(-13)-10(-8) M ET-3 elicited significant vasoconstriction in a dose-related manner without any vasodilation. In the presence of 30 microM methylene blue, the vasodilations induced by ET-3 disappeared. In the presence of 100 microM L-NMMA, 10(-15)-10(-8) M ET-3 elicited significant vasoconstrictions in a dose-related manner, and the vasodilation by ET-3 existed only at 10(-8) M ET-3. These data suggest that the vasodilating effects of low doses of ET-3 through the endothelium overcome the vasoconstricting effects, and that the vasodilating effects of ET-3 are associated with an endothelium-derived relaxing factor as an endothelium-derived nitric oxide.

Animals↗

Effect of elastase on aortic smooth muscle cell proliferation.

We studied the effects of elastase on [3H]thymidine incorporation into aortic smooth muscle cells. When elastase was added to cultured aortic smooth muscle cells, [3H]thymidine incorporation was inhibited in a dose-dependent manner in the presence of fetal bovine serum. Elastase also inhibited this incorporation in cells treated with epidermal growth factor. Epidermal growth factor (50 ng/ml) stimulated thymidine incorporation, without elastase, but with the addition of 20 units/ml of elastase the incorporation was inhibited 70%. The incorporation of thymidine into cells treated with 50 ng/ml epidermal growth factor was also inhibited 50% by a low concentration of elastase (5 units/ml). These inhibitory effects on thymidine incorporation were also observed in cells stimulated with platelet-derived growth factor. Platelet-derived growth factor (20 units/ml) markedly stimulated thymidine incorporation into cells, and elastase inhibited its activity in a dose-dependent manner. These results suggest that elastase has the potential to prevent the development of atherosclerosis by inhibiting smooth muscle proliferation.

Animals↗

Amelioration of nerve Na(+)-K(+)-ATPase activity independently of myo-inositol level by PGE1 analogue OP-1206.alpha-CD in streptozocin-induced diabetic rats.

An oral prostaglandin E1 (PGE1) analogue, OP-1206.alpha-CD, was given to rats with streptozocin (STZ)-induced diabetes to examine the therapeutic effects of OP-1206 on short-term and long-term diabetic neuropathy and its action mechanism with special reference to nerve Na(+)-K(+)-ATPase activity. In the short-term experiment, OP-1206 was administered daily to diabetic rats in 3- and 30-mg/kg doses for 4 wk from the day of STZ injection. In the long-term study, 10 micrograms/kg OP-1206 was also given daily for 8 wk from 7 mo after induction of diabetes. The compound improved decreased sciatic motor nerve conduction velocity in both short-term and long-term diabetic rats. The nerve Na(+)-K(+)-ATPase activity of diabetic rats, reduced by 40% compared with controls, was reversed to the level of controls in both experiments, whereas weight loss and hyperglycemia were unchanged, and neither nerve sorbitol accumulation nor myo-inositol depletion was corrected. In a morphometric analysis of myelinated nerve fibers (MNFs) in long-term diabetes, the mean diameter of the largest 10% of MNFs was significantly reduced in untreated diabetic compared with control rats, but OP-1206 completely reversed this reduction. The results suggest that OP-1206 ameliorates a decrease in nerve Na(+)-K(+)-ATPase activity without any effect on nerve myo-inositol level and that the compound may be not only a potent therapeutic agent for the treatment of diabetic neuropathy but also a useful research tool to investigate the mechanism of nerve Na(+)-K(+)-ATPase activity regulation.

Alprostadil↗

Vitamin E and the peroxidizability of erythrocyte membranes in neonates.

We showed the increased susceptibility of neonatal biomembranes to oxidation by a kinetic analysis using an azo compound as a free-radical initiator and red blood cell (RBC) ghosts as a model membrane. When the RBC ghosts were oxidized, oxygen consumption was suppressed during the induction period in which membrane tocopherol was consumed at a constant rate, while increased oxygen uptake was observed after the tocopherol was exhausted. The total tocopherol content was similar in cord, maternal, and adult RBC ghosts, and there were no differences in the induction period (tinh) among the three types of ghosts. While the oxygen uptake rate during the induction period (Rinh) was similar in cord and adult ghosts, the rate in the subsequent phase (Rp) was considerably faster in the cord ghosts. Fatty acid analysis in the membrane lipids showed that the active bisallylic hydrogen (active H) content was greater in cord ghosts than in adult ghosts. The active H content closely correlated with the Rp, but did not with the Rinh. The kinetic chain length (KCL), i.e., the ratio of the rate of propagation to that of initiation, was calculated from Rp and tocopherol consumption rate and KCL values were higher in cord ghosts than in adult ghosts. The faster Rp and the higher KCL of the cord ghosts were attributable to a greater active H content rather than to the tocopherol content.

Adult↗

Cephalosporin antibiotics. II. Synthesis and biological properties of CS-461 and related compounds.

The synthesis, structure-activity relationships, and biological properties of 3-thiazoliomethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2- methoxyiminoacetamido]-3-[5-(2-hydroxyethyl)-4-methylthiazoliomethyl+ ++]-3- cephem-4-carboxylate sulfate (CS-461) showed potent antibacterial activity against a wide variety of bacteria both in vitro and in vivo. Furthermore, CS-461 exhibited significantly low acute toxicity in mice.

Animals↗

Purification and characterization of tissue plasminogen activator secreted by human embryonic lung diploid fibroblasts, IMR-90 cells.

The anti-urokinase-IgG-resistant plasminogen activator secreted by human embryonic lung diploid fibroblasts, IMR-90 cells (ATCC, CCL186) was purified to homogeneity from serum-free conditioned medium by a four-step procedure. The fibroblast plasminogen activator was identified as tissue plasminogen activator (t-PA) by the N-terminal sequence of the purified material and the complete amino acid sequence deduced from its complementary DNA (cDNA). The apparent molecular weight was the range of 64,000 to 68,000 by SDS-PAGE and was in the range of 69,000 to 72,000 by gel filtration. The fibroblast t-PA showed a stricter substrate specificity than urokinase in enzymatic hydrolysis of various chromogenic substrates. Compared to urokinase, the fibrobrast t-PA was more stable by heating at 95 degrees C for five min and was stable from pH 5 to 10. The fibrorast t-PA had a higher affinity for fibrin than urokinase.

Amino Acid Sequence↗

The inhibitory effect of plant extracts on the collagenolytic activity and cytotoxicity of human gingival fibroblasts by Porphyromonas gingivalis crude enzyme.

It is well known that plant extracts inhibit some enzymatic activities. The present study examined the inhibitory effects of natural plant extracts against the collagenolytic activity of Porphyromonas gingivalis. The enzyme was isolated from a culture supernatant of P. gingivalis 381. The aqueous and 50% ethanolic extracts of Ginkgo biloba, Mosla chinensis, Salvia officinalis, Cinnamomum cassia, and a catechin extract of Camellia sinensis exhibited strong inhibitory effects on collagenolytic activity. The activities of these plant extracts were higher than that of tetracycline-HCl. They also inhibited the cytotoxicity of P. gingivalis crude enzyme against human gingival fibroblasts. C. sinensis catechin was the most effective agent in neutralizing the cytotoxicity of P. gingivalis. The aqueous and 50% ethanolic extracts of C. cassia had relatively strong anti-cytotoxic activity. Although the other samples strongly inhibited the collagenolytic activity of P. gingivalis, they were not effectively anti-cytotoxic. The present findings suggest that C. sinensis and C. cassia extracts are effective in reducing the pathogenicity of periodontopathic bacteria.

Catechin↗

[A case of spinal cord sarcoidosis with interesting MRI findings].

A case of spinal cord sarcoidosis was reported with special reference to MRI findings. A 15-year-old man was admitted to our hospital because of gait disturbance for last six months. Neurological examination on admission showed spastic paraparesis and posterior column signs. MRI of the cervical spinal cord revealed diffuse swelling and low intensity signal in T1-weighted sequences, diffuse high intensity signal in T2-weighted, and multiple micro-nodular lesion in Gd-DTPA enhanced T1-weighted. At first multiple sclerosis was suspected, although the data of cerebrospinal fluid was not suggestive. Four weeks after admission general fatigue, fever, cough, and headache appeared and the neurological symptoms got worse. Chest film and CT revealed diffuse small nodular shadows in the lung field. Abdominal ultrasonography and CT showed hepatosplenomegaly. The general condition became worse in spite of antibiotic and antituberculotic drug therapy, but remitted spontaneously in four weeks. MRI findings also exacerbated and improved during the same period, being compatible with neurological manifestations. The diagnosis of sarcoidosis was made by transbronchial lung biopsy which revealed sarcoid granuloma. Multiple small nodules on Gd-DTPA enhanced T1-weighted MRI had not been reported in patient with spinal cord sarcoidosis.

Adolescent↗

[Antibody responses in human being to pre-S2 and related hepatitis B virus-envelope antigens in vivo and in vitro].

Although hepatitis B (HB) virus-associated pre-S2 Ag may be important in facilitating the uptake of virions into hepatocytes, it is not clear whether the anti-pre-S2 antibody plays a substantial role in the protection from infection in man. The mechanisms underlying the nonresponsiveness to the HB vaccine are not clear. To evaluate the immunological background in nonresponders to pre-S2 Ag, HLA-DR/DQ antigens and the production of antibodies to pre-S2 Ag and HBs Ag were estimated in vitro on medical healthy personnel. Ninety-one males and 213 females were vaccinated with pre-S2 Ag positive plasma-derived HB vaccine three times. Four months after the third vaccination, blood was withdrawn for pre-S2 antibody test by ELISA. Antibodies to pre-S2 Ag were found in 19.8% of the individuals. Nonresponders were observed at a higher frequency in males than females, and they were seen more frequently in the elderly than young individuals. In aged subjects, aging seemed to be the major factor in their unresponsiveness. A high frequency of HLA-DR4.DRw53.DQw3 haplotype was observed in the subjects with nonresponsiveness against pre-S2 Ag. In order to induce the secretion of anti-HBs antibody, we investigated the effect of simultaneous administration of HBs Ag and immunoglobulin containing anti-HBs antibody on the antibody responses in vitro. In vitro stimulation of mononuclear cells from 10 individuals who failed to respond or responded poorly to HB vaccine induced a significant amount of anti-HBs antibody in 5 cases, whereas stimulation with HBs Ag alone failed to induce the antibody secretion in most cases.

Adult↗

[Diagnosis of prosthetic mitral valve regurgitation by Doppler color flow imaging using right parasternal approach: a comparative study with transesophageal method].

Doppler color flow imaging is a useful tool in evaluating mitral regurgitation (MR). However, it is frequently difficult to assess prosthetic valve MR by the conventional transthoracic approach using left parasternal or apical echo-windows, because of the interception of ultrasound by the prosthesis or artifacts produced by its motion. The purpose of this study is to determine the usefulness of the "right" parasternal approach (RPA) in the echo diagnosis of prosthetic MR. Six patients with pathological prosthetic MR determined by transesophageal approach (TEA) were studied. Transthoracic echo was performed using both the RPA and the conventional approach, and the presence or absence and the extent of MR signals by these transthoracic approaches were compared with those by TEA. Prosthetic MR was detected in five of six patients by the RPA and the extent of MR signals by the RPA was very similar to that by TEE in each of the five patients. MR could not be detected by the RPA only in one patient, whose MR was estimated to be very mild by TEE. By the conventional approach, MR could not be detected in three patients and the degree of MR was significantly underestimated in two of the remaining three patients. Thus, the transthoracic RPA is often as useful as TEA in diagnosing prosthetic MR, which is often undetectable or underestimated by the conventional approach. Because the RPA is less invasive than TEA, the RPA should be encouraged in patients with suspected prosthetic mitral valve dysfunction.

Adult↗

[Clinical course and prognosis in SLE patients with pulmonary hypertension: a comparative study with primary pulmonary hypertension].

Recently pulmonary hypertension (PH) has been recognized as one of life threatening complications which determine the prognosis of patients with systemic lupus erythematosus (SLE). Clinical aspects and pathology in patients with SLE complicated by PH (SLE-PH) have been reported to have a close similarity to those in patients with primary pulmonary hypertension (PPH), the prognosis of which is very poor in general. However, the long-term prognosis for patients with SLE-PH is not clear yet. Mainly because of some technical limitations for determining the severity of the PH, long-term follow-up studies have been inconclusive. In this study, 7 patients with SLE-PH and 6 patients with PPH were studied by using two-dimensional echocardiography. The interventricular septal curvature (R) was measured from the parasternal short axis view and the reciprocal value (1/R) was applied as a severity index of the PH. In 4 patients with SLE-PH and 6 with PPH, pulmonary arterial pressure was measured by cardiac catheterization concomitantly. There were no significant differences in 1/R and pulmonary arterial pressure between the two groups when PH was diagnosed for the first time. In the PPH group, the mean period of follow-up study was 25.3 months and all of the patients died during that period. In SLE-PH group, the mean period of follow-up study was 50.6 months, and only 3 patients (43%) died during that period. No patients in the PPH group showed improvement in 1/R, but 3 patients with SLE-PH improved in 1/R during a long follow-up period (60, 96 and 103 months respectively). Thus, the prognosis for SLE-PH was better than that for PPH, and there were some differences in the course and worsening behavior of PH in SLE-PH compared with that in PPH during the long-term follow-up study with reference to the echocardiographic investigation using 1/R value.

Adolescent↗

[Clinico-statistical study on pyometra in high-aged outpatients].

We clinico-statistically studied outpatients with pyometra aged 60 or older who visited our outpatient clinic during the past four years. 1. Pyometra was diagnosed in 48 cases (13.6%) of 353 in which the uterine cavity could be examined. The incidence became significantly higher with age (p less than 0.01). 2. Thirty-two patients with pyometra were found to require a wheelchair or to be in an immobilized state (bedridden). These patients with poor activity in daily living amounted to 76.2% of 42 cases which were not a complication of malignant uterine tumor or tuberculous endometritis. 3. Pyometra was diagnosed in 29 patients of 96 with urinary and/or rectal incontinence (30.2%). This incidence was significantly higher than that in our patients without incontinence (5.5%) (p less than 0.01). 4. Hematological and blood chemistry study revealed abnormality of the peripheral leucocyte count in 34.5% and CRP abnormality in 70.4% of all the cases of pyometra. 5. Mixed infection by both aerobic and anaerobic bacteria was observed in 16 cases of 36 in which strain could be determined by pus culture. Streptococcus sp. and Bacteroides sp. were predominant as aerobic and anaerobic bacteria, respectively. The present study on pyometra cases of aged people demonstrated that poor activity in daily living and incontinence were significant factors causing this disease. It also revealed the various features of pyometra in aged people.

Aged↗

[Experimental evaluation of the reliance of coronary sinus blood flow (CSF) and great cardiac vein blood flow (GCVF) measured by local thermodilution method].

A closed circuit was made to evaluate the reliance of coronary sinus blood flow (CSF) and great cardiac vein blood flow (GCVF) measured by local thermodilution method using multi-thermister catheter. The circuit consists of four parts: a constant-temperature water bath, a reservoir, a rotary pump and a polyethylene tube with a cock. Using this circuit and thermodilution catheters, flow rate was measured under various conditions. Measurements were repeated in changing injection rate of indicator, thermister interval of the catheter, diameter of the polyethylene tube and temperature difference between the room and the water bath. Indicator injection rate and thermister interval were important factors in flow rate measurement. Measured data and real flow were well correlated until 300 ml/min in injection rate of 40-50 ml/min. Other factors did not significantly influence the flow measurement. These results indicate that local thermodilution method is reliable if only injection rate of indicator and thermister interval are suitably settled.

Body Temperature↗