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Biomedical subjects

S Kawashima

Publications and source records attributed to S Kawashima.

At least 343 records · Page 19Linked to original sources
PubMed1990

Three-dimensional analysis of averaged electro-retinograms: normal appearance and bioelectric artifacts.

In 10 normal subjects, three-dimensional analysis (X-Y plane and time) was carried out of the dominantly photopic and scotopic components of the electroretinograms (ERG) for the purpose of functional imaging of the retina, after having evaluated bioelectric artifacts. The study of the artifacts had revealed that the major causes of distorting the topographical distribution were blinking, myogenic activities, eye movement, eye position and background activities of the electroencephalograms. In normal subjects, the maximal amplitude of the dominantly scotopic components was located around the lower eyelid, while that of the dominantly photopic components was situated around the upper eyelid. The mechanisms of the equivalent dipole axis of the dominantly photopic and scotopic components were different. However, similar changes in the equivalent dipole axes were found during the periods of eccentric eye positions. Similar topographical characteristics were noted in the latency mapping. The isopotential line of the dominantly scotopic components had a steep gradient and were suggestive of a superficial (peripheral retinal) origin, while that of the dominantly photopic components had a gradual gradient and seemed to be of deep (central retinal) origin. ERG topography would make functional imaging of the retina possible and would be of great diagnostic value.

Adult↗
PubMed1990

[Evaluation of BPA secretory ability from blood mono-nuclear cells in uremic patients after renal transplantation or rEpo treatment].

Conditioned media (CM) of phyto-hemagglutinin-stimulated lymphocytes from chronic uremic patients were studied for burst promoting activity (BPA), using methylcellulose cultures with cord blood cells as a target population. Renal transplantation procedure was followed by a prompt rise of BPA, as well as the number of blood burst-forming unit erythroid (BFU-E) and hemoglobin levels, while no change in BPA and blood BFU-E number was observed in patients receiving rEpo and recovering from anemia. Thus, low BPA secretion from blood cells may have a role in the development of anemia in uremic patients.

Adult↗
PubMed1990

[Surgical treatment of descending thoracic aortic aneurysm under temporary bypass with antithrombogenic tube and bio-medicus centrifugal pump].

Four patients with descending thoracic aortic aneurysm were successfully operated on under temporary bypass with an antithrombogenic tube and a Bio-Medicus centrifugal pump. The bypass flow ranged from 1.0 to 2.4 l/min with the mean femoral artery pressure of 50 to 70 mmHg. No complications such as paraplegia, hepatic dysfunction or renal failure were encountered in all the patients. Temporary increment of the serum amylase level occurred in all the patients, but any apparent clinical symptoms were not present. The temporary bypass method with an antithrombogenic tube and a centrifugal pump is useful and reliable for surgical treatment of descending thoracic aortic aneurysm.

Aged↗
PubMed1989

Properties of erythrocyte membrane binding and autolytic activation of calcium-activated neutral protease.

The binding of a calcium-activated neutral protease (CANP) with high calcium sensitivity (muCANP) to erythrocyte membranes and its subsequent autolytic activation on the membranes were analyzed by an immunoblot technique. In the presence of calcium ions, muCANP bound to the erythrocyte membranes as a heterodimer of 79- and 28-kDa subunits and was converted quickly on the membranes to an active form with a 76-kDa large subunit. The active form was then released from the membranes to the soluble fraction. These sequential reactions, however, were not specific to inside-out vesicles, but occurred also, except for some Ca2+-independent binding, on right side-out vesicles. A rapid degradation of some membrane proteins was observed after binding of muCANP to the membranes. The binding of muCANP to erythrocyte membranes was inhibited by substrates and the endogenous CANP inhibitor, which is also a suicide substrate. These results strongly suggest that muCANP binds to membranes by recognition of membrane proteins as substrates and not at a special site for activation. Thus, a possible mechanism for muCANP activation on membranes is that muCANP first binds to substrates on membranes, is activated, and then degrades the substrates to deform the membrane structures.

Animals↗
PubMed1989

Calcium-induced localization of calcium-activated neutral proteinase on plasma membranes.

The location of calcium-activated neutral proteinase (CANP) was determined in human erythrocytes by crosslinking CANP to co-localizing proteins using a photolabeling bifunctional reagent, 4,4'-dithiobisphenylazide (DTBPA). The crosslinked products were selectively isolated by immunoprecipitation with a polyclonal anti-CANP antibody and analyzed by SDS-polyacrylamide gel electrophoresis after cleavage of the crosslinkage. In the calcium-free incubation medium the main proteins crosslinked with CANP were cytosolic proteins such as hemoglobin. In the presence of calcium ions, on the other hand, membrane skeletal proteins such as spectrin, band 4.1, 4.2 and 6 proteins as well as band 3 were crosslinked with CANP. Addition of calcium ionophore further increased the amount of crosslinked membrane proteins. These results suggest that in the absence of calcium ions CANP exists diffusely in the cytoplasm and is crosslinked with cytoplasmic hemoglobin nonspecifically while in the presence of calcium ions CANP associated with membrane where it is crosslinked specifically with the lining proteins. Thus it is demonstrated biochemically that the localization of CANP is dynamic depending on the presence of calcium ions.

Calcimycin↗
PubMed1989

Kinetic study of internalization and degradation of 131I-labeled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems.

The behavior of 131I-labeled follicle-stimulating hormone (FSH) after binding to cell-surface receptors in cultured Sertoli cells of C57BL/6NCrj mice was investigated. Sertoli cells cultured in F12/DME were pulse-labeled with 131I-FSH for 10 min at 4 degrees C, followed by cold chase for various periods of time. After the cold chase Sertoli cells were treated with 0.2 M acetate (pH 2.5) to dissociate membrane-bound 131I-FSH (surface radioactivity). The medium containing radioactivity after cold chase was mixed with 20% trichloroacetic acid, centrifuged, and the radioactivity of the supernatant was measured (degraded hormone). The radiolabeled materials associated with each process (surface binding, internalization, and degradation) were concentrated with ultrafiltration and characterized with gel filtration and/or thin layer chromatography. The effects of lysosomotropic agents, NH4Cl and chloroquine, were studied. The cold chase study at 32 degrees C showed that the surface radioactivity was the largest among the three kinds of radioactivities associated with each process immediately after pulse labeling, but the surface radioactivity rapidly decreased, while the internalized radioactivity increased. The cold chase study at 4 degrees C did not show such time-related changes in radioactivities, and a high level of surface radioactivity constantly persisted. The surface and internalized radioactivities were due to 131I-FSH, and the degraded radioactivity was mainly due to [131I]monoiodotyrosine. When Sertoli cells were cultured with lysosomotropic agents, the internalized radioactivity increased, while the degraded radioactivity decreased. Based on these observations, a kinetic model was proposed and the relationships among the surface, internalized, and degraded radioactivities and cold chase time were calculated algebraically. The rate constants of dissociation, internalization, and degradation were calculated to be 8.28 x 10(-4), 4.30 x 10(-2), and 6.46 x 10(-3) min-1, respectively. The simulated theoretical values of surface, internalized, and degraded radioactivities were almost the same as our experimental data. The present results indicate that 131I-FSH bound to the cell-surface receptors internalizes into Sertoli cells and that the degraded products are instantaneously released from the cells as [131I]monoiodotyrosine. The intracellular processes may be subdivided into 1) translocation, 2) net degradation of internalized hormone in the lysosomes, and 3) release of degraded hormone mainly as [131I]monoiodotyrosine. The rate-limiting step of these serial reactions was in the degradation of 131I-FSH, which consisted of a few substeps.

Ammonium Chloride↗
PubMed1989

Fragmentation of an endogenous inhibitor upon complex formation with high- and low-Ca2+-requiring forms of calcium-activated neutral proteases.

The interaction of an endogenous inhibitor for the calcium-activated neutral protease (CANP or calpain EC 3.4.22.17) with CANP was examined by SDS-polyacrylamide gel electrophoresis, immunoblot analysis, and gel filtration. Fragmentation of the inhibitor (Mr 110K) by mCANP, a high-Ca2+-requiring form, was shown only in the presence of Ca2+ ions of millimolar order, with decreased inhibitor activity recovered from gel extracts in the 110-kDa area. This fragmentation took place even when the inhibitor could completely inhibit the caseinolytic activity of mCANP. The fragmented inhibitor retained considerable inhibitor activity after the CANP-inhibitor complex was dissociated by the addition of EDTA, and 69% of the initial activity was recovered from the mixture reacted with excess mCANP lacking the 110-kDa band. A C-terminal fragment of CANP inhibitor produced in Escherichia coli (Mr 40K) was also hydrolyzed by mCANP in the presence of Ca2+. The interaction of both forms of the inhibitor with mu CANP, a low-Ca2+-requiring form, led to the same phenomena in the presence of micromolar levels of Ca2+. CANP inhibitor could not completely inhibit the autolysis of mCANP and mu CANP, indicating that these were intramolecular events. Gel filtration analysis revealed that the mass of the smallest fragment with inhibitor activity was about 15,000 daltons. These results suggest that CANP inhibitor may act in the manner of a suicide substrate.

Animals↗
PubMed1989

Changes in the testicular binding of luteinizing hormone and plasma testosterone concentrations in the Djungarian hamster subjected to different photoperiods and temperatures and effects of long-term testosterone treatment on the binding.

The effects of artificial photoperiod, temperature, and long-term testosterone treatment on testicular luteinizing hormone (LH) binding were studied in adult male Djungarian hamsters. In hamsters transferred to long-day (LD; 16 hr light, 8 hr dark) photoperiod 8 weeks after adaptation in short-day (SD; 8 hr light, 16 hr dark) photoperiod of 25 degrees C, testicular growth was associated with an increase in the total LH binding per two testes and a decrease in LH binding per unit testicular weight. Plasma testosterone levels reached a peak 47 days after transfer to LD and tended to decrease thereafter, while the testes continued growing. In contrast, when hamsters reared under LD conditions at 25 degrees C for 12 weeks were transferred to SD, testicular regression was associated with a decrease in plasma testosterone and the total LH binding per two testes and an increase in LH binding per unit testicular weight. A significant decrease in LH binding per unit weight compared to SD controls was observed in those hamsters exposed to SD with continuous testosterone treatment. The testosterone treatment tended to induce decrease in the total LH binding. Scatchard plot analyses of the binding suggested that changes in LH binding were due to changes in the number of binding sites. When sexually mature male hamsters were subjected for 8 weeks to two different ambient temperatures (7 degrees C and 25 degrees C) and photoperiods (LD and SD), the difference between the two temperature groups was statistically not significant regarding the weights of testes, epididymides, and prostates; plasma testosterone levels; and LH binding in either LD or SD group. These results suggest that photoperiod is a more important environmental factor than temperature for the regulation of testicular activity and LH receptors and that testosterone reduces the number of LH receptors per unit testicular weight in adult male Djungarian hamsters.

Animals↗
PubMed1989

Properties of follicle-stimulating hormone receptors and changes during annual breeding cycle in the testis of short-tailed bandicoot rat, Nesokia indica.

Some properties and seasonal changes of follicle-stimulating hormone (FSH) receptors in the testis of short-tailed bandicoot rat, Nesokia indica, were studied. The binding of FSH was highly specific for mammalian FSHs and located primarily in the testis. The Scatchard plot analyses of the binding of FSH to the testicular preparations of N. indica showed straight lines similar to those of albino Wistar rats, suggesting the presence of a single class of FSH-binding sites. The mean dissociation constants (Kds) for FSH receptors of N. indica were 1.416 (0.964-2.667, 95% confidence interval) nM in December, 1986; 1.348 (0.885-2.849) nM in April, 1987; and 3.039 (1.678-16.127) nM in August to October, 1987. No significant differences were found among the three groups, but they were all significantly greater than those in Wistar rats. The FSH binding per unit weight of tissue during non-breeding phase (June, 1987) was lower than those during other phases (December, 1986; April and August-October, 1987). Calculated numbers of FSH-binding sites showed no statistically significant differences among the latter three phases. In June preparations the number of binding sites was not determined due to their extremely low binding capacity.

Animals↗
PubMed1989

The neurite-initiating effect of a tripeptide aldehyde protease inhibitor on PC12h cells.

We report here the possible involvement of a new protease in neurite initiation by PC12h cells. Addition of a leupeptin analogue (Ac-Leu-Leu-Nle-al, ALLNal) to PC12h cells on culture plates coated with collagen type I caused de novo neurite outgrowth. Other protease inhibitors (Ac-Leu-Leu-Met-al, leupeptin, E64c, E64d, soybean trypsin inhibitor, hirudin, aprotinin, diisofluorophosphate, 6-aminocapric acid, and pepstatin A) could not mimic this neurite-initiating action. ALLNal induced the initiation of one or two long neurites from the cell body, and increased the cellular level of acetylcholinesterase to an extent similar to nerve growth factor (NGF). However, ALLNal-induced neuritogenesis is different from that induced by NGF, in which many neurites are induced from a single cell body. In addition, in contrast to neurons induced by NGF, which survive for a long time, ALLNal-induced differentiation was transient, and after 48 h percentage of cells bearing neurites started to decrease. After about 120 h exposure to ALLNal, neurites had mostly disappeared and the acetylcholinesterase activity level was not as great as that produced by NGF. These results provide evidence that ALLNal and NGF elicit neurite initiation by different mechanisms, and suggest the existence of a regulatory system of neuronal differentiation through specific protease-protease inhibitor interaction.

Acetylcholinesterase↗
PubMed1989

Effect of food on nifedipine sustained-release preparation.

The effect of food on the bioavailability of a nifedipine sustained-release preparation was studied. Each of seven male volunteers received a single oral 20 mg dose with 100 mL of water under two conditions, fasting and after a meal, with a crossover after a seven-day wash-out period. Blood samples were drawn at time zero (just prior to dose), and 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Nifedipine assays were performed by gas chromatography. The area under the serum concentration-time curve (AUC) from 0 to 12 hours and maximum serum concentration (Cmax) were significantly increased by food. Blood pressure was significantly decreased by food. The mean AUC for fasting and meal conditions were 315.0 and 411.4 ng.h/mL, and the mean Cmax were 42.6 and 86.6 micrograms/mL, respectively. The results indicate that food may increase the bioavailability of nifedipine sustained-release preparation.

Adult↗
PubMed1989

Studies on sustained-release suppositories. II. Evaluation of polymer electrolyte containing acidic groups for prolonged rectal absorption of bacampicillin in rabbits.

Rectal absorption of bacampicillin hydrochloride (BAPC) was found to show the best bioavailability with Witepsol H-15 as suppository base among various Witepsol bases. However, an effective plasma concentration of drug (above 0.5 micrograms/ml) was only maintained for 2 h, so sustained-release suppositories of BAPC were studied. Bacampicillin reacts with acidic polymer electrolytes such as pectic acid (Pc), chondroitin sulfate (Cd) and precipitates as its adduct with the polymer in an aqueous solution. The dissolution rate of BAPC from the adducts in a solution was slower than that of BAPC itself. The absorptions of BAPC from the suppositories containing the adducts were prolonged, but the bioavailabilities were decreased compared to that from the suppository containing BAPC alone. Similar prolonged absorption could be obtained simply by mixing Pc or Cd with BAPC in a base. Further, the absorption rate was found to be controlled by the amount of the polymer addition, and both a high plasma level and excellent bioavailability were obtained. This desirable outcome may be due to the simultaneous occurrence of rapid absorption of BAPC itself and formation of the adducts.

Ampicillin↗
PubMed1989

Kinetic behavior and interaction of bacampicillin in alginic acid solution at neural pH region.

Stabilization of bacampicillin (BAPC) in suspension was examined by the addition of alginic acid (Alg). BAPC formed a slightly water-soluble adduct (BAPC-Alg) with Alg, in which BAPC and Alg were presumed to be linked by ionic bonding. However, the suspension of this chemically stable adduct showed a lability to a suspension of BAPC alone; chemically very unstable particles of BAPC base were deposited in the suspension. In contrast, when BAPC-Alg adduct was suspended in 1.0% Alg solution at the same pH region, the precipitation of the particles of BAPC base were not observed. This stabilization is supposed to be due not only to the chemical stability of the adduct, but also to an inhibition of the deposition of an unstable BAPC base particles by Alg.

Alginates↗
PubMed1989

Studies on sustained-release suppositories. I. Effect of alginic acid addition on rectal absorption of bacampicillin in rabbits.

Sustained-release suppositories of bacampicillin (BAPC) were prepared by the use of the adduct which was precipitated from an aqueous solution containing BAPC and alginic acid (Alg). As the suppository base, Witepsol H-15 and macrogol were used. Absorptions of BAPC from the suppositories were prolonged in rabbits, but the bioavailabilities were decreased compared to that after administration of BAPC alone. However, these absorptions were improved enormously by the addition of surface-active agents, that is, an excellent prolonged absorption and high bioavailability were obtained. Interestingly, similar prolonged absorption could be obtained only by mixing Alg with BAPC in a suppository base. Further, this absorption rate was found to be controlled by the amount of Alg addition. The absorption profiles from a suppository containing the mixture differed from that containing the adduct in exhibiting both high plasma level and prolonged absorption. This may be due to simultaneous fast absorption of BAPC itself and formation of the adducts. Thus, it seemed that BAPC preparations containing Alg may be practically useful as a rectal preparation with prolonged action and giving a high plasma level.

Alginates↗
PubMed1989

Baroreceptor reflex to neck suction and its modification by diltiazem in man.

The carotid sinus baroreceptor reflex was studied in 15 healthy young men by a variable pressure neck suction chamber. Neck suction produced a reduction in blood pressure and an increase in RR interval, which were augmented by an increase of stimuli. Both responses occurred promptly and were attenuated with time. The reproducibility of the response was examined in 6 subjects. There were no differences in either hypotensive or bradycardiac responses between 2 runs separated by 1 hour, indicating good short-term reproducibility. In a long-term reproducibility study involving 2 runs separated by 2 weeks, hypotensive responses showed similar changes, whereas bradycardiac responses showed a wide variation. Based on this good reproducibility of responses, the effects of diltiazem on baroreflex function were studied in 9 men. Following the administration of diltiazem (20 mg, P.O.), the hypotensive responses to neck suction stimuli were significantly augmented compared to preadministration responses. On the other hand, diltiazem did not have a significant influence on heart rate responses. Thus, the present study shows that the neck chamber method is a feasible approach to studying the influence of given interventions on baroreflex function and demonstrates an enhancement of baroreflex-mediated hypotension by diltiazem.

Adult↗
PubMed1989

Calcium-activated neutral protease inhibitor (E-64c) and reperfusion for experimental myocardial infarction.

We examined the efficacy of the combination of coronary reperfusion and calcium-activated neutral protease (CANP) inhibitor (E-64c) for the treatment of acute myocardial infarction in dogs. In 34 dogs, the left anterior descending artery (LAD) was occluded and reperfused after 1 hour (Groups A and B). In the remaining 49 dogs, the LAD was ligated (Groups C and D). E-64c (100 mg/kg, Groups A and C) or vehicle (Groups B and D) was injected intravenously before and after the coronary occlusion or ligation. After 24 hours the hearts were removed. The proportion of the infarct size in the LAD perfusing area (risk zone) in Group A was 47.3 +/- 9.7%, significantly lower than in Group C (54.8 +/- 8.2%, p less than 0.05) or Group D (58.7 +/- 10.0%, p less than 0.01). There was a significant difference between Group B (52.9 +/- 8.6%) and Group D as well (p less than 0.05). The effects of reperfusion (p = 0.0016) and E-64c (p = 0.0226) per se on infarct size were significant, but the combination of reperfusion and E-64c was not additive. The decrease in CPK activity in the risk zone was significantly lower in the reperfused group (p = 0.0001). The mCANP activity was higher in the border zone and lower in the infarct zone. The trend in the mu CANP activity was similar to that of mCANP. Thus, treatment with a CANP inhibitor in the early phase of acute myocardial infarction may be marginally beneficial in combination with reperfusion.

Animals↗