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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 973 records · Page 54Linked to original sources
PubMed1988

Cholesteryl ester accumulation in smooth muscle cells after uptake of necrotic products from atherosclerotic lesions.

Cholesterol-ladened plasma membrane vesicles were used to load smooth muscle cells (SMC) with cholesterol. Plasma membrane vesicles (PMV) were isolated from rabbit atherosclerotic lesions, and characterized as to size, cholesterol content, and marker enzyme (plasma membrane, lysosome, endoplasmic reticulum) composition. PMV were regarded as a necrotic product since they are produced upon injury to cells. Degradation of PMV was proportional to the PMV protein concentration in the culture medium, suggesting bulk intake of PMV. Cholesterol accumulation of SMC varied with the cholesterol content of the vesicle. Incubation for 3 days with PMV having 0.39 and 0.62 mg cholesterol/mg protein induced the accumulation of 8 and 29 micrograms of esterified cholesterol/mg cell protein, respectively. Incorporation of oleate into cholesteryl ester during a 24-hr period under these conditions, however, was the same. The contribution of cholesterol ester synthesis to the esterified cholesterol content of SMC was 40 and 11% of the total when exposed to PMV having, respectively, low and high contents of cholesterol. This study suggests that cholesterol-bearing PMV in lesions can be utilized to load lesion-SMC. These observations suggest that lipid-bearing elements other than low density lipoprotein may be responsible for cholesterol-loaded SMC in lesions.

Animals↗
PubMed1988

Exercise-induced precordial ST-segment depression in prior inferior myocardial infarction with single-vessel disease; with special reference to its mechanisms and distinction from multi-vessel disease.

We investigated the mechanisms of exercise-induced precordial ST-segment depression on the electrocardiogram in prior inferior myocardial infarction with single-vessel disease and attempted to differentiate the ST-segment depression between single- and multi-vessel disease. Subjects included three groups: group Ia (n = 11), inferior myocardial infarction with single-vessel disease that showed no precordial ST-segment depression; group Ib (n = 7), inferior myocardial infarction with single-vessel disease accompanied by precordial ST-segment depression; and group II (n = 10), inferior myocardial infarction with multi-vessel disease. The subjects underwent 12-lead exercise electrocardiography, stress Tl-201 myocardial imaging and stress radionuclide ventriculography. Exercise-induced precordial ST-segment depression observed in group Ib was associated with large infarction and infarction extending into the inferoseptal wall of the left ventricle on myocardial image. On stress ventriculography, worsening of the septal wall motion was more frequently observed in group Ib than in group Ia. Coronary arteriography revealed a higher rate of rich collateral vessels to the infarcted zone in group Ib than in group Ia. When we compared the diagnostic ability for detecting multi-vessel disease in prior inferior myocardial infarction, although sensitivity was not different among three tests, both exercise electrocardiography and radionuclide ventriculography had poor specificity and predictive value compared to stress Tl-201 myocardial imaging. Thus we concluded that exercise-induced precordial ST-segment depression observed in prior inferior myocardial infarction with single-vessel disease should reflect a peri-infarctional ischemia located in the inferoseptal wall of the left ventricle, and that stress Tl-201 myocardial imaging is the most accurate method for diagnosing multi-vessel disease in prior inferior myocardial infarction.

Cardiac Output↗
PubMed1988

"Calciosome," a cytoplasmic organelle: the inositol 1,4,5-trisphosphate-sensitive Ca2+ store of nonmuscle cells?

Calsequestrin (CS) is the protein responsible for the high-capacity, moderate affinity binding of Ca2+ within the terminal cisternae of the sarcoplasmic reticulum, believed up to now to be specific for striated muscle. The cells of two nonmuscle lines (HL-60 and PC12) and of two rat tissues (liver and pancreas) are shown here to express a protein that resembles CS in many respects (apparent mass and pH-dependent migration in NaDodSO4/PAGE; blue staining with StainsAll dye; Ca2+ binding ability) and is specifically recognized by affinity-purified antibodies against skeletal muscle CS. In these cells, the CS-like protein is shown by immunofluorescence and immunogold procedures to be localized within peculiar, heretofore unrecognized structures distributed throughout the cytoplasm. These structures appear to be discrete organelles, which we propose to be named "calciosomes." By cell fractionation (Percoll gradient and free-flow electrophoresis), the CS-like protein of HL-60 cells is shown to copurify with the markers of the inositol 1,4,5-trisphosphate (Ins-P3)-sensitive Ca2+ store, whereas the markers of other organelles (endoplasmic reticulum, Golgi complex, mitochondria, endosomes) and of the plasma membrane do not. Calciosome might thus be the intracellular target of Ins-P3--i.e., the source of the Ca2+ redistributed to the cytosol following receptor-triggered generation of the messenger.

Animals↗
PubMed1988

K-252a, a potent protein kinase inhibitor, blocks nerve growth factor-induced neurite outgrowth and changes in the phosphorylation of proteins in PC12h cells.

Nerve growth factor (NGF) promotes neuronal differentiation of PC12 pheochromocytoma cells. One of the most prominent and distinguishing features of neuronal differentiation is neurite outgrowth. The mechanism by which NGF causes the cells to elaborate neurites is unknown. This study shows that K-252a, a potent protein kinase inhibitor, blocks NGF-induced neurite outgrowth and the changes in protein phosphorylation elicited by NGF. In the experiment with intact cells phosphorylated with 32P-orthophosphoric acid, an exposure of PC12h cells to NGF (50 ng/ml) caused an increase in the phosphorylation of tyrosine hydroxylase and a 35,000-D protein and a decrease in a 36,500-D protein. Pretreatment of PC12h cells with K-252a (100 nM) inhibited the effects of NGF on the phosphorylation of these three proteins. In the phosphorylation of cell-free extracts with [gamma-32P] ATP, treatment of PC12h cells with NGF (50 ng/ml) caused a decrease in the phosphorylation of Nsp100. Pretreatment of the cells with K-252a (30 nM) almost completely blocked the NGF effect on the phosphorylation of Nsp100 elicited by subsequent treatment of the cells with NGF. Treatment of PC12h cells with NGF promoted outgrowth of neurites. The addition of K-252a (100 nM) into the culture almost completely blocked the generation of neurites elicited by NGF. Earlier studies demonstrated that NGF-induced neurite outgrowth in PC12 cells involves at least two components: the first of these is transcription-dependent and the second is transcription-independent. To determine the component on which K-252a acts, experiments were carried out on NGF-induced priming or regeneration of neurites. When K-252a was present in the priming step, NGF induced only actinomycin D-sensitive neurites, showing that K-252a interferes with the transcription-dependent actions of NGF. When already primed cells were treated with NGF, actinomycin D-resistant neurites were formed and these were blocked by K-252a, showing that the inhibitor interferes with the transcription-independent actions of NGF as well. Although the exact mechanism of inhibition of NGF-promoted neurite formation by K-252a is unknown, the most probable explanation is that both transcription-dependent and -independent components are involved in at least one step of the activation of some specific protein kinase(s) that can be suppressed by K-252a.

Animals↗
PubMed1988

Immunocytochemistry of calciosomes in liver and pancreas.

Calciosomes are small cytoplasmic vacuoles identified in various nonmuscle cell types by their content of protein(s) similar to calsequestrin (CS), the Ca2+ storage protein of the muscle sarcoplasmic reticulum (SR). These entities have been interpreted as the "primitive" counterpart of the SR, and suggested to be the organelle target of inositol-1,4,5-triphosphate action (Volpe, P., K. H. Krause, S. Hashimoto, F. Zorzato, T. Pozzan, J. Meldolesi, and D. P. Lew. Proc. Natl. Acad. Sci. USA. 85:1091-1095). Immunoperoxidase and immunogold experiments carried out in both thick and ultrathin cryosections of rat hepatocytes and pancreatic acinar cells by using antimuscle CS antibodies revealed a specific labeling widely distributed in the entire cytoplasm, while nuclei were negative. Individual calciosomes appeared as small (105 nm) membrane-bound vacuoles intermingled with, and often apposed to ER cisternae and mitochondria. Other calciosomes were scattered in the Golgi area, in between zymogen granules and beneath the plasma membrane. The cumulative volume of the CS-positive organelles was measured to account for the 0.8 and 0.45% of the cytoplasm in liver and pancreas cells, respectively. The real total volume of the calciosome compartment is expected to be approximately twice as large. In hepatocytes, structures similar to CS-positive calciosomes were decorated by antibodies against the Ca2+ ATPase of muscle SR, while ER cisternae were not. By dual labeling, colocalization was revealed in 53.6% of the organelles, with 37.6% positive for the ATPase only. CS appeared preferentially confined to the content, and the Ca2+ ATPase to the contour of the organelle. The results suggested a partial segregation of the two antigens, reminiscent of their well-known segregation in muscle SR. Additional dual-label experiments demonstrated that hepatic calciosomes express neither two ER markers (cytochrome-P450 and NADH-cytochrome b5 reductase) nor the endolysosome marker, luminal acidity (revealed by 3-[2,4-dinitroanilino]-3'-amino-N-methyl dipropylamine). Calciosomes appear as unique cytological entities, ideally equipped to play a role in the rapid-scale control of the cytosolic-free Ca2+ in nonmuscle cells.

Animals↗
PubMed1988

A case-control study of the effectiveness of cervical cancer screening in Osaka, Japan.

In the small town of Nose in Osaka, Japan, a population-based screening program for cervical cancer by Papanicolaou smear has been conducted since 1965. In order to evaluate the effectiveness of screening in terms of the reduction of the mortality and the incidence of invasive cervical cancer, two types of case-control studies were carried out. In the first study, the case series consisted of all women who died of cervical cancer under 80 years of age at the time of diagnosis in 1965-1987 (N = 15). For each case, 10 controls were chosen from living residents, matched by year of birth. It showed that the odds ratio (OR) of dying of cervical cancer for screened versus non-screened women was 0.22 (95% CI = 0.03-1.95). In the second study, the case series consisted of all women who were diagnosed as having invasive cancer under 80 years of age at the time of diagnosis in the same period (N = 28). For each case, 10 controls were chosen from living residents without invasive cancer, matched by year of birth and according to whether or not they were screened at the year of the diagnosis of the matched case. It showed that the OR of getting invasive cancer for screened versus non-screened women was 0.41 (95%CI = 0.13-1.29). From these results, it was estimated that 78% of cervical cancer mortality and 59% of invasive cervical cancer incidence among non-screened women could be prevented by cervical cancer screening.

Adult↗
PubMed1988

Correlation of susceptibility and cytostatic factor-inducing activity of tumour cells to peritoneal macrophages. The role of concanavalin A-binding glycopeptides extracted from the tumour cell surface.

L929, 3T12-3, B16, 3LL, and YAC1 cells with cytostatic factor (CF)-inducing activity from Lactobacillus casei-elicited murine peritoneal macrophages (LCEPM) were susceptible to the cytostatic activity of LCEPM and to LCEPM-produced CF, but L1210, P388D1, and Colon 26 cells, which have no CF-inducing activity, were resistant to that of LCEPM and and to the CF. The resistance of P815 cells to that of LCEPM was stronger than that of 3T12-3 cells, but the CF-inducing activity of P815 cells was about 50% weaker than that of 3T12-3 cells. Release of CF from LCEPM was also caused by heat-killed (100 degrees C, 10 min) 3T12-3 or P815 cells, and this release was inhibited by D-mannose. The CF-inducing activity of heat-killed 3T12-3 or P815 cells was reduced by mild trypsin digestion (37 degrees C for 10 min). A D-mannose-containing glycopeptide or glycoprotein (GP) was separated from 3T12-3 or P815 cells by concanavalin A (Con A) or wheat germ agglutinin (WGA) affinity chromatography. The CF were released from LCEPM by stimulation with the Con A-binding GP of the tumour cells, but the WGA-binding GP had little activity. It is suggested that tumour cells with CF-inducing activity may be susceptible to the cytostatic activity of LCEPM, and those without CF-inducing activity may be resistant to the cytostatic activity of LCEPM and the release of CF from activated macrophages may be caused by the Con A-binding GP of the tumour cell surface.

Animals↗
PubMed1988

Metronidazole neuropathy: a case report.

A 67-year-old man developed peripheral neuropathy characterized by glove and stocking type sensory disturbances after the ingestion of 101.25 g of metronidazole for hepatic amebiasis. The clinical pictures of metronidazole-induced neuropathy appears to be the same as that of myeloneuropathy. The morphological study of a sural nerve biopsy showed a severe loss of myelinated fibers (2,400 per mm2). The density of unmyelinated fibers was at a lower limit of the normal range (23,530 per mm2). Electronmicroscopy confirmed the axonal degeneration of both the myelinated fibers and unmyelinated fibers.

Aged↗
PubMed1988

Electrophysiological effects of melperone on isolated rabbit heart muscles.

1. Electrophysiological effects of melperone on isolated atrial and ventricular muscle preparations of the rabbit were studied by a conventional microelectrode technique. 2. Melperone (3.3 microM) prolonged the action potential duration and effective refractory period of the atrial preparations without affecting the maximum rate of depolarization (Vmax). These effects of melperone on action potential duration and effective refractory period were inhibited by a low potassium perfusate (2.7 mM). 3. A high concentration of melperone (16.6 microM) decreased Vmax of atrial preparations. In ventricular muscles, melperone at either concentration decreased Vmax, although the increase in action potential duration was greater than in the atrium. 4. Depression of Vmax of ventricular muscles by melperone was found to be augmented by an increase of stimulation frequency and drug concentration. 5. The rate of onset of rate-dependent block of Vmax in ventricle was increased with drug concentration and frequency of stimulation. However, the time constant of recovery from rate-dependent block was almost constant. The kinetics of rate-dependent block of Vmax by melperone were approximately similar to those of quinidine and disopyramide. Consequently it is concluded that melperone possesses class 1a antiarrhythmic activity as well as class 3 activity.

Action Potentials↗
PubMed1988

Effect of right ventricular bypass peak flow-rate on intrapulmonary shunt ratio.

The effect of total right ventricular bypass peak flow-rate on the intrapulmonary shunt ratio was quantitatively investigated in animal tests. To give variations in the peak flow-rate (from pulsatile to intermediate to non-pulsatile), three types of blood pump (piston-bellows, screw, and centrifugal) were applied to dogs. The intrapulmonary shunt ratio was calculated from blood oxygen content drawn every 30 min from the outlet of the right ventricular bypass pump and from the femoral artery, while the canine lung was ventilated with 100% oxygen gas by an artificial respirator. The results show that when the intrapulmonary shunt ratio ranged between 0.095 and 0.392 there is no clear relation to the peak-flow-rate index (which varied from 1.1-17.0 l min-1 m-2) over the preceding 30 min. This study demonstrates that the intrapulmonary shunt ratio is able to be kept within the range of control values for 6 h even with a peak-flow-rate index of less than 4.0 l min-1 m-2.

Animals↗
PubMed1988

Presence of the adenovirus E1A-like activity in preimplantation stage mouse embryos.

The presence of the adenovirus E1A-like activity in embryonal carcinoma stem cells has been reported. We now show that preimplantation stage mouse embryonic cells allow transcription of the E1A-dependent E2A gene when infected with E1A-deleted mutant dl312, indicating the presence of the E1A-like activity in morulae and blastocysts. Moreover, such activity seems to decrease or disappear at about the time of implantation.

Adenovirus Early Proteins↗
PubMed1988

Mitochondrial encephalomyopathy with sleep apnea.

A rare case with mitochondrial encephalomyopathy, in association with cerebellar ataxia, peripheral neuropathy, mental retardation and alveolar hypoventilation syndrome with sleep apnea, as demonstrated by polysomnography, was encountered. This combination has not been described previously. From a prognostic point of view, alveolar hypoventilation syndrome with sleep apnea is an important clinical feature is this disease entity. Neither ataxia nor the abnormality of pyruvate metabolism was alleviated after 6 months of therapy with coenzyme Q10.

Brain Diseases↗
PubMed1988

Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure.

Human hepatocyte growth factor (hHGF) has been purified approximately 209,000-fold with 18% yield from plasma of a patient with fulminant hepatic failure. The purification involves heat treatment of plasma, ammonium sulfate precipitation, and chromatography on Affi-Gel Blue, heparin-Sepharose, and hydroxylapatite. Purified hHGF shows several bands with molecular weights between 76,000 and 92,000. Each band shows growth-stimulating activity on cultured hepatocytes which is proportional to the intensity of the band. After reduction of the sample with 2-mercaptoethanol, SDS-PAGE yields two chains with molecular weights of 31,500-34,500 and 54,000-65,000. The effect of hHGF on DNA synthesis by hepatocytes is half-maximal at 3.5 ng/ml. hHGF stimulates proliferation of cultured hepatocytes more effectively than human epidermal growth factor (hEGF) or insulin, and the effect of hHGF is additive or synergistic with the maximal effects of hEGF and insulin. These results suggest that hHGF is a new growth factor which is different from hEGF.

Cell Division↗
PubMed1988

In vivo and in vitro effects of zinc oxide-eugenol (ZOE) on biosynthesis of cyclo-oxygenase products in rat dental pulp.

To determine the in vivo effects of a zinc oxide-eugenol mixture (ZOE) on the cyclo-oxygenase system in dental pulp, we used radioimmunoassay to measure the levels of prostaglandin E2 (PGE2), 13,14-dihydro-15-keto-PG (DHK-PG), thromboxane B2 (TXB2), and 6-keto-PGF1 alpha in the dental pulp of rats. When the dental pulp was irritated by a hole made in the dentin of the mandibular incisors without use of any coolants, the levels of these cyclo-oxygenase products in the pulp were increased to, respectively, 2.8, 1.7, 10.0, and 2.6 times those in the normal pulp at six hr after treatment. In contrast, these increases in cyclo-oxygenase products disappeared immediately when the artificial cavity in the dentin was filled with ZOE (P/L; 1 g/0.25 mL), but were not altered when the cavity was filled with zinc oxidewater (ZOW, 1 g/1.5 mL). Most of the eugenol portion of ZOE was released into the pulp within two hr after the cavity was filled with ZOE. The maximal eugenol content was 35 pmol per mg of pulp. Furthermore, when the cavity was filled either with ZOE or by the addition of 10 mumol/L eugenol to the pulp homogenate, biosynthesis of 14C-6-keto-PGF1 alpha, PGF2 alpha, and PGE2 from 14C-arachidonic acid in the homogenate was inhibited. These results suggest that eugenol released from ZOE in the cavity prepared in the dentin inhibited the biosynthesis of cyclo-oxygenase products during pulp irritation.

Animals↗