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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 631 records · Page 35Linked to original sources

Direct evidence for erythropoietin-induced release of endothelin from peripheral vascular tissue.

The effect of recombinant human erythropoietin (r-HuEPO, 0.1 to 2.0 U/ml) on endothelin-1 (ET-1) release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal rats. r-HuEPO increased immunoreactive (ir-) ET-1 release in a dose-dependent fashion; the maximal percent increment in ir-ET-1 release evoked by r-HuEPO (2.0 U/ml) was about +210% over the basal rate of release. However, r-HuEPO showed no effect on release of angiotensin II, thromboxane B2 or vasodilatory prostaglandin I2 from the vasculature. These results not only provide direct evidence that r-HuEPO has the potential to specifically stimulate release of ET-1 from peripheral vascular beds, but, hence, suggest a contributory role of ET-1 in r-HuEPO-induced hypertension in anemic human subjects undergoing r-HuEPO therapy.

6-Ketoprostaglandin F1 alpha↗

Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differentiation of leukemia HL-60 cells.

Camptothecin (CPT) and 4'-demethylepipodophyllotoxin ethylidene-beta-D-glucoside (VP16) at concentrations of 0-10 nM and 0-400 nM, respectively, have weak synergistic effects with retinoic acid (RA) on the induction of differentiation and growth inhibition of HL-60 cells. However, pretreatment of HL-60 cells with the above respective concentrations of CPT or VP16 for 1 h, had no influence on the differentiation of HL-60 cells induced by the following treatment with RA: when HL-60 cells were pretreated with CPT or VP16 at concentrations of 80 nM or 16 microM, respectively, the following treatment with RA had a synergistic effect on the induction of differentiation and growth inhibition. Morphology and biochemical markers were used to show that the differentiation-inducing effect of RA on HL-60 cells was potentiated by pretreatment with higher concentrations of 80 nM CPT or 16 microM VP16. The present results suggest that combination of CPT or VP16 at low concentration with RA or pretreatment with higher concentrations of camptothecin or VP16, followed by RA treatment may be useful for increasing the differentiation effect of RA and decreasing the side effects of RA.

Camptothecin↗

A standard data format for medical information in the IS & C system.

This paper describes the file format of the IS & C standard and the results of IS & C scientific exhibition at Yokohama. The English version of IS & C standard Version 1.0 was published in the spring of 1992 by the IS & C committee. On the basis of this document, the IS & C data format was explained. The enhanced description of color images, wave data and the laboratory data is still under discussion. The data format of the color images was established in March 1993. In April 1992, the IS & C scientific exhibition was held at the general assembly of the Japanese Radiological Society. At this exhibition, the demonstration of the compatibility among IS & C workstations was successful. The consensus on IS & C system was investigated. IS & C system was well understood by observers and the interchangeability of radiological images was recognized as very feasible.

Computer Communication Networks↗

Power spectral analysis of heart rate variability as a new method for assessing autonomic activity in the rat.

The authors studied power spectral analysis of heart rate variability in the rat, hypothesizing that the quantitative information provided by this analysis reflects the interaction between sympathetic and parasympathetic regulatory activities. For this purpose, an electrocardiogram was recorded from conscious and unrestrained Wistar rats (Nippon, Shizuoka) (12-16 weeks old) by a telemetry system and analyzed by a power spectrum. Because it was thought that the electrocardiogram recorded by the telemetry system could provide more reliable data to assess autonomic nervous activity than the tethering system, the telemetry recording system was used. There were two major spectral components in the power spectrum at low frequency (LF) (0.6 Hz) and high frequency (HF) (approximately 1.4 Hz). On the basis of these data, the authors defined two frequency bands of interest: LF (0.04-1.0 Hz) and HF (1.0-3.0 Hz). The power of LF was higher than that of HF in the normal rat. Atropine (2 mg/kg intraperitoneally) significantly reduced both HF and LF power. Propranolol (4 mg/kg intraperitoneally) also significantly reduced LF power; however, it had no significant effect on HF power. Thus, this study in the rat confirmed earlier observations in the conscious dog and human. Furthermore, the decrease in the parasympathetic mechanism produced by atropine was reflected by a slight increase in the LF/HF ratio. The LF/HF ratio appeared to follow the reductions of sympathetic activity produced by propranolol. From these results, the LF/HF ratio seemed to be a convenient index of parasympathetic and sympathetic interactions in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells.

We found that bufalin, an active principle of the Chinese medicine chan'su, has selective inhibitory effects on the growth of various human cancer cells. In order to examine whether the growth-inhibitory effect of bufalin on human cancer cells is associated with apoptosis, human leukemia cells were treated with bufalin. HL-60, ML1, and U937 leukemia cells treated with bufalin at 10(-8) M and above had condensed and fragmented nuclei. Flow cytometric analysis of these cells treated with bufalin showed fragmented DNA smaller than that of the G1 phase. DNA of HL-60 cells treated with bufalin showed a ladder pattern characteristic of apoptosis, as analyzed by agarose gel electrophoretic analysis. DNA synthesis and topoisomerase II activity of HL-60 cells were markedly inhibited as the concentration of bufalin was increased. The concentration needed for inducing apoptosis of HL-60 cells was 10(-8) M, which is comparable to that of camptothecin, but lower than those of other antitumor drugs such as cisplatin, VP16 and all-trans retinoic acid. Apoptosis was not observed when human mononuclear and polymorphonuclear cells were treated with 10(-6) M bufalin for 24 h. These results indicate the association of the growth-inhibitory effect of bufalin with the induction of apoptosis, at least in HL-60 cells, and suggest the usefulness of bufalin for differentiation-apoptosis-inducing therapy for cancer.

Antineoplastic Agents↗

Increase in the proportion of granulated CD56+ T cells in patients with malignancy.

Evidence is presented for the existence of a unique T cell population which expressed one of the natural killer (NK) markers, CD56 antigen, in humans. Although such CD56+ T cells were a minor population in the peripheral blood (< 10%), they were abundant in the liver (up to 50%), which was recently demonstrated to be a major organ for extrathymic T cell differentiation in mice. As in the case of extrathymic T cells in mice, these CD56+ T cells in humans contained a higher proportion of gamma delta T cells than did CD56- T cells, contained double-negative CD4-8- cells, and had the morphology of large granular lymphocytes. This unique population of CD56+ T cells tended to be elevated in the blood and among tumour-infiltrating lymphocytes in patients with colorectal cancer, especially in advanced cases. These results raise the possibility that, as in mice, CD56+ T cells with extrathymic T cell properties may also be associated with tumour immunity in humans.

Adult↗

Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin levels in bronchial asthma.

Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.

Acute Disease↗

[Retrospective analysis of deep-seated candidiasis among cases autopsied between 1982 to 1991].

Candida is present in the flora of the oral cavity, skin, intestinal tract and vagina, and is also known to be an opportunistic pathogen. Infection with this fungus has been increasing annually along with wide spread use of broad-spectrum antimicrobial agents. The subjects included 95 patients (48 males and 47 females) who had been diagnosed as having had deep-seated candidiasis, among patients autopsied between 1982 to 1991. In regard to annual changes in deep-seated candidiasis, the incidence reached a peak in the 1985 to 1988 period, and thereafter decreased. The number of cases with leukemia as the underlying disease was the largest, 36 (37.9%), followed by malignant lymphoma in 10, and aplastic anemia 5. The number of cases with infection of the stomach was largest, 42 (44.2%), followed by the esophagus in 33 (34.7%), the lung and kidney. The cases with deep-seated candidiasis showed low values of or level of lymphocyte, hemoglobin, CRP, total protein and cholesterol and high values or levels of LDH, urea N, creatinine and total bilirubin. Cases with marked decrease in neutrophils showed no regional infiltration of inflammatory cells in any of the organs infected with Candida. Cases with disseminated candidiasis showed vascular invasion by Candida. The laboratory findings also showed that most of the cases had been undernourished and had high values of CRP which supports the presence of inflammation. Common sites of infection are the esophagus, stomach, and intestinal tract. In the presence of granulocytopenia and immunodeficiency, tissue invasion become severe and associated with vascular invasion.

Aged↗

Exoproduct secretions of Pseudomonas aeruginosa strains influence severity of alveolar epithelial injury.

To determine whether exoenzyme S plays a role in alveolar epithelial injury, two parental strains of Pseudomonas aeruginosa, PAK and PA103, were tested that produced large quantities of exoenzyme S. Strains PAK and PA103 differ in the form of exoenzyme S they produce. Strain PAK produces a 53-kDa protein that does not possess ADP-ribosyltransferase activity and large quantities of a 49-kDa protein that expresses ADP-ribosyltransferase activity. Strain PA103 produces the 53-kDa protein and low amounts of exoenzyme S activity. A quantitative experimental protocol was used to measure the protein permeability of the alveolar epithelium and the dissemination of the bacteria to the pleural space and circulation. The results indicate that instillation of PAK and PA103 resulted in significant lung injury. Control experiments utilizing isogenic, exoenzyme S-deficient, regulatory mutants in the infection model reduced the lung injury and the dissemination of instilled bacteria. Taken together these results suggest that alveolar epithelial injury correlated with the production of the 53-kDa form of exoenzyme S or other coordinately regulated factors.

ADP Ribose Transferases↗

Right atrial pressure and ANP release during prolonged exercise in a hot environment.

To investigate the relationship between right atrial pressure (RAP) and atrial natriuretic peptide (ANP) release during prolonged exercise in a hot environment (30 degrees C, 20% relative humidity), we studied with a Swan-Ganz catheter five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min. The ANP level increased from 14 +/- 3 (SE) to 69 +/- 10 pg/ml (P < 0.001) during the first 10 min of exercise as RAP rose from 4.3 +/- 0.8 to 6.9 +/- 1.1 mmHg (P < 0.001). The 10-min ANP level was significantly correlated with RAP (r = 0.88, P < 0.05) but not with heart rate, pulmonary arterial blood temperature, plasma norepinephrine, or plasma epinephrine. The 10-min RAP value was inversely correlated with blood volume (r = -0.98, P < 0.01) and also with stroke volume (r = -0.96, P < 0.01). In the next 20 min of exercise, ANP continued to increase to 101 +/- 12 pg/ml (P < 0.02 vs. 10 min) and remained at this level until 50 min of exercise, whereas RAP decreased and reached a level not significantly different from baseline at 50 min (5.7 +/- 1.0 mmHg; P < 0.01 vs. 10 min). This dissociation of ANP and RAP may have been related to the significant increases from the 10-min values of heart rate, blood temperature, norepinephrine (all P < 0.01), and epinephrine (P < 0.02) during the same period. These results suggest that ANP release is primarily controlled by atrial distension at the onset of exercise but that other stimulators may be involved thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Anti-ulcer effects of lactic acid bacteria and their cell wall polysaccharides.

The anti-ulcer effects of bifidobacteria, lactobacilli and streptococci were examined using the acetic acid-induced gastric ulcer and ethanol-induced erosion models in rats. Bifidobacterium breve YIT4014 and 4043, and Bifidobacterium bifidum YIT4007 were administered orally, and anti-ulcer effects were confirmed for not only these organisms but also their polysaccharide fractions (PSFs). The major component of these anti-ulcer polysaccharides was rhamnose. In particular, polysaccharides in which the rhamnose content exceeded 60% were more effective in healing gastric ulcers. After administration of the PSF from B. bifidum YIT4007, the levels of epidermal growth factor and basic fibroblast growth factor increased in gastric tissues. Similar results were observed for the culture supernatant of gastric epithelial cells cultured with PSF. Furthermore, the production of 6-ketoprostaglandin F1 alpha by macrophages was also enhanced by PSF. These results indicated that these bacteria and their polysaccharides induced host repair and protective systems in the gastric ulcer model.

6-Ketoprostaglandin F1 alpha↗

Fibrin-specific fibrinolysis induced by recombinant staphylokinase.

We compared the thrombolytic properties of recombinant staphylokinase (SAK) with those of streptokinase (SK), a tissue-type plasminogen activator (t-PA) and a urokinase-type plasminogen activator (u-PA) in the jugular vein thrombosis model in the rabbit in vivo and a circulating human plasma system in vitro. 50% thrombolysis was observed at 360 min after intravenous infusion into rabbits of 150 micrograms/kg of SAK or 500 micrograms/kg of t-PA, respectively. And the fibrinogen level in the blood was not affected by either agent. 50% clot lysis in vitro was observed at 120 min with 1.8 micrograms/ml of SAK, 22.1 micrograms/ml of SK, 2.1 micrograms/ml of t-PA, or 4.7 micrograms/ml of u-PA, respectively. All the plasminogen activators with the exception of SAK decreased the residual fibrinogen level in the circulating plasma at their moderate concentration for clot lysis. SAK had less influence on the plasminogen and alpha 2-plasmin inhibitor (alpha 2-antiplasmin) levels than the other plasminogen activators. These findings suggest that SAK is a potent fibrin-specific thrombolytic agent.

Animals↗

Involvement of protease inhibitors in staphylokinase-induced fibrin-specific fibrinolysis.

We compared the fibrinolytic properties of recombinant staphylokinase (SAK), a fibrin-specific plasminogen activator, with those of streptokinase and tissue-type plasminogen activator (t-PA) by means of the amidolytic method. We also investigated the involvement of alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin in SAK-induced fibrin-specific fibrinolysis. Both SAK and t-PA activated plasminogen efficiently in the presence of fibrin in human plasma. Although t-PA activated plasminogen dependently on fibrin in the reconstituted plasma system, SAK activated plasminogen independently of fibrin without alpha 2-plasmin inhibitor (alpha 2-antiplasmin, alpha 2-PI). These findings suggest that fibrin and alpha 2-PI play important roles in plasminogen activation by SAK but not by t-PA. Furthermore, protease inhibitors such as alpha 2-PI, alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin inhibited plasminogen activation by SAK and the inhibitory actions of these protease inhibitors disappeared in the presence of fibrin. This shows that alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin, other than alpha 2-PI, contribute to the fibrin-specificity of SAK.

Amino Acid Sequence↗

Statistical analysis of data in mutagenicity assays: rodent micronucleus assay.

To evaluate chemical safety, many kinds of short-term mutagenicity assays are performed together with long-term assays in animals. Rationales and methodology for these assays have been well discussed and documented. No statistical method, however, has been singled out as the method of choice for the evaluation of mutagenicity assay data, although a number of reports on statistical methods to evaluate such data have been published. Among the mutagenicity assays, the micronucleus assay using mouse bone marrow erythropoietic cells have been widely used to assess cytogenetic activities of test chemicals. A statistical evaluation procedure for this assay is proposed herein, combining the use of historical control data and dose-response relationships. The probability of type I errors and the power of this method are compared with those of some other conventional methods by Monte Carlo simulation.

Animals↗

Biotransformation of a new synthetic retinoid, 4-[(5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (Am-80), in the rat. Structure elucidation of the metabolites by mass and nmr spectrometry.

1. The major metabolites of Am-80 in rat bile were examined by tlc-radiochromatography and hplc-radiochromatography after the intravenous administration of 14C-Am-80, and > 15 metabolites were detected. 2. Intact and Glusulase-treated bile were analysed by both tlc-radiochromatography and hplc-radiochromatography. As both samples gave similar patterns in both chromatography systems, we have concluded that neither glucuronide nor sulphate conjugates were present. 3. 2H3-Am-80 and 2H6-Am-80 were administered to rats, and the major metabolites in bile were detected and their structures elucidated by GC-MS. 4. The chemical structures of seven major biliary metabolites, including unchanged Am-80, were identified by mass and two-dimensional nmr spectrometry, and included 6-hydroxy-Am-80 (M-3), 7-hydroxy-Am-80 (M-4), 6-oxo-Am-80 (M-5), unchanged Am-80 (M-0) and the taurine conjugates of M-3 (M-1), M-4 (M-2) and M-0 (M-6).

Animals↗

IgG+, CD5+ human chronic lymphocytic leukemia B cells. Production of IgG antibodies that exhibit diminished autoreactivity and IgG subclass skewing.

Several questions exist regarding CD5+ B cells. These include the ability of these cells, as compared to CD5- B cells, to undergo an Ig isotype class switch, the subclasses utilized, and the effects that switching may have on antigen binding. To address these issues, ten patients with chronic lymphocytic leukemia (CLL) whose CD5+ leukemic B cell clones produced IgG were studied. Monoclonal IgG was collected from PMA-stimulated CLL cells and from heterohybridomas constructed with these cells, and then analyzed for IgG subclass utilization, autoreactivity, and DNA idiotype expression. The monoclonal B cells from 80% of the CLL patients produced IgG1 and those from 20% produced IgG3. None produced IgG2. In contrast to the known autoreactivity of IgM-producing CD5+ CLL cells (> 50% autoreactive), none of these IgG antibodies reacted significantly with the autoantigens tested. However, three did react significantly with autoantigen after artificially increasing antibody valency by crosslinking. Whereas five of the IgG molecules expressed a cross reactive idiotypic (CRI) marker characteristic of non-mutated kappa anti-DNA antibodies, three expressed a CRI displayed primarily on mutated IgG anti-DNA antibodies. Thus, some CD5+ human B cells can undergo an isotype class switch that for these CLL cells is biased against IgG2 and in favor of the IgG1 and IgG3. In their native state the IgG molecules secreted by these isotype-switched CD5+ cells have diminished autoreactivity, as compared to IgM-producing CLL cells. Since some of the IgG antibodies could be made auto- and poly-reactive by increasing antigen-binding valency, while others expressed idiotypic markers of mutated antibodies, certain of these CD5+ B cells probably utilize non-mutated Ig V genes coding for polyreactive antibodies, whereas others may use genes that have undergone somatic mutation and that code for more restricted specificities. Therefore, both valency and VH gene mutation may account for the diminished autoreactivity of these CD5+ B cell-derived IgG antibodies.

Adult↗

[Three dimensional image analysis on retroperitoneal lymph node metastasis of testicular cancer].

The effects of chemotherapy on the metastasis of retroperitoneal lymph nodes from testicular cancer have been generally evaluated with bi-dimensional imaging methods. Since the structure of these lymph nodes seems to be complicated, it is expected that three dimensional imaging methods could achieve more correct evaluation of the disease extension and the treatment effects when compared with bi-dimensional ones. The present study was undertaken to reconstruct the three dimensional imaging from CT films using personal computer system. Twenty one patients with bulky retroperitoneal nodal metastases were examined before and after chemotherapy. The evaluation of treatment effects based on three dimensional imaging method reflected the clinical course more adequately than the bi-dimensional one. When shrinkage rate of the tumor volume was less than 65%, viable tumor cells remained in all cases. Only one of six cases with more than 90% shrinkage revealed viable tumor cells. All patients in whom the metastases were estimated to be more than 100 cm3 in volume before chemotherapy and less than 50 cm3 after chemotherapy were shown to have completely necrotic tissues. In conclusion, three dimensional imaging was useful to estimate the post-treatment volume and shrinkage rate which correlated to the effects of treatment and prognosis.

Adolescent↗