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Biomedical subjects

H Hata

Publications and source records attributed to H Hata.

At least 145 records · Page 8Linked to original sources

Subclinical and reversible hepatic effects of occupational exposure to trichloroethylene.

To detect early hepatic effects of chronic exposure to low-level trichloroethylene (TCE), serum total cholesterol (T-C), high-density-lipoprotein cholesterol (HDL-C) and activities of three serum enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT)] were determined in 148 workers (a cross-sectional study) and in 13 workers (a 2-year follow-up study) occupationally exposed to TCE in air. In the cross-sectional study, three exposure groups were defined by urinary total trichloro-compounds (U-TTC) levels of the workers [low-exposure group (n = 49): U-TTC < 10 mg/g creatinine; moderate-exposure group (n = 56): U-TTC 10- < 100; high-exposure group (n = 43): U-TTC > or = 100]. With increasing exposure levels, T-C (P = 0.143 by ANOVA) and HDL-C (P = 0.080 by ANOVA) slightly increased. The exposure, however, had no effect on the activities of the three serum enzymes. In the follow-up study, the fluctuations in U-TTC were well reflected in subclinical changes in HDL-C, AST, and GGT, but not in T-C or ALT. These results suggest that exposure to low-level TCE influences hepatic functions, affecting cholesterol metabolism rather than causing hepatic cell damage, and that these influences are subclinical and reversible. The increases in HDL-C caused by exposure to low-level TCE may be an example of "chemical hormesis" in humans.

Adolescent↗

Effects of a new calcium antagonist, CD-832, on experimental coronary artery spasm in miniature pigs.

The effects of a new calcium antagonist, CD-832, on experimental coronary artery spasms were studied in Göttingen miniature pigs. Pigs underwent endothelial denudation at the left anterior descending coronary artery using a balloon catheter. Changes in the diameter of the denuded and nondenuded site in response to an intracoronary administration of serotonin (10 micrograms/kg) or histamine (10 micrograms/kg) were assessed quantitatively by selective coronary arteriography 1 week after endothelial denudation. Percent reductions of the coronary artery diameter induced by serotonin or histamine in the denuded site were significantly greater than those in the nondenuded site (p < 0.01). Coronary artery spasm induced by serotonin or histamine in the denuded site was attenuated in a dose-dependent manner by intravenous infusion of CD-832 (10 and 30 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min). The degrees of inhibition of coronary artery spasm by CD-832 were similar to those produced by nifedipine. CD-832 and nifedipine at the high dose caused comparable increases in the basal coronary artery diameter. These results suggest that CD-832 may be a useful drug for the treatment of coronary artery spasm.

Animals↗

Inhibitory effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury in hypercholesterolemic miniature pigs.

OBJECTIVES: The present study aimed to clarify the effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury. BACKGROUND: The mechanisms of coronary artery vasoconstriction after coronary angioplasty are not well understood. METHODS: After being fed a cholesterol-rich diet for 1 month, 71 Göttingen miniature pigs were randomly allotted to five groups: 16 pigs with no pretreatment (group A); 21 pigs pretreated with heparin, 3,000 U (group B); 13 pigs pretreated with aspirin, 50 mg/day orally for 2 days (group C); 11 pigs pretreated with ketanserin, 1 mg/kg body weight (group D); 10 pigs pretreated with aspirin, 50 mg/day for 2 days, heparin, 6,000 U and ketanserin, 1 mg/kg (group E). After this pretreatment, the left anterior descending or the left circumflex coronary artery, or both, was denuded by a 2F balloon catheter. RESULTS: The coronary vasoconstriction at the injured sites reached a peak level 6 min after the arterial injury and subsided within 30 min. The coronary vasoconstriction at the injured site 6 min after arterial injury was 56 +/- 5% in group A, which was significantly greater than that in group B (28 +/- 6%, p < 0.01), group C (25 +/- 5%, p < 0.01), group D (26 +/- 7%, p < 0.01) or group E (24 +/- 5%, p < 0.01), whereas there was no significant difference in the coronary vasoconstriction among the latter four groups. CONCLUSION: These results suggest that serotonin released from aggregating platelets plays a major part in the platelet-dependent coronary artery vasoconstriction after arterial injury.

Angioplasty, Balloon, Coronary↗

Neutrophil chemotactic factors produced by malignant fibrous histiocytoma cell lines.

The clinicopathological features of malignant cells are sometimes modified by autologous cytokine production. Inflammatory fibrous histiocytoma (IFH) is characterised by leukocyte infiltration and is a variant of malignant fibrous histiocytoma (MFH). We demonstrated that three MFH cell lines (MF-1, MF-3, and MF-4) have the potential to promote neutrophil chemotaxis and to express mRNA for the cytokines, granulocyte-macrophage colony stimulating factor (GM-CSF) and/or interleukin 8/neutrophil attractant/activation protein 1 (IL-8/NAP-1), both with and without interleukin 1 beta (IL-1 beta) stimulation. MF-1 cells showed the spontaneous production of neutrophil chemotactic activity and the expression of both of GM-CSF and IL-8/NAP-1 mRNA, which was enhanced by exogenous IL-1 beta. In contrast, MF-3 cells showed the expression of GM-CSF and IL-8/NAP-1 mRNA with IL-1 beta stimulation but not without it, and MF-4 cells expressed only IL-8/NAP-1 mRNA when stimulated with IL-1 beta (time- and dose-dependent expression). These findings suggest that neutrophil chemotactic cytokines derived from IFH cells might be responsible for the prominent infiltration of neutrophils in this disease.

Blotting, Northern↗

The role of endothelium-derived nitric oxide in acetylcholine-induced coronary vasoconstriction in closed-chest pigs.

BACKGROUND: The effects of an inhibitor of endothelium-derived nitric oxide on acetylcholine (ACh)-induced coronary vasoconstriction were examined in 13 anesthetized closed-chest pigs. METHODS: Coronary blood flow was measured using a previously implanted ultrasonic transmit-time flow probe. The diameter of the large epicardial coronary arteries was assessed by coronary arteriography. RESULTS: Intracoronary infusions of ACh (0.1, 0.3, and 1.0 micrograms/kg/min) resulted in dose-dependent decreases in coronary blood flow. Arterial pressure and heart rate were minimally altered by ACh. The high dose of ACh decreased coronary blood flow by 67 +/- 11% and caused myocardial ischemia, demonstrated by ST-segment elevation. Coronary arteriograms revealed diffuse narrowing of peripheral coronary arteries and a filling delay of the contrast medium evoked with ACh. Vasospasm of the large epicardial coronary arteries was not observed. The decreases in coronary blood flow with ACh were inhibited by atropine (0.2 mg). Intracoronary administration of an inhibitor of endothelium-derived nitric oxide, NW-nitro-L-arginine (NNLA, 1.0 mg/kg), slightly increased arterial pressure but did not change baseline coronary blood flow. The percentage decreases in coronary blood flow induced by ACh were significantly augmented by NNLA administration, but those induced by prostaglandin F2 alpha (0.5 microgram/kg/min) were not affected by NNLA. The response of the large coronary arteries to ACh was not altered by NNLA. CONCLUSIONS: Our results suggest that, in pigs, ACh decreased coronary blood flow and caused myocardial ischemia as a result of the direct cholinergic vasoconstriction of peripheral small coronary arteries. The augmentation of ACh-induced coronary vasoconstriction by NNLA suggests that ACh facilitated the release of endothelium-derived nitric oxide, which attenuated the direct coronary vasoconstriction induced by ACh.

Acetylcholine↗

Arginine-dependent generation of reactive nitrogen intermediates is instrumental in the in vitro killing of protoscoleces of Echinococcus multilocularis by activated macrophages.

The interaction between protoscoleces of Echinococcus multilocularis and activated murine macrophages was examined in this study. Marked protoscolicidal activity was displayed by peritoneal macrophages (PM) activated with interferon-gamma (IFN-gamma), or IFN-gamma plus lipopolysaccharide. Pretreatment of the parasites with heat-inactivated specific murine infection serum, but not with normal serum rendered them more susceptible to PM killing. NG-monomethyl-L-arginine, a competitive inhibitor of L-arginine completely inhibited the killing activity of activated PM, while reconstitution of arginine-free medium with L-arginine restored the killing properties of the activated PM. The results show that activated PM have the ability to kill E. multilocularis protoscoleces in vitro and suggest that reactive nitrogen intermediates (RNI) play an important role in the mechanism. An oxygen-mediated mechanism did not appear to play a role because scavengers of reactive oxygen species did not reduce the killing activity. The arginine-dependent killing mechanism was enhanced by superoxide dismutase (SOD), probably because SOD might prolong the effect of nitric oxide. Secretion of RNI by activated macrophages may be capable of a significant role in preventing of the dissemination of E. multilocularis infection in vivo.

Animals↗

Expression of fibronectin and adhesion to fibronectin in myeloma cell lines.

Fibronectin (FN) expression in six myeloma, two mature B-cell lines, and four T-cell lines was analyzed. All myeloma cell lines expressed FN at various levels, while mature B- and T-cell lines apparently had less FN. Moreover, an extramedullary plasmacytoma-derived myeloma cell line, KHM7, was found to secrete FN into the culture medium. Fibronectin receptors, VLA4 or VLA5, were expressed at various levels on all myeloma cell lines. An adhesion assay revealed three of six myeloma cell lines bound to FN. However, there was no correlation between binding to FN and FN receptor expression, indicating a complicated FN binding pathway. The mechanism and pathological significance of FN expression and FN binding in myeloma cells are discussed.

B-Lymphocytes↗

A novel ornithine transcarbamylase present in mycoplasma-infected myeloma cells.

A myeloma cell line (KHM-4) from a patient with multiple myeloma and idiopathic hyperammonemia, and another myeloma cell line (RPMI8226) were seen to have activity to form ammonia from arginine. High activity of ornithine transcarbamylase (OTC), a hepatic urea cycle enzyme, was detected in these cell lines. OTC of these cells was much more heat-stable than the liver enzyme, and did not cross-react with an antibody against the liver enzyme. As the OTC activity was also detected in the culture medium of the myeloma cells and because the activity was markedly decreased by the antimycoplasma drug MC-210, the OTC activity was assumed to be associated with mycoplasma infection. Polymerase chain reaction, using degenerate oligonucleotide mixtures corresponding to the two highly conserved sequences of OTC, amplified a DNA sequence that apparently encodes a portion (about 67% in length) of mycoplasma OTC. The predicted amino acid sequence of the mycoplasma enzyme was 33-47% identical with those of the enzymes of bacteria, yeast and mammals.

Amino Acid Sequence↗

Serotonin-induced coronary spasm in a swine model. A minor role of defective endothelium-derived relaxing factor.

BACKGROUND: Coronary spasm may be caused by endothelial dysfunction, vascular smooth muscle hyperreactivity, or both. We aimed to determine the relative role of endothelial dysfunction and vascular smooth muscle hyperreactivity in the pathogenesis of coronary artery spasm in the swine model in vivo. METHODS AND RESULTS: In Göttingen miniature pigs given a high cholesterol diet, a segment of the left coronary artery was denuded and irradiated with x-ray (total, 30 Gy). Three months after endothelial denudation and irradiation, vasomotor responses of the denuded and control sites to agonists were assessed by quantitative arteriography. Serotonin (10 micrograms/kg) provoked coronary spasm at the denuded site (diameter reduction, 79 +/- 6%) associated with ST elevation but not at the nondenuded control site (21 +/- 6%). Intracoronary infusion of N omega-nitro-L-arginine methyl ester (LNNA, an inhibitor of endothelium-derived nitric oxide) of 1 and 3 mg/kg potentiated constriction evoked with serotonin (1, 3, 10 micrograms/kg) at the control site but did not alter it at the denuded site. However, serotonin-induced constriction after LNNA was still less at the control site (31 +/- 3%) than at the denuded site (80 +/- 5%). Endothelium-dependent vasodilation with substance P (0.1, 1, 10 ng/kg), which was inhibited by LNNA, was less (P < .01) at the denuded site than at the control site, whereas vasodilation with the nitrovasodilator SIN-1 (0.1, 1, 10 ng/kg) was comparable between the two sites. Histological study revealed regenerated endothelial cells and intimal thickening at the denuded site. CONCLUSIONS: The results suggest that the denuded segment of the coronary artery with regenerated endothelium was associated with defective endothelium-dependent vasodilation mediated by nitric oxide and vascular smooth muscle hyperreactivity to serotonin. However, provocation of coronary spasm with serotonin resulted primarily from vascular smooth muscle hyperreactivity but not by defective nitric oxide production in this swine model.

Animals↗

In vitro cultivation of the third and fourth stage larvae of Angiostrongylus cantonensis.

The third and fourth stage larvae of Angiostrongylus cantonensis were cultured in various media. When the third stage larvae were cultured in RPMI 1640 supplemented with 20% fetal calf serum for four weeks, about 30% developed to the late third stage. On the other hand, when the fourth stage larvae recovered from rat brains were cultured in Waymouth's chemically defined medium (MB 752/1) for one week, the worms grew rapidly and 74% developed into young adults. The mean body length of the worms in Waymouth's medium showed a 1.4-fold increase in size compared with that before culture.

Angiostrongylus cantonensis↗

Experimental studies of the influence of priming solutions on the systemic activation of complement during cardiopulmonary bypass: comparison between the use of albumin, hydroxyethyl starch and HWA-138.

Cardiopulmonary bypass surgery may be complicated by a systemic inflammatory reaction, which has been ascribed to activation of complement. For such activation, the choice of priming solution for the heart-lung machine may be of importance. The peripheral blood of three groups of eight donors was exposed to albumin, hydroxyethyl starch (HES) or to HWA-138 (pentoxifylline analogue) in addition to the priming solutions. The study confirmed that activation of complement is a consistent phenomenon during cardiopulmonary bypass surgery. The concentration of the C3 activation product C3a in the plasma was significantly increased after simulated extracorporeal circulation. However there were no differences within the increase of C3a concentrations between the various priming solutions.

Albumins↗

[Coronary artery bypass surgery in patients older than 75 years of age].

There is controversy whether the short-term and long-term results of coronary artery bypass surgery in elderly patients justify the commencement of the procedure. Between February 1988 and July 1992, 113 patients underwent CABG in our hospital, of whom 15 (13.3%) patients were 75 years old or older (mean 76 years). They consisted of 5 men and 10 women, and all were in New York Heart Association class III or IV. Unstable angina was observed in 13, left main trunk stenosis was in 4, and left ventricular dysfunction, ejection fraction of less than 0.30 was in 2 of 15 patients. The mean number of bypass grafts was 2.7 per a patient, and only autologous greater saphenous vein was used. In seven (47%) cases, CABG was performed urgently or emergently. There was neither operative nor hospital death, although some complications occurred in 11 (73%) patients. Post-operatively, 13 patients were in NYHA class I and 2 in class II. Only one patient died of pneumonia one year after operation. Although high risks of operative mortality and morbidity with coronary artery bypass surgery for elderly patients, particularly in urgent or emergent cases, had been reported, the long-term survival rate and freedom from angina were excellent, justifying continuous commencement of coronary bypass surgery in the selected patients over 75 years of age.

Aged↗

[In vitro study for hormones and growth factors dependent cell proliferation of endometrial adenocarcinoma cells].

Sex steroid hormone dependent cell proliferation and inducing growth factors of endometrial carcinoma cells were investigated using in vitro culture systems. The cell proliferation of Ishikawa cells derived from well-differentiated endometrial adenocarcinoma which possess both estrogen and progesterone receptors were stimulated by either estradiol added to culture media or EGF and TGF-alpha acting through EGF receptors. These stimulatory effects of TGF-alpha were antagonized by the anti TGF-alpha and EGF-receptor antibodies. The cell proliferations of other endometrial cancer cells were also inhibited by those antibodies. All endometrial cancer cells secrete TGF-alpha into their culture media measured by TGF-alpha ELISA methods. The expression of TGF-alpha mRNA and secretion of TGF-alpha of Ishikawa cells were induced by estradiol but not of hormone independent HEC-50 cells. Thus suggest that estradiol dependent growth factor should be TGF-alpha in human endometrial carcinoma cells.

Carcinoma, Endometrioid↗

Immunocytochemical determination of estrogen and progesterone receptors in human endometrial adenocarcinoma cells (Ishikawa cells).

The regulation of both estrogen and progesterone receptor levels in human endometrial adenocarcinoma cells of the Ishikawa line was investigated immunocytochemically by using monoclonal antibodies. Positive staining for estrogen and progesterone receptors was observed in the nuclei of Ishikawa cells. Intercellular heterogeneity in receptor content was evident from the presence of receptor-positive or -negative cells and from differences in staining intensity of positive cells. Quantitative analysis was performed by scoring the staining intensity and the proportion of positively stained cells. The time and dose-dependent stimulatory effect of estradiol added to culture media on progesterone receptor levels was studied by applying both immunocytochemical and biochemical methods. Estradiol at 10 nM (optimal concentration) increased the intensity score for PR from an initial value of 10.1 to 78.3 after 72 h incubation, and the proportion of the positive staining cells from 6.7 to 42.7%. Promegestone (R5020) was effective at 1 microM concentration in decreasing the intensity score for ER from 31.1 to 14.6 after 72 h exposure and the proportion of positive cells from 19.0 to 11.4%.

Adenocarcinoma↗

Cultivation of the third-stage larvae of Necator americanus in vitro.

When filariform larvae of Necator americanus, enclosed within the second sheath, were cultured in various semi-defined media, the best larval development was achieved in Waymouth's MB 752/1 with 20% foetal calf serum (FCS). In this medium, most of the filariform larvae cast off the second sheath and developed into third-stage larvae with provisional buccal capsules and some larvae developed further; 26% were fourth stage after 49 days of culture. Of several supplements tested, only FCS supported such development and no further development occurred if the medium was further supplemented with human red blood cells, liver extract, intestinal extract or tryptose phosphate broth. Larval development stopped at or before early third stage in Eagle's Basal Medium, F-12, NCTC 135 and L-15, even when these media were supplemented with FCS.

Animals↗

Human T-cell leukemia virus-1-positive cell line established from a patient with small cell lung cancer.

A stable cell line, KHM-3S, was established from a patient with small cell lung cancer (SCLC), who had a high serum level of soluble interleukin 2 receptors (sIL2-R) and was seropositive for human T cell leukemia virus (HTLV)-1. KHM-3S cells were positive for IL2-R (Tac) and NKH-1, but negative for other lymphocytic markers such as OKT 11, OKT 4, OKT 8, T cell receptor (WT 31), B 1, and B 4. Moreover, the KHM-3S cells were negative for leukocyte common antigen and strongly positive for neuron-specific enolase (NSE). Secretion of sIL2-R and NSE by the KHM-3S line was detected by an enzyme-linked immunosorbent assay. Rearrangement of the T cell receptor gene and monoclonal HTLV-1 integration were found by Southern blot analysis of KHM-3S DNA. However, Northern blot analysis showed no T cell receptor mRNA. KHM-3S may be useful for studies on the role of HTLV-1 in carcinogenesis and IL2-R expression in SCLC.

Antigens, Surface↗

Effects of recombinant tumour necrosis factor on antibody-dependent eosinophil-mediated damage to Schistosoma japonicum larvae.

Human recombinant tumour necrosis factor (rTNF) enhanced monoclonal IgE-dependent eosinophil-mediated cytotoxicity to schistosomula of Schistosoma japonicum in a dose-dependent manner. The enhancing effect of rTNF was also observed for the antibody-dependent cytotoxicity of a human eosinophilic leukemia cell line, EoL-3, but not of another cell line, EoL-1. Observation by a slow-motion movie camera demonstrated that activated EoL-3 cells adhered to the surface of schistosomula by 6 h after incubation, which triggered intracellular movement of eosinophil granules. The granules were concentrated toward the surface of the larvae and then degranulation started. The cell membrane was left as a balloon-like remnant. Cell sorting analysis by FACStar indicated that the expression of receptors for C3bi (CR3) and low affinity FcR for IgE (Fc epsilon RII) increased on the surface of EoL-3 cells after stimulation with rTNF, while this was not observed for EoL-1 cells.

Animals↗