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Biomedical subjects

H Hata

Publications and source records attributed to H Hata.

At least 163 records · Page 9Linked to original sources
PubMed1992

DNA repair pathways in mammalian cells analyzed by isolation of ACNU-sensitive Chinese hamster ovary cells.

1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) causes chloroethylation of DNA strand followed by cross linking through an ethylene bridge. We recently isolated two ACNU sensitive mutants from mutagenized Chinese hamster ovary cells, and found them to be new drug sensitive recessive mutants (Hata et al. 1991). The O6-methyl guanine DNA methyl transferase (MT) activities of these cells were undetectable as the parental cell line, indicating that the sensitivity of the mutant cell lines to ACNU was not due to the decreased cellular level of this enzyme. By complementation analysis with the 7 established UV-sensitive CHO cell lines, one of the mutants, UVS1, turned out to complement their UV-sensitivity and, therefore, build a new complementation group among all the CHO cell lines ever reported. The other mutant, CNU1 showed hypersensitivity only to chlorethylating agents (ACNU, CCNU) and exhibited a slightly reduced unscheduled DNA synthesis (UDS) induced by UV. It is, therefore, suggestive that this mutant is defective in a specific step of DNA repair systems, which is important for the processing of DNA damages produced by ACNU. Only cell lines from the complementation group 1 and 4 out of 7 established complementation groups of UV-sensitive CHO mutants were more sensitive to ACNU than UVS1 and CNU1, indicating some steps of excision repair pathways as well as specific repair system play important roles in repairing ACNU-induced DNA damages.

Animals↗
PubMed1992

Human myeloma cell line (KHM-4) established from a patient with multiple myeloma associated with hyperammonemia.

A cell line of plasma cells with high ammonia (NH3) production (KHM-4) was established from a patient with multiple myeloma complicated by hyperammonemia and abnormal serum concentrations of amino acids. Surface marker studies of KHM-4 cells showed that the cells were positive for cytoplasmic immunoglobulins (IgA kappa), HLA-DR, and T 10. Secretion of ammonia by the KHM-4 cells was detected by the addition of L-glutamine and L-arginine into the culture medium of amino acid-free RPMI 1640. In the presence of L-glutamine, KHM-4 cells secreted a greater amount of ammonia than the T cell line, CEM. However, production of ammonia by L-arginine was not observed in other cell lines. These observations provide evidence for the existence of a peculiar amino acid metabolism in the myeloma cells causing hyperammonemia and serum amino acid disturbance.

Ammonia↗
PubMed1992

Cardiovascular effects of the new generation calcium antagonist 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitropheny l) octyl ester.

The cardiovascular effects of 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl) oxtyl ester (NP-252, CAS 132031-81-3) were examined in anesthetized closed- or open-chest dogs and Langendorff perfused rabbit hearts, and compared with those of nifedipine (NF) and nicardipine (NC). In anesthetized closed- and open-chest dogs, NP-252 (i.v.) selectively increased vertebral and coronary blood flow with a fall in mean blood pressure (MBP). These effects were nearly equipotent with those of NF and NC, but more durable. A similar effect was obtained by intraduodenal administration of NP-252. Also, NP-252 (i.v.) decreased MBP, total peripheral resistance (TPR), left ventricular pressure and dLVP/dtmax while cardiac output (CO) and stroke volume (SV) increased without apparent changes in heart rate and myocardial contractility index. Decreases in MBP and TPR by NP-252 were equipotent with NF and NC, whereas increases in CO and SV were more potent than those of the two drugs. These actions of NP-252 were longer than those of the reference agents. Further, in perfused rabbit hearts, NO-252 increased coronary perfusion flow (CPF), accompanying a slight negative inotropy. Its effect in CPF was equipotent with NF and 2 times less than that of NC, however the duration was much longer than those of the reference drugs. On the other hand, the negative inotropic effect of NP-252 was less than NF, but greater than that of NC. In the preparations controlled by pacing, NP-252 and NF lengthened atrio-His bundle conduction time, without affecting His bundle-ventricular conduction time. Lengthening effect of NP-252 was about 4 times less than that of NF. These results suggest that NP-252 acts more selectively on vascular smooth muscle than cardiac muscle, and has almost equipotent but markedly longer vasodilating actions as compared to NF and NC. It may be expected that NP-252 is a new generation of tissue specific and long acting Ca2+ antagonist.

Anesthesia↗
PubMed1991

[MR imaging of pontine infarction within 2 weeks after ictus].

Magnetic resonance (MR) images of 10 patients with pontine infarction were reviewed. A total of 17 examinations were performed on a 1.5 Tesla high-field scanner (GE) within two weeks after ictus. The infarcted area was detected by MR as early as 20 hours after stroke in one case. However, MR images obtained in two cases three and nine hours after onset were unremarkable. It is therefore suggested that follow-up study should be performed when initial MR images within 20 hours postictus are normal. T1-weighted images at four, nine and twelve days after ictus were interpreted as normal. In two of these three examinations, the infarcted areas were clearly demonstrated as hyperintense lesions on T2-weighted images. In the other examination, however, an area of mildly increased signal intensity was seen on T2-weighted images. This case suggests that the fogging effect is also observed on MR imaging and that a small pontine infarction may be overlooked during the subacute stage. Basilar artery occlusion was detected as an absence-of-flow void in three of the ten patients. In conclusion, MR imaging proved to be a relatively useful diagnostic modality for evaluating acute and subacute pontine infarctions.

Acute Disease↗
PubMed1991

Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines.

1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links.

Animals↗
PubMed1991

Alteration of nuclear proto-oncogene expression by erythropoietin (Epo) in Epo-responsive murine cell lines.

The signal transduction system of erythropoietin (Epo) and the accompanying molecular control mechanism of proliferation and differentiation of erythroid progenitors remains largely unknown. In this study, the effect of Epo on the expression of nuclear oncogenes was investigated in two murine cell lines which respond to the hormone in different ways: ELM-I-1 cells proliferate independently of Epo, but differentiate in response to the hormone, while the growth of DA-1ER cells is absolutely dependent on Epo or interleukin (IL) 3. The cell lines were stimulated with Epo or IL-3, and total RNA was extracted. Then expression of nuclear proto-oncogenes (c-myc, c-fos and c-myb) was analyzed by northern blotting. The change in c-fos expression observed during the first two h following stimulation with either stimulant were common to both cell lines; a rapid and temporary increment. Before stimulation, c-myc and c-myb were strongly expressed in both lines. No apparent change in c-myc expression was observed during the first two h of stimulation, while c-myb expression in ELM-I-1 cells was slightly reduced 1 h after stimulation with Epo but not with IL-3. Three days after stimulation with Epo, but not with IL-3, only ELM-I-1 produced hemoglobin and expressed a lower amount of c-myb mRNA. These data suggest the importance of c-fos in the early signaling system of Epo, and the involvement of c-myb in erythroid differentiation but not in proliferation.

Animals↗
PubMed1991

Serial MR imaging in Creutzfeldt-Jakob disease.

Serial magnetic resonance (MR) imagings of two autopsied patients with Creutzfeldt-Jakob disease (CJD) are presented. Both patients showed a dramatic progression of brain atrophy. The initial MR imagings were, however, interpreted as normal except for localized mild cortical atrophy in one patient. When a normal MR image is obtained in a demented middle-aged or aged patient, CJD may still need to be ruled out: follow up MR imaging may be useful.

Aged↗
PubMed1991

Effects of heterologous helminth infections on passive transfer of immunity using a mouse monoclonal IgE antibody against Schistosoma japonicum.

Passive transfer of immunity using a mouse monoclonal IgE antibody against Schistosoma japonicum was found to be enhanced by heterologous helminth infections. BALB/c mice were infected with Toxocara canis or Nippostrongylus brasiliensis so as to induce eosinophilia prior to a challenge infection with S. japonicum. Recovery of adult schistosomes decreased in a group of mice that had been infected with T. canis and challenged with cercariae at the cutaneous site of sensitization with the IgE antibody as compared with that in mice that had been similarly treated with normal serum in the absence of T. canis infection. Histological examinations revealed a close association of polymorphonuclear cells, including eosinophils, with damaged schistosomula in the skin of T. canis-infected mice that had received the IgE antibody. An enhancement in worm reduction was also observed in mice harboring either of both nematodes when the monoclonal antibody had been injected intraperitoneally during the phase of migration of schistosomula from the skin to the lungs. In vitro studies on macrophage-mediated damage to schistosomula suggested that the enhancement in worm reduction was at least partly due to the activation of macrophages induced by the heterologous infections.

Animals↗
PubMed1991

Angiostrongylus costaricensis: culture of third-stage larvae to young adults in a defined medium.

The third-stage larvae of Angiostrongylus costaricensis were successfully cultured to young adults in a chemically defined medium. The most suitable medium for the development was Waymouth's medium among eight defined media examined. Twenty-eight days after cultivation in this medium, 77% of the larvae developed to young adults, although these worms gradually died thereafter. When Waymouth's medium was supplemented with mouse red blood cells, these young adult worms continued their development. The mean body lengths of the worms cultivated in Waymouth's medium supplemented with RBCs were significantly larger than those of the worms in the medium without RBCs on Days 14 and 21 after cultivation. Addition of RBCs was essential for their further development. At 28 days after cultivation, the maximum body length of the worms was 2.1 mm for males and 3.3 mm for females. Additions of serum, yeast extract lactalbumin hydrolysate, and growth factors to Waymouth's medium did not provide any additional benefits for worm development.

Angiostrongylus↗
PubMed1991

Sister-chromatid exchanges in lymphocytes from 12 chromium platers: a 5-year follow-up study.

To detect the mutagenic effects of hexavalent chromium (Cr) in humans, sister-chromatid exchange (SCE) frequency in lymphocytes and urinary Cr was determined in 66 blood-urine paired samples from 12 male Cr-platers during 5 years (1984-1989). Multiple regression of SCE frequency on age, urinary Cr and smoking habits was analyzed in all 66 samples. Neither age (P = 0.204) nor urinary Cr (P = 0.056) was a significant predictor for SCE frequency. Although urinalysis revealed obvious exposure to Cr in the platers, exposure was unable to influence SCE frequency. Smoking habits were a highly significant (P less than 0.001) positive predictor for SCE frequency, and smoking of one cigarette per day was associated with an increase of 0.054 SCEs/cell in SCE frequency. SCE frequency significantly fluctuated from year to year in 3 subjects. The smoking habits of these 3 subjects did not change during the follow-up period. The results suggest that there are other unknown factors influencing SCE frequency in addition to smoking habits.

Adult↗
PubMed1991

[The physiological function of human endometrium].

The cyclic change of human endometrial cells are controlled by the interaction between hypothalamus, pituitary gland and ovaries, thus making the endometrium proliferate, differentiate, exfoliate and then reproduce. The menstrual cycle is divided into three phases which are called follicle, ovulatory and luteal phase by the morphological change of the ovarium. The endometrial cycle is also classified to proliferative, secretory and menstrual phase. Estradiol (E2) stimulates the proliferation of endometrial cells by the indirect positive mechanism activated by the binding of E2 to E2 receptor. Growth factors (IGF- I, EGF, TGF- alpha etc.) induced by the transcription of the gene promote the proliferation of endometrial cells. Progesterone (P) has antagonistic effects on E2 actions and transform proliferative phase to secretory phase in endometrium. It is suggested that the possible mechanism of carcinogenesis of normal endometrium is the progression of endometrial hyperplasia due to the prolonged and unphysiological exposure to E2. The additional role of oncogenes (fos, fms, myc, myb, erb-B, neu) and growth factors on the mechanism of carcinogenesis of hyperplasia to cancer is very interested.

Cell Differentiation↗
PubMed1991

[Comparison between FIGO old and new staging criteria of endometrial carcinoma].

FIGO proposed new criteria for corpus cancer staging in 1988. One hundred and seventy-one cases of endometrial cancer were classified by these new staging criteria, and differences between grouping and survival rates for the new and old criteria were compared. 1) The number of cases grouped in old stages I, II, III and IV were 67, 86, 8 and 10, whereas those for new criteria 94, 25, 35 and 10, respectively. In 7 cases new staging was not possible because of preoperative radiation therapy and inoperability. 2) Cases of old stage I were reclassified as new stage I 54(80.5%), stage II 2(3.0%) and stage III 8(12.0%), and 3 cases were not classified. Those of old stage II were 39(45.2%), 21(24.55%), 25(29.1%) and 1(1.2%) and old stage III were 1(12.5%), 2(25.0%), 2(25.0%) and 3(37.5%), respectively. 3) Survival rates for the cases with both stage I and II cancer were very good without any apparent difference between them. Those for new stage III were very poor in comparison with old stage III. 4) In cases of stage I according to the new criteria, the depth of myometrial invasion correlated well with the survival rate. The prognosis of G3 cases with myometrial invasion over 1/2 was the poorest. 5) Survival rates among subclassifications of stages II and III were not significantly different from each other.

Female↗
PubMed1991

[A case of chronic constrictive pericarditis with rheumatic valvular heart disease successfully treated by surgery].

Chronic constrictive pericarditis and rheumatic valvular heart disease are common surgical conditions, but the simultaneous occurrence of both is extremely rare and poses problems in diagnosis and treatment. A 47-year-old male with constrictive pericarditis and rheumatic valvular heart disease was successfully treated with operation. The valvular dysfunction had included aortic, mitral and tricuspid regurgitations. He had also complicated severe hepatic dysfunction due to the cardiac constriction and the secondary tricuspid valve regurgitation. With the aid of cardiopulmonary bypass radical pericardiectomy was performed for almost all cardiac surfaces including that of both ventricles, the right atrium, and the venae cavae. After the pericardiectomy, aortic valvular replacement, mitral and tricuspid valvular annuloplasties were performed. Postoperative course was uneventful and the hemodynamic abnormalities (elevated right atrial and ventricular end diastolic pressures) as well as the depressed hepatic functions were dramatically improved postoperatively.

Chronic Disease↗
PubMed1990

Human T-cell leukemia virus type 1 associated with small cell lung cancer.

A patient with small cell lung cancer (SCLC) whose serum contained high levels of soluble interleukin-2 receptors is reported. Soluble interleukin-2 receptors in the supernatant of cultured SCLC cells obtained from the patient's pleural effusion while he had malignant pleuritis, increased almost linearly from the time of cell seeding. The expression of interleukin-2 receptors (Tac) on the SCLC cells were demonstrated by an immunofluorescence study. However, other lymphocytic markers, including OKT 11, OKT 4, OKT 8, B 1, and B 4, were not found on the cells with the exception of the natural killer cell marker, NKH-1. Southern blot analysis indicated the rearrangement of the T-cell receptor of the cancer cells. Moreover, monoclonal integration of human T-cell leukemia virus type 1 (HTLV-1) provirus in DNA from the cancer cells was also demonstrated. These observations suggest that some SCLC in HTLV 1 endemic areas are associated with HTLV-1.

Biomarkers, Tumor↗
PubMed1990

Evidence that endogenous catecholamines are involved in alpha 2-adrenoceptor-mediated modulation of the aortic baroreceptor reflex in the nucleus tractus solitarii of the rat.

Microinjections of alpha-methylnoradrenaline and tyramine into the rat nucleus tractus solitarii (NTS) potentiated the depressor and bradycardiac responses to aortic nerve stimulation whereas yohimbine injected similarly inhibited them. NTS pretreatment with yohimbine inhibited the baroreflex potentiation effects of alpha-methylnoradrenaline and tyramine whereas intraventricular pretreatment with 6-hydroxydopamine inhibited only that of tyramine. These results provide evidence that endogenous catecholamines in the rat NTS are involved in alpha 2 adrenoceptor-mediated modulation of the aortic baroreceptor reflex.

Animals↗
PubMed1990

Angiostrongylus cantonensis: in vitro cultivation from the first-stage to infective third-stage larvae.

The first-stage larvae of Angiostrongylus cantonensis were cultured in various media at 27 degrees C. The most suitable medium for the development was Chernin's balanced salt solution supplemented with 10% L-15, 10% tryptose phosphate broth, 20% fetal calf serum, and 26 mM sodium bicarbonate. Addition of sodium bicarbonate to the medium facilitated early development of the first-stage larvae. When the first-stage larvae were cultured in the medium under 5% CO2 in air, the worms developed gradually to become quiescent and showed the C shape. Thereafter, the larvae developed to the second stage, retaining their first sheath. About 23 days later, the larvae began to develop to the third stage, being enclosed within the sheaths of the first and second molts. Under these conditions, the larvae developed uniformly and 82% of the larvae reached the third stage 50 days later. About 70% of the third-stage larvae discarded their two sheaths, showing almost the same size as those obtained in vivo. When these exsheathed larvae were inoculated into rats, they developed into adult worms and deposited numerous first-stage larvae.

Angiostrongylus↗