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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 541 records · Page 30Linked to original sources

[Treatment of coronary artery disease with poor left ventricular function: comparison of medical and surgical treatments in relation to the numbers of the diseased vessel].

The operative mortality and short-term (average 20 months) survival of 100 surgically or medically treated patients, who had coronary artery disease with poor left ventricular function, were examined. One hundred patients with myocardial infarction and radionuclide-documented left ventricular dysfunction (LVEF at rest less than or equal to 40%) were subjects of this study; 85 patients among them underwent simultaneous coronary arteriography. Fifty-six patients whose average age was 59.7 years, and an average LVEF was 30.0%, were treated medically; 44 patients with an average age of 56.0 years, and an average LVEF of 30.9%, were treated surgically, 41 with bypass grafts, two with left ventricular surgery, and one with both these procedures. The medically treated patients consisted of four groups. Group I comprised 15 patients, in whom coronary angiography was contraindicated. Their average age was 67.1 and an average LVEF was 26.2%, Group II, included six patients, who had no indication for surgery because of severely diseased distal coronary arteries. This group had an average age of 57.5 years and an average LVEF of 22.5%. There were one with two-vessel disease and five with three-vessel disease. Group III included five surgical candidates who refused surgery. Their average age and an LVEF were 67.0 and 35.0%, respectively. In this group, there were one with two-vessel disease and four with three-vessel disease. Group IV, comprised 22 patients who did not need surgical therapy. Their average age was 55.3 and average LVEF was 32.5%. They included 22 with one-vessel disease, seven with two-vessel disease and one with three-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Competitive binding enzyme immunoassay for zonisamide, a new antiepileptic drug, with selected paired-enzyme labeled antigen and antibody.

We assessed the competitive binding between zonisamide (ZNS) in serum samples and beta-galactosidase-labeled ZNS derivatives, using competing antibodies to ZNS derivatives, and selected the best enzyme-labeled antigen and antibody for accurate enzyme immunoassay (EIA) of ZNS in serum without interference from its metabolites or from other antiepileptic drugs. This EIA, based on use of antibody linked to bacterial cell walls, has advantages over HPLC in simplicity, speed (50 samples per hour), and lack of requirement for special equipment. The concentrations of ZNS in serum as measured by the EIA correlated well with those by HPLC (n = 33, r = 0.977).

Antibodies↗

[Role of testosterone propionate and insulin in the regeneration and growth of bone].

In order to clarify the effects of androgens and insulin (Ins) on the growth and regeneration of bone in growing rats, and to examine the interaction of the two hormones on the bone growth and regeneration, I carried out both in vivo and in vitro experiments using male rats and clonal osteoblastic cells, respectively. In vivo: 1) Three week-old male rats were castrated, and one week after the castration two holes were drilled into their calvariae, followed by subcutaneous administration of 2 mg/kg of testosterone propionate (TP) and/or 20 mg/kg of cyproterone acetate (CPA). After the daily administration of the drugs for two weeks, the calvariae containing wound holes were isolated, and a soft X-ray photograph was taken. The area of the hole in the X-ray film was measured. The calcium (Ca) and the hydroxyproline (HP) contents and alkaline phosphatase (ALPase) activity in the wound and non-wound portions of the calvariae were also determined. 2) Streptozotocin (STZ, 80 mg/kg) was administered intravenously to immature male rats (25-day-old); and three days after the administration, wound holes were made in their calvariae. Ins (10 units/kg) and/or TP (2 mg/kg) were/was administered daily for two weeks starting two weeks after the operation. The length and weight of the femur, and the area of the hole of the calvariae seen in a soft X-ray photograph were measured. The Ca and HP contents in the wound portion, and serum Ca and phosphate (P) levels and ALPase activity were also determined. In vitro: Mouse clonal osteoblastic cells (MC3T3-E1) were incubated in alpha-MEM mudium containing 10% FBS or 0.1% BSA with or without 10(-9)-10(-6) M TP and/or 10(-9)-10(-6) M Ins, the number of cells was counted, and [3H] thymidine incorporation into the cells was assayed for assessment of DNA synthesis. ALPase activity of the cells was also assayed. The results obtained were as follows: 1. The reduction in the wound-hole area was significantly delayed after the castration and was accelerated by TP. This effect of TP was inhibited about 60% by the simultaneous administration of CPA, though this inhibition was not statistically significant. 2. The reduction in HP content of the wound portion by castration was inhibited by TP, and this effect was antagonized by CPA.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkaline Phosphatase↗

Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes.

Two independent transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 50% of transgenic offspring had tumors within 18 months. The tumors developed in restricted tissues and about 60% of affected mice had angiosarcomas. The transgenes were expressed both in the tumors and in all normal tissues. However, somatic mutational activation was detected only in the transgenes of the tumors. The point mutation at the 61st codon, from CAG(Gln) to CTG(Leu), was detected in all angiosarcomas (22/22), some lung adenocarcinomas (3/11) and Harderian gland adenocarcinomas (4/7) in both lines. The other point mutation at the 12th codon from GGC(Gly) to GTC(Val) was detected in two of the four skin papillomas. No mutations on these codons were detected in normal tissues of transgenic mice. Nontransgenic littermates had no tumors at all. From these results, it was strongly suggested that the mouse tumors do not develop only by the expression of the transgenes, and that definite somatic point mutation of the human c-Ha-ras transgenes in certain cell types may be a causative event in tumorigenesis in these transgenic mice.

Animals↗

[Assessment of ischemic damage of the cardiac sympathetic nerve function by semiquantitative analysis of 123I-MIBG (metaiodobenzylguanidine)-SPECT--comparison with 201Tl-Cl-SPECT].

Recently 123I-MIBG scintigraphy has been developed for evaluating the function of cardiac sympathetic nerve. To assess its ischemic damage, dual SPECT with 123I-MIBG and 201Tl-Cl were performed in 24 patients with ischemic heart disease and 8 normal subjects. In order to evaluate extent and severity of ischemic damage, Tl and MIBG abnormal scores were calculated by Bull's eye map. In patients with Non-Q wave myocardial infarction (NQMI), MIBG abnormal scores were significantly higher than Tl scores (p less than 0.01). In the regions where regional wall motion showed hypokinesis, MIBG abnormalities were detected in all cases whereas Tl abnormalities existed only in 42%. MIBG abnormality score in NQMI group with negative T wave and wall motion asynergy was significantly higher than that of NQMI group without T wave abnormality and asynergy (p less than 0.01). Ischemic damage of cardiac sympathetic nerve seemed to contribute to negative T wave and stunned myocardium. 123I-MIBG scintigraphy was thought to be a sensitive and useful method for clinical evaluation of ischemic heart disease.

3-Iodobenzylguanidine↗

Effect of chitin heparinoids on the activation of peritoneal macrophages and on the production of monokines in mice.

Sulfonated derivatives of chitin which showed anticoagulant activity (chitin heparinoids) were studied with regard to the activation of mouse peritoneal macrophages and the production of monokines. In comparison with 70% deacetylated chitin (DAC-70), which was the most adjuvant-active derivative of chitin, all chitin heparinoids were less effective for the augmentation of cytolytic activity of peritoneal macrophages. The number of macrophages was hardly increased or decreased by intraperitoneal injection of chitin heparinoids, and the activity of circulating colony-stimulating factor was not changed by their treatment. Only N-sulfonated DAC-70 stimulated the production of interleukin-1 by thioglycolate-induced peritoneal macrophages in vitro. However, its effect was weaker than that of DAC-70. Chitin heparinoids showed no or weak mitogenic activity on normal mouse spleen cells.

Adjuvants, Immunologic↗

Evaluation of brain edema using magnetic resonance proton relaxation times.

Experimental and clinical studies on the evaluation of water content in cases of brain edema were performed in vivo, using MR proton relaxation times (longitudinal relaxation time, T1; transverse relaxation time, T2). Brain edema was produced in the white matter of cats by the direct infusion method. The correlations between proton relaxation times obtained from MR images and the water content of white matter were studied both in autoserum-infused cats and in saline-infused cats. The correlations between T1 as well as T2 and the water content in human vasogenic brain edema were also examined and compared with the data obtained from the serum group. T1 and T2 showed good correlations with the water content of white matter not only in the experimental animals but also in the clinical cases. The quality of the edema fluid did not influence relaxation time and T1 seemed to represent almost solely the water content of the tissue. T2, however, was affected by the nature of existence of water and was more sensitive than T1 in detecting extravasated edema fluid. It seems feasible therefore to evaluate the water content of brain edema on the basis of T1 values.

Animals↗

Electron microscopic study of perivascular structure associated with experimentally induced brain edema in cats.

The fine structural features and water content of white matter associated with the resolution process of brain edema were sequentially investigated in the model produced by infusion of autoserum, mock CSF, or ferritin into the centrum semiovale of cats. The correlation between water content and morphological features was good. Mock CSF-infused edema disappeared within 3 days, serum infused edema within 6 days. In a fine structural study of serum-infused white matter, the distended extracellular spaces were found to be occupied with electron-dense materials, active phagocytosis of the dense materials being observed in the macrophages. Around the postcapillary venules, edematous changes were characterized by wide expansion of the perivascular spaces between endothelial cells and astrocytic endfeet. In some instances, the dense materials in the cytoplasm or in the membrane-bound vacuoles of the astrocytic endfeet were continuous with those in the perivascular space, through the hiatuses of the perivascular astrocytic endfeet being separated at their margins. At 3 days after infusion, wide distension of the extracellular space persisted, but the dense materials had markedly diminished. These results strongly suggest that water clearance of vasogenic brain edema does not commence until proteinaceous macromolecules are degraded and removed from the extracellular space. Perivascular channels around the postcapillary venules might also have some role on the movement of edematous fluid.

Animals↗

[A case of ectopic large pituitary adenoma].

Ectopic pituitary adenomas are very rare and only 17 cases have been reported. In this paper we present a case of large pituitary adenoma originating in the suprasellar region. A 26-year-old man was admitted to our clinic with a chief complaint of headaches. Neurological examination revealed slight disorientation and bilateral choked disk. Hormonal study revealed that the serum prolactin level was 3300ng/ml and serum growth hormone level was 29.5ng/ml. Computed tomography showed a large mass in the suprasellar region extending upward to the third ventricle and backward to the pons. T1-weighted MR imaging revealed that the intensity of the mass was the same as that of the cerebral cortex and the pituitary gland was showing high intensity in the pituitary fossa. The tumor was radically removed via the transpetrosal transtentorial approach. Histologically, the tumor was a prolactin-growth hormones producing pituitary adenoma. The literature was reviewed and the origin of the tumor was discussed.

Adenoma, Chromophobe↗

Functional expression of the calcium release channel from skeletal muscle ryanodine receptor cDNA.

Combined patch-clamp and fura-2 measurements were performed to study the calcium release properties of Chinese hamster ovary (CHO) cells transfected with the rabbit skeletal muscle ryanodine receptor cDNA carried by an expression vector. Both caffeine (1-50 mM) and ryanodine (100 microM) induced release of calcium from intracellular stores of transformed CHO cells but not from control (non-transfected) CHO cells. The calcium responses to caffeine and ryanodine closely resembled those commonly observed in skeletal muscle. Repetitive applications of caffeine produced characteristic all-or-none rises in intracellular calcium. Inositol 1,4,5-trisphosphate (IP3) neither activated the ryanodine receptor channel nor interfered with the caffeine-elicited calcium release. These results indicate that functional calcium release channels are formed by expression of the ryanodine receptor cDNA.

Animals↗

Spin-labeling proton NMR study on aromatic amino acid residues in the guanine nucleotide binding site of human c-Ha-ras(1-171) protein.

A truncated human c-Ha-ras gene product, ras(1-171) protein, was prepared and chemically modified with maleimide spin-label (MSL). By trypsin digestion of the MSL-labeled ras(1-171) protein, MSL-labeled peptide fragments were isolated and sequenced. The cysteine residue in position 118 of the protein, but not the other cysteine residues, Cys-51 or Cys-80, was found to be specifically labeled by MSL. The ESR spectrum of the MSL-labeled ras(1-171) protein indicates that the MSL group attached to Cys-118 is strongly immobilized. Proton NMR spectra at 400-MHz were measured for this MSL-labeled ras(1-171) protein and also for a control sample of a labeled ras(1-171) protein whose MSL was reduced by sodium ascorbate. In the difference spectra for these two proteins, resonances of protons in the vicinity of the MSL group attached to Cys-118 of the ras(1-171) protein were observed. Thus, the MSL group was found to be in the vicinity of the protein-bound GDP. A phenylalanine residue and two histidine residues, which were characterized by 2D HOHAHA and DQF-COSY spectra, were also found to be in the vicinity of MSL. NOE and pH titration analyses indicate that this phenylalanine residue is close to the bound GDP and one of the two histidine residues. By carboxypeptidase digestion, the two histidine residues near MSL were identified as His-27 and His-94.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Conformation of guanosine 5'-diphosphate as bound to a human c-Ha-ras mutant protein: a nuclear Overhauser effect study.

1H NMR spectra of a GDP/GTP-binding domain of human c-Ha-ras gene product (residues 1-171) in which glutamine-61 was replaced by leucine [ras(L61/1-171) protein] were analyzed. By one-dimensional and two-dimensional homonuclear Hartmann-Hahn spectroscopy and nuclear Overhauser effect (NOE) spectroscopy of the complex of the ras(L61/1-171) protein and GDP, the ribose H1', H2', H3', and H4' proton resonances of the bound GDP were identified. The guanine H8 proton resonance of the bound GDP was identified by substituting [8-2H]GDP for GDP. The dependences of the H1' and H8 proton resonance intensities on the duration of irradiation of the H1', H2', H3', and H8 protons were measured. By numerical simulation of these time-dependent NOE profiles, the conformation of the protein-bound GDP was elucidated; the guanosine moiety takes the anti form about the N-glycosidic bond with a dihedral angle of chi = -124 +/- 2 degrees and the ribose ring takes the C2'-endo form. Such an analysis of the conformation of a guanine nucleotide as bound to a GTP-binding protein will be useful for further studies on the molecular mechanism of the conformational activation of ras proteins on ligand substitution of GDP with GTP.

Base Sequence↗

In vitro phosphorylation of the tumor suppressor gene RB protein by mitosis-specific histone H1 kinase.

The major components of the mitosis-specific histone H1 kinase are CDC2 kinase and cyclin and the consensus amino acid sequence for phosphorylation by this enzyme has been proposed. We have noted the presence of such sequences in six sites of the tumor suppressor gene RB protein and determined whether or not RB protein is in fact phosphorylated by this kinase. Highly purified enzyme was used for this purpose. HeLa cell extracts immunoprecipitated with anti-RB antiserum as well as RB proteins expressed in E. coli cells were shown to be phosphorylated by this kinase in vitro. Synthetic peptides for the six expected sites were also phosphorylated. These results suggest the possibility that the function of RB protein is regulated by CDC2 kinase.

Amino Acid Sequence↗