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Biomedical subjects

N Nishimura

Publications and source records attributed to N Nishimura.

At least 181 records · Page 10Linked to original sources

A study of growth regulators of renal cortical tubular cells in the rabbit liver.

Two growth regulators, a growth stimulator for cultured renal tubular cells and a growth inhibitor, were observed in this study in rabbit liver homogenate after a unilateral nephrectomy. These regulators appeared in the liver on the third day after this nephrectomy, decreased on the seventh day, and disappeared by the fourteenth day. The growth stimulatory activity, termed a tubular cell growth factor (TuCGF), was a heat- and acid stable 15 to 20 KDa protein. The additive effects of TuCGF on the epidermal growth factor (EGF), the insulin-like growth factor-I (IGF-I), and the fibroblast growth factor (FGF) were observed; the results suggest that TuCGF differs from EGF, IGF-I, or FGF. In contrast, the growth inhibitory activity, termed a tubular cell growth inhibitor (TuCGI), was a heat- and acid-labile protein with a molecular weight of about 150 to 200 KDa. This factor potently inhibited the DNA synthesis of tubular cells in the presence of insulin and EGF. These results suggest that TuCGI is not identical with transforming growth factor-beta (TGF-beta). The regulation of these activities by target cell density is also discussed.

Animals↗

Vitamin K concentrations in the plasma and liver of surgical patients.

Vitamin K deficiency has been reported in patients who were treated with antibiotics and placed on poor diets after surgery. High-performance liquid chromatography (HPLC) was used to study the influence of dietary intake on vitamin K concentrations in surgical patients (n = 22). Plasma phylloquinone decreased rapidly from 1.19 +/- 0.16 to 0.47 +/- 0.12 nmol/L (means +/- SEM, n = 11) on a low-phylloquinone diet and from 1.16 +/- 0.12 to 0.36 +/- 0.07 nmol/L (n = 11) by postoperative fasting. A small amount of phylloquinone and a large amount of menaquinone were found in liver tissue. Phylloquinone concentration was 28.0 +/- 4.3 pmol/g liver (wet weight) on the standard diet (n = 7) whereas it was 6.8 +/- 1.1 pmol/g on the low-phylloquinone diet after 3 d (n = 8). Because phylloquinone is rapidly depleted by fasting, it may be difficult to prevent vitamin K deficiency by dietary phylloquinone alone during long-term fasting after surgery.

Adult↗

Effects of thiopental, pentobarbital, and ketamine on endothelin-induced constriction of porcine cerebral arteries.

Contractile mechanisms of endothelin, a newly isolated vasoactive substance from endothelium, were evaluated in anterior cerebral arteries (ACA). Furthermore, the effects of thiopental, pentobarbital, ketamine, and diltiazem on the endothelin-induced cerebral vasoconstriction were also studied. Endothelin induced cerebral arterial contractions in concentrations above 3 X 10(-10) M. The median effective concentration (ED50: X10(-9) M) of endothelin was 2.1 +/- 0.7 (n = 6). Endothelin did not elicit contractions in preparations soaked in Ca2(+)-free solution, but addition of 2.5 mM Ca2+ to the baths induced marked contractions. Thiopental and pentobarbital attenuated endothelin-induced contractions at concentrations above 3 X 10(4) M, while ketamine was effective above 10(-3) M. In contrast, diltiazem decreased endothelin-induced vasoconstriction at 10(-6) M. The findings suggest that endothelin may cause contractions of porcine cerebral arteries by influx of Ca2+ through Ca2+ channels. The cerebral vasomotion induced by endothelin, however, does not seem to be influenced by clinical doses of barbiturates and ketamine.

Animals↗

A clinicopathologic study of tumors and tumor-like lesions of the penis.

A total of 147 specimens from 93 patients with penile lesions were examined at Nagasaki University Hospital during a 27-year period from 1961 to 1987. The most frequent malignant tumor was squamous cell carcinoma (SCC, 33 cases, 35.5%), followed by extramammary Paget's disease, transitional cell carcinoma, and Bowen's disease. The benign tumors and tumor-like lesions included condyloma acuminatum, cyst of the genitoperineal raphe, and lymphangioma. SCC of the penis accounted for less than 0.1% of all specimens and less than 0.62% of malignant tumors in men filed at our hospital. True phimosis accompanied 81.5% of the SCC cases. The 5- and 10-year survival rates for SCC were 77.2% and 71.3%, respectively. Two patients died of penile SCC. It was considered that an absence of both keratohyaline granules in the granular layer and melanin pigment in the basal layer can serve as a useful histologic indicator for diagnosis of well differentiated SCCs that are otherwise difficult to identify.

Adolescent↗

Isolation of glutamyltaurine from bovine brains and proof of its gamma-linkage by the B/E linked scan SIMS technique.

We isolated a glutamyltaurine from bovine brains and determined its structure as gamma-glutamyltaurine (gamma-Glu-Tau; glutaurine) by use of a new mass spectrometric technique [B/E linked scan sputtered ion mass spectrometry (SIMS)], which we have recently shown to be useful for distinguishing the gamma- from the alpha-isomer of glutamyl-dipeptides. Neither the alpha-isomer of glutamyltaurine nor any aspartyltaurines could be detected in bovine brain.

Animals↗

Endothelial modulation of norepinephrine-induced constriction of rat aorta at normal and high CO2 tensions.

Endothelial modulation of norepinephrine (NE)-induced constriction of the isolated rat aorta was studied at normal (PCO2, 41 +/- 0 mmHg) and high CO2 tensions (PCO2, 91 +/- 1 mmHg). In preparations with intact endothelium, increased CO2 tension resulted in rightward shift of the NE dose-response curve with attenuation of maximal contraction. This effect of CO2 was not modified by indomethacin. Treatment with hemoglobin or rubbing of the endothelium meant that increased CO2 tension still resulted in rightward shift of the NE dose-response curve but without altering the maximal contractile response. The basal guanosine 3',5'-cyclic monophosphate (cGMP) levels in control and NE-treated aortic preparations were not affected by increasing the CO2 tension. Thus the inhibitory action of CO2 on NE-induced contraction in the presence of endothelium may not be derived from facilitation of endothelium-derived relaxation factor (EDRF)-induced cGMP synthesis. Increasing the CO2 tension attenuated the sustained contraction induced by the addition of NE and Ca2+ (2.5 mM) to intact endothelium preparations previously bathed in Ca2(+)-free solution. Further addition of Ca2+ (total 5.0 mM) did not increase the contraction. These findings suggest that the intrinsic activity of NE is greatly modified by endothelium at a high CO2 tension. Vasodilation during hypercapnia may be induced at least in part by synergistic actions of EDRF and CO2 on smooth muscle cells.

Animals↗

Localization of metallothionein in the genital organs of the male rat.

We studied the immunohistological localization of metallothionein (MT), a low molecular weight metal binding protein, in male rat genital organs (testis, epididymis, ejaculatory duct, seminal vesicle, coagulating gland, and prostate) by use of the avidin-biotin-peroxidase complex method. MT concentrations in testis, seminal vesicle, and prostate ranged from 15-30 micrograms/g tissue. In testis, seminiferous tubules with mature spermatozoa exhibited weak MT staining, whereas the tubules containing differentiating spermatogenic cells but not containing spermatozoa showed strong MT staining. No MT immunostaining was observed in Leydig cells. In growing rat testes, the pattern of MT immunostaining was found to change with development: MT was found in supporting cells only on Day 7, spermatogonia adjacent to basement membrane on Day 14, and spermatocytes localized in the central part of the tubules on Day 21. Strong MT immunostaining in the basal cells was a common feature in other genital tissues, except the ductus efferentes. In prostate, the strongest MT staining was found in the lateral lobe, and MT was localized in apocrine secretions in the dorsal lobe. The present results suggest a close association of MT with cell proliferation and differentiation, as well as possible involvement of MT in supply or storage of zinc ions.

Animals↗

Simultaneous determination of the free and total carbamazepine concentrations in human plasma by high-performance frontal analysis using an internal-surface reversed-phase silica support.

High-performance frontal analysis (HPFA) was applied to simultaneous determinations of the free and total carbamazepine (CBZ) concentrations in human plasma. When 1.5ml of human plasma containing CBZ at a clinical therapeutic level (free fraction, about 30%) was directly injected into an internal-surface reversed-phase silica column, the CBZ was separated from the plasma blank and was eluted as a zonal peak with a plateau height corresponding to the free CBZ concentration in protein binding equilibrium. Slow and continuous introduction of the plasma sample and the use of titanium filters permitted us to inject the sample repeatedly while avoiding a rapid increase in column pressure. The free and total CBZ concentrations were determined simultaneously from the peak height at the plateau region and the area of the CBZ peak, respectively. The within-run and day-to-day reproducibilities were satisfactory (C.V. less than or equal to 1.63%, n = 5).

Carbamazepine↗

[Effect of anti-ulcer drugs and PGE2 on the proliferation of rat gastric cultured cells].

The effects of anti-ulcer drugs and PGE2 on the proliferation of rat gastric cultured cells were investigated. To study the cell proliferation, the rate of incorporation of 3H-thymidine into the cultured cells was measured. ULTROSER G, corresponding to fetal bovine serum, was found to dose-dependently increase the incorporation of 3H-thymidine into the cultured cells at a dose range of 1-4%. The incorporation of 3H-thymidine was highest at 36 hr after the inoculation of cells. Therefore, the effect of the drugs on the proliferation was performed under the condition of 2% ULTROSER G and evaluated at 36 hr. Aldioxa, cetraxate HCl, cimetidine (10(-7)-10(-5) M) and PGE2 (10(-8)-10(-6) M) had no effect on the cell proliferation, while indomethacin (0.35-1.41 x 10(-3) M) inhibited the proliferation in a dose-dependent manner. Aldioxa, cetraxate HCl (10(-5) M) and PGE2 (10(-6), 10(-8) M) antagonized the inhibitory effect by indomethacin at a concentration of 0.5 x 10(-3) M, but cimetidine (10(-7)-10(-5) M) did not. From the above results, it was concluded that this method was useful for investigating the effect of drugs on the proliferation of gastric cultured cells.

Animals↗

[Effect of feeding on recording characteristics of electrogastrography (EGG) in normal subjects].

Cutaneous recording of electrogastrography reflects gastric mechanical activity. Epigastric leads are superior in recording characteristics than meso-gastric leads, in fasting state, 3.0 cpm waves dominate EGG recording in fasting state. In this study, we analyzed the EGG recording characteristic after feeding in 10 normal subjects. Though the physical changes of gastric shape and volume after feeding, EGG recording was dominated by 3.0 cpm waves. Epigastric leads are still superior in recording characteristics, amplitude of EGG waves and read-abilities, than meso-gastric leads, after feeding. Amplitude of EGG waves increased after feeding when compared to fasting state, suggesting increased mechanical activity of the stomach. We conclude that epigastric leads are suitable in recording of EGG in fasting and in fed state in normal subjects. This position could be most standard recording leads for EGG in clinical settings.

Action Potentials↗

Vitamin K (menaquinone-4) metabolism in liver disease.

We measured menaquinone-4 (MK-4) and MK-4 epoxide concentrations in plasma and liver tissue after intravenous injection of 200 micrograms/kg MK-4 in 42 patients who underwent hepatectomy. They were classified into normal (N; n = 10), chronic hepatitis (CH; n = 12), and liver cirrhosis (LC; n = 20) groups, on the basis of the diagnosis given by the pathologist after examining resected liver specimens. The plasma MK-4 epoxide concentration reached maximum level (Cmax) 60 min after MK-4 injection. The Cmax in groups LC and CH were 85.9 and 126.3 nmol/l, respectively, which is significantly reduced compared with that of group N (184.4 nmol/l) (p less than 0.01 and p less than 0.05, respectively). The MK-4 concentrations in liver tissues of 24 patients 60 min after MK-4 injection were 2.77 in group N, 3.79 in group CH, and 3.83 nmol/g in group LC, and the MK-4 epoxide concentrations were 4.01, 3.09, and 2.62 nmol/g in the respective groups. Consequently, the ratio of MK-4 epoxide to total MK-4 (MK-4 + MK-4 epoxide) in groups CH and LC was significantly lower than in group N (p less than 0.01). It is concluded that the Cmax of MK-4 epoxide after MK-4 injection may serve as an indicator of liver function and that the low ratio of MK-4 epoxide to total MK-4 in the liver shows impairment in vitamin K metabolism.

Carcinoma, Hepatocellular↗

Prostaglandin E1 modifies porcine cerebral arterial tone through cyclooxygenase related eicosanoid(s) release.

The effects of prostaglandin E1 (PGE1) on porcine cerebral arteries were studied in the absence and presence of cyclooxygenase inhibitors, 5 x 10(-6) M indomethacin or 10(-4) M aspirin. In preparations placed at a resting tension, 3 x 10(-9) to 10(-6) M PGE1 caused dose-dependent contractions. In prostaglandin F2 alpha (PGF2 alpha)- contracted preparations, low concentrations of 10(-9) and 3 x 10(-9) M PGE1 did not modify arterial tone and higher concentrations of 10(-8) to 10(-6) M PGE1 further increased the arterial tone in all preparations tested. In contrast, in the presence of the cyclooxygenase inhibitors, low concentration of 10(-9) and 3 x 10(-9) M PGE1 markedly decreased the arterial tone induced by PGF2 alpha and higher dose of 10(-8) to 10(-6) M PGE1 increased the arterial tone in 15 of 18 preparations (83%). These findings suggest that PGE1 modifies porcine cerebral vascular tone at least partly through cyclooxygenase-related eicosanoid(s) production.

Animals↗

Measurement of vitamin K in human liver by gradient elution high-performance liquid chromatography using platinum-black catalyst reduction and fluorimetric detection.

A sensitive and precise method for measuring endogenous phylloquinone (K1) and menaquinone (MK-n) in human liver was developed, based on gradient elution high-performance liquid chromatography using platinum-black catalyst reduction and fluorimetric detection. Subnanogram levels of vitamin K compounds in 1 g of liver specimen were detectable. We measured vitamin K concentrations in 38 human resected livers. K1 and MK-4 to MK-13 were detected. The concentrations of MK-10 to MK-12 in livers with chronic hepatitis (n = 10) and cirrhosis (n = 22) were significantly lower than in normal livers (n = 6). It is suggested that the decreased concentrations indicate functional damage of the hepatocytes.

Catalysis↗

Correlation between mammary tumor and blood glucose, serum insulin, and free fatty acids in mice.

The blood glucose level and serum levels of insulin, glucagon, and free fatty acids were examined in 7- to 8-mo-old female SHN mice with or without spontaneous mammary tumors (MT). Blood glucose levels in the females with MT were significantly higher than in those without MT, rising in proportion to the increase in size of MT up to 30 mm in diameter. In 4-mo-old male SHN and 11-mo-old female C57BL mice bearing mammary tumor grafts (MTg), the blood glucose level was significantly higher than in mice without MTg. Serum insulin and free fatty acids in female SHN mice with MT rose to higher levels than in mice without MT, whereas serum glucagon levels were unaltered. In 50% of mice with MT, pancreatic islets contained a large number of pyknotic cells. Livers of mice with MT or MTg were significantly heavier than those of mice without MT or MTg. In both female SHN mice with spontaneous MT and male SHN and female C57BL mice with MTg, the total number of hepatocytes and the total amount of liver DNA increased significantly compared with values from corresponding controls without MT or MTg. These findings suggest that MT or MTg induce a hyperglycemic state and an enhanced production of free fatty acids and insulin, which may in turn stimulate the growth of mammary tumors and the liver.

Animals↗

Quantitative immunohistochemistry of metallothionein in rat placenta.

The presence of metallothionein (MT) was demonstrated in placentae from cadmium-exposed and control rats by an immunohistochemical technique, using peroxidase as label and the diaminobenzidine procedure for the staining reaction. The protein was found in different regions of the placenta, i.e. in trophoblastic labyrinth, in spongiotrophoblast and in visceral yolk sac. Cytophotometric analysis of the final reaction product revealed that the amount of MT was increased in the placental labyrinth of cadmium-exposed rats. Increases were found in both nuclei and cytoplasm of trophoblast cells in the labyrinth region. Possible roles of MT in the transport of zinc and in the carbohydrate metabolism are discussed.

Animals↗