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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 163 records · Page 9Linked to original sources

A human melanoma cell line highly susceptible to influenza C virus.

The relative amounts of influenza C virus-specific receptors of 25 established lines of mammalian cells including four lines of human malignant melanoma origin were compared by virus binding experiments. All the human melanoma cell cultures studied possessed two to four times more receptors than were found on MDCK cells, a cell line known to be highly susceptible to influenza C virus. It may therefore be a feature common to human melanoma cells that O-acetylsialic acid, a determinant for the attachment of influenza C virus, exists in large quantities on their surface. This is not specific to melanoma cells, however, since several human cell lines derived from lung cancer, gastric cancer, and placenta specimens also exhibited high levels of virus binding. Twenty of 25 virus-binding cell cultures were further examined for their ability to support the replication of influenza C virus. In the presence of trypsin (5 to 20 micrograms/ml), the virus was found to undergo multiple cycles of replication much more efficiently in the HMV-II line of human melanoma cells than in MDCK cells. Additionally, by using HMV-II cells as a host, we succeeded in isolating two influenza C strains (C/Yamagata/1/88, C/Yamagata/2/88) from 241 throat swabs collected from patients with acute respiratory illness.

Adhesiveness

Skin pigmentation associated with minocycline therapy.

A patient on long-term minocycline therapy developed blue-black discoloration on the legs. Skin biopsy specimens from the pigmented areas were examined by light and electron microscopy and energy-dispersive X-ray microanalysis. Pigmented granules were present at all levels of the dermis and subcutaneous fat tissues. Ultrastructural examination showed electron-dense granular material within the cytoplasm of dermal macrophages and energy-dispersive X-ray microanalysis indicated that the granules contained iron. Thyroid tissue obtained by aspiration biopsy showed the presence of fine brown granules within the cytoplasm of the follicular epithelial cells. An extract of skin from the pigmented areas was subjected to high performance liquid chromatography and minocycline was detected.

Female

A study of drug efficacy in the treatment of ovarian cancer.

One hundred and nine cases of common epithelial ovarian cancer treated in our department during the past decade were entered into this study, which dealt with direct therapeutic effects and prognosis, comparing the groups administered cisplatin with those administered other anticancer drugs. 1) In 38 patients with measurable lesions, high response rates were achieved through the administration of anticancer drugs containing cisplatin in both the primary cancer and recurrent cancer groups. 2) Preventive chemotherapy was performed in patients in whom complete surgery was achieved at the initial operation. No significant difference in prognosis was observed through the administration of cisplatin and other anticancer drugs. 3) In patients in whom reduction surgery was carried out to the maximum possible degree at the initial operation, an improvement in prognosis was observed through the administration of cisplatin. These results imply that a cisplatin-based regimen should be aggressively used, except in cases that underwent complete debulking surgery.

Adenocarcinoma

Mechanism of resistance to benzalkonium chloride by Pseudomonas aeruginosa.

The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied. The effluence of cell components was observed in susceptible P. aeruginosa by electron microscopy, but resistant P. aeruginosa seemed to be undamaged. No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found. The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P. aeruginosa were higher than those in the cell walls of susceptible P. aeruginosa. The amounts of BC adsorbed to PL and FNL of cell walls of BC-resistant P. aeruginosa were lower than those for BC-susceptible P. aeruginosa. Fifteen species of cellular fatty acids were identified by capillary gas chromatography and gas chromatography-mass spectrometry. The ability of BC to permeate the cell wall was reduced because of the increase in cellular fatty acids. These results suggested that the resistance of P. aeruginosa to BC is mainly a result of increased in the contents of PL and FNL. In resistant P. aeruginosa, the decrease in the amount of BC adsorbed is likely to be the result of increases in the contents of PL and FNL.

Benzalkonium Compounds

Postreceptor defect in insulin action in streptozotocin-induced diabetic rats.

To clarify the mechanism(s) responsible for the insulin resistance in streptozotocin (STZ)-treated diabetic rats, we studied insulin-induced glucose disposal by using the glucose clamp technique and measured insulin receptor and glucose transporter of muscles. The insulin dose-response curve of the metabolic clearance rate (MCR) of glucose revealed a decrease of the maximal response without a rightward shift in STZ rats. Maximal MCR was even lower when clamped at 300 rather than 150 mg/dl of blood glucose levels. Insulin binding to the crude plasma membrane of muscles from STZ rats was increased compared with controls. The number of glucose transporter of the plasma and microsomal membranes were significantly decreased in STZ rats. These in vivo and in vitro studies using skeletal muscles suggest that in STZ-treated diabetic rats 1) a defect or defects exist in the signal transduction mechanism of insulin in postbinding steps, 2) the decreased maximal MCR is related at least partly to the decrease of glucose transporter numbers, and 3) a defect in glucose metabolism (postglucose transport defect) is also present.

Animals

Sodium chloride and water transport in the thin descending limb of Henle of the quail.

Birds and mammals can produce hyperosmotic urine, but their renal morphology and urine-concentrating mechanisms differ. To elucidate the countercurrent urine concentration mechanism in birds, we examined the structure and transport properties of the descending limb (DL) of Henle of mammalian-type nephrons in Japanese quail, Coturnix coturnix. In the avian renal medulla, a prominent ring of collecting ducts and scattered thick limbs surrounds a core of capillaries and DLs. Epithelial cells in the upper DL (DLu) have abundant microvilli and shallow, tight junctions; cells in the lower DL are flat and have little interdigitation. Transepithelial voltage was zero when the DLu was perfused and bathed in isosmotic avian Ringer solution. The efflux coefficients (10(-7) cm2/s) for Na (31.7 +/- 2.3) and Cl (24.9 +/- 3.6) were not significantly different and were unaltered by ouabain (10(-4) M) (32.5 +/- 2.2). Diffusional water permeability measured by [3H]H2O was low (73.0 +/- 7.8, 10(-7) cm2/s). Volume flux was nearly zero and increased only slightly when an osmotic gradient was imposed. These results suggest the DLu is highly permeable to Na and Cl and virtually impermeable to water; thus NaCl extruded actively from the thick ascending limb may enter the DL unaccompanied by water. This countercurrent multiplication system by use of single-solute recycling and a transport cascade of graded hairpin turns may help establish an osmotic gradient along the medullary cone. Thus avian and mammalian renal countercurrent multiplication systems may differ.

Animals

Localization of metallothionein in female reproductive organs of rat and guinea pig.

We demonstrated the localization of metallothionein (MT) in rat uterus and ovaries and in guinea pig mammary glands. During the cyclic changes from one estrous period to the next, strong MT immunostaining was found in the glandular epithelium of the endometrium and weak immunostaining was observed in the simple columnar epithelium. Interestingly, during estrus, the intensity of MT immunostaining decreased in the cytoplasm, whereas during metestrus, diestrus, and proestrus the intensity of strong and similar immunostaining was observed in both the cytoplasm and nucleus. During proestrus and estrus, the number of vaginal epithelial cells containing MT increased on the luminal side of the epithelium and inside the lumen. In rat ovary, strong immunostaining was observed in the cytoplasm and nucleus of granulosa-lutein cells of the corpus luteum and in the cytoplasm of the ovum. In mammary gland of non-pregnant guinea pig, very strong but scattered MT immunostaining was demonstrated in both cytoplasm and nucleus of some epithelial cells of the lactiferous ducts. The mammary tissue of the pregnant guinea pig showed an increase in MT staining in alveolar cells that had proliferated due to pregnancy. The presence of MT in the female reproductive organs, the tissues of which actively grow under the control of female sex hormones, indicates some as yet unknown association of MT with cell proliferation and differentiation.

Animals

Immunohistochemical localization of metallothionein in developing rat tissues.

Metallothionein (MT) is a cysteine-rich, low molecular weight protein inducible by heavy metal ions and various endogenous factors. Using an indirect immunofluorescent technique, we studied the localization of MT in developing rat tissues (kidney, small intestine, and liver). In kidney of the neonate and fetus, MT was found in both the cytoplasm and the nucleus of renal tubular epithelia. Localization of MT changed with shift of zonation in the renal cortex during development. Metallothionein was found mainly in the inner zone of the cortex but not in tubules of the neogenic zone on Day 4. Until Day 18, tubular cells containing MT were observed in a part of the cortex adjacent to the medulla, followed by a significant decrease in immunostaining by Day 27. In small intestine of the neonate, MT was localized predominantly in Paneth and goblet cells which play secretory roles. The number of goblet cells with strong immunostaining for MT was maximal on Day 27. In liver of 20-day fetuses and of 4-day-old neonates, both the cytoplasm and the nucleus of hepatocytes exhibited strong immunofluorescence. The intensity of MT staining diminished with development, and by 18-27 days after birth no immunofluorescence was observed in the nucleus. We further studied a possible association of MT with development by localizing MT in livers obtained from partially hepatectomized and laparotomized rats. Hepatectomy led to the appearance of MT not only in the nucleus and cytoplasm of hepatocytes but also in sinusoids and bile canaliculi. After laparotomy, MT immunofluorescence was observed only in the cytoplasm. The present results suggest a possible involvement of MT in cell proliferation and differentiation, as well as in transport and secretion of this metal-binding protein.

Animals

Deterioration of baroreceptor reflex by transient global cerebral ischemia in dogs.

Influence of transient global cerebral ischemia on baroreceptor reflex sensitivity (BRS) was investigated in anesthetized dogs. Cerebral ischemia was produced by the combined occlusions of the left subclavian (LSA) and the brachiocephalic (BCA) arteries with preceding ligations of the intercostal arteries (ICA). BRS was assessed by phenylephrine-induced reflex bradycardia. Ischemia of 5- and 10-min duration produced a significant decrease in BRS during the reperfusion period of 60-120 min. On the other hand, such a change was not observed following the ischemia of less than 2-min or occlusions of LSA and BCA without preceding ligations of ICA. Heart rate response to the electrical stimulation of the vagal afferent nerve was attenuated by 10-min ischemia, while response to the vagal efferent nerve stimulation and ECG parameters were not influenced. These results indicate that some regions vulnerable to the relatively short duration of cerebral ischemia may be involved in the central pathway of the baroreflex mechanism.

Animals

Thalidomide may inhibit proliferation of mesenchyme in human limb buds.

Limb buds from 4- and 4.5-week-old human embryos were cultured on agar medium consisting of Medium 199, chick embryo extract and horse serum for 4 days with or without thalidomide (1-1.5 microgram/ml), and the direct effect of thalidomide was examined morphologically in histological preparations. In the explants treated with thalidomide, mitotic figures of mesenchymal cells were significantly decreased both in overall explant and in mesenchymal cell aggregates, but the extracellular matrix in the mesenchymal cell aggregates was seen in the experimental and control explants. These findings suggest that thalidomide affects undifferentiated and differentiated mesenchymal cell proliferation but not the chondrogenic capacity of the mesenchyme.

Cartilage

Effects of propentofylline on energy metabolism of the ischemic brain studied by in vivo 31P nuclear magnetic resonance spectroscopy.

The effects of 3-methyl-1-(5'-oxohexyl)-7-propylxanthine (propentofylline, HWA 285) on transient cerebral ischemia were studied in Mongolian gerbils by measuring the in vivo 31P nuclear magnetic resonance (NMR) spectra and cerebral water content. Transient ischemia was produced by bilateral common carotid artery occlusion for 30 min, which was followed by 60 min of reperfusion. Propentofylline (1, 2.5 or 30 mg/kg) or normal saline was administered intravenously at 2 min after the reperfusion. The 31P spectra during the occlusion showed a marked reduction in adenosine triphosphate (ATP) and phosphocreatine (PCr) with elevation of inorganic phosphate (Pi) in all groups. The intracellular pH (pHi) calculated from the chemical shift of Pi was markedly reduced in all groups. After the reperfusion, ATP, PCr, Pi and pHi gradually recovered towards the normal levels in the control group. In the 2.5 mg/kg propentofylline group, the energy recovery was significantly faster than in the controls. The cerebral water content measured at the end of reperfusion was significantly lower in the 2.5 mg/kg propentofylline group than in the controls. However, such cerebral protective effects were not observed in the 1 mg/kg and 30 mg/kg groups. The present results suggest that propentofylline may accelerate the energy recovery of the transiently ischemic brain and suppress the development of post-ischemic cerebral edema. The effects, however, were not dose-dependent in manner. The detailed mechanism of the effects requires further investigation.

Adenosine Triphosphate

[Prognostic factors of common epithelial ovarian cancer treated by surgery and cisplatin based combination chemotherapy].

Retrospective analysis of prognostic factors in 171 patients who had common epithelial ovarian cancer (WHO) and treated by surgeries and cisplatin based combination chemotherapies were performed by survival assay and multivariate analysis. In FIGO stage 3, the estimated parameter values were in following order: residual tumour age grade performance status histological type. On analysing Stage patients, histological grading and histological typing had an effect on prognosis. Patients with grade 2 or tumours had a worse prognosis than did those with grade 1 tumours, and patients with clear-cell carcinoma or undifferentiated adenocarcinoma showed a poor prognosis.

Adult

Angiotensin II vascular receptors in fowl aorta: binding specificity and modulation by divalent cations and guanine nucleotides.

In the domestic fowl, angiotensin (ANG) II causes a unique vasodepressor response in vivo and vascular relaxation of aortic rings in vitro that appear to be mediated by ANG II receptors. In initial studies using radioligand binding techniques, we identified specific vascular ANG II receptors in the fowl aorta. In the present study, we have characterized fowl vascular ANG II receptors in terms of binding specificity and their modulation by divalent cations and guanine nucleotide, to understand how the fowl receptor might differ from mammalian vascular ANG II receptors that mediate vasoconstriction. Competitive displacement of [125I] ANG II binding by ANG agonist and antagonist analogs revealed a unique pattern of receptor specificity, with the potency rank order: [Asn1, Val5]ANG II greater than [Asp1, Ile5]ANG II greater than [Asp1, Val5, Ser9] ANG I = [Asp1, Val5]ANG II much greater than [Val5]ANG III greater than [sarcosine(Sar)1, Ile5]ANG II greater than [Sar1, Ile8]ANG II much greater than [Sar1, Thr8]ANG II. Divalent cations (Ca++, Mg++ and Mn++) inhibited equilibrium radioligand binding by as much as 50% at 100 mM, with the potency order: Ca++ greater than Mn++ greater than Mg++. Mg++ and Mn++ stimulated binding very slightly (110%) at low doses (1-10 mM). The stable guanine nucleotide analog 5'-guanylyl imidodiphosphate inhibited equilibrium radioligand binding moderately (15% at 100 microM) in the presence of 10 mM MgCl2, but failed to alter the dissociation rate of receptor-bound ligand (half-time = 10.92 min). These results suggest that fowl vascular ANG II receptors exhibit specificity and regulatory properties fundamentally different from those of mammalian vascular ANG II receptors.

Angiotensin I

Chicago sky blue and a helium neon laser abolish endothelium dependent relaxation in vivo in the microcirculation.

Chicago sky blue, also known as Niagara sky blue, is a vital dye that can successfully be used as an intravascular energy absorbing target for the light from a helium-neon (HeNe) laser. The result of this light/dye interaction is endothelium damage which can be controlled by adjusting the duration of the laser exposure and the amount of dye injected intravenously. The endothelial damage probably is the result of the heat generated by the dyes absorption of energy at the interface between plasma and endothelium. The most minimal damage resulted in selective loss of the dilation normally produced by acetylcholine and bradykinin, two endothelium dependent dilators. The dilation produced by sodium nitroprusside, a dilator acting directly on vascular smooth muscle, was preserved. More severe injury (i.e. more prolonged exposure to light and/or more dye, resulted in local platelet aggregation at the site of laser impact.

Acetylcholine

[Current status of CDDP analogs in gynecologic malignancies].

Among the cooperative studies of cisplatin (CDDP) analogs in gynecologic malignancies in Japan, a phase III study of CBDCA in ovarian cancer was completed in 1988, while phase II studies of 254-S and DWA2114R are ongoing at the present time. Phase II preliminary data in ovarian cancer revealed a response rate of 25-38%, almost equi-effective and less toxic to that of CDDP. Approximately 20% response rate was achieved in CDDP refractory cases, in particular, responders were observed in mucinous and mesonephroid cases considered CDDP resistant. A phase III study of CBDCA in ovarian cancer, with a comparative study of CAP regimen suggested that CBDCA-containing regimen has an advantage of unnecessity of hydration, in spite of no significant differences response and toxicity. In the cancer of the uterine cervix, approximately 20% response rate was achieved. Of interest is that 254-S yielded a response of 60%, and the result suggested that the agent may have broad antitumor spectrums, different to that of CDDP.

Adolescent

Identity of soluble thiamine-binding protein with thiamine repressible acid phosphatase in Saccharomyces cerevisiae.

Two secretory glycoproteins of S. cerevisiae, a soluble thiamine-binding protein and a thiamine-repressible acid phosphatase, were shown to be repressed to a similar extent by excess thiamine in the growth medium. Thiamine-repressible acid phosphatase was co-purified throughout the purification of the soluble thiamine-binding protein. Purified and deglycosylated soluble thiamine-binding proteins exhibited both thiamine-binding and acid phosphatase activities on non-denaturing polyacrylamide gel electrophoresis. Heat treatment of the purified soluble thiamine-binding protein caused a decrease in both activities with a similar inactivation profile. Two thiamine-repressible acid phosphatase-defective mutants isolated were found to be also defective in soluble thiamine-binding activity. The uptake of [14C]thiamine phosphate esters, such as thiamine monophosphate and thiamine pyrophsphate, was remarkably impaired in the mutant cells, whereas the uptake of [14C]thiamine by the mutant was almost the same with that by the parent strain. From these results, it was concluded that the soluble thiamine-binding protein is identical to the thiamine-repressible acid phosphatase in S. cerevisiae, which is involved in the hydrolysis of exogenous thiamine phosphate esters in the periplasmic space prior to the uptake of their thiamine moiety by yeast cells.

Acid Phosphatase