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Biomedical subjects

K Ohashi

Publications and source records attributed to K Ohashi.

At least 469 records · Page 26Linked to original sources

Chronopharmacological study of furosemide; (VI). Influence of prolonged exposure to continuous light.

We have previously reported that a time-dependent variability is observed in the diuretic effects of furosemide in rats. The present study was undertaken to examine the influence of prolonged exposure to continuous light on chronopharmacological profiles of furosemide in Wistar rats. In study I, rats were maintained for more than 2 weeks under conditions of light (0700-1900 hrs) and dark (1900-0700 hrs) (L-D). Furosemide (30 mg/kg) was orally given at 1200 hrs or at 2400 hrs. Urine was collected for 8 hours after the drug and urinary excretion of sodium and furosemide were determined respectively. Thereafter, these rats were exposed to continuous light (L-L) for the next 4 weeks, and were again maintained under the L-D cycle. The identical trial of study I was repeated at the end of the L-L (study II) and the second L-D (study III) conditions. Urine volume and urinary excretion of sodium and furosemide following the drug were significantly greater at 1200 hrs than at 2400 hrs under conditions of L-D (study I and III). However these administration time-dependent changes in the effects of furosemide and its urinary amount disappeared with L-L condition (study II). These findings indicate that the mode of the time-dependent changes in the effects of furosemide is altered by prolonged exposure to continuous light.

Animals↗

Current strategy for esophageal varices in Japan.

Management of bleeding esophageal varices in Japan includes tamponade, sclerotherapy, devascularization, and shunt procedures. Sclerotherapy is the most widely used treatment in both acute and chronic management. The Japanese Research Society for Sclerotherapy of Esophageal Varices monitors and surveys this treatment method at 152 institutions. Extensive devascularization operations now include a thoracotomy less frequently than previously, and they have a 6.6% rebleeding rate in elective patients. Shunt operations are applied in 20% of cases of bleeding esophageal varices in Japan. Effective medical and surgical treatments have led to changes in management strategy and to diversity in treatment during the last decade. The timing of treatment, the nature of the disease, the patient's liver function, and the distribution of collaterals should all be considered in selecting treatment.

Balloon Occlusion↗

Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes.

To identify the primary structure of CD59 antigen and to elucidate its function, a full-length cDNA clone of CD59 was isolated. The cDNA sequence contained an open reading frame that encodes an 128-amino-acid peptide. The amino-terminal 25 amino acids represented a typical signal peptide sequence and the carboxy-terminal hydrophobic amino acids were characteristic for phosphatidylinositol-anchored proteins. The predicted mature protein sequence showed 35% homology with murine Ly-6C.1 and 31% with Ly-6A.2. The number and the distribution of cysteine residues were conserved, implying that the CD59 represented a human homologue of murine Ly-6. RNA blot hybridization analysis revealed the expression of CD59 mRNA in placental, lung, and pancreatic tissues. The mRNA was not only expressed in T-cell lines but in some of monocytic, myeloid, and B-cell lines. In all of these tissues and cell lines, at least four mRNA species were detected. DNA blot hybridization analysis revealed a rather simple genomic structure, which suggested a single gene as compared with the complex multigene family of murine Ly-6.

Amino Acid Sequence↗

Effects of diltiazem on the pharmacokinetics of nifedipine.

To evaluate the effect of diltiazem pretreatment (60 mg three times a day for 3 days) on pharmacokinetics and pharmacodynamic effect of nifedipine, six healthy subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. Diltiazem induced a marked increment of the area under the plasma concentration-time curve (AUC) for nifedipine by a mean of 140% and reduced the total body clearance (Cl) from 0.0043 +/- 0.0019 to 0.0017 +/- 0.0006 ml/min/kg (p less than 0.05, mean +/- SD). The biological half-life (t1/2) of nifedipine was prolonged from 2.46 +/- 0.65 to 3.21 +/- 0.92 h (p less than 0.05) without any changes in indocyanine green (ICG) clearance. Diltiazem did not produce significant changes of AUC, Cl, and t1/2 for the acid metabolite of nifedipine. Blood pressure (BP) after nifedipine administration with diltiazem pretreatment was more decreased than that without diltiazem. Both a decreased hepatic clearance and an increased bio-availability of nifedipine by diltiazem probably explain the significant changes in pharmacokinetics and hemodynamics of nifedipine. A clinically important drug interaction may occur with nifedipine when diltiazem is administered concurrently.

Adult↗

Expression of protein kinase C isozyme in epidermal Langerhans cells of the mouse.

Protein kinase C (PKC) is encoded by a complex of a gene family, and its multiple isozymes are expressed in various mammalian tissues. We examined whether PKC is expressed in epidermal Langerhans cells (LC) of the mouse by using monoclonal antibodies specific to PKC I, PKC II, and PKC III isozymes (respective products of PKC genes gamma, beta, and alpha). Immunohistochemical and immunoblotting studies revealed that LC of adult C57BL/6 mice express PKC II, while PKC I and PKC III were not detected. In keratinocytes, none of the isozymes were detected. These results suggest that PKC II is a novel marker of LC and that it possibly plays a regulatory role in epidermal LC of the mouse in vivo.

Animals↗

Isolation and culture of panning method-enriched Langerhans cells from dispase-dissociated epidermal cells of the mouse.

Langerhans cells (LCs) are bone marrow-derived, Ia-positive antigen-presenting cells in the epidermis which constitute 2-4% of the total epidermal cells. We examined the usefulness of a combination of dispase treatment and the panning method for enriching and culturing mouse LCs. Trunk skin was treated with partially purified dispase (Godo Shusei, type II) to separate epidermal sheets and to dissociate epidermal cells. Suspended cells were treated with ascites or culture supernatant containing anti-Ia monoclonal antibody, and LCs were enriched by the Ia-mediated panning method. Per mouse, 3-4 X 10(5) LCs were recovered with greater than 95% purity and greater than 90% viability. Enriched LCs potently stimulated the allogeneic mixed-leukocyte reaction. Ultrastructural observations revealed that enriched LCs contained many vesicles but almost no Birbeck granules. A laminal structure, which was apparently adhesive to the surface of LCs, was observed when ascites were employed as the anti-Ia antibody. These results indicate that a combination of dispase treatment and the Ia-mediated panning method is very useful for isolating high yields of functionally mature murine Langerhans cells with high purity and viability.

Animals↗

Daily variation in influence of lithium on serum calcium concentration: a preliminary report.

1. One millilitre of 5% glucose (vehicle, n = 10) or 1 mL solution of lithium chloride (LiCl) (0.5 or 2.0 mmol/kg per day, n = 10 for each) was injected intraperitoneally in Wistar rats at 10:00 or 22:00 h for 6 days. Blood samples for ionized and total calcium were taken on day 7. 2. Mild elevations in ionized, but not non-ionized (total-ionized) calcium were observed following LiCl treatment in both administration times. 3. The increment in ionized calcium was greater when LiCl was injected at 22:00 h than when it was given at 10:00 h. 4. These data indicate that: (1) the influence of lithium on calcium metabolism varies with its administration time; and (2) mild hypercalcaemia induced by the agent mainly depends on the elevation in the ionized fraction of calcium.

Animals↗

HLA expression on human ejaculated sperm.

The expression of human leukocyte antigen (HLA) on human ejaculated sperm has been investigated by using cellular binding radioimmunoassay (CB-RIA) with sperm samples purified by Percoll discontinuous gradient and monoclonal antibodies specific to the frame work of HLA molecules. The results in packed sperm obtained from ten healthy males indicated that HLA class II and its subclasses, DP, DQ, and DR, were expressed at a low level on human ejaculated sperm, while HLA class I was not detected. Furthermore, we could not detect the individual variation of HLA expression on ejaculated sperm in the cases of twenty healthy males. K562, which is B lymphoid cell line and lacks HLA class I molecules, showed detectable amounts of HLA class I molecules after exposure to interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha). However, the treatment of sperm with IFN-gamma and/or TNF-alpha had no effect on the expression of HLA class I and class II molecules.

Antibodies, Monoclonal↗

Gene expression of macrophage colony-stimulating factor and its receptor in human placenta and decidua.

Macrophage colony-stimulating factor (M-CSF) induces proliferation of monocyte/macrophage progenitor cells and can also activate some functions of mature cells including fetally derived placental cells. To study the role of M-CSF in the pregnant female reproductive tract, the expression of M-CSF mRNA and its receptor, c-fms proto-oncogene, in human placenta and decidua was identified. M-CSF and c-fms mRNAs, 4.7Kb and 3.9Kb respectively, were detected by Northern blotting in the early stage placenta and subsequently increased during pregnancy. These mRNAs were not detected in the nonpregnant endometrium but were strongly induced in maternal decidua with the same mRNA size as in the placenta. Northern blot hybridization on the endometrium of a pseudopregnant uterus revealed that the expression of endometrial M-CSF and c-fms mRNAs is regulated by synergistic action of female sex steroid hormones. These findings indicate that, in an autocrine and/or paracrine manner, M-CSF is deeply involved in the local proliferation and differentiation of cells at the materno-fetal interface, and support the placental immunotrophism hypothesis.

Blotting, Northern↗

Sphingolipids and glycerolipids. I. Chemical structures and ionophoretic activities of soya-cerebrosides I and II from soybean.

Two glycosphingolipids named soya-cerebrosides I and II were isolated from soybean, the seeds of Glycine max Merrill (Leguminosae), and their chemical structures have been elucidated on the basis of physicochemical evidence and several chemical degradation reactions. By using a newly constructed liquid membrane-type apparatus (W-08) for measurement of ion-transport and ion-binding activities and by employing a method using human erythrocyte membranes for measurement of ion-permeability, it has been found that soya-cerebroside II exhibits ionophoretic activity for Ca2+ ion.

Cerebrosides↗

Site-specific mutagenesis of human chorionic gonadotrophin (hCG)-beta subunit: influence of mutation on hCG production.

The heterodimeric glycoprotein hormones, human chorionic gonadotrophin (hCG), LH, TSH and FSH, consist of two non-covalently linked subunits, the alpha and beta subunits. The beta subunit is specific for each hormone and is responsible for the biological specificity, but the beta subunits of different hormones show some degree of structural homology. The CAGY (cysteine-alanine-glycine-tyrosine) region is one of the amino acid sequences that is homologous in different beta subunits and is highly conserved between species. In the present study, site-specific in-vitro mutagenesis was used to change three individual nucleotides in the centre of the CAGY region of the hCG-beta subunit, and the effects of these mutations on hCG production was determined by in-vitro transcription and then translation in Xenopus laevis oocytes. The results indicate that the CAGY region, particularly the glycine residue at position 36 in the beta subunit, is essential for the production of hCG. This finding is consistent with previous studies showing that this region is necessary for the biological activity of human TSH.

Amino Acid Sequence↗

Induction of Langerhans' cell mitosis in vivo after orchiectomy on mice.

We recently reported that male mice have fewer Langerhans' cells (LCs) than females and that orchiectomy resulted in an increased LC density. In this study we demonstrate that orchiectomy induces a transient increase in the number of paired LCs (PLCs) before the increase in LC density occurs. The results of double staining for adenosine triphosphatase (ATPase) and 5-bromo-2'-deoxyuridine (BrdU) showed that all examined PLCs had incorporated the intraperitoneally injected BrdU, while only 0.7% of the unpaired LCs were BrdU-positive; that supported the notion of PLCs as being divided daughter LCs. Orchiectomy appears to induce a transient increase in mitotic activity of LCs resulting in the increased LC density.

Animals↗

WBN/Kob rats. A new spontaneously occurring model of chronic pancreatitis.

Chronic pancreatitis-like lesions are observed in 100% of male Wistar Bonn/Kobori rats. At 3 mo of age, histopathologic examinations of the pancreas revealed a distinct infiltration of inflammatory cells with interstitial edema in the acini. At the same time, periductal and interstitial fibrosis and adenomatous hyperplasia of the ductular epithelium were observed. Extensive fibrotic exudation developed rapidly with age, and irregular destruction of the parenchyma was noted. The only abnormality, prior to the appearance of glycosuria, that could be detected clinically was lower levels, compared to Wistar rats, of BT-PABA excreted in the urine after oral ingestion. These lower levels indicate a decrease in enzyme secretion in WBN/Kob rats. Ultrastructural observations in histologically normal areas at 2 mo of age showed a swelling of mitochondria, indicating that ischemia was associated with the early pancreatic lesions. Serial pancreatographies were performed at 2-8 mo of age. Irregular widenings of the main pancreatic duct and dilations of the smaller ducts were observed already at 2 mo of age, suggesting a stasis of pancreatic juice in the early stages of the disease. It seems that male WBN/Kob rats are a useful model of human chronic pancreatitis, with an unknown mechanism regulated by the sex hormones.

Amylases↗

[Clinical effects of oxybutynin hydrochloride (Pollakis)--especially in the treatment of pollakisuria, urgency and urinary incontinence].

The effects and the safety of oxybutynin hydrochloride were investigated in 52 patients, 17 male and 35 female, with the chief complaints of pollakisuria, urgency and urinary incontinence. Clinical responses to the drug were assessed mainly by the subjective symptoms of the patients. The diagnoses of these patients were neurogenic bladder in 17, unstable bladder in 16 and others in 19 patients. The average administration period was 66.8 days. The rate of global improvement (excellent and good) was 55% in the 2 mg dose given 3 times daily group, 68.2% in the 3 mg dose given 3 times daily group. Side effects, such as dry mouth, were observed in 2 of the 52 patients (3.8%), but no serious side effects were observed. The rate of global utility (remarkable and moderate) was 67.3%. These data indicate that oxybutynin hydrochloride seems to be useful and safe for the treatment of pollakisuria, urgency and urinary incontinence.

Administration, Oral↗

[Effects of intra-arterial infusion of degradable starch microspheres on liver tissue blood flow].

The effects of intra-arterial infusion of degradable starch microspheres (DSM) on liver tissue blood flow were estimated in rat with liver carcinoma induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) administration. Tissue blood flow of tumor and normal liver was measured simultaneously by Laser blood flowmeter. Tissue blood flow of tumor and normal liver was 13.3 +/- 6.9, 13.2 +/- 4.3 (ml/min/100 g), respectively. After intra-arterial infusion of DSM, tissue blood flow of both tumor and normal liver decreased to the same degree as that at hepatic artery occlusion and then gradually recovered. This gradual recovery of tissue blood flow was supposed to express the process of resolution of DSM by alpha-amylase. The recovery time of tissue blood flow following intra-arterial infusion of DSM was 27.3 +/- 4.0 min (DSM 20 mg/kg) and 70.0 +/- 23.6 min (DSM 30 mg/kg) in tumor and 20.0 +/- 3.3 min and 36.5 +/- 18.0 min, respectively, in normal liver. Thus, the blocking effect of blood flow by DSM was different between tumor and normal liver and proved to be more persistent in the former.

Animals↗