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Y Ogino

Publications and source records attributed to Y Ogino.

At least 55 records · Page 3Linked to original sources
PubMed1998

Aberrant regulation of bone trace elements in motheaten and osteopetrosis mutant mice.

Increasing numbers of genetic diseases involving bone development and models for these diseases have been identified recently. Analysis of these bone diseases have revealed that regulated action of multiple growth factors and subsequent signal transduction are essential for normal bone formation. In this paper, two murine mutant mice viable motheaten and osteopetrosis are analyzed. Mice with the recessive 'viable motheaten' mutation express a severe immunodeficiency syndrome and bone defects. Mutations at the motheaten locus were shown to be the result of aberrant splicing of the gene encoding hematopoietic cell phosphatase (Hcph). Mice homozygous for the osteopetrosis mutation develop congenital osteopetrosis due to a severe deficiency of osteoclasts. It has been recognized that bone trace element composition analysis helps to define bone-related physiological conditions. We have analyzed bone trace element composition in viable motheaten and osteopetrosis mutant animal models in this study. In order to gain insights into the effects of particular genetic defects on bone trace element composition, inductively coupled plasma atomic emissions spectrometry (ICP-AES) analysis was performed. Marked changes in bone trace element levels were found in limb bones of viable motheaten and osteopetrosis mutant mice. An assessment of these trace element spectrum in the two mutant models with respect to each genetic defects are discussed in this paper.

Animals↗
PubMed1997

[CRH-test].

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ACTH Syndrome, Ectopic↗
PubMed1997

[ACTH test].

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Addison Disease↗
PubMed1997

[Metyrapone test].

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ACTH Syndrome, Ectopic↗
PubMed1996

Direct evidence for two distinct G proteins coupling with thrombin receptors in human neuroblastoma SH-EP cells.

Thrombin receptor-G protein coupling was investigated in the human epithelial neuroblastoma cell line, SH-EP. In these cells, both alpha-thrombin and thrombin receptor peptides, SFLLRNP (one-letter amino-acid code), which are newly exposed following cleavage by alpha-thrombin, stimulated GTPase activity about 2-fold over basal activity. Pertussis toxin treatment only partially attenuated alpha-thrombin- and SFLLRNP-stimulated GTPase activity by 50%, whereas antibody raised against synthetic heptapeptide SFLLRNP blocked alpha-thrombin-stimulated phosphoinositide hydrolysis more than 80%. Immunoprecipitation studies using this antibody showed that both Gi2, a subtype of guanine nucleotide-binding regulatory proteins (G proteins) mediating inhibition of adenylyl cyclase, and Gq/G11, a G protein mediating stimulation of phospholipase C, were activated by alpha-thrombin. These data suggest that in these cells the thrombin receptor activates pertussis toxin-sensitive and pertussis toxin-insensitive G proteins simultaneously and directly couples to Gi2 and Gq/G11, which mediate different signaling pathways.

Antibodies↗
PubMed1996

[Endocrine disorders associated with impaired glucose tolerance].

Endocrine disorders associated with diabetes mellitus are described. When blood glucose control deteriorates, observed endocrine abnormalities are as follows. 1) Blood GH levels increase. This elevation is small but enough to disturb insulin secretion and glucose metabolism. Plama insulin-like growth factor-1 levels decrease in spite of their strong relation with diabetic retinopathy. 2) Blood thyroid hormones show the similarity with low T3 syndrome. 3) Hyporeninemic hypoaldosteronism occurs especially with patients who have hypertension or moderate diabetic complications. 4) Plasma pancreatic glucagon levels are elevated. Amino acids induce hypersecretion but hypoglycemia fails to response normally. Glucose administration shows impaired inhibition or paradoxical hypersecretion. 5) Other plasma levels of pancreatic hormones such as gastrin, secretin, motilin and somatostatin are usually elevated.

Diabetes Complications↗
PubMed1995

Effects of endothelin-1 on Ca2+ signaling and secretion in parathyroid cells.

It has been previously reported that parathyroid cells express endothelin (ET) receptors and secrete ET-1 in an extracellular Ca2+ concentration ([Ca2+]e)-dependent manner. Here, we examined the effects of ET-1 on intracellular signaling and parathyroid hormone (PTH) secretion in dispersed bovine parathyroid (bPT) cells, which comprise several cell types including epithelial and endothelial cells, in two cell lines, the rat parathyroid epithelial (PT-r) and the bovine parathyroid endothelial (BPE-1) cells. An RNA-polymerase chain reaction analysis revealed that both ETA and ETB receptors are expressed in bovine parathyroid tissue and BPE-1 cells, and only the ETA receptor is expressed in PT-r cells. PT-r cells also expressed an inositol 1,4,5-trisphosphate (Ins[1,4,5]P3) receptor, and ionomycin induced an increase in the intracellular Ca2+ concentrations ([Ca2+]i) in a Ca(2+)-deficient medium, indicating the presence of an operative intracellular Ca2+ pool in these cells. In cells bathed in 1 mM [Ca2+]e, ET-1 induced a rapid and transient increase in the Ins(1,4,5)P3 production, which was associated with a similar profile of increase in [Ca2+]i and with a peak response of about 800 nM. No changes in the profile of [Ca2+]i responses were observed in ET-1-stimulated cells in the presence of Ca2+ channel blockers, or in Ca(2+)-deficient medium, indicating that Ca2+ mobilization was not associated with Ca2+ entry. Furthermore, a sustained stimulation with ET-1 induced a decrease in [Ca2+]i below the prestimulatory level in a large population of cells, and the percentage of the cell population that shows the sustained decrease of [Ca2+]i increased in higher ET-1 concentrations. [Ca2+]i in PT-r cells was also controlled by a [Ca2+]e-dependent mechanism that changed [Ca2+]i from 28 to 506 nM in a 0.1-3 mM concentration range with an EC50 of 1.2 mM, which is comparable to that reported for bPT cells. In the same range of [Ca2+]e, PTH secretion from bPT cells was inhibited with an IC50 of 1 mM, and ET-1 increased PTH release in a dose-dependent manner but without affecting the IC50 for the [Ca2+]e-dependent inhibition. Thus, the parathyroid epithelial cells appear to respond to ET-1 in a unique way, and the ET autocrine system can be regarded as a possible mechanism to modulate the sensitivity of [Ca2+]e-dependent PTH release.

Animals↗
PubMed1995

Orotate phosphoribosyltransferase from Thermus thermophilus: overexpression in Escherichia coli, purification and characterization.

Orotate phosphoribosyltransferase (OPRTase, EC2.4.2.10) plays a role in de novo synthesis of pyrimidine nucleotide and transfers orotate to 5-phosphoribosyl-1-pyrophosphate (PRPP) to form orotidine-5'-monophosphate (OMP). To obtain heat-stable OPRTase and to elucidate the mechanism of heat stability, this enzyme from Thermus thermophilus was expressed in Escherichia coli and purified. The pyrE gene of T. thermophilus which encodes OPRTase, contains an open reading frame of 549 base pairs with 69% G+C content. Since this gene expressed itself inefficiently in E. coli, the 5' and 3' ends of the coding regions were replaced with synonymous codons which contain more A+T and corresponds to major codons for E. coli. Introduction of the modified gene fragments into a plasmid having a tac promoter resulted in production of a polypeptide of molecular weight (M(r)) 20,000 in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG) in E. coli. This protein represented as much as 16% of the bacterial total protein and showed the OPRTase activity. Three purification steps, consisting of heat treatment at 65 degrees C, 40% ammonium sulfate fractionation, and KCl gradient elution from DEAE-Sephadex A-50, resulted in highly purified single polypeptide. The optimum activity of the purified OPRTase was observed at 150 mM KCl, pH 9.0, 75-80 degrees C, and in the presence of 100 microM PRPP. The activation energy of this enzyme reaction was 20.3 kJ/mol. The Km of this enzyme for orotate as a substrate was 75 microM and the maximum specific activity was 300 units/mg protein under the optimum conditions. The purified OPRTase was stable for 20 min at 85 degrees C.

Amino Acid Sequence↗
PubMed1995

Human thrombin receptors are insensitive to thrombin-like snake venom enzymes.

Thrombin-like snake venoms enzymes, flavoxobin, and okinaxobin I isolated from Trimeresurus flavoviridis and Trimeresurus okinavensis, respectively, were examined in SH-EP cells and evaluated whether or not they can activate human thrombin receptors. Flavoxobin was almost completely inactive in both assays for phosphoinositide turnover and DNA synthesis. In contrast, okinaxobin I stimulated phosphoinositide turnover in a dose dependent manner, but considerably weakly. The EC50 value was about 100 nM, which was 4,000 times larger than that of alpha-thrombin. This stimulation was not inhibited by hirudin, an effective inhibitor of alpha-thrombin. Okinaxobin I also induced a very weak stimulation of DNA synthesis. These results suggest that thrombin-like snake venom enzymes interact with human thrombin receptors in inefficient ways. Weak interactions of the enzymes with thrombin receptor and inhibitor were ascribed to the incomplete formation of a lysine-cation cluster necessary for electrostatic molecular recognition.

Amino Acid Sequence↗
PubMed1995

[Phase 3 multicenter clinical study of 111In-DTPA-D-octreotide (MP-1727) in patients with gastrointestinal hormone producing tumors].

A phase 3 multicenter clinical study was performed to investigate the efficacy, safety and usefulness of MP-1727, a novel tumor imaging agent which binds to somatostatin receptors, in 23 patients with gastrointestinal hormone producing tumor. The efficacy was graded effective or very effective in 16 cases (76.2%) out of 21 cases who could be evaluated. Positive predictive accuracy was 77.8% (7/9) for carcinoids, 100% (5/5) for gastrinomas and 40.0% (2/5) for insulinomas. In three cases, tumor lesions which had been unknown were detected by MP-1727 scintigraphy. The consistent ratio between scintigraphically positive sites and preinjection localizations was 82.0% (41/50 sites) in total. Although adverse drug reactions were observed in two cases, the safety was graded 'not problematic at all' in all of 23 cases. These results show that MP-1727 is a very useful radiopharmaceutical for detection and localization of gastrointestinal hormone producing tumors.

Adult↗
PubMed1994

Differential roles of two consecutive phenylalanine residues in thrombin receptor-tethered ligand peptides (SFFLRNP) in thrombin receptor activation.

A synthetic heptapeptide H-Ser-Phe-Phe-Leu-Arg-Asn-Pro-NH2, which corresponds to the ligand peptide latent in rodent thrombin receptors, was able to activate the thrombin receptor with no thrombin. In order to evaluate the structural requisites of two consecutive phenylalanines, three sets of analogs with substitutions at position either 2 or 3 were synthesized and examined for their stimulatory activity in phosphoinositide turnover in SH-EP epithelial-like cells. The replacement of Phe-2 by Ala completely eliminated the activity, while that of Phe-3 retained about 50% activity with a full stimulation. The Phe/Leu substitution resulted in a large increase (37-fold) in EC50 value for Phe-2, but in insignificant change for Phe-3. Substitution of para-fluorophenylalanine ((p-F)Phe) for Phe-2 enhanced strongly (4-fold) the activity, in contrast to a reduction by the Phe-3/(p-F)Phe substitution. Elimination of either Phe-2 or Phe-3 resulted in a complete loss of activity. These results indicated that Phe-2 and Phe-3 play different roles in the receptor activation. A highly specific aromatic phi-phi interaction was suggested between Phe-2-phenyl and thrombin receptor binding site, while Phe-3 appeared to be important for retaining a bioactive conformation.

Amino Acid Sequence↗
PubMed1994

Effects of chronic, urea-induced osmotic diuresis on kidney weight and function in rats.

To study the effects of chronic osmotic diuresis which were not associated with hyperglycaemia on the rat kidney, osmotic diuresis was induced by i.v. infusion of urea. A 5 mol/l urea solution was continuously infused at a rate of 100 ml.kg-1 x day-1 on the basis of body weight on day 0. Duration of infusion was 2, 6, 10 or 14 days. Control rats received continuously infused Ringer's solution. Urea-treated groups developed osmotic diuresis (urine flow = about 0.04 ml.min-1 x 100 g body weight-1) comparable to that in rats with experimental diabetes mellitus induced by i.v. streptozotocin (55 mg/kg), however urea-induced osmotic diuresis was not associated with blood glucose level increases. Compared with their controls, rats receiving urea for 2-14 days had markedly increased kidney weight. Rats receiving urea for 10 days showed greatest kidney weight increase, 0.565 +/- 0.044 g/100 g body weight (mean +/- SD), representing a 53% increase compared with the control (0.369 +/- 0.034 g/100 g body weight). Kidney weight was associated with increases in kidney protein content. In contrast, none of control kidney weight values differed significantly from day 0 values (= normal rats; 0.387 +/- 0.028 g/100 g body weight). Creatinine clearance values in urea-treated groups were also higher than those in controls. The maximum value, 0.65 +/- 0.17.ml-min-1 x 100 g body weight-1, was recorded in the 14-day group and was significantly higher than the corresponding control value (0.34 +/- 0.07 ml.min-1 x 100 g body weight-1) (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗