Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 901 records · Page 50Linked to original sources

PubMed1994

Urinary pyridinoline and deoxypyridinoline in prostate carcinoma patients with bone metastasis.

Bone metastases from prostate carcinoma are predominantly osteoblastic. Recently, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) have been employed as indicators of bone resorption. In this study, we evaluated urinary Pyr and Dpyr levels in 19 prostate carcinoma patients, of whom 12 had bone metastasis and seven had not, and 11 age-matched control subjects. There was a significant difference in Pyr levels between the control group and the patients with metastasis (mean +/- s.d., 19.5 +/- 7.2 vs 73.3 +/- 67.1 nmol mmol-1 creatinine, P < 0.05). The mean level of Dpyr in the patients with metastasis (10.8 +/- 8.0 nmol mmol-1 creatinine) was significantly higher than that in the control group (3.1 +/- 2.1 nmol mmol-1 creatinine, P < 0.01), and also higher than that in the patients without metastasis (3.5 +/- 1.9 nmol mmol-1 creatinine, P < 0.05). There was no significant difference in Pyr and Dpyr levels between the control group and the patients without metastasis. These results suggest that bone resorption is also accelerated in prostate carcinoma patients with bone metastasis.

Aged↗

PubMed1994

Effect of mitral valve surgery on severely impaired pulmonary function.

To evaluate the effect of surgery on severely impaired pulmonary function associated with mitral valve disease, we examined the relationship between postoperative improvements in pulmonary function and pulmonary circulation in 238 patients who underwent mitral valve surgery. Of these patients 17 met the preoperative criteria for severely impaired pulmonary function: forced expiratory volume in 1 second = FEV1 < or = 1000 ml. They showed average values for vital capacity (VC) of 1343 +/- 203 ml, for % of vital capacity for predicted values (%VC) of 52.0 +/- 6.5%, and for FEV1 of 851 +/- 104 ml. Moderate elevations of mean pulmonary arterial pressure (PAP: 36.2 +/- 10.2 mmHg), mean pulmonary arterial wedge pressure (PAWP: 23.0 +/- 9.6 mmHg), and pulmonary vascular resistance (PVR: 329 +/- 147 dyne.sec.cm-5) were also observed. Postoperatively, 4 of the 17 patients required long-term respiratory support for more than one week, and 3 patients died in hospital; this mortality rate, however, was not significantly different to that of patients with preoperative FEV1 > 1000 ml. In long-surviving patients, pulmonary function improved in the late postoperative period. Significant relationships were recognized between delta FEV1 (delta: postoperative value--preoperative value) and delta PAP, delta PAWP, and delta PVR. The delta VC and delta %VC also correlated significantly with delta PAP, delta PAWP and delta PVR. In conclusion, in patients with mitral valve disease impaired pulmonary function cannot be used to exclude patients from operation. Furthermore, severely impaired pulmonary function should improve with the improvement of pulmonary circulation after surgery.

Adult↗

PubMed1994

The effects of two different kinds of quilt on human core temperature during night sleep.

Effects of two kinds of quilt with different thermal insulation properties between the upper and lower halves on human core temperature during night sleep were compared at an ambient temperature of 16 degrees C and a relative humidity of 50% in five healthy adult women. One quilt has a thick part (110 mm) in the upper half and a thin part (63 mm) in the lowest half (Quilt A), and the other has a thin part (63 mm) in the upper half and a thick part (110 mm) in the lower half (Quilt B). Subjects, wearing shirts with half-sleeves and breeches, slept on a bed with sleeping mat, being fully covered by either Quilt A or Quilt B from 22:00 to 06:00. The major finding was that rectal temperature fell more quickly in Quilt B after retiring at 22:00, being kept at a lower level during one third of the whole night. We suggest that the reduced level of rectal temperature in Quilt B might be ascribed to lower thermal insulation in the upper half side of the Quilt B and partly to different core-peripheral blood redistribution in the lower extremities between the two kinds of quilt. Rapid fall and lowered level rectal temperature in Quilt B might be of significance for ease in sleep onset and sleep depth.

Adult↗

PubMed1994

Efficiency of oxetanocin-G, a novel nucleoside against the woodchuck hepatitis virus.

Oxetanocin-G (OXT-G), a potent antiviral agent, is a novel nucleoside isolated from the culture filtrate of Bacillus megaterium. We investigated the antiviral effect of oral administration of OXT-G for five days on woodchuck hepatitis virus (WHV), in vivo, using 12 woodchucks. Woodchucks were randomized into each of four treatment groups according to the dose of OXT-G. Two out of six woodchucks treated with 1.0 or 2.0 mg/kg/day of OXT-G died. After treatment with OXT-G, serum levels of WHV-DNA significantly decreased in all woodchucks. However, the antiviral effect was only partial and levels of serum WHV-DNA returned after the cessation of treatment. The amount of viral replicative intermediates was decreased in livers of woodchucks treated with OXT-G. Although further study of the toxicity of this compound would be essential before studies in man can be carried out, OXT-G has potent antiviral activity against WHV and may deserve evaluation as an antiviral agent in the treatment of chronic hepatitis B infections in humans.

Animals↗

PubMed1994

Relationship between ultrasonography and histopathological changes in polycystic ovarian syndrome.

We investigated retrospectively the relationship between the ultrasonographic appearance of the ovaries and histopathological findings in patients with polycystic ovarian syndrome (PCOS) and compared these histopathological findings with endocrine concentrations. A total of 20 patients with PCOS were studied. Each patient had a history of infertility, menstrual disturbance and > 10 small cysts in each ovary that were detected by transvaginal ultrasound. Ovarian ultrasound appearance was classified as a general cystic pattern (GCP) or peripheral cystic pattern (PCP). Histological examination of specimens from patients undergoing ovarian wedge resection by laparotomy were compared with ultrasonographic images. In 15 of the 16 ovaries with GCP, the histopathological findings were consistent with the ultrasonographic images. In all 24 ovaries with PCP, the histopathological and ultrasonographic images were consistent. The mean ovarian capsular thickness was significantly higher in the GCP than the PCP. Androstenedione was significantly higher in the GCP than the PCP, whereas the ratio of luteinizing hormone to follicle-stimulating hormone was significantly higher in the PCP than the GCP. Therefore, our results suggested that GCP and PCP correspond to histopathological differences. Histological GCP and PCP appear to differ endocrinologically.

Adult↗

PubMed1994

Vasoactive intestinal peptide induces differentiation and MAP kinase activation in PC12h cells.

Vasoactive intestinal peptide (VIP), a neuropeptide coupled with adenylate cyclase, was found to induce neurite extension of PC12h cells. Neurites appeared within 1 h after addition of VIP and extended for at least 24 h. The half-maximal concentration for the effect of VIP was 50 nM. In addition to the morphological change, VIP induced expression of VGF protein, a neuron-specific protein associated with neuronal differentiation. Western blotting with anti-phosphotyrosine antibody showed that VIP stimulated tyrosine phosphorylation of two proteins of 42 and 44 kDa, which may be two isoforms of MAP kinase, erk1 and erk2. Activation of MAP kinases was confirmed by ion-exchange chromatography on a Mono Q column, from which VIP-induced kinase activity was co-eluted with MAP kinase-immunoreactivity. Tyrosine-phosphorylation of MAP kinases was also stimulated by forskolin or dibutyryl cAMP, indicating that activation of MAP kinases by VIP might be mediated by cAMP. These results suggest that VIP-induced differentiation of PC12 cells is associated with cAMP-dependent activation of MAP kinases.

Animals↗

PubMed1994

Vasoactive intestinal peptide induces tyrosine phosphorylation in PC12h cells.

Vasoactive intestinal peptide (VIP) is a neuropeptide that induces neuronal differentiation through a cAMP-dependent mechanism. We have previously shown that VIP induces tyrosine phosphorylation and activation of MAP kinases in PC12h cells [J. Biochem. 115, 304-308 (1994)]. In the present study, we showed by Western blotting with anti-phosphotyrosine antibodies that in PC12h cells VIP induced tyrosine phosphorylation of proteins of 140, 120, 110, and 70 kDa in addition to MAP kinases. The immunoprecipitates with anti-phosphotyrosine antibody from VIP-treated cells contained high activity of protein kinase phosphorylating poly(glu-tyr) and enolase; the activity from VIP-stimulated cells was 1.5-2 times higher than that from unstimulated cells. In vitro kinase reaction without extrinsic substrates resulted in tyrosine phosphorylation of doublet proteins which migrated slower than pp125FAK on SDS-PAGE. An increase in kinase activity of the immunecomplex was detected when the cells were stimulated with forskolin. These results suggest that protein tyrosine phosphorylation is involved in differentiation of neuronal cells stimulated by VIP and that it is regulated by a cAMP-dependent mechanism.

Animals↗

PubMed1994

Depolarization-induced tyrosine phosphorylation in PC12h cells.

Depolarization induced by KCl was found to induce tyrosine phosphorylation of cellular proteins in PC12h cells. By Western blotting with anti-phosphotyrosine antibody, we detected tyrosine phosphorylation of proteins with molecular weights of 120, 110, 105, 95, 75, 70, 66, 44, and 42 kDa in response to KCl. The immunoprecipitates from KCl-treated cells with the antibody contained large amounts of tyrosine-phosphorylated proteins and increased activity of tyrosine kinase. Incubation of the immunoprecipitates with [gamma-32P]ATP resulted in tyrosine phosphorylation of two proteins with the molecular weights of 120 and 140 kDa. These effects were completely abolished by the addition of EGTA before KCl treatment, suggesting that the depolarization-induced tyrosine phosphorylation may require calcium entry into the cells from the medium. Increased activity of tyrosine kinase phosphorylating the 120 and 140 kDa proteins was also recovered from cells stimulated with nerve growth factor, basic fibroblast growth factor, epidermal growth factor, and vasoactive intestinal peptide. Among them, depolarization by KCl elicited the strongest effect. These results indicate that a protein tyrosine kinase that phosphorylate the 120 and 140 kDa proteins is phosphorylated or activated in response to calcium ion, cAMP, and growth factors acting through tyrosine kinase receptors.

Animals↗

PubMed1994

Regulation of Src family kinases in the developing rat brain: correlation with their regulator kinase, Csk.

We have so far suggested that the functions of Src family protein-tyrosine kinases are under the control of their regulator kinase, Csk. To evaluate the role of Csk-mediated regulation in neural tissues, we examined the correlation between the activities of Src family kinases and the expression level of Csk during development of the rat brain. Csk was expressed at high levels in the developing embryonic brain and then rapidly decreased as the brain matured. Consistent with the decrease in the Csk level, the kinase activity of a member of the Src family, Fyn, was greatly enhanced, but that of Src was not correlated inversely with the level of Csk expression. Src exhibited elevated activity in the developing brain, in which a neuronal form of Src (N-Src) is expressed as the dominant form of Src. Although N-Src was readily down-regulated by Csk when coexpressed in yeast, it showed much higher specific activity than c-Src, even in the repressed form. These findings suggest that neural tissues acquire high activities of Src family kinases, which might be important for differentiation and development of the nervous system, through induction of the active form of Src (N-Src) and down-regulation of their suppresser, Csk.

Amino Acid Sequence↗

PubMed1994

Repression of retinoic acid-induced transactivation by embryonal LTR binding protein.

The mechanism of repression of transcription by ELP, the embryonal long terminal repeat binding protein, was investigated. ELP represses the Moloney murine leukemia virus long terminal repeat by binding to a site which overlaps with a sequence element for retinoic acid receptor binding. This suggests possible competition of ELP with retinoic acid receptor for the same sequence elements. Oligonucleotides corresponding to ELP and/or retinoic acid receptor binding elements were placed upstream of the SV40 promoter and their effect on gene expression was analyzed by CAT assay. Elements which have affinity to both ELP and retinoic acid receptor were activated by retinoic acid receptor and these activations were repressed by ELP. An ELP binding element without affinity to retinoic acid receptor was insensitive to both activation by retinoic acid receptor and repression by ELP. Furthermore, cellular ELP binding elements and the Moloney leukemia virus long terminal repeat were activated by retinoic acid. These data suggest that one of the mechanism of transcriptional repression by ELP is competition for binding sites with transactivators such as retinoic acid receptors.

3T3 Cells↗

PubMed1994

End-tidal sevoflurane concentration for tracheal intubation and minimum alveolar concentration in pediatric patients.

BACKGROUND: Sevoflurane is a new inhalational anesthetic agent having low solubility in blood and a relatively nonpungent odor. As such it should be useful as an inhalation induction in pediatric patients. The objectives of the study were to determine both the minimum alveolar concentration (MAC) and the concentration required for tracheal intubation (MACEI) of sevoflurane in pediatric patients. METHODS: The study group consisted of 36 ASA physical status 1 elective surgical patients, aged 1-9 yr. MACEI determination: After establishing and maintaining the end-tidal concentration for 15 min, tracheal intubation was attempted with an uncuffed tracheal tube without neuromuscular relaxants or other adjuvants. Each concentration at which tracheal intubation was attempted was predetermined according to the up-and-down method (with 0.5% as a step size). MAC determination: The patients examined were the same as those for MACEI determination except that for the exclusion of those to whom neuromuscular relaxants or other adjuvants drugs were administered. End-tidal sevoflurane concentration was determined according to the up-and-down method (with 0.5% as a step size) and held constant for at least 15 min before a skin incision. RESULT: MACEI of sevoflurane was 2.69% (95% fiducial limits: 2.23% and 3.37%); MAC of sevoflurane was 2.03% (95% fiducial limits: 1.51% and 2.53%); and the MACEI/MAC ratio was 1.33. CONCLUSION: Sevoflurane appears to be suitable for use in pediatric patients as an induction agent, permitting tracheal intubation without neuromuscular relaxants.

Anesthetics↗

PubMed1994

Mitotic activation of c-Src is suppressed by Csk.

The kinase activity of the proto-oncogene product, c-Src, increases during mitosis through partial dephosphorylation of Tyr527, the negative regulatory site of c-Src. To examine whether or not Csk, a candidate kinase specific for Tyr527, is involved in this regulation, we developed a Balb/c 3T3 cell line overexpressing Csk and a Csk-deficient cell line. The overexpression of wild-type Csk caused significant suppression of the c-Src activity during mitosis. A membrane-targeted Csk, which has an amino-terminal myristylation signal of c-Src, exhibited an effective suppression of the c-Src activity, even though its expression level was lower than that of endogenous Csk. Concomitant with the suppression of the c-Src activation, the level of tyrosine phosphorylation of a cortactin-related protein, a potential substrate of c-Src in vivo, was reduced. In contrast, the Csk-deficient cells exhibited constitutive activation of c-Src, which showed no significant change in its activity during mitosis. These results suggest that Csk indeed participates in the regulation of the c-Src activity during mitosis.

3T3 Cells↗

PubMed1994

Cloning, sequencing, and expression in Escherichia coli of the Bacillus subtilis gene for phosphatidylserine synthase.

The Bacillus subtilis pss gene encoding phosphatidylserine synthase was cloned by its complementation of the temperature sensitivity of an Escherichia coli pssA1 mutant. Nucleotide sequencing of the clone indicated that the pss gene encodes a polypeptide of 177 amino acid residues (deduced molecular weight of 19,613). This value agreed with the molecular weight of approximately 18,000 observed for the maxicell product. The B. subtilis phosphatidylserine synthase showed 35% amino acid sequence homology to the yeast Saccharomyces cerevisiae phosphatidylserine synthase and had a region with a high degree of local homology to the conserved segments in some phospholipid synthases and amino alcohol phosphotransferases of E. coli and S. cerevisiae, whereas no homology was found with that of the E. coli counterpart. A hydropathy analysis revealed that the B. subtilis synthase is very hydrophobic, in contrast to the hydrophilic E. coli counterpart, consisting of several strongly hydrophobic segments that would span the membrane. A manganese-dependent phosphatidylserine synthase activity, a characteristic of the B. subtilis enzyme, was found exclusively in the membrane fraction of E. coli (pssA1) cells harboring a B. subtilis pss plasmid. Overproduction of the B. subtilis synthase in E. coli cells by a lac promoter system resulted in an unusual increase of phosphatidylethanolamine (up to 93% of the total phospholipids), in contrast to gratuitous overproduction of the E. coli counterpart. This finding suggested that the unusual cytoplasmic localization of the E. coli phosphatidylserine synthase plays a role in the regulation of the phospholipid polar headgroup composition in this organism.

Amino Acid Sequence↗

PubMed1994

Gastrointestinal amyloidosis: radiologic features by chemical types.

PURPOSE: To determine the correlation between the radiographic and histologic findings of amyloidosis according to chemical type of amyloid protein. MATERIALS AND METHODS: The 49 patients with amyloidosis were examined radiographically, and gastrointestinal tract biopsy specimens were studied histologically. RESULTS: Considerable differences were found between amyloid proteins. On immunohistochemical studies, amyloid A produced a coarse mucosal pattern with innumerable fine granular elevations, which reflected expansion of the lamina propria by amyloid deposits. Polypoid protrusions and invariable thickening of the folds were evident only in light chain protein, correlating with massive amyloid deposits in the muscularis mucosae and submucosa. beta 2-Microglobulin produced marked delay in transit time and dilatation of the small and large intestines, relating to extensive amyloid deposits in the muscularis propria. The prevalence of these radiographic changes was highest in the small intestine for every chemical type. CONCLUSION: Characteristic radiographic changes of each chemical type of amyloid protein can be detected well in the small intestine.

Adult↗

PubMed1994

Insulin acts centrally to enhance reflex tachycardia in conscious rats.

Systemic and central insulin treatment for 10 days were compared in conscious rats given insulin either by daily subcutaneous injection or by continuous intracerebroventricular infusion. To measure changes in baroreflex sensitivity, heart rate responses elicited reflexly by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside were recorded before and after insulin treatment. Although reflex bradycardia and basal mean pressures and heart rates were unaffected, reflex tachycardia was consistently more pronounced in rats treated with insulin (whether given systemically or centrally) than in vehicle-treated controls. Plasma glucose was reduced and plasma insulin was elevated but only in insulin-treated rats injected subcutaneously and not in those infused intracerebroventricularly. Inasmuch as reflex tachycardia was still enhanced when insulin was infused intracerebroventricularly despite the absence of hypoglycemia and hyperinsulinemia, our results are compatible with the interpretation that insulin acts directly on the brain to enhance reflex tachycardia. This interpretation furthermore implies that insulin, even after chronic systemic treatment, could reach the brain and alter baroreflex regulation.

Animals↗

PubMed1994

Selective enhancement in SHR of hypotension and bradycardia caused by NTS-injected serotonin.

To examine whether serotonergic mechanisms in the nucleus tractus solitarius (NTS) become altered by hypertension, responses to serotonin (5-HT) or L-glutamate injected into the NTS were compared in anesthetized rats. Because isotonic saline had appreciable effects whereas artificial cerebrospinal fluid did not, artificial cerebrospinal fluid was routinely used as the vehicle. Microinjections of 5-HT or L-glutamate always reduced mean pressure, heart rate, and renal nerve activity. Depressor and bradycardic responses to 5-HT were consistently more pronounced in spontaneously hypertensive rats than in either regular Wistar or Wistar-Kyoto rats, but similar responses elicited with L-glutamate did not differ between rat groups. By contrast, attendant inhibition of renal nerve activity was the same in all rats, thereby suggesting that it either is not a good indicator of sympathetic activity or does not contribute to the hypotensive effects of 5-HT. Our results are compatible with the interpretation that hypotensive responses to 5-HT were enhanced because serotonergic mechanisms for cardiovascular regulation in the NTS were sensitized in spontaneously hypertensive rats.

Animals↗

PubMed1994

Stimulation of prolactin secretion by melatonin is not mediated by opioids.

To clarify the role the opioid system plays in mediating the stimulation of prolactin release by melatonin, we performed two separate studies between the 6th and 8th days of the follicular phase in normal young women. In the first study, serum prolactin concentrations were determined every 20 min over a 4-hour period following oral administration of melatonin (1 mg given at 13.00 h) in the presence of continuous intravenous infusion of saline or naloxone (1.6 mg/h), an opiate antagonist. In the second study, plasma beta-endorphin concentrations were measured over a 3-hour period following oral melatonin administration (1 mg given at 13.00 h). Oral melatonin administration alone induced a significant increase in serum prolactin concentration, which was maximal 3 h after melatonin administration. Prolactin release following melatonin administration was not affected by continuous intravenous infusion of naloxone. No significant change in plasma beta-endorphin concentrations was observed following melatonin administration. These findings strongly suggest that the stimulation of prolactin release by melatonin is not mediated by opioids.

Adult↗

PubMed1994

Histochemical and cytological characterizations of mucosal and connective tissue mast cells of Mongolian gerbils (Meriones unguiculatus).

Mast cells in jejunum, skin, and tongue of Mongolian gerbils (Meriones unguiculatus) were examined in terms of their histochemical, enzyme-histochemical, and ultrastructural properties. When glycosaminoglycans of mast cells in jejunum and tongue were characterized by measuring the critical electrolyte concentration, the salt concentration at which 50% of mast cells could be stained was > 1.0 M for those in the jejunum and also in the tongue, indicating that mast cells in both sites contained heparin. Enzyme-histochemical study revealed that mast cells in the jejunum of Mongolian gerbils were strongly positive for chymase and tryptase, whereas those in tongue and skin were essentially negative for both proteases. By electron microscopy, granular morphology and distribution of surface microfolds of mast cells in the jejunum were different from those in the ear skin. After in vivo stimulation with compound 48/80, however, mast cells in both sites showed remarkable degranulation. From these results, although Mongolian gerbils also have distinct mast cell subsets, their phenotypic properties are different from those of the previously known mast cell subsets of other animals.

Animals↗