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T Oka

Publications and source records attributed to T Oka.

At least 1,063 records · Page 59Linked to original sources
PubMed1987

Biochemical mechanisms underlying cyclosporine-induced nephrotoxicity. Effect of concomitant administration of prednisolone.

Biochemical mechanisms underlying cyclosporine (CsA)-induced nephrotoxicity and the effect of concomitant administration of prednisolone (Pr) on the nephrotoxicity were studied. Male Wistar rats were treated with the vehicles used for CsA and Pr administration (group 1), Pr alone (group 2), CsA alone (group 3), or CsA plus Pr (group 4), respectively. The dose of CsA was 5 mg/kg/day, i.p. for the initial 7 days, and was decreased to 2.5 mg/kg/day i.p. thereafter. The dose of Pr was always maintained at one-tenth of that of CsA. At 10, 30, and 90 days after the initiation of these treatments, blood urea nitrogen (BUN) and serum levels of creatinine and CsA were determined. The syntheses of DNA, RNA, and protein, Na+, K+-adenosine triphosphate (ATP)ase activity, and ATP content were measured using homogenates of the renal cortex obtained from each experimental group. At an early stage (at 10 and 30 days) of CsA administration, the impairment of renal function and inhibition of the synthesis of DNA and RNA appeared in groups 3 and 4. The magnitude of these changes was found to be greater in group 3 (CsA alone) than in group 4 (CsA plus Pr). Group 3 also showed a significant reduction of Na+, K+-ATPase activity as well as ultrastructural abnormalities. At a later stage (at 90 days), however, such differences in nephrotoxicity between groups 3 and 4 were not detected. These results strongly suggest that inhibition of the synthesis of DNA and RNA and the activity of enzymes related to the functions of cell membrane, such as Na+, K+-ATPase, may be involved in the occurrence of CsA-induced nephrotoxicity. The present results also suggest that the concomitant administration of Pr with CsA may reduce the nephrotoxicity of CsA at early stages of CsA administration, but this preventive effect of Pr may disappear if the administration of CsA is prolonged.

Adenosine Triphosphate↗
PubMed1987

Effects of neuromedin B and neuromedin C on exocrine and endocrine rat pancreas.

Neuromedin B and neuromedin C are novel decapeptides that have recently been isolated from porcine spinal cord and canine intestinal mucosa and show striking sequence homology with bombesin and gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin B and C on exocrine pancreatic function and insulin release have been compared with bombesin and GRP-27 in isolated pancreatic acini and isolated perfused pancreas in rat. Neuromedin B and C as well as bombesin and GRP-27 were able to cause stimulation of amylase release. The relative efficacy of neuromedin B, C, bombesin, and GRP-27 was the same as that of cholecystokinin octapeptide (CCK-8). Bombesin and GRP-27 were equipotent, and both were approximately 15-fold less potent than CCK-8. Neuromedin C was approximately 2-fold more potent, whereas neuromedin B as approximately 10-fold less potent than bombesin and GRP-27. All of these peptides stimulated insulin release that was limited to the first 3 min of a 20-min perfusion. However, GRP-27 and its related peptides were weak stimulants of insulin release compared with their abilities to stimulate exocrine pancreatic secretion. Bombesin and neuromedin B id not stimulate insulin release at doses stimulating pancreatic exocrine secretion. Neuromedin B was also approximately 10-fold less potent than neuromedin C, bombesin, and GRP-27 in eliciting insulin secretion. Because bombesin-like immunoreactivity is found to be present in nerves in the pancreas, neuromedin B and C may be neurotransmitters or neuromodulators and exert a direct local neurocrine action on enzyme secretion by acinar cells and insulin secretion by the islets.

Amylases↗
PubMed1987

A possible physiological role of milk epidermal growth factor in neonatal eyelid opening.

The eyelid opening of newborn mice occurs normally on day 13.9 +/- 1.8 after birth. When newborn mice were injected with anti-epidermal growth factor (EGF) antibody every other day starting on day 1 after birth, the eyelid opening was delayed by approximately 3 days. The effect of anti-EGF became less prominent as the treatment was started at later times: when it was given from day 7, no delay in eyelid opening was observed. On the other hand, eyelid opening was enhanced by approximately 3 days by EGF injection given on day 3 for every other day. This effect of EGF was antagonized by simultaneous administration of the anti-EGF antibody. EGF was present at a concentration of 6.6 ng/ml in the plasma of 1-wk-old pups nursed by their mother, but it was not detectable (less than 0.1 ng/ml) in the plasma of 3-wk-old weaned pups. EGF concentration in the submandibular glands, however, was 17 times greater in 3- than in 1-wk-old pups, i.e., 4.66 and 0.28 ng/mg of wet tissue, respectively. These results suggest that milk EGF may play a physiological role in eyelid opening during the neonatal period.

Animals↗
PubMed1987

Role of magnesium in the growth of calcium oxalate monohydrate and calcium oxalate dihydrate crystals.

Since about 85% of synthesized calcium oxalate dihydrate (COD) crystals proved not to have changed into calcium oxalate monohydrate (COM) crystals at 30 min of incubation time at 37 degrees C when our evaluation method of the COD-to-COM ratio was being used, we made a comparative study of the inhibitory effects of magnesium, one of the well-known inhibitors of calcium oxalate stone formation, on the growth of seeded COM and COD crystals. The results demonstrated that magnesium in identical concentrations might have stronger inhibitory effects on the growth of COM crystals than on that of COD crystals and suggested that these different effects of magnesium on the growth of COM and COD crystals might arise not only from the difference between the specific surface areas of COM and COD crystals, but also from that between the direct inhibitory effects of magnesium on these two types of calcium oxalate crystal growth.

Calcium Oxalate↗
PubMed1987

Bilateral ureteral stricture due to ureteral fibrosis. Case report.

A case of bilateral ureteral fibrosis is reported. The patient, a 32-year-old man, was admitted as a result of acute renal failure. Ultrasonography showed bilateral hydronephrosis, so that in-dwelling percutaneous nephrostomy tubes were immediately inserted in the bilateral kidneys. Since retrograde and antegrade pyelograms revealed bilateral midureteral stricture, idiopathic retroperitoneal fibrosis at first suspected, but no mass in the retroperitoneal space was found by a computed tomogram. An exploratory laparotomy showed no fibrous mass in the retroperitoneal space either, but that the wall of the ureter was thickened. Biopsy of the ureter led to a histological diagnosis of fibrosis. Since evidence of inflammation such as elevation of the erythrocyte sedimentation rate and cross-reacting protein was found, 50 mg of prednisolone has been administered every other day, with the result that inflammation is now under control. This report deals with specific ureteral fibrosis related to idiopathic systemic fibrosis and collagen disease.

Adult↗
PubMed1987

Clinical use of CA 125 and its combination assay with other tumor marker in patients with ovarian carcinoma.

The serum levels of CA 125 and CA 19-9 were determined by an immunoradiometric assay employing the monoclonal antibody OC 125 and anti-CA 19-9 antibody in 88 patients with ovarian carcinoma. When a cut-off value of CA 125 was set below 35 U/ml in the control group, serum elevated levels of CA 125 were found in 86.7% of the patients with surgically demonstrable ovarian serous cystadenocarcinoma, in 100% (4/4 cases) of clear-cell carcinoma, in 50% (2/4 cases) of endometrioid carcinoma, in 100% (5/5 cases) of undifferentiated carcinoma, and in 80% of the recurrent cases. Using a cut-off value of 37 U/ml, serum elevated levels of CA 19-9 were detected in 68.2% of mucinous cystadenocarcinoma, in 28.9% of serous cystadenocarcinoma, in 75% (3/4 cases) of metastatic ovarian carcinoma, and in 37.5% of the recurrent cases. A statistical analysis of the combination assay using CA 125, CA 19-9, tissue polypeptide antigen (TPA), immunosuppressive acidic protein (IAP), ferritin and CEA was carried out by multivariate method (discriminatory analysis) in 45 patients with ovarian carcinoma and 50 healthy subjects. As a result before treatment, positive rates of a single tumor marker were 79.7% with CA 125, 42.7% with CA-19-9, 73.1% with IAP, 61.7% with TPA, 64.3% with ferritin and 25.4% with CEA, respectively. A combination assay of these markers was useful for detecting identification of ovarian carcinoma, by which it gave a higher accuracy of ovarian cancer detection.

Adenocarcinoma↗
PubMed1987

1,25-Dihydroxycholecalciferol receptor regulation in hormonally induced differentiation of mouse mammary gland in culture.

Mammary explants from pregnant mouse cultured in the presence of insulin, cortisol, and PRL express their differentiated function by producing milk proteins such as casein. Sucrose density gradient analysis of high salt extract of cultured explants showed the presence of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3 specific binding activity sedimenting at 3.3 S. Specific 1,25-(OH)2D3 binding activity in mammary explants varied as a function of the hormonal milieu in culture. The highest activity was found in explants cultured in the presence of insulin, cortisol, and PRL, whereas only a marginal activity was present in explants cultured with insulin. The comparison of 1,25-(OH)2D3 binding activity in explants cultured with insulin and with the three hormone combination by Scatchard plot analysis indicated that the synergistic actions of insulin, cortisol, and PRL increased the number of 1,25-(OH)2D3 specific binding proteins as much as 6-fold; however, the affinity constant of the binding protein was relatively constant in the two systems. Time course studies showed that the increase in 1,25-(OH)2D3 binding activity was detectable as early as 12 h after the addition of cortisol and PRL to insulin-primed explants. The increase was inhibited by the presence of actinomycin D and cycloheximide, suggesting that the hormonal stimulation of 1,25-(OH)2D3 binding activity involves both transcriptional and translational process. These results indicate that insulin, cortisol, and PRL stimulate the specific 1,25-(OH)2D3 binding activity during the induction of mammary functional differentiation when milk protein synthesis takes place.

Animals↗
PubMed1987

Characterization of receptors for human recombinant interferon-gamma in human cells.

Highly purified human recombinant interferon-gamma (ReIFN-gamma) was radioiodinated with 125I-Bolton-Hunter reagent and used to characterize the receptor for ReIFN-gamma. 125I ReIFN-gamma specifically and saturably bound four human cells tested, FL, WISH, Daudi, and HL-60, which were reported to have ReIFN-gamma binding sites. Scatchard analysis of the binding data of FL cells revealed the presence of 5200 binding sites per cell and a Kd value of 2.1 X 10(-10) M. Although the binding of 125I ReINF-gamma was inhibited by unlabelled natural IFN-gamma and ReIFN-gamma, it was not inhibited by unlabelled human ReIFN-alpha and ReIFN-beta, suggesting that receptors for (Re)IFN-gamma were different from those for IFN-alpha or IFN-beta. However, ReIFN-gamma displaced the binding of 125I ReIFN gamma 3 to 5 times more effectively than IFN-gamma. Internalization of 125I ReIFN-gamma bound to the cell surface receptor was observed at 37 degrees C. Pretreatment of FL cells with unlabeled ReIFN-gamma caused a concentration-dependent down-regulation in the ReIFN-gamma receptor, which was specific for IFN-gamma and reversible. From these studies, we concluded that although the ReIFN-gamma is not identical to putative IFN-gamma, the recombinant form binds to the same binding sites for IFN-gamma and does not bind to the binding sites for IFN-alpha or beta.

Binding, Competitive↗
PubMed1987

Estimation of relative importance of three enzymes in the inactivation of [Met5]-enkephalin and [Met5]-enkephalin-Arg6 in three isolated preparations by employing the inhibitor specific for each enzyme.

The relative importance of three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A and phosphoramidon-sensitive endopeptidase-24.11, to inactivate two opioid peptides, [Met5]-enkephalin and [Met5]-enkephalin-Arg6, was investigated in three in vitro isolated preparations, guinea-pig ileum, mouse vas deferens and rat vas deferens, by estimating the magnitude of the enhancement of the inhibitory potency of the opioid peptide by each peptidase inhibitor. Results showed that the relative importance of the three enzymes in the inactivation of the opioid peptide, whether it was [Met5]-enkephalin or [Met5]-enkephalin-Arg6, in guinea-pig ileum was significantly different from that in either mouse vas deferens or rat vas deferens. Additionally, the relative importance of the three enzymes in the preparation, whether it was guinea-pig ileum, mouse vas deferens or rat vas deferens, in the inactivation of [Met5]-enkephalin was significantly different from that of [Met5]-enkephalin-Arg6. The significance of the presence of plural inactivating-enzymes for opioid peptides was discussed.

Aminopeptidases↗
PubMed1987

Effect of N-methyltetrazolethiol on liver microsomal gamma-glutamylcarboxylation: modification of the in vitro action of N-methyltetrazolethiol.

Vitamin K-dependent gamma-glutamylcarboxylation activity in rat liver microsomes was monitored using the incorporation of 14CO2 into exogenous pentapeptide and endogenous protein substrates as indicators. Detergent solubilization of the microsomal enzymes was required for the activity to develop, but higher concentrations of detergent inhibited the enzymatic reaction. Pyridoxal-5'-phosphate (PAL-P) and dithiothreitol (DTT) stimulated the enzyme activity. The enzyme activity was observed when the hydroquinone form of vitamin K or the quinone form plus NADH was employed as the cosubstrate, but little activity was detected in the reaction system containing vitamin K-epoxide plus NADH plus DTT. N-Methyltetrazolethiol (NMTT), the substituent at the 3'-position of several beta-lactam antibiotics, inhibited the enzyme activity in vitro only in the reaction system containing NADH. Addition of DTT diminished the in vitro action of NMTT, while PAL-P and detergent did not affect it. The results indicate that the in vitro inhibitory action of NMTT is observable under some specific and restricted assay conditions. This paper also discusses the differences between the in vitro action and the in vivo effect of NMTT.

Animals↗
PubMed1987

Pharmacokinetics of latamoxef and N-methyltetrazolethiol in rats associated with the development of disulfiram-like effects.

The disulfiram-like effect of beta-lactam antibiotics, having an N-methyltetrazolethiol (NMTT) as a 3'-position substituent of the cephalosporin nucleus, was determined in rats using latamoxef (LMOX) as a model. Intravenous and subcutaneous administrations of these antibiotics caused a decrease in the low Km aldehyde dehydrogenase (ALDH) activity in liver mitochondria and an increase in blood acetaldehyde level during ethanol metabolism, as in the case of disulfiram. When the antibiotic was administered intravenously to biliary fistula rats, the blood acetaldehyde level did not increase. On the other hand, oral administration of antibiotic to normal and biliary fistula rats caused pronounced development of disulfiram-like effects in both animals. When LMOX was injected to normal rats, the rapid and slow eliminations of LMOX and NMTT, respectively, were observed from blood and liver. After oral administration of LMOX, NMTT remained in the blood and liver for a long time with higher concentrations, although LMOX could not be detected in the body. With biliary fistula rats, intravenous injection of LMOX led to rapid urinary excretion of both LMOX and NMTT. These results indicate that the development of disulfiram-like effects of NMTT-containing antibiotics is closely related to the pharmacokinetic profile of NMTT released from its parent drugs.

Acetaldehyde↗
PubMed1987

Effect of sialoadenectomy, treatment with epidermal growth factor (EGF) antiserum and replacement of EGF on the epidermis in mice.

Epidermal growth factor (EGF) was present at a mean concentration of 266 +/- 18 (S.E.M.) pmol/mg wet tissue in the submandibular gland of 3-month-old male mice; it was also present in plasma at a concentration of 364 +/- 149 pmol/l. Sialoadenectomy (removal of the submandibular glands) decreased the plasma EGF content to undetectable levels (less than 16.5 pmol/l), lowered the concentration of EGF in the skin from 1.22 +/- 0.11 to 0.47 +/- 0.08 fmol/mg wet tissue and reduced the thickness of the epidermis from 28.9 +/- 2.7 to 11.0 +/- 0.8 micron in 3 weeks (P less than 0.001). Epidermal growth factor antiserum given to sialoadenectomized mice further decreased the thickness of the epidermis to 8.3 +/- 0.6 micron. No appreciable change was observed in the dermis and subcutaneous tissue. In sialoadenectomized mice, replacement of EGF prevented the decrease in thickness of the epidermis in a dose-dependent manner when started immediately after the operation. Treatment with EGF also effectively restored the normal morphology of the epidermis when its thickness had declined to its lowest level. These results suggest that EGF plays a physiological role in the maintenance of the epidermis.

Animals↗
PubMed1987

[Subcutaneous injection of spleen cells from mice bearing large methylcholanthrene-induced sarcoma enhances subcutaneous tumors and artificial pulmonary metastases].

To examine the effect of spleen cell on host antitumor immunity, spleen cells from mice bearing large Methylcholanthrene-induced sarcoma (MCA-F) (F4w spc) were injected subcutaneously into mice which had been inoculated subcutaneously with MCA-F cells or intravenously with the subline from MCA-F cells which had high potential of metastasis (FLn2). F4w spc enhanced significantly the growth of subcutaneous MCA-F tumor in a dose-dependent fashion (p less than 0.05) and increased the number of metastatic lesions induced by intravenous FLn2, but not spleen cells from normal mice or spleen cells from mice bearing MCA-D tumor which is antigenically different from MCA-F. These results suggest that spleen cells of mice bearing a large tumor have a component suppressing specifically antitumor immunity. In this study, effects of spleen cells were assessed by the subcutaneous injection into tumor bearing mice instead of Winn's assay, and this method was thought to be useful for analysis of effector cells in tumor immunity.

Animals↗