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Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 901 records · Page 50Linked to original sources
PubMed1989

Longer survival after resection of non-small cell lung cancer in Japanese women.

From 1974 to 1988, 492 patients (361 male and 131 female) with non-small cell lung cancer underwent pulmonary resection at our department. A retrospective study was done with special reference to the sex of the patients. There was no sex-related association with age distribution, operation, pathological T or N status, or staging. On the other hand, 77.9% of women had an adenocarcinoma and only 44.6% of men had this type of lesion. This was considered at least partly a result of sex difference in smoking habits. Women survived for a significantly longer time (p = 0.0036), and this difference could not be explained by differences in histological type. Presumably, hormonal factor(s) may contribute to the prognosis.

Adenocarcinoma↗
PubMed1989

The effect of renal transplantation on a major endogenous ligand retained in uremic serum.

The effects of renal transplantation on serum concentrations of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and indole-3-acetic acid (IAA), which are endogenous ligands retained in uremic serum, and on phenytoin binding to serum protein were investigated. IAA, a weakly bound ligand, was rapidly excreted by the transplanted kidney during the first one to three days after renal transplantation, but CMPF, a strongly bound ligand, was slowly excreted. The binding defect of phenytoin was partially corrected by transplantation during the period of study. The results suggested that the prolonged drug binding defect observed despite successful renal transplantation is caused by a slower decrease of strongly bound ligands such as CMPF retained in uremic serum; hypoalbuminemia, usually observed after transplantation, may also contribute to this phenomenon.

Adult↗
PubMed1989

Epidermal growth factor deficiency associated with diabetes mellitus.

The production of epidermal growth factor (EGF) in the submandibular gland and its circulating level were studied in diabetic mice. In genetically diabetic (C57BL/KsJ db/db) mice, EGF concentrations in the submandibular gland and plasma were reduced to 13% and 30% of the control levels, respectively. In streptozotocin-treated diabetic mice, they were reduced to 18% and 20% of controls, respectively, 5 weeks after the drug injection. Furthermore, levels of submandibular prepro-EGF mRNA in these diabetic mice were decreased almost in parallel with the glandular EGF concentrations, while there was no change in the levels of submandibular beta-actin mRNA and kidney prepro-EGF mRNA. In addition, histological examination of the submandibular glands indicated that the size of the granular convoluted tubules, which produce EGF, was substantially reduced in the diabetic mice. Insulin administration to streptozotocin-treated mice almost completely reversed the decrease in EGF content in the submandibular gland, substantially elevated the level of the glandular prepro-EGF mRNA and plasma EGF concentration, and increased the size of the granular convoluted tubules in the gland. These results indicate that EGF deficiency occurs in diabetes mellitus and that insulin may be important in maintaining the normal level of EGF in the submandibular gland and plasma.

Animals↗
PubMed1989

Purification and some properties of rat intestinal ornithine decarboxylase.

Ornithine decarboxylase (ODC) was induced in rat small intestine by treatment with hypotonic solution in vitro and purified by two procedures, a conventional procedure and an immunoaffinity procedure. SDS-polyacrylamide gel electrophoresis showed that the molecular weight of the preparation purified by the immunoaffinity procedure (Mr = 53,000) was slightly larger than that of the preparation obtained by the conventional procedure (Mr = 52,000). Values for the Km for L-ornithine (0.1 mM), the isoelectric point (5.4), and the final specific activity (5.1-5.5 x 10(5) nmol CO2/mg protein/30 min) of the two preparations were similar to those reported for the rat liver ODC. Addition of a protease inhibitor (limabean trypsin inhibitor) to the crude extract prevented the appearance of the smaller enzyme (Mr = 52,000) obtained by the conventional purification procedure. Our result indicates that the large enzyme is native ODC and the smaller one is a partial proteolysis product of native ODC.

Animals↗
PubMed1989

Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. I. Inhibition of expression of alloantigen-activated suppressor cells, as well as induction of alloreactivity.

The effect of FK506 on in vitro human lymphocyte responses was assessed in comparison with cyclosporine. FK506 suppressed, in a dose-dependent fashion, the lymphocyte response to stimulation with PHA and with alloantigens in primary mixed lymphocyte reactions at a 70-100-fold lower concentration than CsA--namely, 50% inhibition (IC50) was obtained with 8.6 nM FK506 and with 750 nM CsA in the PHA response, and with 0.21 nM FK506 and with 20 nM CsA in MLR. Allocytolytic T lymphocyte induction was also inhibited by FK506, whereas the ability of CTL to lyse targets was not affected by the agent, indicating that FK506 did not affect the recognition and binding of alloantigen by CTL. FK506 inhibited, in a dose-dependent fashion, both IL-2 receptor and transferrin receptor expression on the alloactivated lymphocytes--whereas this agent inhibited only incompletely both expression of both receptors on lymphocytes stimulated with PHA. Lymphocytes from primary MLR cultured in the presence of FK506 were tested for suppressor cell activity on day 8 of culture. FK506 did not allow for the expression of alloantigen-activated suppressor cells when used in a dose sufficient to inhibit CTL generation.

Adult↗
PubMed1989

Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. II. Inhibition of the production of IL-2 and gamma-IFN, but not B cell-stimulating factor 2.

The mechanism whereby FK506 inhibits immune responses was assessed in in vitro human studies. FK506 inhibited in a dose-dependent manner both interleukin 2 and gamma-interferon secretion of PBMC stimulated with PHA. Complete inhibition was obtained at the concentration of 0.25 nM of FK506 for IL-2 and 1 nM of FK506 for gamma-IFN production. Inhibition of 50% (IC50) was detected with 0.06 nM for IL-2 and 0.25 nM for gamma-IFN production. On the other hand, FK506 could not inhibit the B cell-stimulating factor 2 (BSF-2) production of PBMC, indicating the possibility that FK506 might spare the B cell function. Cloned T cells and cloned B cells, once activated, were scarcely affected by the agent; neither IL-2-driven proliferation of cloned T cells nor BSF-2-driven proliferation of cloned B cells was inhibited by FK506 at any concentration.

Adult↗
PubMed1989

Characterization and analysis of soluble suppressor factor from early human decidual cells.

To assess the role of decidual cells (DC) in the maintenance of pregnancy, immunosuppressive activity of culture supernatants from human DC were investigated. Dispersed DC suspensions from decidual tissue of early pregnancies were prepared by an enzyme digestion method using collagenase and DNase, and were enriched over 90 per cent without contamination of macrophages and lymphocytes in the fraction, with specific gravity between 1.033 and 1.044 (fraction 2 [Fr2] ) by a Percoll discontinuous density gradient method. The culture supernatants of Fr2 cells suppressed the responses of normal peripheral blood lymphocytes to PHA, MLR, and killer T cell generation at the 50 per cent concentration. To determine the mechanism of the immunosuppressive activity of the culture supernatants, the effect of the supernatants on interleukin-2 and gamma-interferon production, as well as IL-2 receptor expression, on PBL was investigated. The supernatants from 3 x 10(6)/ml of DC cells inhibited not only IL-2 and gamma-INF production, but also IL-2 receptor expression, compared with normal controls. The supernatants also suppressed immunoglobulin (IgG and IgM) production by pokeweed mitogen-stimulated B cells. To purify the suppressor factor from culture supernatants of DC, serum free culture supernatants of 3 x 10(6)/ml of DC, which showed 32 per cent of inhibitory activity on MLR, were applied to gel filtration. Fractions between mw 67,000 and 43,000 suppressed the MLR. These results suggest that DC from decidua of early pregnancy excrete an immunosuppressive factor with a molecular weight between 43,000 and 67,000 daltons.

Centrifugation, Density Gradient↗
PubMed1989

Active specific chemoimmunotherapy of lymph-node metastasis from a poorly immunogenic murine fibrosarcoma.

The fibrosarcoma MCA-SP, which was recently induced with methylcholanthrene (MCA) in C3H/HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA-SPN1, which bears a tumor-specific transplantation antigen (TSTA) cross-reactive with the parental line MCA-SP, was selected because of its proclivity for axillary lymph-node metastases. Although these lymph-node metastases were resistant to sinecomitant (post-excisional) immunity, they were susceptible to combined active and passive specific chemoimmunotherapy, using tumor-specific, 1-butanol-extracted, preparative isoelectric focusing-purified, TSTA (1 microgram weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re-stimulated in vitro with extracted TSTA and interleukin-2. This triple regimen both reduced the incidence of spontaneous lymph-node metastases, and prolonged the survival of tumor-bearing, as well as tumor-resected hosts. The results from local adoptive transfer assay using T-lymphocyte subpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2+ cytotoxic T-lymphocytes (CTL) mediated in vivo tumor-neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA-SP tumor and its lymph-node metastases.

Animals↗
PubMed1989

Effect of amniotic fluid volume on umbilical cord length.

To study effect of amniotic fluid volume on umbilical cord length, 939 pregnant women at 24-41 weeks of gestation, including 10 twin cases, 51 preterm premature rupture of the membranes (PROM) and 70 premature delivery cases, were examined for their amniotic fluid volume within a week of delivery by the ultrasound procedure and these 949 newborns were also examined for umbilical cord length and incidence of fetal distress. In the polyhydramnios group (pocket size of more than 8 cm), 8 of 20 infants (40%) had longer cords and 6 infants (30%) had shorter cords, while only one of 49 infants (2%) with oligohydramnios (pocket size of less than 2 cm) had a longer cord and 36 infants (73.5%) had shorter cords than the mean cord length (+/- SD) of the normal group. The 20 twins had significantly shorter cords than those of the normal group (P less than 0.05) and the polyhydramnios group (P less than 0.01). The PROM group showed significantly higher incidence of oligohydramnios (P less than 0.05) and fetal distress (P less than 0.01), which suggests that intrauterine space availability is important for assuring fetal well-being.

Amniotic Fluid↗
PubMed1989

Possible role of Tamm-Horsfall glycoprotein in calcium oxalate crystallisation.

The role of Tamm-Horsfall glycoprotein (THGP) in the crystallisation of calcium oxalate was investigated. The results showed THGP to have a weak inhibitory effect on crystal growth. In contrast, urinary macromolecules showed a strong inhibitory effect. THGP should, therefore, not be considered the main component of urinary macromolecules which have a strong inhibitory effect on crystal growth. However, THGP did enhance crystal production in the early phase of crystallisation. It appears that THGP should be viewed as a promoter rather than an inhibitor of calcium oxalate crystallisation at physiological concentrations.

Adult↗
PubMed1989

Experimental study on the adsorption of excess heparin with anion exchange resin fiber.

Anion exchange resin fiber (Ionex) was used as a heparin adsorbent. Ionex has the adsorption capacity of 70 mg/g (weight by desiccation) for heparin, and was used in an attempt to remove the heparin from blood-perfused artificial organs, before the blood was transfused back into the patients. In the ex vivo study, the 5 systemically heparinized dogs (500 U/kg) were treated with a 35-40 g column of Ionex, by direct hemoperfusion (DHP). The concentration of heparin was significantly reduced, within 15 to 60 minutes, using the Ionex. This suggested the possibility of removing excess heparin from the living body. In in vitro, the relationship between the amount of heparin by Ionex and the blood-flow volume were evaluated. Whole blood taken from dogs was added to 5 U/ml of heparin. This was then introduced into a small column containing 0.9 g Ionex, at blood-flow rates of 0.8, 1.6, and 3.2 ml/min. A good adsorption capacity was shown at the blood-flow rate of 0.8 ml/min. One possible explanation for this is that the heparin dispersed in the blood cells gradually was passed on into the plasma and, so, did not have time to be adsorbed at the faster flow rates.

Adsorption↗
PubMed1989

Impaired production of nerve growth factor in the submandibular gland of diabetic mice.

The production of nerve growth factor (NGF) in submandibular glands was examined in two kinds of diabetic mice. In genetically diabetic (C57BL/KsJ db/db) mice, which manifest marked insulin resistance and hyperglycemia, the concentration of NGF in the submandibular gland was less than one-tenth that of the nondiabetic controls. In streptozotocin-induced diabetic C57BL/KsJ mice, which show pancreatic insulitis leading to insulin deficiency and hyperglycemia, the glandular NGF concentration fell in a time-dependent manner to 26% of control level at 5 wk after the streptozotocin injection. A daily administration of insulin to the streptozotocin-induced diabetic mice restored the NGF concentration to almost the control level. The molecular size of NGF (13 kDa) in the glandular extracts of the genetically diabetic (db/db) mice in Western blots was indistinguishable from that of the control mice, but its level was reduced in the glands of the diabetic (db/db) animals. Although plasma NGF concentrations were normally below the sensitivity of the assay (less than 0.80 ng/ml) in both the control and the diabetic (db/db) mice, administration of cyclocytidine, which stimulates NGF release from the submandibular gland into the blood circulation, increased the plasma NGF level to 5.95 ng/ml in the control mice, but it failed to do so in the diabetic (db/db) mice. These findings suggest that, in diabetic mice, NGF production in the submandibular gland and its capacity to release NGF into the circulation are decreased.

Animals↗
PubMed1989

Growth control and differentiation in mammary epithelial cells.

Growth and differentiation of the mammary gland are controlled by various hormones and other environmental factors. The role of hormones and growth factors in mammary development is discussed with regard to animal species, physiological stages, and the various experimental systems in vitro. In the female embryo, mammary morphogenesis is induced by the mesenchyme and is hormone independent, whereas androgens cause the partial necrosis of mammary epithelium in the male. Ductal growth during adolescence requires estrogen and prolactin or growth hormone. During pregnancy, progesterone participates in the development of the lobuloalveolar structure of the gland. After parturition, changes in the hormonal environment lead to production and secretion of milk. Proliferation and differentiation of mammary epithelium can be induced in culture systems. Insulin and epidermal growth factor (EGF) stimulate mammary cell proliferation in vitro. EGF is required for the optimal growth of the mammary gland during pregnancy. EGF also appears to play an important role in mammary tumorigenesis in certain mouse strains. Production of milk proteins can be induced in vitro by the synergistic interactions of prolactin, insulin, and glucocorticoids and is inhibited by EGF and progesterone. Complete or partial sequencing of several milk protein genes and comparative analysis have led to identification of a sequence of high homology and conservation in the 5' flanking region that is likely to be involved in the regulation of milk protein gene expression.

Animals↗
PubMed1989

Identification and partial characterization of mesenchyme-derived growth factor that stimulates proliferation and inhibits functional differentiation of mouse mammary epithelium in culture.

The effect of mesenchyme on both proliferation and differentiation of mammary epithelial cells was investigated in a primary cell culture system. Mammary cells cultured on collagen gel for 4 days produced casein in response to the synergistic action of insulin, cortisol, and prolactin. When mammary epithelial cells were co-cultured with fibroblasts derived from three different kinds of fetal mesenchymal tissues, casein production was suppressed. The addition of conditioned media obtained from cultures of these mesenchymal cells stimulated DNA synthesis and reduced casein synthesis in a dose-dependent fashion in the cultured mammary cells. Although such biological actions are similar to those of epidermal growth factor (EGF), the capability to compete with EGF for EGF receptor was not found in this conditioned medium. Sephadex G-200 column chromatography revealed that molecular weight of the peak which has these biological activities was around 100,000. These results indicate that fetal mesenchymal cells secrete a substance(s) which has a stimulatory effect on proliferation and an inhibitory effect on differentiation of mammary epithelial cells.

Animals↗
PubMed1989

Decreased expression of hepatic epidermal growth factor receptor gene in diabetic mice.

The expression of hepatic epidermal growth factor (EGF) receptor gene was studied in genetically diabetic (C57BL/KsJ db/db) mice and streptozotocin-induced diabetic mice. The binding of 125I-labelled EGF to hepatic membrane preparations of genetically diabetic mice was only 35% of that of non-diabetic mice. Levels of EGF receptor messenger RNAs (10 and 6 kb) in the liver of the diabetic animals were also reduced by about 75%. In streptozotocin-induced diabetic mice, levels of hepatic EGF binding and messenger RNAs for EGF receptor were decreased to 27 and 30% of control levels respectively, at 5 weeks after injection of the drug. There were, however, no significant differences in levels of messenger RNAs for the structural protein beta-actin in the liver. In addition, levels of EGF receptor messenger RNAs in the kidney were similar between control and the two kinds of diabetic mice. Daily administration of insulin to the streptozotocin-induced diabetic mice increased the hepatic levels of EGF receptor messenger RNAs to almost normal levels. These results indicate that EGF binding to its receptor decreases in the liver of diabetic mice, involving alterations in the level of EGF receptor messenger RNAs, and that insulin is important for the regulation of EGF receptor gene expression in the liver but not in the kidney.

Actins↗
PubMed1989

The regulation by thyroid hormones and androgen of epidermal growth factor synthesis in the submandibular gland and its plasma concentrations in mice.

The effects of androgen and thyroid hormones on epidermal growth factor (EGF) synthesis in the submandibular gland and on plasma EGF concentrations in mice were examined. Testosterone propionate was administered alone or in combination with L-thyroxine (T4) to female mice for 2 weeks. The submandibular EGF concentrations were increased by the administration of testosterone propionate in a dose-dependent fashion; the maximal increase, 20-fold, being produced by a dose of 2 mg every other day. The EGF levels were increased sevenfold by T4, which also enhanced the stimulatory effect of suboptimal doses of testosterone propionate. Cyproterone acetate, an anti-androgen, inhibited the testosterone propionate-induced increase, but not the T4-induced increase. Plasma EGF concentrations were raised by testosterone propionate but not by T4. Both hormones stimulated the accumulation of 4.7 kb preproEGF mRNA in the submandibular gland, which occurred almost in a parallel manner with the increase in submandibular EGF concentrations. These results suggest that EGF synthesis in the submandibular gland is regulated by alterations in the level of its mRNA by thyroid hormones and androgen, and that the rise in plasma EGF concentrations is under the influence of androgen but not of thyroid hormones.

Animals↗