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Biomedical subjects

S Takada

Publications and source records attributed to S Takada.

At least 289 records · Page 16Linked to original sources

Modulation of the transferred mouse 26K casein gene in mouse L cells by glucocorticoid hormone.

The cloned 26K casein gene was transferred to mouse L-cells and its expression was measured by Northern blot hybridization. When the lambda clone with 5'- and 3'-flanking sequences was transferred, transcripts were detected without glucocorticoid, but in the presence of glucocorticoid, the level of the transcripts of heterogeneous sizes increased and their pattern was similar to that observed in the mammary glands of non-lactating mice. When the 6.7 kb EcoRI fragment containing most of the coding region was transferred, putative precursor and mature mRNAs were detected without glucocorticoid. Surprisingly, with the addition of glucocorticoid, the level of the transcripts greatly decreased. The presence of multiple sequences responsible for glucocorticoid receptor binding was detected in the 5'-flanking region of the gene in a competition assay using the subfragments of casein gene and on sequence analysis. These results suggest that the 26K casein gene has multiple regulatory domains which interact with glucocorticoid receptors, and these domains may play different roles in the regulation of the casein gene.

Animals↗

Inhibitory action of bilirubin on superoxide production by polymorphonuclear leukocytes.

To assess the interaction of bilirubin with albumin and to determine the site of bilirubin toxicity in cells, a study was made of the O2- production of neonatal neutrophils (PMNs) by two different stimulators: (1) concanavalin A (Con A) plus cytochalasin D (Cyt D), which acts on the cell surface, and (2) phorbol myristate acetate, which acts intracellularly. PMNs that had been separated from cord blood were incubated for 60 min at 37 degrees C in the solution with different molar ratios of bilirubin/albumin (unbound bilirubin, ranging from 0.35 to 3.92 micrograms/dl). The unbound bilirubin was determined by peroxidase oxidation method. A PMN viability of more than 96% was maintained after the incubation in each of solutions. The O2- production rate of PMNs stimulated by Con A plus Cyt D was inhibited in the presence of unbound bilirubin levels as low as 1.12 micrograms/dl, and the rate decreased as the levels of unbound bilirubin rose. The O2- production rate stimulated by Con A plus Cyt D was more remarkably inhibited than that by phorbol myristate acetate, which directly activates intracellular protein kinase C. These findings suggest that bilirubin toxicity to PMN can be shown at levels of unbound bilirubin as low as those in hyperbilirubinemic sera, and the critical site at which bilirubin exerts its toxicity is mainly in membrane level rather than on intracellular functions.

Bilirubin↗

Vascular pattern of the mammalian ovary with special reference to the three-dimensional architecture of the spiral artery.

Casts of blood vessels in the ovaries of the female rat, pig and monkey were made with methacrylate, dissected out under a dissecting microscope and observed in a scanning electron microscope (SEM). The ovarian arteries and their branches were characterized by the presence of a spiral configuration. The spiral course of the arteries, however, varied greatly in detail among the different species. The arteries in the pig and monkey ovaries had tightly spiraling configurations, while there was only an image suggestive of a spiral in the rat ovarian arteries. The former species showed a rich plexus of the spiral arteries in the hilus and medulla of the organ. Their branches straightened at the transitional region between the medulla and cortex but again showed spiral configurations in the cortex. Further, the arterial branches supplying the growing and mature follicles showed a much more marked extent to the spiral configurations as compared with those of the corpus luteum. In this paper morphological findings shall be discussed in correlation with their physiological implications.

Animals↗

T cell regulatory disturbances in the rheumatic diseases.

Significant immunoregulatory abnormalities have been described in both SLE and RA. In SLE, deficient suppressor T cell activity may result from depletion of CD8+ suppressor precursors, depletion of CD4+ suppressor-inducer cells, or impaired lymphokine production and deficient CD4+ cell activation of suppression by CD4+ cells. The net result is an apparent failure to inhibit antibody synthesis. The defects in RA are less well defined, although in RA there also is evidence that either deficient suppression or deficient suppression-induction plays a role in the pathogenesis of disease. There is evidence for local lymphocyte activation in the synovium, with possibly impaired local immunoregulation. However, the precise nature of the immune reactions in the synovium and their relationship to systemic immunoregulatory abnormalities remain unclear.

Antigens, Differentiation, T-Lymphocyte↗

[Distribution and constitutional changes of edema fluid in cytotoxic brain edema analyzed by electron microscopy and differential scanning calorimetry].

To understand the pathogenesis of brain edema, we studied distribution and constitutional changes of brain-tissue water by morphological and thermoanalytical methods in cytotoxic brain edema induced by 6-aminonicotinamide (6-ANA). Ninety-two Wistar rats were divided into three groups; Group I rats receiving physiological salt solution intraperitoneally served as controls. Group II and III animals were intraperitoneally given 120 mg/kg and 36 mg/kg of 6-ANA respectively. All animals were starved after injection of drugs to exclude differences in water intake. Then they were decapitated at 3, 6, 12, 24, 36 or 48 hours to measure specific gravity (SG) of large brain tissue (1.1-1.5 g), and to evaluate water content (WC) and free water ratio (FWR) of small brain-tissue samples (15-35 mg) taken from the frontal cortex; WC was measured by a drying-weighing method, and FWR was analyzed with a differential scanning calorimeter. Moreover morphological changes of the frontal cortex of the brain were studied in Group II (n = 12) at 3, 6, 12, 24 and 48 hours with an electron microscope. Neurological status of animals administered 6-ANA (Group II and III) deteriorated with time. Morphological studies showed that perivascular astrocytes and astrocytic processes in the cerebral cortex were swollen most remarkably at 48 hours. However neuronal and endothelial cells were almost intact. The FWR of Group I decreased significantly about four per cent (p less than 0.001) after being starved for 48 hours. But the SG and WC of the group showed little change.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Aminonicotinamide↗

Deficiencies in suppressor T cell activity seen in patients with active systemic lupus erythematosus are due to the dilution of normally functioning suppressor T cells by nonsuppressor T cells.

Concanavalin A (Con A)-activated T lymphocytes from patients with active, but not inactive, systemic lupus erythematosus (SLE) failed to express normal suppressor activity, regardless of the phenotype of CD4+ or CD8+. Con A-activated CD4+ or CD8+ T lymphocytes from the SLE patients and from normal controls were further separated into two populations, using the autologous erythrocyte rosette technique. One population very rich in cells capable of forming rosettes with autologous erythrocytes from the active patients showed the same degree of suppressor activity, as did that from normal controls; the CD4+ or CD8+ population poor in autorosetting cells derived from Con A-activated T lymphocytes from both the controls and patients did not express suppressor activity. Moreover, when autorosetting T cells from the active patients and nonrosetting cells from the same patients were mixed at a normal ratio (4:6), normal suppressor activity could be restored. It was notable that the frequency of autorosette-forming cells was markedly reduced in the Con A-activated T lymphocytes from the active, but not inactive, SLE patients, regardless of the phenotype of CD4+ or CD8+. These findings indicate the presence of a normally functioning suppressor T cell population in patients with active SLE. It seems that the lack of suppressor T cell function in patients with active SLE is due to the dilution of a few normal suppressor T cells by large numbers of nonsuppressor T lymphocytes.

Adult↗

Generation of antigen receptor-specific suppressor T cell clones in man.

We have shown previously that CD8+ T cells proliferate upon exposure to autologous, antigen primed CD4+ T cells, and suppress the response of fresh T cells to the priming antigen but not irrelevant antigens. The stimulus and target of suppression in this system appears to be the antigen receptor on the surface of CD4+ cells, rather than the nominal antigen. In the current study, alloantigen primed CD4+ inducer cells and IL-2-containing medium were used to generate clones of suppressor cells from several individuals. The clones inhibited the response of fresh autologous T cells only to the original allogeneic stimulator cell and to stimulator cells that shared HLA-DR antigens with the priming cell. The clones were also genetically restricted, since they inhibited the response of HLA-A,B-compatible but not HLA-A,B-incompatible individuals. The availability of a method for reproducibly generating antigen receptor-specific suppressor T cell clones in vitro should make it possible to clarify the mechanism, whereby such cells are activated and exert their suppressive effect.

Clone Cells↗

Analysis of interleukin-2 activity in patients with Behçet's disease. Ability of T cells to produce and respond to interleukin-2.

We examined interleukin-2 (IL-2) activity in patients with Behçet's disease. T cells from all patients with Behçet's disease were able to produce normal levels of IL-2 in response to phytohemagglutinin; however, responsiveness to IL-2 was impaired in their concanavalin A-activated lymphoblasts. This defect was due to decreased numbers of cells bearing IL-2 receptors in patients with early active disease; in patients with chronic active or with inactive disease, there was a decrease in density of IL-2 receptors on T cells bearing these receptors. Unresponsiveness of T cells to IL-2 may thus contribute to immunologic aberrations in Behçet's disease.

Adult↗

An increase in water content of mouse erythrocytes infected with Plasmodium yoelii.

Mean cell volume and mean cell water content were examined in Plasmodium yoelii-infected mouse erythrocytes by gas chromatography and 3H-sucrose. Mean cell volume increased by 16% in infected erythrocytes with late trophozoites and schizonts. Mean cell water content further increased by 23% in the infected erythrocytes. Measurement of the erythrocyte potassium and sodium concentrations by an atomic absorption spectrophotometer revealed that the infected erythrocytes contained highly elevated sodium and slightly reduced potassium levels when calculated per single erythrocyte. It is suggested that membrane transport processes of sodium and potassium are changed in P. yoelii-infected erythrocytes and that a passive inflow of sodium takes place, which results in an increase in intra-erythrocytic water content.

Animals↗

Stimulation of human neuroblastoma DNA polymerase alpha and primase activities by a protein factor isolated from rat liver chromatin.

Nuclear protein factor type 1 (NPF-1) that simulates IMR-32 primase-associated DNA polymerase alpha 1 and alpha 2 activities has been purified from a high-salt extract of liver chromatin from 6-month-old rats. The final purified factor lacks DNA polymerase alpha, RNA polymerase, and DNA-unwinding or topoisomerase type I activities. The stimulatory activity is destroyed by trypsin (60 min at 37 degrees C), DNase II (60 min at 37 degrees C), and heat treatment (2 min at 68 degrees C). The 125I-labeled NPF-1 does not bind to activated calf thymus DNA or poly(dC). However, it forms a ternary complex with DNA in the presence of DNA polymerase alpha-primase complex (alpha 1 and alpha 2). The ternary complex sediments on sucrose density gradient as a heavier band (11S). The NPF-1 also stimulates (2.5-fold) primase-catalyzed incorporation of GMP and dGMP from the corresponding triphosphates on poly(dC) template even in the presence of a high concentration of alpha-amanitin (400 micrograms/ml). The labeled duplex containing the poly(dC) template, [32P]-GTP, and [3H]dGTP loses 80% of the 32P label and 70% of the 3H label after treatment with 0.3 M KOH and DNase I, respectively. The products were isolated from reaction mixtures incubated with and without NPF-1 and subjected to alkaline sucrose-density-gradient sedimentation analysis. The results suggest that the rate of synthesis of DNA short chains is increased in the presence of NPF-1 without a concomitant increase in the chain length of the newly synthesized products.

Animals↗

Relationship between exposure and environmental concentrations in organic solvent workplaces.

The correlation between the exposure concentration (ExpC) of workers and the environmental concentration (EnvC) in their workplaces were examined in 143 printing, painting, gluing, degreasing and other solvent workplaces manned by 535 workers of both sexes. ExpC was measured with carbon felt dosimeters, and EnvC was with grab sampling of air into poly-tetrafluoroethylene bags; both were followed by GC analyses. When ExpC and EnvC were compared on both group and individual basis, the correlation was found to be positive but rather weak, and individual difference in ExpC within the workers of the same workplace was not negligible. Workplaces were classified after regulatory practice into three categories, and attempts were made to find out the conditions so that none among the 174 workers in the 43 Category 1 (i.e., "clean" from regulatory view point) workplaces would be exposed to solvent vapors over the current occupational exposure limit (OEL). Accordingly, it was found that the requirement will be met in case half the OEL is taken as the E value (the EnvC limit set by the regulation). Thus, the same conclusion was reached through the analyses of two separate batches of experiences, i.e., one in the present study and the other in the previous report (Ikeda and Ohtsuki 1985).

Environmental Exposure↗