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Biomedical subjects

Y Kimura

Publications and source records attributed to Y Kimura.

At least 19 recordsLinked to original sources

Effect of bradykinin to cyclic AMP levels and response of murine lymphocytes.

No information is available on the pharmacological effect of bradykinin to lymphocytes and immunological responses of them. In this study it was clarified that bradykinin as well as histamine elevated cyclic adenosine 3',5' monophosphate (cAMP) levels of murine splenic or lymph node lymphocytes and mature thymocytes (cortisone-resistant thymus), but did not increase cAMP levels of immature thymocytes as well as histamine. The increased cAMP ratios in T cell-enriched splenic lymphocytes by the impulse of bradykinin were higher than that in splenic and lymph node lymphoid cells by the stimulation of bradykinin. It was also demonstrated that bradykinin as well as histamine suppressed DNA synthesis by mitogenic (PHA-P, Con-A) stimulation of splenic lymphocytes, but not a effect to the response of lymphocytes by mitogenic (LPS) stimulation was observed. These facts suggest that bradykinin may play an important role in the regulation of immunologic lymphocyte responses.

Animals

Protection of mice against virulent virus infection by a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.

Experimental infection with HVJ (haemagglutinating virus of Japan-the Sendai strain of parainfluenza 1 virus) in mice was studied. Aerosol infection of newborn mice with the wild-type virus (HVJ-W) retarded the development of body weight and killed the animals within a few weeks. Large amounts of virus were isolated from both the lungs and the nasal turbinates of infected mice. In contrast, newborn mice exposed by inhalation to a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture showed no clinical signs and grew equally well as mock-infected animals. No infectious virus could be recovered from the lungs although the ts mutant grew to moderate titre in the nasal turbinates. The prior inoculation of newborn mice with the ts mutant virus induced a state of significant resistance to subsequent challenge with the virulent wild-type virus. No replication of challenge virus in both lungs and nasal turbinates could be detected and the animals were protected a lethal infection. It is suggested that an avirulent temperature-sensitive mutant which has lost the capacity to replicate in the lower respiratory tract but is still capable of multiplying in the nasal turbinates may be a promising candidate for use in live vaccines especially against the infectious disease of the lower respiratory tract.

Animals

Characterization of the polypeptides synthesized in cells infected with a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.

The intracellular synthesis of virus-specific polypeptides in cells infected with the wild-type virus of HVJ (HVJ-W) (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) and with a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture has been analysed by polyacrylamide gel electrophoresis. At the permissive temperature (32 degrees C), all of the known virus structural polypeptides were identified in cells infected with each strain of virus and in addition to the non-structural polypeptides B and C, another polypeptide at the region with a molecular weight of 26,000 to 27,000 (26 to 27K) could be detected in infected cells. At the non-permissive temperature (38 degrees C), the synthesis of the polypeptide M was markedly restrained in cells infected with HVJ-pB, while other major virus polypeptides were present in approximately comparable amounts to cells infected with the wild-type virus. A non-structural polypeptide with a molecular weight of 105K was dominant in ts mutant infected cells at higher temperatures and disappeared after temperature-shift from 38 degrees to 32 degrees C. The production of the non-structural polypeptides B and 27K was also temperature-sensitive. The molecular weights of the polypeptides B, M and 27K in HVJ-pB infected cells were larger than those of the corresponding polypeptides in HVJ-W infected cells. The synthesis of the M protein in HVJ-prinfected cells started just after lowering the incubation temperature and the newly made M protein was successfully incorporated into virus particles.

Animals

Tryptic peptide analysis of the structural proteins of a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.

The individual structural polypeptides of HVJ (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) were examined by tryptic peptide analysis. [3H]-methionine-labelled structural proteins of the wild-type virus of HVJ (HVJ-W) and [35S]-methionine-labelled corresponding constituent proteins of a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture were compared by ion-exchange chromatography on columns of P-type chromobeads. The tryptic peptides of the individual structural proteins showed characteristic elution profiles. In all the structural proteins tested, the chromatographic elution profiles of both strains generally showed a close resemblance. However, certain minor peaks which were present in one strain but absent in the other strain were detected in the preparations of the P, HN, and F polypeptides. Further, analysis of the NP polypeptide showed that a major peak of one strain appeared at a position in the pH gradient different from a seemingly corresponding major peak of the other strain. In the M protein some possibly homologous minor peaks were found to differ between the two strains.

Mutation

Assembly of viral structural proteins in cells infected with a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture. Brief report.

The processing of virus polypeptides synthesized in cells infected with HVJ (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) was studied. Maturation of a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture was inhibited at 38 degrees C incubation. A considerable amount of viral components were made at the restrictive temperature. They were, with the exception of the polypeptide HN, well preserved without a great loss of their function and successfully incorporated into virus particles released after lowering the incubation temperature. The membrane (M) protein seems to be essential for virus morphogenesis.

Animals

Inhibition of interferon action by chinoform.

Chinoform, iodochlorhydrozyquin, was found to suppress the antiviral action of interferon. Chick embryo fibroblast cells treated with the mixture of interferon and chinoform were more sensitive to Sindbis virus infection than cells treated with interferon alone. No evidence for a direct inactivation of interferon molecule by chinoform was obtained. Treatment with chinoform of cells previously exposed to interferon also removed a cellular antiviral state induced by interferon. Chinoform suppressed intracellular ribonucleic acid (RNA) and protein syntheses. It is suggested that the inhibitory effect of chinoform on the action of interferon is due to a suppression of continued production of antiviral proteins.

Animals

Partial purification, physicochemical characterization and biological function of a rosette-decreasing factor (RDF) extracted from guinea pig thymus.

A factor that decreases rosette formation between guinea pig T-cells and rabbit red blood cells (RRBC) was extracted from the thymus of the guinea pig. The active factor could be extracted from the spleen as well as the thymus, but not from the liver or kidney. The active factor of the thymic extract was found in the precipitates produced by 80% saturated ammonium sulfate and it was separated from the water-soluble fraction of the precipitates. The molecular weight of the partially purified substance was estimated to range between 10,000 and 30,000 by filtration through a diaflow membrane. From the studies on physicochemical characterization, it might be a heat-resistant basic peptide probably bound to a ribonucleotide moiety. This factor reduced rosette formation between RRBC and guinea pig T-cells, but did not reduce erythrocyte-antibody-complement rosette formation. This factor also inhibited mitogen (concanavalin A, phytohemagglutinin-P)- induced DNA synthesis of guinea pig lymphocytes and antigen-induced DNA synthesis of sensitized guinea pig lymphocytes.

Animals

Adjuvant activities in production of reaginic antibody by bacterial cell wall peptidoglycan or synthetic N-acetylmuramyl dipeptides in mice.

This paper is concerned with the adjuvant activity in stimulatory immunoglobulin E production against ovalbumin (OA) by bacterial cell walls, cell wall peptidoglycan (PG), and their PG fragments and synthetic N-acetylmuramyl (MurNAc) dipeptides in A/J mice. A PG isolated from Streptococcus pyogenes, PG subunit polymer and dimer obtained from Staphylococcus epidermidis, and water-soluble fragments of cell walls or PG prepared from Nocardia corynebacteriodes and Streptomyces gardneri were found to enhance both the primary and secondary responses of anti-OA immunoglobulin E antibody production. It was suggested that the PG portion, either intact or highly degraded, was capable of enhancing the immunoglobulin E antibody production, and there was no need for the non-PG moiety or intactness of PG structure for the adjuvant activity. This finding was confirmed and extended by the use of synthetic MurNAc dipeptides. Among eight MurNAc dipeptides tested, MurNAc-l-Ala-d-isoGln, MurNAc-l-Ala-d-Gln, MurNAc-l-Ala-d-Glu, and MurNAc-l-Ser-d-isoGln were found active as an adjuvant in the stimulation of the primary and secondary reaginic anti-OA antibody production in a similar way to the cell wall PG and their fragments. None of the synthetic MurNAc-l-Ala-l-isoGln, MurNAc-l-Ala-l-Gln, MurNAc-l-Ala-l-Glu, and MurNAc-l-Ala-d-isoAsn, on the other hand, stimulated the anti-OA immunoglobulin E antibody production in either primary or secondary response, indicating the importance for the adjuvancy in immunoglobulin E production of the configuration of the glutamic acid residues adjacent to the l-Ala (or l-Ser) in muramyl dipeptides.

Acetylmuramyl-Alanyl-Isoglutamine

[Effects of diethyldithiocarbamate on ejaculatory inhibition and change in monoamine levels of accessory glands (author's transl)].

Effects of diethyldithiocarbamate(DDC) on erection and ejaculation were investigated and monoamine levels in central nervous system, gonad and accessory glands were determined in dogs. Intraperitoneal administration of 50, 75 and 100 mg/kg of DDC suppressed ejaculation 1 hour after administration, although penial erection did occur. This suppression of ejaculation was recovered to some extent 3 hours after DDC and completely recovered 24 hours after DDC. One hour after the administration of 100 mg/kg of DDC, noradrenaline (NA) level in the caudate and serotonin (5-HT) level in the posterior hypothalamus decreased significantly, as compared with the control. However, there were no significant changes in the regions of anterior hypothalamus and hippocampus which are known to play an important role in sexual behavior. In the epididymis, NA and adrenaline levels decreased significantly, though 5-HT levels increased, as compared with those of the control. In the prostate and posterior urethra, NA levels decreased significantly, as compared with the control. The seminal emission induced by hypogastric nerve stimulation induced a gradual rise in the posterior urethral pressure. When the pressure reached the maximum level, rhythmic alterations of the pressure considered to be a phenomenon associated with ejaculation occurred. DDC (100 mg/kg) abolished both seminal emission and rhythmic alterations of the posterior urethral pressure. These findings indicate that the sperm transport may be inhibited by decrease of NA level in accessory glands.

Amines

Effects of intraventricularly administered serotonin, noradrenaline, dopamine and metaraminol on the reserpine-induced spikes recorded from the medial nucleus trapezoides in rabbits.

Effects of intraventricularly administered serotonin (5HT), noradrenaline (NA), dopamine (DA) and metaraminol on the reserpine-induced spikes recorded from the medial nucleus Trapezoides (Trap. m.) in rabbits were investigated. 5HT (30, 50 micrograms) produced marked decreases in the amplitude and discharge rate of the spikes 3 to 5 min after intraventricular administration. NA (30, 50 micrograms) also produced similar effects to those of 5HT, but DA at the same dosage produced no significant changes in the amplitude and discharge rate of spikes. Metaraminol, a metabolite of alpha-methyl-m-tyrosine, produced gradual and long-lasting, potent suppression of spikes. Ninety min later, spikes were completely suppressed, and no recovery was observed within 6 hours after intraventricular administration. These results indicate that NA has a similar suppressing action to that of 5HT on the generation of the reserpine-induced spikes.

Action Potentials

Effect of 1 alpha-hydroxyvitamin D3 in rats with experimental renal osteodystrophy.

A model of experimental renal osteodystrophy was established in the rats with chronic renal failure induced by partial nephrectomy and therapeutic effects of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) were studied. Male Wistar rats weighing 180 g were 5/6 nephrectomized and fed a normal diet (Ca and P : 1%) for 6 months. After the surgery, serum creatinine levels increased 60% and thereafter continued to rise gradually with their growth for 4 to 5 months, followed by rapid increase. The serum phosphorus levels were also elevated concomitantly and the serum calcium concentrations were normal. Marked bone resorption accompanied with hypertrophy of parathyroid glands was observed by histological examinations (Tetrachrome-Fuchsin stain, contact microradiography and H-E stain). The bone resorption seemed to be due to secondary hyperparathyroidism. Treatment with 0.25 micrograms/kg/day p.o. of 1 alpha-OH-D3 for 10 days in the uremic state resulted in remarkable new bone formation which was confirmed by histological examinations. These results clearly demonstrated that the reduction of nephron mass play a critical clue of renal osteodystrophy and 1 alpha-OH-D3 appears to have a good potential for clinical use in patients with renal failure and metabolic bone diseases.

Animals

Anti-androgen TSAA-291. V. Effects of the anti-androgen TSAA-291 on the androgen-receptor complex formation from [3H]testosterone in rat ventral prostates.

Intramuscular administration of a new steroidal anti-androgen, TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one), in doses of 0.05, 0.5 and 5 mg/kg body weight reduced the in vivo uptake of [3H]testosterone by the ventral prostate of castrated rats of 78, 59 and 37% of the control level, respectively. Analysis on subcellular fractions of the prostate by gel-filtration and sucrose density-gradient centrifugation followed by thin layer chromatographic identification of testosterone metabolites revealed that 5 alpha-dihydrotestosterone (5 alpha-DHT) which was found to be largely bound to macromolecules in the cytosol and nucleus was the predominant metabolite even in the presence of the anti-androgen, and radioactivities corresponding to the 5 alpha-DHT-macromolecular complexes were decreased by the anti-androgen. TSAA-291 also inhibited the in vitro formation of the 5 alpha-DHT-macromolecular complexes in both cytosol and nucleus from minced prostates incubated with [3H]testosterone. The importance of the findings is discussed in connection with the mode of anti-androgenic action of TSAA-291 in terms of the interaction with the androgen receptor.

Androgen Antagonists

Examination of latent infection in germfree mice for some murine viruses.

Sera from some groups of germfree mice were examined for reactivity against Sendai, reo 3, Theiler's GD VII, ectromelia, and mouse hepatitis virus antigens. Of 51 sera collected in September and October 1976 and in August and September 1977 from one germfree mouse breeding colony, there was no positive reaction against all the antigens tested. Moreover, the attempt of virus isolation from homogenates of various organs including lungs, liver, kidneys, and intestines of 6 germfree mice was unsuccessful.

Animals