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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 973 records · Page 54Linked to original sources

The interaction between two forms of cytochrome P-450 during drug oxidation in the reconstituted system containing limited amount of NADPH-cytochrome P-450 reductase.

The activities of drug oxidation in a reconstituted system which contains two forms of cytochrome P-450 and a limiting amount of NADPH-cytochrome P-450 reductase were determined. Cytochrome P-450 (termed MC P-4481 and MC P-4482) purified from liver microsomes of 3-methyl-cholanthrene-treated rats was active in both 2- and 4-hydroxylation of biphenyl but cytochrome P-450 (termed PB P-450) purified from liver microsomes of phenobarbital-treated rats was active in 4-hydroxylation of biphenyl only. PB P-450, MC P-4481 and MC P-4482 were most active toward benzphetamine N-demethylation, aniline hydroxylation and 7-ethoxycoumarin O-deethylation, respectively. PB P-450 inhibited the activity of biphenyl 2-hydroxylation supported by MC P-4481 or MC P-4482. On the contrary, no inhibition of PB P-450 supported benzphetamine N-demethylation was observed when MC P-4481 or MC P-4482 was added to the system containing PB P-450 and limited amount of the reductase. The apparent Km of PB P-450 for the reductase obtained from double reciprocal plot of the reductase concentration and the activity of biphenyl hydroxylase or benzphetamine N-demethylation was lower than that of MC P-4481 or MC P-4482. These and other results suggest that there is a certain hierarchy among the cytochrome P-450 species for receiving electrons from reductase.

Animals↗

Isolation of a novel antibody, which precipitates ribonucleoprotein complex containing threonine tRNA from a patient with polymyositis.

We have isolated and characterized a novel antibody from a patient with polymyositis, which precipitates threonine tRNA and an unknown small RNA molecule from 32P-labeled HeLa extract. Fingerprint analysis showed that the human threonine tRNA precipitated was nearly identical to the murine tRNA described by Harada [(1978) Seikagaku 50, 397-411]. Nucleotide analysis suggested that the other small RNA molecule might be transfer RNA. Since phenol extraction resulted in the loss of immunoprecipitability, the protein portion was presumed to be involved in the recognition of the antigen. Immunofluorescence staining of HeLa cells with the antibody clearly demonstrated that the antigen was located predominantly in the cytoplasm.

Autoantibodies↗

The 6S RNA transcribed from rodent total DNA in vitro is the transcript of the type 2 Alu family.

We have performed in vitro transcription, using total DNA isolated from mouse and a cloned mouse DNA fragment containing a representative type 2 Alu sequence characterized by Kominami et al. (1983) as templates. From each template, 6S RNA was transcribed. The fingerprint of the 6S RNA produced from in vitro transcription of total DNA showed a very clear pattern of oligonucleotides. By comparing the oligonucleotides of the 6S RNA produced from each template, we demonstrated that the 6S RNA transcribed from mouse total DNA is the in fact the transcript of type 2 Alu sequences. The composition of the oligonucleotides of the 6S RNA transcribed from mouse total DNA seems to reflect well that of the consensus sequence of the type 2 Alu family proposed by Krayev et al. (1982). In vitro transcripts of rat or hamster total DNA showed fingerprint patterns nearly identical to that of mouse DNA, confirming that rodents have equivalent type 2 Alu sequences whose transcripts have the same length and similar compositions of oligonucleotides. Thus total DNA transcription provides a novel approach to the detection and analysis of type 2 Alu sequences transcribed in vitro.

Animals↗

Lipomas in the corpus callosum and the forehead, associated with a frontal bone defect.

This report concerns a case of lipomas in the corpus callosum, possibly both lateral ventricles, and the forehead, which were associated with a defect in the frontal bone. It is thought that the lipoma originated in the interhemispheric fissure and extended to the forehead by at least the second month of gestation. It interfered with the development of the corpus callosum, and the collagenous capsule of the lipoma remained till birth. It caused a defect in the frontal bone in the midline, in spite of the development of both frontal bones.

Brain Neoplasms↗

Chronic mononucleosis syndrome.

We present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection. Two thirds were women, and the average age at onset was 29.6 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome. Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied. Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission. Comparison is made with other reported chronic, recurrent, and persistent EBV syndromes, and tentative diagnostic criteria for chronic mononucleosis syndrome are presented. Recently available EBV serologic techniques allow for identification of patients who have reactivated EBV infection, and this reactivation may be related to symptoms.

Adolescent↗

Enforcement of specific unresponsiveness by the long-term presence of allogeneic heart grafts.

Mechanisms underlying the maintenance of long-term heart allografts were analyzed in rats treated with Cyclosporine. It was shown that acceptance of allografts after cyclosporine did not involve the attenuation of immunogenicity of the grafts. This conclusion was drawn from two observations: (1) Pretreatment of the donors with cyclosporine did not cause prolongation of graft survival time; and (2) cyclosporine stabilized allografts were normally rejected by secondary recipients when retransplanted on day 30. Studies of the acceptance of skin grafts from the heart donor strain indicated the existence of a mechanism to maintain donor-specific unresponsiveness in the presence of a stable allograft in a time-dependent manner. Thus, the mean rejection time of F344 skin grafts on WKA rats bearing F344 hearts was more than 80 days when transplanted on day 210, but it was 32 days when they were transplanted on day 30. Active participation of specific suppressor cells in the maintenance of unresponsiveness was suggested because data obtained in the cell transfer experiments was statistically significant. Transfer of lymphocytes from rats bearing long-term grafts showed a tendency to delay rejection of skin grafts by sublethally irradiated hosts, but it failed to delay the rapid rejection by normal lymphocytes cotransferred to the same recipients.

Animals↗

The comparative ototoxicities of panimycin and gentamicin in cynomolgus monkeys (Macaca fascicularis).

In order to comparatively examine damage to vestibular and auditory organs, aminoglycoside antibiotics, panimycin (DKB) and gentamicin (GM), were intramuscularly injected to cynomolgus monkeys in an identical daily dose regimen (25 and 50 mg/kg) for a 35-day period. No damage to these organs was found in the DKB 25 mg/kg group, but slight vacuole formation was found in 33% of the cristae ampullares in the DKB 50 mg/kg group. In the GM 25 mg/kg and GM 50 mg/kg groups, similar vacuole formations, as well as sensory hair cell loss even at the basal end of the cochlea were found. Compared to the DKB groups, the GM groups exhibited greater damage to the vestibular and auditory organs, and even fatal effects. The ototoxicity of GM seemed to be stronger in cynomolgus monkeys than in guinea pigs.

Acoustic Maculae↗

Effect of (+/-)-2-[p-(2-thenoyl)phenyl] propionic acid (suprofen) on experimental allergic reactions.

The effects of (+/-)-2-[p-(2-thenoyl)phenyl] propionic acid (suprofen), a new anti-inflammatory agent, on experimental allergic reaction and antibody formation were examined. The action was compared with those of ketoprofen, ibuprofen, indomethacin, tranilast, chlorpheniramine, prednisolone and/or cyclophosphamide. Suprofen inhibited homologous PCA in rats, immunological histamine release from rat peritoneal mast cells and guinea pig lung tissues, Forssman cutaneous vasculitis (FCV) and the Arthus reaction in guinea pigs. The potency for inhibition of the PCA reaction was similar to that of ketoprofen and more potent than ibuprofen and trailast. As for the release of anaphylactic mediators, suprofen was less potent than tranilast in terms of histamine release, but not the release of the slow reacting substance of anaphylaxis (SRS-A). Suprofen inhibited FCA more potently than other nonsteroidal anti-inflammatory drugs (NSAID). The inhibition of the Arthus reaction by suprofen was similar to those of other NSAID and prednisolone. Suprofen hardly affected delayed hypersensitivity in guinea pigs and antibody (IgM or IgE) formation in mice or rats.

Animals↗

Membrane stabilizing action of NCO-650 and its congeners.

NCO-650 and its congeners and two other antiallergics, disodium cromoglycate and tranilast, were studied to determine the degree of protection of rat erythrocytes against hypotonic hemolysis, the reduction of the surface tension of dipalmitoylphosphatidylcholine (DPPC) monolayer and the depression of the phase-transition temperature of DPPC liposome bilayers. NCO-650 was found to show the greatest hemolysis protection, reduction of the surface tension and depression of the phase-transition temperature, indicating that it possesses a significant affinity to cell membranes and a significant ability to stabilize cell membranes. Disodium cromoglycate and tranilast showed neither cell membrane affinity nor hemolysis protection, although they inhibit histamine release from mast cells like NCO-650 and its congeners. The significant membrane stabilizing action of NCO-650 must be related, at least in part, to its extraordinarily high lipid solubility.

Animals↗