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Biomedical subjects

K Ichikawa

Publications and source records attributed to K Ichikawa.

At least 397 records · Page 22Linked to original sources

Non-adenomatous inappropriate TSH hypersecretion and euthyroidism requires no treatment.

The syndrome of inappropriate TSH secretion is described in a euthyroid girl and her father. Based on nuclear T3 binding studies in fibroblasts, generalized tissue resistance was associated with a lower binding affinity for T3 in nuclear extracts suggestive of a structurally abnormal receptor for T3. Early recognition of the syndrome and observation of the short-term response to thyroid medication prevented unnecessary trials of antithyroid medication and later radical ablative thyroid treatment.

Child, Preschool↗

Modification of deoxyribonucleic acid-thyroid hormone receptor interaction by histones.

The effects of histones on receptor-DNA interaction were examined using an in vitro DNA-cellulose-binding assay of [125I]T3 receptor. H1 histones bound to DNA-cellulose strongly inhibited binding of receptor to DNA-cellulose. DNA-cellulose column chromatography showed that 80% of T3-binding activity attached to DNA-cellulose could be eluted using 1 mg H1 histone/ml at low ionic strength. The potent inhibitory activity of H1 histones on receptor-DNA binding was reversed by removal of H1 histones from DNA-cellulose or by removal of H1 histones from receptor. The interaction was specific for the DNA-binding activity of receptor, since H1 histones inhibit neither T3-binding activity nor core histone-binding activity of receptor. In contrast, low concentrations of core histones enhanced binding of T3 receptor to DNA-cellulose. This effect was also seen when DNA-cellulose was treated with core histones and then deprived of free core histones. The enhancement was reversed by removal of core histones bound to DNA-cellulose. A tryptic fragment of the receptor, which lost DNA-binding activity but retained hormone and core histone-binding activities, was capable of binding to DNA-cellulose in the presence of core histones. These data suggest that enhanced binding of receptor to DNA-cellulose by core histones is mediated through the core histone-binding activity of receptor. A heat-labile protein factor in nuclear extracts (possibly receptor itself) also enhanced receptor binding to DNA-cellulose. Our data suggest important roles of histones in the organization of nuclear thyroid hormone receptors in chromatin. Since H1 histone participates in condensation of chromatin and is enriched in transcriptionally inactive chromatin, inhibition of DNA-binding activity of receptor by H1 histone bound to DNA could explain the preferential binding of nuclear thyroid hormone receptor to transcriptionally active chromatin.

Animals↗

[The pharmacological properties of a new anti-allergic agent, KP-136, in cutaneous models].

The pharmacological properties of KP-136 were studied using cutaneous reactions in rats and guinea pigs. KP-136 remarkably inhibited the passive cutaneous anaphylaxis (PCA) with intravenous and oral dosing. However, the inhibitory effect of KP-136 had an apparent species difference. Thus, KP-136 was more effective on rat PCA than that of guinea pig. In four rat cutaneous reactions produced by three allergic reactions and compound 48/80, KP-136 was remarkably effective on two homologous PCA induced by IgE and IgGa. The intravenous and oral doses for 50% inhibition on the PCA were 0.2 mg/kg to 0.4 mg/kg and 0.5 mg/kg to 0.9 mg/kg, respectively. KP-136 was scarcely effective on cutaneous reactions elicited by intradermal injection of histamine and serotonin which are main chemical mediators in rat homologous PCA. However, KP-136 blocked the degranulation of mast cells and decrease of histamine content in skin elicited by the PCA. In addition, KP-136 showed a potent inhibition on the immunological release of histamine from rat peritoneal exudate cells. The concentration for 50% inhibition on the histamine release was 5 ng/ml. These findings indicate that KP-136 is an oral potent inhibitor on PCA, and it acts by blocking the release of chemical mediator(s) from mast cells.

Administration, Oral↗

Effect of thyroid hormone on peroxisomal flavin enzymes in rat liver and kidney.

The effect of thyroid hormone on peroxisomal enzyme activity was studied in thyroidectomized- and T4-administered-thyroidectomized rats. In liver, the activities of isozyme A of L-alpha-hydroxyacid oxidase, D-amino acid oxidase, urate oxidase and catalase were decreased by thyroidectomy, and the diminished enzyme activities were restored by T4 administration to rats. These modifications induced by thyroidectomy or by T4 administration, however, were prominent only in immature animals (20-day-old rats). Although the changes in-alpha-hydroxyacid oxidase and D-amino acid oxidase activities, induced by thyroidectomy or by T4 administration, were also observed in 40-day-old rats, those in urate oxidase and catalase activities were not significant in 40-day-old rats. Acyl CoA oxidase activity was not affected by thyroidectomy or by T4 administration in either 20- or 40-day-old rats. In the kidney, isozyme B of L-alpha-hydroxyacid oxidase activity was reduced by thyroidectomy and the diminished enzyme activity was restored by T4 administration in both 20- and 40-day-old rats. D-Amino acid oxidase and catalase activities in kidney, however, were not significantly modified by thyroidectomy or by T4 administration in either 20- or 40-day-old rats. The results suggest that thyroid hormone can modify the peroxisomal enzyme activity, which is prominent in immature animals.

Alcohol Oxidoreductases↗

Hepatocellular carcinoma growing in the pulmonary arteries, complicated with venous thrombosis.

A case of hepatocellular carcinoma (HCC) complicated with vascular invasion of the portal vein, hepatic vein, and pulmonary artery, accompanied by inferior vena caval and renal vein thrombosis, is reported. The patient was a 38-year-old female, positive in serum HBsAg and anti-HBe. Because portal trunk thrombosis was pointed out at the first diagnosis, incomplete transcatheter hepatic arterial embolization was carried out three times and one-shot therapy of anti-cancer agent given once. Four months after the first therapy, the patient died of oliguria and hypotension of sudden onset. The autopsy revealed not only intrahepatic vascular invasion but also tumor growth in the bilateral pulmonary arteries and thrombosis from the inferior vena cava to both renal veins unaccompanied by right atrial growth. Because the renal vein was thrombosed and HCC was accompanied by vascular invasion, especially pulmonary arterial invasion, the patient was thought to have become oliguric and hypotensive before severe hepatic failure. The metastatic tumor had grown in the pulmonary trunk without intra-atrial expansion because of the histological tight junction between the tumor and the wall of that vessel.

Adult↗

Influenza virus depresses the PFC response of mice by affecting T-cell function.

Five influenza virus strains of type A and one strain of type B were used to elicit suppressive effect on the formation of antibody producing cells in response to sheep red blood cells (SRBC) both in vivo and in vitro. Not only live virus but also the formalin inactivated one exerted immunosuppression (IS). Although intranasal infection only could cause disease in mice, it exerted no IS which, in contrast, occurred after intraperitoneal or intravenous injection of the virus. In nude mice these effects were not seen, but they could be elicited when transferred with normal T cells. The antibody response to T cell independent antigen such as DNP was normal. Thus, it was proved that influenza virus induced T cell dependent immunodeficiency. However, T cell enriched population from infected mice when cultured with normal spleen cells could not suppress their PFC response in vitro. This suggested that suppressor T cells were not required for the immunodeficiency caused by influenza virus.

Animals↗

Separation of DNA binding domain from hormone and core histone binding domains by trypsin digestion of rat liver nuclear thyroid hormone receptor.

Rat liver nuclear thyroid hormone receptor was subjected to limited trypsin digestion, and the tryptic fragment of the 3,5,3'-triiodo-L-thyronine (T3)-receptor complex was characterized. Rat liver nuclear thyroid hormone receptor is an asymmetrical protein with Stokes radius of 34 A, sedimentation coefficient of 3.4 S, and molecular weight of 49,000. A globular T3-receptor complex with Stokes radius of 22 A, sedimentation coefficient of 2.8 S, and molecular weight of 26,000 was obtained by tryptic digestion. This fragment had no DNA binding activity, whereas undigested receptor showed significant DNA binding activity. Addition of undigested receptor to the tryptic fragment did not restore DNA binding activity of digested receptor, nor did mixing inhibit DNA binding activity of undigested receptor complex. Undigested receptor bound to core histones, and this activity was stronger than with other proteins tested (H1 histone, cytochrome c, and ovalbumin). The tryptic fragment of receptor maintained core histone binding activity comparable to that of undigested receptor. The tryptic fragment had affinity for T3 comparable to undigested receptor as assessed by Scatchard analysis and the same rate for dissociation of [125I]T3 from receptor. The tryptic fragment of the T3-receptor complex was more stable than undigested receptor at 43 degrees C. Digestion of receptor unoccupied by T3 caused a significantly larger loss of T3 binding capacity than did digestion of T3-occupied receptor, suggesting a protective effect of T3 on a second trypsin-sensitive site on the receptor, which, when cut, destroys T3 binding activity.

Animals↗

Two cases of retinal degeneration with an unusual form of electroretinogram.

An unusual form of retinal degeneration is reported in 15-year-old girl and 11-year-old girl with different pedigrees, which resembles the cases reported by Gouras and associates (1983). The subjective symptoms in these patients included decreased visual acuity, photophobia, anomalous color vision and night blindness. Electroretinograms (ERGs) in these two patients were identical in substance and revealed drastic alterations in both photopic and scotopic functions. The stimulus versus intensity response curve in a single-flash ERG showed an unusual form. This peculiar supernormal response was elicited by bright stimuli although the stimulus threshold was extremely elevated.

Adolescent↗

Nuclear thyroid hormone receptors in cultured human fibroblasts: improved method of isolation, partial characterization, and interaction with chromatin.

In order to characterize the nuclear thyroid hormone receptors in human tissue, an improved method for isolation of nuclei from cultured human fibroblasts was developed. This method provided nuclei with a protein/DNA ratio of 2.8 and recovery of 42%. The purity of nuclei was verified by phase contrast and electron microscopy, which showed normal appearance of chromatin structure. Nuclear binding assay was performed by incubation of whole cells at 37 degrees C or isolated nuclei at 22 degrees C with L-triiodothyronine (T3). In both cases, an affinity constant (Ka) of 2.0-3.0 X 10(10) M-1 and an average binding capacity of 41 femtomoles of T3/100 micrograms DNA (3,100 binding sites/nucleus) were obtained. During incubation of the nuclei, 13% to 16% of receptors that had an identical Ka was released into the medium. Salt extraction recovered 85% to 90% of the receptors, which had a Ka of 4.5 X 10(10) M-1 and the capacity of 0.13 pmol of T3/mg protein. The Ka fo. L-thyroxine (T4) was seven to 18 times lower than that for T3, but the capacity was the same in isolated nuclei, receptors released during incubation of nuclei, and in salt-extracted receptors. Of the iodothyronines examined, affinity for triiodothyroacetic acid was the highest, followed by L-T3, D-T3, L-T4. Isokinetic glycerol gradient analysis revealed that salt-extracted receptors had a sedimentation coefficient of 3.4 S, whereas micrococcal nuclease digested receptors showed two major (6.0 to 6.5 and 12.5 S), and two minor (17 and 19 S) peaks. These results were virtually identical to those obtained with rat liver nuclei analyzed in parallel studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Models for quick activation of transducin and spontaneous deactivation of activated rhodopsin in rod outer segments.

Serial-parallel activation (S-P) and parallel-parallel activation (P-P) models had been proposed to account for the quick activation of transmitter molecules (transducin) in the visual transduction process in rod outer segments. In these models, unbleached rhodopsin molecules are activated by bleached rhodopsin molecules, and both bleached and activated rhodopsin molecules activate transducin. This activation mechanism enables bleached rhodopsin molecules to transfer the information of photon detection quickly to transducin. In the previous models, however, the rhodopsin photoisomerization process and the deactivation process of activated rhodopsin molecules were excluded. In the present study, these two processes are incorporated into the models. The deactivation process of activated rhodopsin molecules is assumed to proceed spontaneously. It is presented that, in spite of the incorporation of these two processes, the present S-P and P-P models can account for the quick activation of transducin in rod outer segments.

Animals↗