Search PubMed⌕ Search

Biomedical subjects

K Ichikawa

Publications and source records attributed to K Ichikawa.

At least 307 records · Page 17Linked to original sources
PubMed1991

Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism.

BACKGROUND: Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS: The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS: The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism.

Adolescent↗
PubMed1991

Purification of cytosolic 3,5,3'-triiodo-L-thyronine(T3)-binding protein(CTBP) which regulates nuclear T3 translocation.

The NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine(T3)-binding protein(CTBP) was purified from rat kidney using Mono Q-Sepharose, Red sepharose and T3 affinity chromatography. CTBP which was partially purified by Red Sepharose column chromatography was adsorbed to T3 affinity column in the presence of 50 uM NADPH. The CTBP was eluted from the gel with the buffer which did not contain NADPH. One molecule of the purified CTBP(58 kDa) bound one molecule of T3 with 2.44 x 10(9) M-1 of affinity constant. The purified CTBP was activated not only by NADPH but also by NADP in the presence of dithiothreitol. The NADPH-activated form did not transfer T3 to nuclei, whereas NADP transformed the NADPH-activated CTBP to active form which was able to transfer T3 to nuclei. These results suggested that CTBP-dependent transport of T3 to nucleus is controlled by NADPH and NADP.

Animals↗
PubMed1991

An autopsy case of mitochondrial encephalomyopathy with prominent degeneration in olivo-ponto-cerebellar system.

We describe a sporadic case of adult-onset, complex I deficiency mitochondrial encephalomyopathy (MEM), the clinical and pathological features of which failed to fit any of the known subgroups of MEM, such as Kearns-Sayre syndrome, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes or myoclonus epilepsy with ragged-red fibers. Clinically, this patient had only progressive cerebellar ataxia, generalized muscle weakness and hearing loss. The principal finding at autopsy was degeneration of the olivo-ponto-cerebellar system. This case suggests that mitochondrial disease could underlie some cases of olivo-ponto-cerebellar atrophy.

Cerebellum↗
PubMed1991

Cellular binding proteins of thyroid hormones.

Cellular binding proteins of thyroid hormones are present in the cell nucleus, cytosol, cell membrane, and mitochondria. While nuclear binding is proven to mediate hormone action, the exact roles of the other binding sites remain to be established. Nuclear receptor associates with DNA, core histone, and nuclear matrix and preferentially distributes in transcriptionally active chromatin due to interaction with H1 histone. Of particular importance is the binding of nuclear receptor to specific DNA sequences of target genes, termed thyroid-responsive elements. The binding is stabilized by non-receptor nuclear protein. Upon binding thyroid hormone, nuclear receptor is activated through alterations in the steric configuration, leading to changes in the rate of transcription of the target genes. Multiple nuclear receptor forms exist with likely distinct functional roles. Cytosolic thyroid hormone binding proteins are also heterogeneous. One form is under the control of cell metabolism (NADP and NADPH) and it may have a role in transport of the hormone to mitochondria and nucleus. Membrane-linked thyroid hormone binding proteins may have dual functional roles: one is to mediate hormone action and the other is to support active uptake of hormones by cells. Mitochondrial function may be regulated by thyroid hormone through mitochondrial binding sites in cooperation with nuclear receptor-mediated pathway. Further studies are required to elucidate the exact functional roles of non nuclear thyroid hormone binding proteins.

Animals↗
PubMed1991

A model for self-organization of receptive fields and orientation-selective columns in the striate cortex.

In area 17 of the cat visual cortex, simple cells form a hypercolumn in which the optimum orientation from one column to the next gradually changes, composing a complete set of orientation-selective columns (orientation column). This article proposes a model for the development of the bar-shape receptive field of a simple cell and the self-organization of orientation columns. The receptive field of an immature cell in area 17 is assumed to be composed of a circular center and surrounding regions whose synaptic modification rules are different. The synaptic modifications also differ depending on whether the response of a cell is locally maximal or not. The modification of the efficacy of both excitatory and inhibitory synapses is determined according to the combination of activities of the visual cortical cell and the lateral geniculate neuron. The simulation of this model shows the development of the bar-shape receptive field and the self-organization of orientation columns of more than one cycle from 0 degrees to 180 degrees. The abnormal presentations of visual stimuli to this model result in the abnormal development of the orientation column. These simulation results are in good agreement with reported experimental results. Possible neural circuits to achieve this model are proposed. The neural circuits for the synaptic modification are built on the assumption that cortical cells release molecules to modify synaptic efficacies. The neural circuits for the detection of the maximally responding cell are composed of two kinds of inhibitory interneurons. The bar-shape receptive field is assumed to be a consequence of the topographic projection of visual afferents, radial branching of dendrites of a simple cell, and the existence of an inhibitory interneuron.

Animals↗
PubMed1991

Molecular definition of human beta 2-glycoprotein I (beta 2-GPI) by cDNA cloning and inter-species differences of beta 2-GPI in alternation of anticardiolipin binding.

Human beta 2-glycoprotein I (beta 2-GPI) is involved in cardiolipin (CL) binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). We examined the inter-species differences of beta 2-GPI in alternation of CL binding of aCL. beta 2-GPI preparations were obtained from human, bovine, and rat sera by sequential CL--polyacrylamide affinity, DEAE--cellulose, and anti-human IgG-conjugated Sepharose CL-4B column chromatography, and they had apparent molecular weights of 50, 53, and 55 kDa respectively. Human beta 2-GPI not only enhanced CL binding by aCL in SLE but also depressed it by those in syphilis. Either bovine and rat beta 2-GPI exerted no or quite small inhibition of the binding of syphilitic aCL compared with human beta 2-GPI whereas all three species of beta 2-GPI generated binding of aCL in SLE to a similar degree. Further, a complete cDNA clone, p beta 2-GPI, was isolated from a human hepatoma cell line, HepG2, and its nucleotide sequence was analyzed. The sequences of bovine and rat counterpart molecules (beta 2-GPI) are highly homologous to that of the deduced sequence, and their corresponding regions are 84.0 and 82.5% identical to the complete domain and to the amino acid sequence 53-326 of human beta 2-GPI respectively. One of major differences appears at position 154 in human beta 2-GPI, and might be associated with the inhibitory effect on the binding of syphilitic aCL. The sequencing analysis of these beta 2-GPI proteins might provide leads to functional sites of domains which would be associated with such serological phenomena.

Amino Acid Sequence↗
PubMed1991

Clinical anatomic study of pure dysarthria.

Nine patients with pure dysarthria underwent computed tomography or magnetic resonance imaging. Eight patients had infarcts of lacunar or larger size in the internal capsule: four in the superior portion of the anterior limb or adjacent corona radiata and four in the superior portion of the genu or the adjacent corona radiata. In one patient, there was a small infarct in the bulbar motor cortex. Dysarthria was transient and characterized by poor articulation in all cases. Five patients also had contralateral facial weakness, and three patients with lesions in the genu had minimal and transient involvement of the contralateral fingers. These three cases appeared to be variants of the dysarthria-clumsy hand syndrome. We submit that this syndrome should sometimes be regarded as a stroke syndrome rather than always as a lacunar syndrome.

Aged↗
PubMed1991

Purification and characterization of thyroid hormone-responsive rat hepatic proteins.

Bernal et al. identified two proteins in rat hepatic nuclear extract, t- and n-proteins, that were enriched by thyroidectomy or T3 treatment, respectively. We purified these proteins, raised monospecific antibodies, and characterized them by Western blotting. Anti-n and anti-t-protein antibodies did not recognize t- and n-proteins, respectively. The n-protein was present in nuclear and cytosolic fractions, was present at low levels in the microsomal fraction, and was absent in the mitochondrial fraction of rat liver. The t-protein was more abundant in mitochondrial and microsomal fractions than in the nuclear fraction. The t-protein had the same molecular mass and shared immunological properties with peroxisomal enoyl-coenzyme-A (CoA) hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme. The total cellular amount of n-protein increased 12 h after the administration of 1 microgram T3/100 g BW to thyroidectomized rats. Induction was obvious at 0.1 microgram T3/100 g BW after 24 h. Maximal induction was observed at 0.3 microgram T3/100 g BW. The n-protein was induced when thyroidectomized rat liver was perfused with 10(-7) M T3 for 6 h, excluding the possibility that the effect of T3 was mediated by an extrahepatic factor. The n-protein was detected in liver and brain, but not in kidney, heart, testis, or spleen. However, the amount of n-protein in brain was not thyroid hormone dependent. Hepatic n-protein does not correspond to any other T3-responsive protein in terms of its molecular mass and intracellular localization and may be a novel T3-responsive protein.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1991

A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein (CTBP; 5.1S) in rat liver: a comparison with 4.7S NADPH-dependent CTBP.

A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) was purified by sequential fractionation of rat liver cytosol on Q-Sepharose, phenyl-Sepharose, red-Sepharose, and polyacrylamide gel electrophoresis under nondenaturing conditions. The CTBP had a sedimentation coefficient of 5.1S, a Stokes' radius of 35 A, and a calculated mol wt of 76,000. The apparently homogenous protein consisted of a dimer of a polypeptide chain with a mol wt of 38,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. NADPH increased both the affinity and maximal binding capacity for T3 in the 5.1S CTBP. The maximal activity to bind T3 was obtained by 3.0 x 10(-8) M NADPH. The calculated maximal affinity constant was 2.4 x 10(9) M-1, and the maximal binding capacity was 21,000 pmol T3/mg 5.1S CTBP. The order of affinity of iodothyronine analogs to the 5.1S CTBP was as follows: D-T3 greater than L-T3 greater than L-T4 greater than triiodothyroacetic acid. The optimal pH for T3 binding was 7.2-7.5. Ca2+, Mg2+, and Mn2+ (0.1-10 mM) did not influence T3 binding to CTBP. Zn2+ (1.0 mM), however, inhibited the binding. These results suggested that 5.1S NADPH-dependent CTBP, which is distinct from 4.7S CTBP that had been purified in our laboratory from rat kidney, is present in rat liver.

Animals↗
PubMed1991

Ontogenesis of the high affinity NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein in rat.

Studies were undertaken to define the concentration of the high affinity NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) in various tissues of adult rats and in those of developing rats. The maximal binding capacity (MBC) for T3 binding was calculated from the data obtained by Scatchard analysis of T3 binding to the charcoal-extracted cytosol in the presence of 50 microM NADPH. There were no significant differences in the affinity constant among various tissues, whereas the MBC was different among tissues in adult rats. When the levels of MBC were expressed by moles/DNA concentration, the order was as follows; kidney greater than heart greater than or equal to cerebrum greater than or equal to liver much greater than testis greater than cerebellum greater than spleen. The CTBP was not detected before birth in liver, heart, and spleen. The CTBP in these tissues emerged 5 days after the birth, and increased during 6 weeks after the birth. The CTBP in kidney was not detected before birth but was detected at the time of birth. The level of MBC in kidney increased during 3 weeks after the birth. In contrast, the CTBP was detected 5 days before birth, and the level of MBC increased at the time of birth both in cerebrum and cerebellum. The MBC in cerebrum gradually decreased after birth, but began to increase again 2 weeks after the birth. The level of MBC in cerebellum did not increase again. These results suggested that the target tissues of thyroid hormone are enriched with NADPH-dependent CTBP, and that the changes in the concentration of the CTBP are related to the growth of tissues. It was speculated that the CTBP has a specific function in cerebrum at the time of birth although the action of the CTBP is not certain.

Animals↗
PubMed1991

Purification and some properties of a Bacillus cereus mouse lethal toxin.

A mouse lethal toxin (MLT) produced by Bacillus cereus isolated in vomiting-type food poisoning was purified by chromatography on DEAE-Sephadex A-25 followed by gel filtration on Sephadex G-75. Purified MLT possessed a molecular weight of 33,000-34,000. It showed mouse lethality and hemolytic (HL) activity on sheep and rabbit erythrocytes; the latter erythrocytes were more weakly hemolyzed than the former ones. However, fluid accumulation in mouse ligated intestinal loops was not induced by purified MLT at the highest concentration used. Both MLT and HL activities were stable at pH 6-9, during storage at -20 degrees C for 8 weeks, and resistant to papain, cholesterol, lecithin, and dithiothreitol treatments. Most activity was lost during storage at 4 degrees C or 25 degrees C for 2 weeks or upon treatment with trypsin, trypanblue, or ethanol. The activities were resistant to heating at 37 degrees C for 5 min, less resistant at 98 degrees C for 5 min, and sensitive at 60 degrees C for 5 min. It can be concluded from the results that MLT is different from the diarrheagenic toxin produced by B. cereus isolated in diarrheal-type food poisoning, but is similar to, if not identical, hemolysin II.

Animals↗
PubMed1991

Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) regulation of insulin receptor function: phosphorylation of insulin receptor with A kinase decreases the insulin binding activity.

The effect of phosphorylation of insulin receptor with adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) on its insulin binding activity was investigated by using insulin receptors prepared from rat liver in vitro. A 95 KDa protein was phosphorylated by stimulation of insulin receptor kinase. This protein was also phosphorylated by A kinase. Analysis of phosphoamino acid showed that tyrosine residue(s) was phosphorylated by activation of insulin receptor kinase, whereas phosphoserine and phosphothreonine were dominantly generated by activation of A kinase. [125I] Iodoinsulin binding activity was decreased by prior phosphorylation of the receptor with A kinase. Scatchard analysis showed that the affinity for insulin was decreased by the phosphorylation with A kinase. Although the maximal activity of insulin receptor kinase was not affected by phosphorylation with A kinase, the insulin concentration which induced half maximal activity (ED50) of the receptor kinase was increased by the phosphorylation with A kinase. These results suggested that counter regulatory hormones whose actions are mediated by the generation of adenosine 3',5'-cyclic monophosphate regulate the insulin binding to the alpha subunit through phosphorylation of the beta subunit of insulin receptor.

Adenosine Triphosphate↗
PubMed1991

Evidence for the presence of protein kinases which stimulate phosphorylation of c-erb A protein in rat kidney nuclei.

Protein kinases were separated from rat kidney nuclear extract by hydroxylapatite column chromatography. Five (I-V) different protein kinases were isolated when histone was used as a substrate. Two (I and III) of them stimulated phosphorylation of c-erb A-beta protein (50 kDa) expressed in Escherichia coli. The c-erb A product has an activity of high affinity T3 binding. One (I) of the kinases was dependent on cyclic adenosine 3',5'-monophosphate (cyclic AMP). The other kinase (III) was not dependent on cyclic nucleotides. The latter kinase was eluted from hydroxylapatite column with 0.05 M PO4 at pH 7.4. The sedimentation coefficient(s) estimated by continuous sucrose density gradient centrifugation was approximately 6.0 Km values for ATP were estimated by double reciprocal analyses, which gave 110.0 microM in the protein kinase I (in the presence of 10(-6) M cyclic AMP) and 25 microM in the protein kinase III, respectively. The data showed that 1.0 mol phosphate was incorporated into 80 mol of c-erb A protein (50 kDa) either in the presence of protein kinase I (with 10(-6) M cyclic AMP) or in the presence of protein kinase III. These results suggested that there are protein kinases for c-erb A protein, whose functional properties are similar to those of nuclear T3 receptor, in rat kidney nuclei.

Adenosine Triphosphate↗
PubMed1991

Purification of human c-erb A beta protein.

Human thyroid hormone receptor (c-erb A protein) produced by Escherichia coli expression vector plasmid was purified sequentially using polyethylenimine precipitation of DNA, hydroxylapatite column chromatography, ammonium sulphate precipitation, Sephacryl S-300 gel filtration and mono Q-Sepharose column chromatography. These column procedures resulted in 41.3-fold purification of 3,5,3'-tri-iodo-L-thyronine (T3) binding activity over the initial E. coli extract. Purified protein as well as crude preparation showed high-affinity binding to T3. The c-erb A protein enriched by column purification was further purified by electroelution after electrophoresis. Rabbit antibody against the c-erb A protein was prepared and used for the Western blotting analysis. The antibody recognized c-erb A protein but not the bacterial proteins in crude E. coli extract. When partially purified rat hepatic nuclear thyroid hormone receptor was analysed, a 56 kDa receptor was specifically recognized by the antibody.

Antibodies↗
PubMed1991

The sources of chemical substances in allergic nasal fluid.

The sources of different chemical substances in the NF of allergic patient, such as albumin, secretory IgA, histamine, leukotriene, kinin and substance P were investigated. To accomplish this, we challenged the inferior turbinate on one side, but separately collected NF from both sides in patients with nasal allergy to house-dust. Provocation was done with paper disc containing dried allergen extract. Collection was done by suction for the first five minutes immediately after the onset of a positive response to nasal provocation. The total amount of the chemical substances on each side was analyzed separately and compared. Significant differences were seen between both sides only for histamine and leukotriene. In consideration with the previous reports, it is suggested that in nasal allergen challenge the major sources are glandular secretion for secretory IgA, and albumin, and secretion for migrating cells for histamine and leukotriene. The major sources responsible for kinin and substance P, however, are not defined.

Adolescent↗
PubMed1990

Human c-erb A protein expressed in Escherichia coli: changes in hydrophobicity upon thyroid hormone binding.

The human c-erb A beta gene sequence was inserted in an Escherichia coli expression vector plasmid. The E. coli cells transformed with this plasmid produced proteins with molecular masses of 52 and 50 kDa. These products bound 3,5,3'-triiodo-L-thyronine (T3) with an affinity constant of 4.3 x 10(9) liter/mol. The order of affinity for iodothyronine analogs was triiodothyroacetic acid greater than T3 greater than 3,5,3'-triiodo-D-thyronine greater than L-thyroxine. Affinity labeling experiments showed that the 50 kDa protein was covalently labeled with [125I]T3, and this was competed by triiodothyroacetic acid, T3, and L-thyroxine (from potent to weaker competitor). The c-erb A protein bound to calf thymus DNA-cellulose and the binding was inhibited by 0.3 M KCl or 10 mM pyridoxal 5'-phosphate. Aqueous two-phase partitioning studies showed that the c-erb A product became less hydrophobic upon T3 or triiodothyroacetic acid binding. The same finding was obtained when T3 bound to partially purified rat liver nuclear thyroid hormone receptor. However, thyroxine binding globulin became more hydrophobic upon T3 binding. Since the T3 molecule partitioned preferentially into the upper polyethylene glycol-rich phase, the alteration of partitioning behavior of thyroxine binding globulin was explained by a simple additive effect of T3. In contrast, the alteration of partitioning behavior of the c-erb A product or receptor reflected a conformational transition upon T3 binding. The c-erb A protein expressed in E. coli showed various characteristics similar to classical thyroid hormone receptor and may be useful in studying the structure and function of the thyroid hormone receptor.

Base Sequence↗