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Biomedical subjects

K Ichikawa

Publications and source records attributed to K Ichikawa.

At least 253 records · Page 14Linked to original sources

Effect of interferon-gamma on HLA class 2 expression by antigen-presenting cells inducing Dermatophagoides farinae-specific interleukin-2 responsiveness of lymphocytes in asthmatic children.

As previously reported, antigen-specific IL-2 responsiveness of lymphocytes from patients with bronchial asthma was induced by stimulation with Dermatophagoides farinae, antigen-specifically, in the context of HLA-DQ antigen. We analysed the antigen-presenting processes in the induction of IL-2 responsiveness. Non-adherent responder cells cultured with Df-pulsed autologous adherent cells acquired IL-2 responsiveness, which decreased after prolonged culture of adherent cells for 72 h before recombination with fresh autologous non-adherent cells. HLA-DQ expression on cultured adherent cells also decreased in parallel with the reduction of their ability to induce IL-2 responsiveness. However, the treatment of adherent cells with IFN-gamma restored the expression of these HLA-Class 2 antigens mainly on CD14+ antigen-presenting cells (monocytes), but not on CD20+ cells (B cells), which overcame the decrease of Df-induced IL-2 responsiveness during prolonged culture. These data suggest that IFN-gamma potentiates the up-regulation of Df-specific IL-2 responsiveness, which is likely to depend on the restoration of HLA-DQ expression on monocytes.

Animals↗

Age-related therapeutic response to antithyroid drug in patients with hyperthyroid Graves' disease.

OBJECTIVE: To determine whether there is an age-related difference in the therapeutic response to antithyroid drugs in hyperthyroid Graves' disease. DESIGN: Retrospective analysis of treatment duration and recurrence rate. PATIENTS: Two hundred and twenty-two patients who have triiodothyronine-suppressible thyroids within 4 years of methimazole treatment. MEASUREMENTS: Serum thyroid hormone levels, serum thyrotropin receptor antibody titer, and thyroidal radioiodine uptake. MAIN RESULTS: A longer period of methimazole treatment was needed to normalize serum thyroid hormone levels and to restore normal thyroidal triiodothyronine suppressibility in young than in aged patients. There was an average 10-month lag between normalization of thyrotropin receptor antibody titer and restoration of thyroidal triiodothyronine suppressibility in both young and aged patients. Recurrence after discontinuation of methimazole was more frequent in young than in aged patients. CONCLUSIONS: Aged patients with hyperthyroid Graves' disease show a more favorable response to antithyroid drugs than young counterparts.

Adolescent↗

Effects of TNF-alpha on hemodynamic changes and circulating endothelium-derived vasoactive factors in dogs.

To elucidate the relation of tumor necrosis factor-alpha (TNF-alpha)-induced hemodynamic change to endothelium-derived vasoactive factors, we simultaneously measured hemodynamic parameters and circulating endothelin (ET)-1, ET-3, nitrite/nitrate (NOx), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in anesthetized dogs following administration of TNF-alpha with or without NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and indomethacin, a cyclooxygenase inhibitor. Natural human TNF-alpha (10 micrograms/kg, n = 5) with or without L-NNA (1 mg/kg, n = 5) or indomethacin (2 mg/kg, n = 5) was administered intravenously as a bolus, while administration of vehicle served as control (n = 5). After administration of TNF-alpha, mean arterial pressure and cardiac index significantly decreased, whereas systemic (SVRI) and pulmonary (PVRI) vascular resistance index increased. Plasma levels of ET-1, ET-3, NOx, and 6-keto-PGF1 alpha significantly (P < 0.01) increased at 1 h. L-NNA or indomethacin blocked TNF-alpha-induced hypotension and remarkably increased SVRI but did not affect decreased cardiac index. Our data suggest that endogenous ET-1 may partly contribute to TNF-alpha-induced increases in SVRI and PVRI, against which ET-3, NO, and prostacyclin may function as compensatory vasodilators.

6-Ketoprostaglandin F1 alpha↗

Isolated congenital left ventricular diverticulum in an adult. A case report.

A sixty-three-year-old man presented himself with atrial flutter and congestive heart failure. Cardiac catheterization revealed that left ventricular diverticulum was located on the anterobasal wall with narrow connection to the left ventricular cavity. Coronary angiography revealed normal coronary arteries. The patient had been asymptomatic until adult life with no other thoracoabdominal or cardiac anomalies. This is an extremely rare finding in the adult population.

Atrial Flutter↗

Elevated biopterin and homovanillic acid levels in cerebrospinal fluid from children with aseptic meningitis.

To examine biopterin fractions and biogenic amine metabolites in cerebrospinal fluid in aseptic meningitis, the concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and the total, the oxidized form, and the reduced form of biopterin were determined in cerebrospinal fluid specimens from 15 children with aseptic meningitis in the acute phase, 15 children with aseptic meningitis in the recovery phase, and six other children as controls. The concentration of each substance was significantly higher in the acute phase than in the recovery phase. Homovanillic acid in the acute phase was significantly increased compared to that in the control group. The concentrations of the total, the oxidized form, and the reduced form of biopterin, and 5-hydroxyindoleacetic acid were higher in the acute phase than those in the controls; however, the differences were not significant. The concentration of each substance in the recovery phase was not significantly different from that in the controls. There was no difference in the 5-hydroxyindoleacetic acid/homovanillic acid ratio or in the reduced form/total biopterin ratio among the patients in acute and recovery phases and the controls. These results suggested that levels of biopterin and biogenic amine metabolites in cerebrospinal fluid are increased in the acute phase of aseptic meningitis and return to normal during the recovery phase. This is the first report of increased concentrations of biopterin fractions and biogenic amine metabolites in aseptic meningitis.

Biopterins↗

Response of hepatic proteins to 3,5,3'-tri-iodo-L-thyronine in diabetic rats.

In order to study whether peripheral action of thyroid hormones is altered in insulin deficiency and to elucidate the biological consequences of alteration of the cytosolic 3,5,3'-tri-iodo-L-thyronine (T3) binding protein (CTBP), we measured malic enzyme, T3-responsive nuclear n protein, CTBP and nuclear thyroid hormone receptor in the liver and kidney of streptozotocin (STZ)-induced diabetic rats that were treated with or without insulin and/or a receptor-saturating dose of T3. The following results were obtained. 1. Induction of malic enzyme by T3 was apparently diminished in diabetic rats. However, supplementary injection of insulin enabled previously given T3 to take effect in diabetic rats. 2. T3-responsiveness of other hepatic proteins (n protein and CTBP) was not altered by insulin in diabetic rats. 3. The level of n protein was increased by insulin in diabetic rats in vivo and in perfused rat liver, indicating that the hepatic n protein is a novel insulin-responsive protein. T3 and insulin increased the level of n protein non-synergistically in diabetic rat liver. 4. Hepatic nuclear receptor levels were not altered in diabetic rats. 5. Hepatic CTBP levels were decreased in diabetic rats. This was not due to the toxic effect of STZ. Low CTBP level was only partially increased by insulin after 30 days of diabetic period. Renal CTBP levels were not altered in diabetic rats with or without insulin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Current topics in vascular disorders].

Much evidences have been accumulated that antiphospholipid antibodies (aPL), especially anticardiolipin antibodies (aCL) and lupus anticoagulant (LA), were associated with thromboembolism, recurrent fetal loss and thrombocytopenia. These patients with clinical manifestations and aPL are classified into antiphospholipid syndrome (APS). Patients with APS without known well-defined autoimmune diseases are assigned to primary APS. aCL found in sera from patients with the APS recognize epitope(s) on beta 2-glycoprotein I bound to cardiolipin. LA is bound to the complex of prothrombin and anionic phospholipids. Patients with APS can be treated by low dose aspirin, warfarin or heparin. A few patients with aPL develop an acute and multiple organ involvements of APS. These patients are designated as catastrophic APS and are treated intensively by corticosteroid, immunosuppression, plasmapheresis or streptokinase.

Antibodies, Anticardiolipin↗

[Symptomatic laterality and magnetic resonance imaging (MRI) of the putamen in striatonigral degeneration (SND)].

Asymmetric onset of parkinsonism appears not uncommon in SND. This study quantitatively investigated anatomical asymmetry of the putamen using MRI in relation to symptomatic laterality. Our study comprises six patients with SND, two men and four women, ranging in age from 50 to 77. Duration of illness ranged from 1 to 4 years. The Yahr stage was IV in 3 patients and I, III, or V in the others. The diagnosis of SND was made on medical history, neurological examination and MRI. All patients had asymmetric onset of parkinsonism. They subsequently had variable cerebellar ataxia and/or autonomic failure. All of them responded poorly to L-dopa therapy. MRI revealed the pontine and cerebellar atrophy and abnormalities of the putamen in most of the patients. MRI was performed using a 1.5 Tesla in 5 patients and 0.5 Tesla in one. Inversion Recovery (IR) image were utilized as T1-weighted images and proved optimal in showing anatomic detail. Spin-echo sequences were used to provide T2-weighted images. For measurement of the putaminal area and length in SND patients and 12 normal controls, we used two horizontal slices. One is passing through dorsal portion of the putamen, and the other through the ventral putamen. All the patients had the onset of hemi-parkinsonism and the symptoms progressed dominantly on the side of onset. With T1-weighted IR sequences, putaminal atrophy was demonstrated in all patients, more intense on the contralateral side to more symptomatic limbs. The anatomical asymmetry and the symptomatic laterality were less pronounced in advanced patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Spontaneous IgE production in asthmatic children].

In this study, we demonstrated spontaneous IgE production by peripheral blood mononuclear cells of asthmatic children. In 26 asthmatic children, the level of spontaneous IgE ranged 0.1-15.0 IU/ml and in 5 healthy normal children showed under 0.051 IU/ml. In 5 of asthmatic children, specific antibody of Dermatophagoides farinae was detected from PBMC by CAP RAST. In healthy normal children, specific antibody of Df was not detected. Spontaneous IgE production by PBMC and serum IgE level showed well correlation (gamma = 0.835, p < 0.001). Spontaneous IgE production and specific antibody of Df by PBMC also showed well correlation (gamma = 0.717, p < 0.001) IgE production of asthmatic children was inhibited by IFN-gamma.

Adolescent↗

V gene analysis of anticardiolipin antibodies from MRL-lpr/lpr mice.

We analyzed the VH and V kappa genes of 14 hybridomas producing anticardiolipin antibodies (aCL) from MRL-lpr/lpr mice, in an attempt to address the question of whether aCL are generated by Ag-driven stimulation or by polyclonal B cell activation. Five of six aCL from one mouse and both aCL from the other mouse carried 98 to 100% homologous VH and V kappa genes, respectively, thereby indicating that aCL were derived from the oligoclonal B cell precursor in that individual mouse. Of nine clones, six (67%) used the VH gene of the J558 family, and three (43%) of seven clones used the V kappa gene of the V kappa 23 group. Three to five somatic mutations were detected in all VH and V kappa genes of the examined aCL. These results suggest the possibility that usage of VH/V kappa genes in aCL is not random and that aCL consist of somatically mutated Ig genes.

Amino Acid Sequence↗

Calponin phosphatase from smooth muscle: a possible role of type 1 protein phosphatase in smooth muscle relaxation.

Smooth muscle myosin bound phosphatase (MBP) purified from chicken gizzard, which is a holoenzyme of type 1 delta protein phosphatase and dephosphorylated intact myosin, catalyzed the dephosphorylation of calponin phosphorylated by protein kinase C (PK-C). The Km of MBP for calponin was 0.6 microM and the Vmax was 350 nmol/min/mg. All of the multiple sites of phosphorylation by PK-C of calponin were completely dephosphorylated by MBP. Functionally, calponin dephosphorylated by MBP recovered its inhibitory effect on the actin-activated Mg(2+)-ATPase activity of myosin. Therefore, these results suggest that a type 1 delta protein phosphatase causes relaxation of smooth muscle by the dephosphorylation not only of myosin but also of calponin.

Animals↗

Amino acid sequence of alkaliphilic serine protease from silkworm, Bombyx mori, larval digestive juice.

Alkaliphilic protease, P-IIc, from silkworm, Bombyx mori, larval midgut digestive juice consists of 232 amino acids. It has a catalytic triad, Asp-His-Ser, invariably found in a serine protease. A shift of optimal pH value towards the alkaline side diminished at mu = 1.0. This suggests the existence of an electrostatic interaction that affects the proteolytic activity. The higher Arg content may be responsible for this phenomenon. Two cysteine residues probably exist unpaired in a novel position among serine proteases.

Amino Acid Sequence↗

Brefeldin A inhibits muscle-specific gene expression during differentiation in C2C12 myoblasts.

In analyzing regulatory mechanisms underlying differentiation-dependent expression of muscle proteins, we have found that mouse C2C12 myoblast cells treated with Brefeldin A (BFA), which specifically blocks the intracellular transport of protein from endoplasmic reticulum (ER) to the Golgi apparatus, failed to differentiate. BFA reversibly inhibited myotube formation at a threshold concentration of 1.0 micrograms/ml. The same concentration of BFA completely blocked accumulation of secretory proteins, e.g., fibronectin into the culture medium, probably due to retention in ER. Interestingly, the induction of muscle creatine phosphokinase (MCK) activity was sensitive to BFA, although a constitutive expression of lactate dehydrogenase, one of the cytosolic housekeeping enzymes, was resistant to BFA. In the kinetic analysis of MCK induction, translation of existing MCK mRNA was not inhibited by BFA since MCK activity became resistant to BFA once levels of MCK transcript accumulated. The differentiation-dependent accumulation of MCK transcript was also suppressed by BFA treatment to approximately 30% of control, although neither general transcriptional activity in vivo nor stability of existing mRNAs was affected even in the presence of BFA. Moreover, induction of muscle regulatory genes, MyoD1 and myogenin, which are upstream of the MCK gene, were inhibited at their transcription level by BFA. Such an effect on muscle regulatory gene transcription by BFA suggests that transport of some factor(s) to the cell surface may be a prerequisite for the muscle-specific gene expression upon differentiation of C2C12 myoblasts.

Animals↗