Search PubMed⌕ Search

Biomedical subjects

K Ichikawa

Publications and source records attributed to K Ichikawa.

At least 145 records · Page 8Linked to original sources
PubMed1998

A novel method of estimating real [Ca2+]i dynamics from fluorescence signals.

To detect changes in the concentration of intracellular calcium ions ([Ca2+]i), fluorescence measurement techniques are used in experimental studies. When the calcium concentration is calculated from fluorescence signals, an equilibrium between calcium ions and the fluorescent dye is assumed in conventional methods. However, using this assumption, calculated calcium concentrations would not be an accurate representation of [Ca2+]i if the dynamics of [Ca2+]i are so fast that the reaction between calcium ions and the dye cannot reach equilibrium. In this report, we propose a new method of estimating [Ca2+]i in dye-free conditions from fluorescence signals of the dye using differential equations expressing reactions between calcium ions and the dye without assuming equilibrium. We compared our method with a conventional method with respect to calculations of [Ca2+]i using a model of a dendritic spine. Simulation results showed that our method gave a better estimation of the changes in [Ca2+]i than did the conventional method.

Calcium↗
PubMed1998

Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I (beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system.

It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via beta2-GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of beta2-GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of beta2-GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL+ patients had a positive titre in the presence of cardiolipin (CL) and beta2-GPI, but binding was not found in the absence of beta2-GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of beta2-GPI and that of anti-beta2-GPI antibody (r = 0.802, P = 0.0001). We further analysed the interaction between protein C, phospholipids, beta2-GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of beta2-GPI to protein C and its phospholipid dependency were investigated. Beta2-GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of beta2-GPI (virtually anti-beta2-GPI antibodies) was evaluated in the presence of cardiolipin and beta2-GPI. All three human monoclonal aCL bound to protein C in the presence of CL and beta2-GPI, whereas they did not in the absence of either beta2-GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and beta2-GPI, leading to protein C dysfunction.

Adolescent↗
PubMed1998

Reduced IL-1 production in adolescents with mite antigen asthma in remission.

To determine the immunological mechanisms associated with outgrowing mite antigen-induced bronchial asthma during adolescence, we studied the relationship between clinical status and Dermatophagoides farinae (Df) antigen-induced peripheral cell activation by measuring IL-1alpha and IL-1beta production in patients with bronchial asthma. After antigen-driven restimulation in vitro, there was increased IL-1alpha, IL-1beta production by peripheral blood mononuclear cells (PBMC) from patients with active bronchial asthma, while cellular IL-1alpha, IL-1beta production was reduced in patients with asthma in remission. IL-1alpha and IL-1beta production by PBMC (possibly reflecting airway inflammation) after exposure to Df antigen might be down-regulated in patients outgrowing mite antigen-induced asthma, because lipopolysaccharide-induced IL-1alpha, IL-1beta production (seen in both normal individuals and patients with active asthma) was also reduced when patients were in remission.

Adolescent↗
PubMed1998

Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship.

Bioassay-guided fractionation of a methanolic extract of a Thai crude drug, derived from heartwood of Anaxagorea luzonensis A. Gray (Annonaceae), resulted in the isolation of 8-isopentenylnaringenin (1) as an estrogen agonist with a activity of about an order of magnitude greater than genistein. Various flavonoids possessing isopentenyl side chains in the A-ring have been prepared and evaluated for their ability to bind estrogen receptor. In addition, enantiomers of 1 were separated and the respective enantiomers were assayed. These studies have demonstrated that the presence of an 8-isopentenyl group is an important factor for binding. Flavones, flavanones and flavonols having an isopentenyl substituent at C-8 exhibited an appreciable affinity for estrogen receptor. Conversely, isoflavones possessing an 8-isopentenyl substituent at C-8 did not show this activity. Movement of the isopentenyl group from position 8 to 6 resulted in loss of the activity. No significant difference was observed between 2(S)- and 2(R)-enantiomers of 1 in their binding affinity. Prenylflavonoids are reported to possess a wide range of biological activities; however, estrogenic activity has not been described.

Breast Neoplasms↗
PubMed1998

Atherosclerosis: coagulation and fibrinolysis.

Tissue factor (TF) protein was overexpressed by macrophages and smooth muscle cells (SMCs) and deposited in the extracellular matrix of atherosclerotic intimas, probably resulting in enhanced procoagulant activity and the intimate participation in either thrombus formation or intimal fibrin deposition after the exposure of flowing blood and permeated fibrinogen to TF in atherosclerotic lesions. On the other hand, APO(a) was localized both in the stroma and within some macrophages. Fibrin deposition, which was more frequently detected in the matrix of advanced lesions than in that of early lesions, occasionally colocated with cell- and matrix-associated TF and APO(a) deposited in the matrix. These findings further support the hypothesis that the coagulation and fibrinolysis systems can play an essential role in the initiation and progression of atherosclerosis through fibrin deposition both in atherosclerotic plaques and on the arterial surface by neointimal hypercoagulability and a hypofibrinolytic state, which can also participate in SMC proliferation due to the decreased activation of TGF-beta by embedded and deposited APO(a). The clinical implications of these phenomena may thus contribute to future investigations in the prevention and treatment of atherosclerotic diseases.

Animals↗
PubMed1998

Radiation-induced painless thyrotoxic thyroiditis followed by hypothyroidism: a case report and literature review.

A 68-year-old woman presented with a small painless goiter and thyrotoxic symptoms immediately after 50-Gy external radiation for mucoepidermoid carcinoma of the submandibular gland. Elevated serum thyroid hormone and thyroglobulin levels, and undetectable serum thyrotropin level, together with extremely low thyroidal radioiodine uptake established the diagnosis of painless thyrotoxic thyroiditis. Thyroidal autoantibodies were negative. At follow-up without medication, all the symptoms disappeared, and laboratory abnormalities normalized within 6 months. One year later, the patient developed compensated hypothyroidism as indicated by elevated serum thyrotropin level with low normal serum thyroid hormone levels.

Aged↗
PubMed1998

Ligand- and nuclear factor-dependent change in hydrophobicity of thyroid hormone beta1 receptor.

An aqueous two-phase partitioning assay was performed using in vitro translated human thyroid hormone beta1 receptor (TRbeta1). Wild-type TRbeta1 was less hydrophobic in the presence of both triiodothyronine (T3) and nuclear extract. This reflects a conformational change, or change in electrostatic properties, of the TRbeta1-nuclear factor complex as a result of T3 binding. Mutant TRbeta1s with reduced T3 binding affinity required a higher concentration of T3 for the shift of hydrophobicity, and a mutant without T3 binding activity did not show any shift, even in the presence of 1 mM T3. The unique mutant receptor, R243Q, has impaired transcriptional function despite virtually normal binding affinity for T3. When this mutant was examined in this assay, the shift of hydrophobicity was significantly impaired even in the presence of both nuclear extract and a high concentration of T3. Nuclear extract of COS1 cells did not affect the T3-binding affinity of R243Q. These results indicate that the R243Q mutant has impaired a ligand-dependent conformational change and interaction with nuclear factor(s). Inability of R243Q to interact normally with nuclear factor(s) may explain, in part, the molecular mechanism of discordance between ligand binding and transactivation function of this mutant.

Animals↗
PubMed1998

Recurrent annular erythema in a case of seronegative Sjögren's syndrome.

We describe a case of Sjögren's syndrome who repeatedly developed annular erythema on her extremities. Her anti-nuclear antibody, anti-SSA/Ro antibody, and anti-SSB/La antibody were all negative. Characteristics of the annular erythema included a tendency to appear on the extremities especially in summer, spontaneous regression after 1-2 weeks, and residual slight pigmentation. The histological findings revealed dermal perivascular lymphocytic infiltration admixed with some neutrophils. Slight exsudative changes were found in the upper dermis. There were no epidermal changes. This case suggests the existence of annular erythema which may not be related to the anti-SSA/Ro or anti-SSB/La antibody. Unknown factors other than those antibodies may be involved in the pathogenesis of the annular erythema.

Antibodies, Antinuclear↗
PubMed1998

Epitopes on beta2-GPI recognized by anticardiolipin antibodies.

Anticardiolipin antibodies (aCL) found in sera from patients with antiphospholipid syndrome recognize a cryptic epitope that appears on the beta2-glycoprotein I (beta2-GPI) molecule when beta2-GPI interacts with a lipid membrane composed of negatively charged phospholipid or when beta2-GPI is adsorbed on a polyoxygenated polystyrene plate. A homology based model of beta2-GPI was constructed based on the NMR coordinates of sushi domains of human factor H. The conformation was like a cylinder consisting of five domains, its IV and V domains being glued by electrostatic interaction. We used phage-displayed random peptide libraries to search the epitopes of human aCL. Structures similar to consensus sequences selected by a biopanning method was found on domain IV of beta2-GPI.

Amino Acid Sequence↗
PubMed1998

Obesity induced by neonatal monosodium glutamate treatment in spontaneously hypertensive rats: an animal model of multiple risk factors.

The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases.

Animals↗
PubMed1998

Pheochromocytoma arising from an accessory adrenal gland in a patient with multiple endocrine neoplasia type 2A: transient development of clinical manifestations after hemorrhagic necrosis.

A case of pheochromocytoma arising from an accessory adrenal gland in a patient with multiple endocrine neoplasia type 2A (MEN 2A) is reported. This tumor resulted in autonecrosis which caused transient expression of clinical symptoms. Scintigraphy of the abdomen identified the existence of an additional accessory adrenal gland because of which the patient did not require a supplement of hydrocortisone after bilateral total adrenalectomy. Pheochromocytoma arising from an accessory adrenal gland is rarely reported, and spontaneous remission of clinical symptoms due to necrosis of the pheochromocytoma without a clinical emergency is also unusual. Accessory adrenal glands can be the cellular basis for pheochromocytoma, and the importance of continual follow up for pheochromocytoma in subjects with MEN 2A should be emphasized.

Adrenal Gland Neoplasms↗
PubMed1998

[Aging and Hashimoto's thyroiditis].

Analysis of patients with persistent hypothyroidism due to Hashimoto's thyroiditis suggested that metabolism of thyroxine (T4), including deiodination to triiodothyronine (T3), was reduced in the elderly. The increase in the serum levels of T4 after oral administration of T4 was augmented in the elderly, whereas increase in the serum T3 level was not. Possibly due to the reduction in the pituitary deiodinase, suppression by T4 administration of serum thyrotropin (TSH) level was the same in elderly as in younger subjects despite a larger increase in the serum levels of T4 in the elderly. Consequently, the amount of T4 required to maintain a normal serum TSH level did not differ between elderly and younger subjects. Other characteristics of elderly patients with Hashimoto's thyroiditis were that goiter size was smaller, that hypothyroidism was more frequent, and that Graves' disease was less frequent.

Adult↗
PubMed1998

[Influence of covering gingival sulcus with denture base on periodontal tissue--pH value in gingival sulcus and amount of gingival crevicular fluid].

The purpose of this study was to clarify the effect of covering gingival sulcus with denture base on periodontal tissue. Six subjects participated in this study. An experimental denture was inserted to a test tooth of each subject that was prepared for a full crown. Each experimental denture was designed to cover the gingival sulcus around the tooth. All subjects used them for two weeks. The parameters were as follows: 1) pH in gingival sulcus, 2) amount of gingival crevicular fluid, 3) tooth mobility, 4) temperature in gingival sulcus, 5) probing depth, 6) GI, and 7) P1I. Measurements were performed during the following periods: 1) pre-examination, 2) after cementation of provisional restoration, 3) during insertion of experimental denture, 4) after cementation of final restoration. A repeated-measures ANOVA was used for statistical analysis. The results were as follows: 1. pH value and amount of GCF increased after insertion of the experimental denture, and returned to same level as pre-examination after cementing of the final restoration. 2. Tooth mobility decreased during insertion of the experimental denture. 3. The changes of the other parameters were not significant. These results suggested that subclinical inflammatory change occurred in periodontal tissue in an early stage accompanied with covering of the gingival sulcus.

Adult↗
PubMed1998

IgA class anti-beta2-glycoprotein I in patients with systemic lupus erythematosus.

OBJECTIVE: To search for a possible relationship between the presence of IgA class anti-beta2-glycoprotein I antibody (abeta2-GPI) and clinical manifestations, including thrombotic episodes, in patients with systemic lupus erythematosus (SLE). METHODS: Serum IgA abeta2-GPI levels in 124 Japanese patients with SLE were measured using a phospholipid independent enzyme immunoassay. Relationships to clinical histories and to various laboratory data including IgG and IgM class abeta2-GPI were examined. RESULTS: Twenty-five percent of patients with SLE were positive for IgA abeta2-GPI. Patients with a history of thrombosis had significantly higher probabilities for positivity of IgA abeta2-GPI, compared to those without. The presence of IgA abeta2-GPI was correlated with presence of lupus anticoagulant and/or biological false positive result for serological syphilis test. Titer of IgA abeta2-GPI significantly correlated with values of IgG abeta2-GPI, IgM abeta2-GPI, and anti-DNA antibodies. CONCLUSION: The presence of IgA abeta2-GPI may be related to the occurrence of thrombosis in patients with SLE. Measurements of IgA abeta2-GPI may be of value for evaluating risk of thrombosis in patients with SLE.

Antibodies, Anticardiolipin↗