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Biomedical subjects

A Kawa

Publications and source records attributed to A Kawa.

At least 19 recordsLinked to original sources
PubMed1999

Antiepileptic teratogen valproic acid (VPA) modulates organisation and dynamics of the actin cytoskeleton.

The antiepileptic drug valproic acid (VPA) and teratogenic VPA analogues have been demonstrated to inhibit cell motility and affect cell morphology. We here show that disruption of microtubules or of microfilaments by exposure to nocodazole or cytochalasin D had different effects on morphology of control cells and cells treated with VPA, indicating that VPA affected the cytoskeletal determinants of cell morphology. Furthermore, VPA treatment induced an increase of F-actin, and of FAK, paxillin, vinculin, and phosphotyrosine in focal adhesion complexes. These changes were accompanied by increased adhesion of VPA-treated cells to the extracellular matrix. Treatment with an RGD-containing peptide reducing integrin binding to components of the extracellular matrix partially reverted the motility inhibition induced by VPA, indicating that altered adhesion contributed to, but was not the sole reason for the VPA mediated inhibition of motility. In addition it is shown that the actomyosin cytoskeleton of VPA-treated cells was capable of contraction upon exposure to ATP, indicating that the reduced motility of VPA-treated cells was not caused by an inhibition of actomyosin contraction. On the other hand, VPA caused a redistribution of the actin severing protein gelsolin, and left the cells unable to respond to treatment with a gelsolin-peptide known to reduce the amount of gelsolin bound to phosphatidylinositol bisphosphate (PIP2), leaving a larger amount of the protein in a potential actin binding state. These findings indicate that VPA affects cell morphology and motility through interference with the dynamics of the actin cytoskeleton.

Actins↗
PubMed1998

Studies on the teratogen pharmacophore of valproic acid analogues: evidence of interactions at a hydrophobic centre.

Propyl-4-yn-valproic acid (2-propyl-4-pentynoic acid), an analogue of valproic acid with a triple bond in one alkyl side chain, potently induces exencephaly in mice. Given that propyl-4-yn-valproic acid is a branched chain carboxylic acid, we synthesized a series of analogues with n-alkyl side chains of increasing length and correlated their potential to induce neural tube defects and to inhibit proliferation and induce differentiation in cells of neural origin, the latter being crucial to the orderly structuring of the embryo. All analogues significantly increased the incidence of neural tube defects in the embryos of dams exposed to a single dose of 1.25 mmol/kg on day 8 of gestation. This effect occurred in a dose-dependent manner and the rate of exencephaly increased with the progressive increase in n-alkyl side chain length. Moreover, increasing chain length resulted in a dose-dependent inhibition of C6 glioma proliferation rate over a concentration range of 0-3 mM and this was independent of the cell type employed and mode of estimating proliferative rate. The antiproliferative action of these analogues was associated with profound shape change in neuro-2A neuroblastoma involving extensive neuritogenesis and an associated increase in neural cell adhesion molecule (NCAM) prevalence at points of cell-cell contact, the latter exhibiting a dose-dependent increase when the n-alkyl chain was extended to five carbon units. These results suggest an interaction with a specific site in which the n-alkyl side is proposed to serve as an 'anchor' within a hydrophobic pocket to facilitate the ionic and/or H-bonding of the carboxylic acid and high electron density of the carbon-carbon triple bond.

Animals↗
PubMed1998

A simple procedure for morphometric analysis of processes and growth cones of neurons in culture using parameters derived from the contour and convex hull of the object.

Morphometric estimation of neuronal processes is currently laborious and time-consuming, since the individual processes (axons and dendrites) have to be traced manually. In order to facilitate the measurement of cellular processes, we have tested a series of parameters derived from the contour and the convex hull of an object and estimated to which extent they reflect process length and number. The parameters included the area, perimeter and form factor of the object and convex hull, their ratios as well as object length, breadth, width, length/width and spreading index. Some new parameters derived from the contour and convex hull of the object, were also computed: process index (the number of areas contained within the convex hull outside the object contour), process domain (the total area contained within the convex hull outside the object contour), their ratio and the square root of the process domain (SR process domain). In total, 18 parameters were estimated. Populations of motoneurons, growth cones of cerebellar granule cells and N2a neuroblastoma cells were utilized due to their diversity in morphological features. The processes of each object were drawn by hand to establish the actual length and number. Total process length per object correlated strongly with object perimeter, process domain and SR process domain. The number of processes per object correlated well with perimeter ratio, process index and form factor, whereas object length, convex hull perimeter and spreading index correlated acceptably with the average process length. Using these parameters for the evaluation of neurite outgrowth in developing of hippocampal neurons in vitro, variables such as object perimeter, process domain and SR process domain were found to be very well suited for estimation of the total length of neurites. We conclude that based on the contour and convex hull of an object it is possible to calculate a series of parameters which may substitute direct measurements of process length.

Animals↗
PubMed1987

The effect of attenuated vaccinia virus AS strain on multiple myeloma; a case report.

The case of a 67-year-old male with IgA multiple myeloma successfully treated with AS strain of vaccinia virus is reported. The intravenous injection of this virus strain caused a definite decrease in the levels of monoclonal IgA from 1,309 mg/dl in the early stage of the treatment to 432 mg/dl on the 96th day of the regime. NK cell activity rose from 20.0% on the 10th day to 33% on the 106th day of the treatment. No adverse effects were observed throughout the entire course of the treatment. These results strongly suggest that AS strain vaccinia virus is a most promising and safe agent for the treatment of human malignancy. The possible mechanism of the beneficial effects of this virus strain is also briefly discussed.

Aged↗
PubMed1986

Properdin factor B frequencies in four Asian populations.

The distribution of Properdin factor B (Bf) phenotypes and their gene frequencies were investigated in four Asian populations (Chinese, Filipino, Thai and Japanese). The frequency of the BfS phenotype in Filipinos (0.717) was significantly lower than that in Chinese (0.900) and Thai (0.889) (p less than 0.01), but not different from the Japanese (0.840). One variant, BfF 0.65 S, was identified in a Japanese subject. Thus, in the Asian populations studied, Bfs frequencies were high and the frequency of variants other than F and S were low.

China↗
PubMed1983

Comparative studies on immunological characteristics of IDDM among Asian populations.

Very little information is available related to possible differences in immunological characteristics of IDDM among Asian populations, though it has been reported that IDDM is associated with Bw54-DR4 and B17-DR3 in Japanese and Chinese, respectively. There is virtually no report related to comparative studies on Bf-DM association among Asian populations, while Bf-DM association is reported to be stronger than HLA-DM association in Caucasians. In the present paper, the results of our studies on anti-thyroid antibodies (ATA) of IDDM in Japanese, Chinese and Filipinos are presented. In Japanese, the incidence of ATA positive was higher in IDDM with a duration of less than one year (35.7%) than that in the patients with a duration of one year or more (12.5%). But, there was no such a duration dependent decrease in the incidences of ATA among Chinese or Filipino IDDM. The frequency of BfSS in Filipinos is lower than in Japanese or Chinese. However, no association was found between Bf phenotypes and IDDM in Asian populations. These results indicate that autoimmunity is transient in Japanese IDDM, but persistent in Chinese and Filipinos, and that it is too early to postulate in general that Bf-IDDM association in general populations is stronger than HLA-IDDM association.

Autoantibodies↗
PubMed1983

Reliability of HbA1 assay in the mass survey for diabetes mellitus, with special reference to the preservation and transportation of blood samples.

Studies on the reliability of the HbA1 assay in mass surveys for diabetes mellitus were carried out with special reference to the preservation and transportation of blood samples. It is essential to confirm that the preservation and transportation of samples have no effect on values for HbA1, since most of the mass surveys are carried out as field works. In our experience the levels of HbA1 remained unchanged for one week, both in samples kept at 4 degrees C, and in frozen samples kept at -40 degrees C or -80 degrees C and transported on solid CO2. The levels of HbA1 in the samples transported from Manila to Wakayama by the above-mentioned methods did not differ from those obtained in corresponding fresh samples. There was a good correlation between levels of HbA1 and levels of plasma glucose obtained 1 or 2 hr after breakfast (PPG). It was concluded that the use of both criteria (HbA1 of more than 8.00% and PPG of more than 120 mg/100 ml) in the diagnosis of diabetes mellitus is more reliable than use of either one alone.

Blood Glucose↗
PubMed1981

Thyrotrophin-binding inhibitory immunoglobulins and HLA-DRW3-two prognostic factors in Graves' disease.

Thyrotrophin-binding inhibitory immuno-globulin (TBII) activity and HLA typing were performed in 38 Chinese patients with Graves' disease to find out the relationship among TBII activity, HLA antigen and relapse. Twelve out of 13 patients who were TBII-positive at anti-thyroid drug withdrawal relapsed. All seven patients with HLA-DR3 antigen relapsed, whereas all ten patients in remission did not have DR3. Therefore, both TBII activity at drug withdrawal and DR3 antigen could predict subsequent relapse. However, a larger patient sample is required to determine the precise relationship between TBII activity and HLA-DR3 antigen.

Adolescent↗