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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 685 records · Page 38Linked to original sources

Changes in K+,Na+-sensitive actin gelation factor during the differentiation of myeloid leukemia cells.

A homodimer protein consisting of two 38,000 dalton peptides was isolated from a murine leukemia cell line (M1). The binding molar ratio of the 38K-dimer protein to purified skeletal muscle actin was saturated at 1:3, and when the 38K-dimer/actin ratio exceeded 1:12, gelation occurred. This gelation was completely inhibited by the presence of either 10 mM KCl or 20 mM NaCl. The protein induced actin filament bundling, which required a higher 38K-dimer/actin ratio and was not affected by the presence of monovalent cations. During the differentiation of Ml cells, the sensitivity of the 38K protein to monovalent cations was decreased; that is 20 mM KCl or 50 mM NaCl was required to inhibit the gelation by the 38K protein isolated from differentiated cells. On the other hand, the intracellular K+ content of Ml cells decreased from 70 +/- 5 mM to 18 +/- 3 mM, and Na+ increased from 10 +/- 5 mM to 40 +/- 10 mM during the differentiation. These findings suggest that the differentiation brought about conditions favourable for the 38K protein to induce actin gelation, and in turn, the locomotive and phagocytic activities which were induced only after differentiation in this cell line.

Animals↗

Purification and kinetic properties of 3 beta-hydroxysteroid dehydrogenase from bovine adrenocortical microsomes.

3 beta-Hydroxysteroid dehydrogenase was purified from bovine adrenocortical microsomes and its properties were studied. The purified dehydrogenase gave a single homogeneous protein band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and showed no steroid delta 5-delta-4 isomerase activity. The molecular weight of the dehydrogenase was estimated to be 41,000 for the monomer and the isoelectric point was determined to be at pH 6.3. The Km values of the dehydrogenase were 6.2 microM for NAD+, 4.9 mM for NADP+, 2.0 microM for pregnenolone, and 5.3 microM for 17 alpha-hydroxypregnenolone. The mechanism of inhibition by trilostane of the dehydrogenase was also examined kinetically. The inhibition was found to be competitive, with Ki values of 0.14 microM for 17 alpha-hydroxypregnenolone and 0.38 microM for pregnenolone.

17-alpha-Hydroxypregnenolone↗

Decrease in respiration activity related to prodigiosin synthesis in Serratia marcescens.

Variation in the cell respiration rate of pigmented and nonpigmented strains of Serratia marcescens was exhibited. The respiration rate of a pigmented strain decreased earlier than that of nonpigmented strains in the late exponential or early stationary phase. However when prodigiosin synthesis was not induced by exchange of carbon sources in the medium, the decrease in the respiration rate of the pigmented strain was the same as that of nonpigmented strains. Measurement of the oxygen consumption rate in the sonicated cell membrane by adding NADH solution showed that the rate in the pigmented strain was lower than that in nonpigmented strains. Furthermore, the cell membrane of prodigiosin-induced organisms was more sensitive to respiration inhibitors than that of pigment-noninduced organisms of the pigmented strain. These results showed that the respiration activity was decreased by prodigiosin synthesis in S. marcescens.

Cell Fractionation↗

Evaluation of immune-enhancing effects of ibuprofen in an immunodeficiency model.

Three children and one adult with chronic mucocutaneous candidosis with documented deficient cellular immunity to Candida antigen were evaluated as a model to study the specific cellular immune-enhancing potential of the prostaglandin synthetase inhibitor ibuprofen. Oral ibuprofen failed to have any consistent effect during sequential 4-week on and off cycles on the following parameters: delayed hypersensitivity skin testing; lymphocyte transformation to Candida antigen; T-cell subsets as determined by monoclonal antibody techniques; production of human immune interferon in response to staphylococcal enterotoxin A (SEA). Two patients showed a trend toward enhanced lymphocyte transformation to PHA while taking ibuprofen. In two patients who were studied 8-10 weeks after discontinuation of oral ketoconazole therapy, clinical recurrence of CMC was not prevented by oral ibuprofen therapy.

Candidiasis↗

Xanthine calculi in the patient with the Lesch-Nyhan syndrome associated with urinary tract infection.

A Japanese boy with Lesch-Nyhan syndrome who passed xanthine calculi is reported. After pyelolithotomy for a left renal stone, made up of ammonium urate, associated with urinary tract infection, a high dose of allopurinol was given because of the persistence of pyuria. In the present case, the administration of a high dose of allopurinol, given for the prevention of ammonium urate stone formation in infected urine, induced xanthine calculi formation and we had difficulty in the management of this patient with Lesch-Nyhan syndrome associated with urinary tract infection. However, we believe it a basic necessity to cure our patient of his urinary tract infection and prevent recurrent ammonium urate stone formation because of the risk of renal deterioration.

Allopurinol↗

Differences in metabolic properties among cortisol, prednisolone, and dexamethasone in liver and renal diseases: accelerated metabolism of dexamethasone in renal failure.

Since previous reports concerning the altered metabolism of various glucocorticoids in liver or renal diseases were inconsistent, this study was undertaken to reexamine the metabolism of cortisol, prednisolone, and dexamethasone in patients with these diseases. One milligram each of these glucocorticoids was given iv simultaneously to patients with chronic liver disease, patients with chronic renal failure, and normal subjects after 1 mg betamethasone was administered on the previous night to suppress endogenous cortisol secretion. Plasma steroid levels in periodically collected blood samples were assayed by respective RIA after separation by paper chromatography. Prolongation of the t1/2 of cortisol was found in both patients with liver disease and those with renal failure, and prolonged t1/2 and reduced MCR of prednisolone were found in renal failure but not in liver disease. In contrast, while prolonged t1/2 and reduced MCR of dexamethasone were found in liver disease, shortened t1/2 and increased MCR were found in renal failure. These results suggest that different glucocorticoids are metabolized differently in patients with liver disease and those with renal failure, and that these differences may be important when these agents are used for therapeutic purposes or for study of hypothalamic-pituitary-adrenocortical function in patients with liver and renal diseases.

Adult↗

Blocking type antithyrotropin receptor antibody in patients with nongoitrous hypothyroidism: its incidence and characteristics of action.

The incidence, characteristics of action, and pathogenetic importance of blocking type anti-TSH receptor antibody were examined in patients with autoimmune thyroiditis. Serum immunoglobulin G (IgG) from 8 of 20 patients with nongoitrous hypothyroidism contained substantial amounts of TSH binding inhibitor immunoglobulin (TBII) activity. Newborn infants of a patient with the greatest TBII activity had neonatal transient hypothyroidism. In sera of patients with goitrous hypothyroidism and euthryoid chronic thyroiditis, only weakly positive or negative TBII activity was found. IgGs of these patients and those of nongoitrous hypothyroid patients without strongly positive TBII activity did not inhibit TSH stimulation of thyroid adenylate cyclase activity. Seven of 8 IgGs which had strongly positive TBII activity significantly inhibited cAMP generation induced by 9.1 mU/ml TSH, and the eighth IgG inhibited stimulation with 0.5 mU/ml TSH. Although the modes of TSH binding inhibition were variable, markedly close correlation was found between TSH binding- and TSH stimulation-inhibiting activities of these 8 IgGs (r = 0.90; P less than 0.01). These IgGs may exert their inhibitory effects on adenylate cyclase activity by inhibiting TSH binding to its receptor.

Adenylyl Cyclases↗

A monovalent cation-sensitive actin-binding factor in a myeloid leukemia cell line.

Cell extracts of a murine leukemia cell line, M1, apparently contain three kinds of actin-gelation factors; a filamin-like protein, and 38K-dimer and 105K-dimer proteins. Unlike gelation by the filamin-like protein, gelation by the latter two proteins is inhibited by low concentrations of KCl. Our study of the 38K protein has been reported elsewhere (Takagi, K. et al., J. Biochem. Tokyo 97, 605-616, 1985). We here describe the purification and characterization of the 105K protein. The 105K protein differs from the alpha-actinin group of proteins in its antigenicity, peptide components and Ca2+-insensitivity. The saturated binding ratio of the protein to purified skeletal muscle actin is 1:8; when this ratio exceeds 1:20, gelation takes place. This gelation is inhibited completely by the presence of 25 mM KCl. Electron microscopy revealed that, in the absence of KCl, the 105K protein/actin mixture forms short actin bundles that are accompanied by a meshwork of short single filaments. The presence of 25 mM KCl did not prevent actin-bundling, but the bundles became longer and the meshwork of short filaments was no longer present.

Actins↗

[Effect of KC-404 on experimental cerebral infarction in rats].

Experimental cerebral infarction accompanying altered cerebral energy metabolism and cerebral edema was produced in rats by injecting arachidonate into the left carotid artery. In the present study, the effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-alpha]pyridine (KC-404) on these ischemic insults as well as on the regional cerebral blood flow (r-CBF) were studied. 1) Cerebral metabolism: On the 7th day of infarction, a significant decrease in ATP content and an increase in glucose content were observed, especially in the left hemisphere. There were no significant changes in lactate and pyruvate contents as compared with normal rat brain. Treatment with KC-404 (10 mg/kg, p.o.) once on the 7th day or twice on the 6th and 7th days of infarction caused a significant increase in ATP content and a decrease in lactate content. Increased content of glucose tended to be suppressed by KC-404. In normal rats, KC-404 (10 mg/kg, p.o.) caused slight but significant increases in cerebral ATP, glucose and pyruvate contents. 2) Cerebral edema: On the 4th day of infarction, significant increases in water content and Na+/K+ ratio and a decrease in K+ content were observed in the left hemisphere. Treatment with KC-404 (10 mg/kg, p.o.) for three preceding days showed a significant suppression of increased water content with a tendency to improve altered electrolyte levels. 3) r-CBF: KC-404 (0.05 mg/kg/min) infused i.v. for 15 min increased more markedly the r-CBF in the affected left hemisphere as compared with that in normal brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Elimination characteristics of bredinin from patients serum in hemodialysis.

The hemodialysability of bredinin, a new immunosuppressive drug, was investigated in five patients on longterm hemodialysis. Blood samples were collected periodically during and inter-dialysis and measured by high-performance liquid chromatography (HPLC) for bredinin. The half-life (t 1/2) of the elimination phase was 4.8 h in our patients during hemodialysis, a 97% reduction of the 155 h t 1/2 reported in uremic patients. The fraction of drug in the body which is removed by dialysis (f) calculated averaged 0.43. A mean of 43% of the drug in the body was removed during 4-hour hemodialysis. Because of the reduction in elimination t 1/2 and the significant drug removal during dialysis we conclude that bredinin is dialyzable.

Adult↗