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Biomedical subjects

A Shirakami

Publications and source records attributed to A Shirakami.

At least 37 records · Page 2Linked to original sources

Metabolism of plasma fibronectin in rabbits with experimental hyperthyroidism and hypothyroidism.

We previously reported that the concentration of plasma fibronectin (pFN) is increased in patients with hyperthyroidism and decreased in those with hypothyroidism. In this work, labeled pFN was given intravenously to euthyroid, hyperthyroid, and hypothyroid rabbits to examine its metabolism in states of thyroid dysfunction. In euthyroid rabbits, the serum concentration of thyroxine (T4) was 2.94 +/- 0.59 micrograms/dL, and that of pFN was 24.2 +/- 1.2 mg/dL. With 125I-FN as tracer, the half life was estimated as 72.8 +/- 2.6 hours, the fractional catabolic rate (FCR) as 2.08 +/- 0.07%/h, the rate of synthesis (SR) as 3.84 +/- 0.20 mg/kg/day and j1/j2 (the ratio of the exchange coefficients between intravascular and extravascular compartments) of pFN as 0.295 +/- 0.051. With 3H-FN as tracer, these values were not significantly different. In hyperthyroid rabbits, obtained by treatment with I-thyroxine, the serum T4 concentration was increased to 5.73 +/- 1.58 micrograms/dL and the pFN concentration to 29.6 +/- 2.2 mg/dL. In these animals, the half life of pFN was shortened to 59.8 +/- 1.0 hour, the FCR was slightly increased to 3.07 +/- 0.52%/h and the SR was greatly increased to 7.13 +/- 1.17 mg/kg/d. In hypothyroid rabbits, obtained by treatment with methylthiouracil, the serum T4 and pFN levels were reduced to 1.50 +/- 0.36 micrograms/dL and to 20.7 +/- 1.7 mg/dL, respectively, the FCR and SR were also decreased to 1.39 +/- 0.04%/h and 2.26 +/- 0.14 mg/kg/d, respectively. The values of j1/j2 did not significantly change during this work.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical study on effects of cefmetazole on severe infections accompanied by hematologic diseases].

Severe infections accompanied by hematopathy under granulocytopenic conditions were treated with cefmetazole (CMZ). Subject diseases mainly consisted of acute leukemia, agranulocytosis and aplastic anemia; combined infections were septicemia, pneumonia, fever of an undetermined origin, etc. As for causative organisms found in cases that could be examined, Gram-negative bacilli such as Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa and Enterobacter cloacae were isolated, as was Staphylococcus aureus. In general, 4 g of CMZ divided into 2 administrations was given per day through intravenous injection or intravenous drip infusion. On the basis of the judgement criteria for effectiveness established by Takaku et al., the efficacy rate in this study was found to be 68%, including 2 cases that showed excellent responses to treatment of infections caused by S. aureus. Cases that showed pyretolysis within 4 days had over 1,000/microliter of neutrophils, while cases with less than 1,000/microliter showed no pyretolysis. No hepatorenal dysfunctions related to the treatment with CMZ were seen as side effects except increases of transaminase in 1 case. These results indicate that CMZ is a useful drug for the treatment of infections accompanied by hematopathy under granulocytopenic condition.

Adolescent↗

Alterations in lymphocyte subsets and serum immunoglobulin levels in patients with silicosis.

The numbers of total lymphocyte and lymphocyte subsets in peripheral blood of patients with silicosis and their serum immunoglobulin (Ig) levels were studied to evaluate their immune status. The numbers of total lymphocytes and OKT4+ and OKT8+ cells tended to be decreased and the numbers of OKT3+ cells was significantly decreased (p less than 0.001), but that of OKIa-1+ cells was increased (p less than 0.001) in the patients. In the lymph nodes of the lung hilus, the ratio of OKT4+ cells to total lymphocytes was increased but that of OKT8+ cells to total lymphocytes was decreased. The serum levels of IgG and IgA were elevated in the patients with reduction in the numbers of total lymphocytes and OKT4+ cells in peripheral blood. The serum IgE levels in 17 of 82 patients were above 400 IU/ml. In 8 patients with serum IgE 82 patients were above 400 IU/ml. In 8 patients with serum IgE levels of more than 1,000 IU/ml, the numbers of total lymphocytes and OKT3+ and OKT4+ cells were decreased compared with those in controls. The following suggestions are proposed from the results: Increase and activation of helper T cells may be caused by the presentation of silica dust to macrophages in the lymph nodes, and these cells may then stimulate B cell proliferation and Ig production by B cells, resulting in increase in the serum Ig (IgG, IgA and IgE) level. Reduction in the number of OKT4+ cells helper/inducer T cells) in peripheral blood may be due to migration of helper T cells into the lymph nodes. These immunological events in patients with silicosis are probably due to the adjuvant effect of silica dust.

Adult↗

Prothrombin Tokushima: characterization of dysfunctional thrombin derived from a variant of human prothrombin.

A mutant prothrombin, designated prothrombin Tokushima, was purified from plasma of a proband with 12% of normal plasma clotting activity and 42% of normal prothrombin antigen. The purified preparation gave a single band with the same mobility as that of "prothrombin" by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The factor Xa-catalyzed proteolysis of prothrombin Tokushima examined by SDS-PAGE was found to be identical to that of "prothrombin." Subsequently thrombin Tokushima was prepared by CM-Sepharose CL-6B column chromatography after prothrombin activation by factor Xa. The molecular weight of thrombin Tokushima estimated by SDS-PAGE was identical to that of "thrombin." Thrombin Tokushima exhibited less than 22% of normal clotting activity, and the value of kcat/Km (mumol/L-1 second-1) was less than one tenth of that of "thrombin" when Boc-Val-Pro-Arg-4-methylcoumaryl-7-amide was used as a substrate. However, active site titration using p-nitrophenyl-p'-guanidinobenzoate failed to detect any difference between the two. Thrombin Tokushima was 2.5% as effective as "thrombin" in inducing platelet aggregation. Interaction of thrombin Tokushima with antithrombin III was much slower than "thrombin" when followed by SDS-PAGE. Based on the residual thrombin activity, it was 33% as effective as "thrombin" in forming a complex with antithrombin III. These results indicate that the molecular defect resides in the thrombin portion of prothrombin Tokushima and that the binding sites for various substrates appear to be greatly impaired.

Blood Coagulation Disorders↗

[Changes in plasma fibronectin levels in patients with thyroid disease and its mechanism].

Plasma fibronectin (FN) level was determined in normal subjects and patients with thyroid disease by the Laurell method. In vitro effect of triiodothyronine (T3) on FN synthesis by cultured human fetal skin fibroblasts was also studied. Plasma FN level was 32.2 +/- 5.5 mg/dl (mean +/- SD) in normal adults, and no sex difference was observed. The plasma FN concentrations were increased in patients with hyperthyroidism (63.3 +/- 15.2 mg/dl), decreased in patients with hypothyroidism (19.5 +/- 6.5 mg/dl), and in normal range in patients with simple goiter (30.2 +/- 7.0 mg/dl). These FN values have been normalized with a time lag of a short period after their thyroid function became normal. There was a positive correlation between plasma FN concentrations and serum T3 or T4 concentrations, but a inverse correlation between plasma FN concentrations and serum thyroxine binding globulin or cholesterol levels. In vitro studies revealed that the addition of T3 to the incubation medium stimulated FN synthesis by human fetal skin fibroblasts at the concentrations between 10(-8)M and 10(-6)M. These results indicate the usefulness of plasma FN determination in patients with thyroid disease for their management and studying pathophysiology of the disease, and suggest at the fluctuation of plasma FN concentrations in these patients may at least in part due to the effect of thyroid hormone on FN synthesis by the cells.

Adolescent↗

Plasma fibronectin deficiency in eight members of one family.

The proband, a 31-year-old female, had keloids at the sites of surgery and burns. Her plasma fibronectin level measured by Laurell's method was only 10 mg/dl (mean +/- SD in 101 healthy controls 32.2 +/- 5.6 mg/dl) but the electrophoretic mobility was normal. Low levels of plasma fibronectin (range 11-17 mg/dl) were found in the proband's mother, two uncles, two brothers, one daughter, and one nephew. Levels in her father and other family members examined were normal (range 32-51 mg/dl). The proband has been quite healthy, an haematological and haemostatic tests showed no abnormality except reduced phagocytosis by neutrophils. Other family members with low plasma fibronectin levels had no abnormalities on examination and no keloids.

Adolescent↗

Changes in plasma fibronectin levels in thyroid diseases.

The plasma levels of fibronectin (Fn) have been measured in normal subjects and in patients with thyroid diseases. The mean plasma Fn levels in 62 normal adults was 32.0 +/- 6.0 mg/dl, whereas it was elevated to 62.6 +/- 16.1 mg/dl (mean +/- SD) in 25 patients with hyperthyroidism and decreased to 19.2 +/- 8.0 mg/dl in 9 patients with hypothyroidism. The 9 patients with simple goiter have normal values of 29.1 +/- 8.0 mg/dl. With the administration of anti-thyroid drugs, plasma Fn levels normalized, with a time lag, in parallel with normalization of the thyroid function. Positive correlation was obtained between Fn levels and serum levels of triiodothyronine (T3) and thyroxine (T4). The present findings indicate that measurement of plasma Fn both in the basal state and during treatment provides evidence of altered Fn metabolism in thyroid diseases and serves to follow up the effect of treatment.

Adolescent↗