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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 703 records · Page 39Linked to original sources
PubMed1983

Phosphorylation of smooth muscle heavy meromyosin by calcium-activated, phospholipid-dependent protein kinase. The effect on actin-activated MgATPase activity.

Smooth muscle heavy meromyosin (HMM) can serve as a substrate for the Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) as well as for the Ca2+/calmodulin-dependent kinase, myosin light chain kinase. When turkey gizzard HMM is incubated with protein kinase C, 1.7-2.2 mol of phosphate are incorporated per mol of HMM, all of it into the 20,000-Da light chain of HMM. Two-dimensional peptide mapping following tryptic hydrolysis revealed that protein kinase C phosphorylated a different site on the 20,000-Da HMM light chain than did myosin light chain kinase. Moreover, sequential phosphorylation of HMM by myosin light chain kinase and protein kinase C resulted in the incorporation of 4 mol of phosphate/mol of HMM, i.e. 2 mol of phosphate into each 20,000-Da light chain. When unphosphorylated HMM was phosphorylated by myosin light chain kinase, its actin-activated MgATPase activity increased from 4 nmol to 156 nmol of phosphate released/mg of HMM/min. Subsequent phosphorylation of this phosphorylated HMM by protein kinase C decreased the actin-activated MgATPase activity of HMM to 75 nmol of phosphate released/mg of HMM/min.

Actins↗
PubMed1983

Pharmacological properties of platelet strips.

The pharmacological properties of human platelet strips were studied by recording changes in tension after the application of various compounds. The platelet strips were prepared by packing cold re-calcified human platelets over a sheer gelatinized nylon mesh. The contractile response of such a strip was dependent on the number of platelets sticking to the nylon mesh. The strip was contracted by the addition of platelet aggregation inducers such as ADP, norepinephrine, thrombin and collagen, thereby suggesting that the contractile response is mediated through membrane receptors on the platelets. The ED50 values of the aggregation agents which contracted the strip were much the same as those which induced platelet aggregation, thereby suggesting that contraction of the platelet strip is similar to platelet aggregation in platelet rich plasma (PRP). The addition of platelet aggregation inhibitors such as papaverine, W-7 and PGE1 relaxed the platelet strip. The ED50 values of the aggregation inhibitors which relaxed the platelet strip were also similar to those for platelet aggregation inhibition. The time course of the release of the preloaded [14C]serotonin from the platelet strips correlated well with that of the tension developed.

Adenosine Diphosphate↗
PubMed1983

Hypothyroidism associated with positive results of the perchlorate discharge test in elderly patients.

In 172 patients over the age of 55, determinations were made of thyrotropin concentrations in plasma. Although they showed such symptoms or signs of hypothyroidism as puffy face, dry skin, general malaise, cold intolerance, or constipation, there were no clinical indications of overt hypothyroidism. All the patients were apparently in a normal nutritional state, without any specific medication that might cause thyroid abnormalities. Seventeen (six men and 11 women, 9.9 percent) of the 172 patients, aged 58 to 83, had elevated plasma thyrotropin levels, ranging from 12.1 microU/ml to 170 microU/nl. To investigate the characteristics of hypothyroidism in the elderly, the perchlorate discharge test was performed in these patients. In 15 of the 17 patients, 123I thyroid uptake diminished markedly immediately after the administration of 1 g perchlorate. Thirteen of these 15 patients showed markedly diminished thyroxine (T4) levels in serum, whereas the magnitude of diminution in serum 3,5,3'-triiodothyronine (T3) values was small. Two patients with the negative discharge results showed normal T4 and T3 levels in serum. Four patients had a very small goiter, and the remaining 13 patients had no detectable goiter. Fifteen of the 17 patients had no detectable circulating thyroid antibodies in repeated determinations, and the histologic features of Hashimoto's thyroiditis were not found in the thyroid specimens obtained from two patients. These findings suggest the existence of hypothyroidism attributable to iodine organification defect without evidence of autoimmune thyroiditis in some cases in elderly patients.

Aged↗
PubMed1983

Studies on corticoid action on the toad tadpole tail in vitro.

The effect of adrenal corticoids on the shrinkage of tail segments from Bufo bufo japonicus tadpoles was studied in vitro. Deoxycorticosterone acetate (DCA) was effective in accelerating the shrinkage of tail segments if thyroxine (T4) or triiodothyronine (T3) was present in the medium. The shrinkage caused by DCA was dose dependent. In the absence of thyroid hormone, DCA did not induce tail resorption. Shrinkage of tail segments induced by DCA and T4 was blocked by prolactin. Among the steroid hormones testes in vitro, aldosterone and corticosterone exhibited a potent activity in accelerating shrinkage of tail segments in the presence of T4. The nature of the corticoid action is discussed.

Adrenal Cortex Hormones↗
PubMed1983

Change in ratio of the two hepatic isometallothioneins with development from prenatal to neonatal rats.

Concentrations and contents of essential metals in the livers of prenatal and neonatal rats were determined simultaneously by inductively coupled plasma-atomic emission spectrometry. The concentrations and contents changed with development in a mode characteristic to the respective metals. Changes in the concentrations and contents of zinc and copper were correlated to those bound to metallothionein, the two metals being high in concentration during prenatal and neonatal periods. The relative ratio of the two isoforms of metallothionein changed with development, the form I being predominant in prenatal livers.

Animals↗
PubMed1983

Induction of outer and inner ring monodeiodinases in human thyroid gland by thyrotropin.

The effects of TSH on iodothyronine 5- and 5'-deiodinations were investigated using cultured thyroid tissues from patients with Graves' disease. The addition of TSH to the culture medium stimulated all of the iodothyronine-deiodinating activities of thyroid tissues cultured for more than 4 days. Peak TSH-induced activities were found on the fifth day of culture, and increased activities were found up to 9 days. On the fifth day of culture, TSH enhanced both outer and inner ring monodeiodinations in a dose-responsive manner between 62.5 and 250 microU/ml. This stimulation by TSH was blocked by the addition of actinomycin D or propylthiouracil. Incubation of thyroid tissues with (Bu)2cAMP mimicked the action of TSH, and theophylline potentiated the action of TSH. These results suggest that TSH, in an action probably mediated by cAMP, induces synthesis of iodothyronine deiodinases in the thyroid gland.

Bucladesine↗
PubMed1983

Serum concentrations of 3, 3'-diiodothyronine, 3', 5'-diiodothyronine, and 3, 5-diiodothyronine in altered thyroid states.

To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Synaptosomal T3 binding sites in rat brain: their localization on synaptic membrane and regional distribution.

Previous studies have shown the existence of specific high affinity T3 binding sites in rat cerebrocortical synaptosomes. In this study, to define the localization of the binding sites, T3 binding to disrupted synaptic membrane fractions was compared with the binding to intact synaptosomes obtained from the rat cerebral cortex. Scatchard analysis revealed two orders of T3 binding sites with almost identical apparent dissociation constant (Kd) in synaptosomes and synaptic membrane fractions. However, the maximal binding capacity (MBC) of the higher affinity binding sites for synaptic membrane fractions was significantly greater than that for intact synaptosomes (4.2 +/- 0.2 vs 3.0 +/- 0.3 pg T3/mg protein). Regional distribution of the synaptosomal T3 binding sites in various areas of the rat brain was also studied. The Kd values were not significantly different in discrete brain regions. On the other hand, the MBCs of the higher affinity binding sites were greater in the cerebral cortex and hypothalamus (72.8 +/- 1.4 and 64.8 +/- 9.5 pg T3/g tissue) than in the cerebellum (22.1 +/- 1.6 pg T3/g tissue). Similar difference was also observed in the lower affinity sites. These results indicate that the specific T3 binding sites in brain synaptosomes are localized mainly on synaptic membranes and that the MBC is different in discrete brain regions.

Animals↗
PubMed1983

[The suppressive effect of melilotus extract on the thermal edema of rats].

The effect of melilotus extract (ME) and Esberiven (ES) which contain coumarin on the thermal edema, which is one of high protein edema, was evaluated by both quantitative and qualitative assays. The intraperitoneal injection of ME immediately after burn greatly reduced the amount of swelling and effectively inhibited the occurrence of necrosis and induration in the injured leg-skin as compared with the saline controls in which a 3rd degree of thermal injury was observed. Administration of ES also induced a similar suppressive effect. Furthermore, either intraperitoneal or subcutaneous local injection of ME 4 hr before burn was effective in reducing the edema and thermal injury. No increase of the lymph flow and output of lymphocytes and protein from the thoracic duct lymph was observed in thermally injured rats given an injection of ME. The massive infiltration of neutrophils and macrophages 6 to 24 hr after the subcutaneous injection of ME was histologically observed in the dermal lesion of normal rats. Twenty-four hr later, macrophages, fibroblasts, and lymphocytes became predominant. The present data taken together suggest that ME exerts the suppressive effect on thermal injury by either prior or post administration, and these effects might be induced in an indirect manner, through the action of phagocytic cells accumulated in the injured lesion, not via lymphatic drainages of excess fluid and protein.

Animals↗
PubMed1983

"Nonalcoholic steatohepatitis" induced by massive doses of synthetic estrogen.

We have noticed that functional disorders of the liver characterized by hepatomegaly and an increase in serum gamma-glutamyl transpeptidase develop in patients with prostatic cancer who are placed under longterm therapy with massive doses of estrogen after castration. We performed laparoscopy in six cases of prostatic cancer with hepatomegaly so that we could study the morphology of the liver. Our findings were as follows. In five, the histological features of the liver biopsies were very similar to those seen in alcoholic hepatitis. In spite of this fact, two of the five had no history of alcohol consumption. Furthermore, in one other case, liver damage resembling alcoholic hepatitis developed during abstinence. The findings in these three cases suggested that long-term, massive doses of synthetic estrogen may lead to liver injury similar to alcoholic hepatitis in nonalcoholics. The ultrastructural findings of the liver cells were also suggestive of the adverse effect of treatment. All cases were negative for hepatitis B surface antigen. Recent reports have demonstrated some nonalcoholics with histological features of the liver indicative of alcoholic hepatitis. This particular condition was termed "nonalcoholic steatohepatitis" by Ludwig et al. It is quite likely that synthetic estrogen is also responsible for "nonalcoholic steatohepatitis" when it is used in massive doses.

Aged↗
PubMed1982

[The prognosis of Graves' disease after antithyroid drug treatment: clinical significance of the T3 suppression test and abnormal thyroid stimulators].

The prognostic significance of both the triiodothyronine (T3) suppression test and the detectability of thyroid stimulating immunoglobulins in patients with Graves' disease who had been treated with antithyroid drugs was evaluated. Eighty-three patients underwent a T3 suppression test after having been euthyroid for at least 6 months. In 33 patients, the human thyroid stimulator (HTS) was assayed by measuring cyclic AMP increase in cultured thyroid adenoma cells, and TSH-binding inhibitor immunoglobulins (TBII) were measured by using the radioreceptor assay of TSH. Among 43 patients who had discontinued the drug treatment, 37 patients were under observation for 6-42 months. When a fall in 30-minute thyroid 99mTcO4- uptake of 50% or more after T3 administration was defined as positive suppression, the relapse rate was 30% in non-suppressive cases and 26% in suppressive cases. The relapse rate was lower in cases whose pre-suppression uptake was less than 3.0% (3 out of 17 patients) or in cases whose uptake after T3 administration was less than 0.8% (1 out of 9 patients). Of 15 patients with negative suppression, 5 (33.3%) were positive in HTS and 4 (26.7%) were positive in TBII. On the other hand, two (11.1%) each of 18 patients with positive suppression were positive in HTS and TBII respectively. Neither HTS nor TBII had been detected at the cessation of therapy in any of the 12 patients who remained euthyroid during the follow-up period. On the other hand, four (44.4%) out of 9 patients who relapsed had been positive in either HTS of TBII. Thus the Graves' disease specific immunoglobulins were found to be significantly associated with the relapse of the disease (p less than 0.05). The above data indicates that regardless of the suppressibility of 99mTcO4- uptake after T3 administration, the rate of recurrence is high when the uptake after T3 is more than 0.9% and/or when either HTS or TBII are positive.

Adult↗
PubMed1982

Calmodulin and acidic compounds alter basic protein phosphorylation by the protein kinase from human platelets.

A cyclic nucleotide-independent protein kinase of human platelets, which phosphorylated histones, myelin basic protein and protamine and did not catalyze the phosphorylation of acidic proteins such as casein, phosvitin and myosin light chain, has been purified approx. 1,500-fold from the crude extract by steps of DEAE-cellulose, Sephadex G-200, hydroxylapatite and phosphoryl cellulose column chromatography. The substrate phosphorylation by this kinase was markedly enhanced by calmodulin even in the absence of Ca2+, when mixed histone was used as a substrate. The interaction of the kinase with mixed histone resulted in an irreversible inactivation of the enzyme. Calmodulin prevented this inactivation, and this compound produced an apparent increase in histone phosphorylation by the kinase. It should be noted that acidic polypeptides such as troponin-C, phospholipids and nucleic acids have a similar ability. The addition of Ca2+ reduced the effect of calmodulin more than the effects of other acidic compounds.

Blood Platelets↗