[Synergism of the calcium reversal phenomenon of potassium depolarizing in the rat uterine muscle by Bay k-8644, a calcium agonist].
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Biomedical subjects
Publications and source records attributed to S Uchida.
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Metal ion-activated acid ATPase was present in chicken liver lysosomes. The enzyme catalyzed the hydrolysis of nucleoside tri-, di-, and monophosphates and cleaved the phosphodiester linkage. Among the substrates studied, ATP was hydrolyzed at the highest rate at pH 5.4. The enzyme activity was stimulated 3.5 approximately 7.5-fold by divalent cations such as Ca2+, Mg2+, and Zn2+, but inhibited by EDTA or Hg2+.
In an attempt to elucidate the relationship between phosphatidylinositol breakdown and alpha-adrenergic responses, effects of phosphatidic acid and phosphatidylinositol related metabolites on Ca2+ mobilization and glucose output in cultured hepatocytes were examined. Norepinephrine induced the net 45Ca2+ efflux from preloaded cells and stimulated glucose output via alpha-adrenergic receptor stimulation, whereas phosphatidic acid caused 45Ca2+ uptake to cells and did not stimulate glucose output. Myo-inositol-monophosphate, diglyceride and arachidonic acid, which are released by phosphatidylinositol breakdown, had no effect on 45Ca2+ efflux and glucose output in cells. These results suggest that phosphatidic acid and phosphatidylinositol related metabolites can not mimic the alpha-adrenergic actions in cultured hepatocytes.
Multiple site models of muscarinic acetylcholine receptors (mAChR) for agonist binding were applied to curves for the inhibition of QNB binding by carbachol by using nonlinear least square regression analysis. The effects of a guanine nucleotide guanyl-5'-yl imidodiphosphate (Gpp(NH)p) and a sulfhydryl reagent 5,5'-dithiobis(2-nitrobenzoic acid (DTNB) on the curves were also analyzed. The results suggested that mAChR of dog and guinea pig heart had three types of sites with different affinities for carbachol (super-high (SH), high (H) and low (L]. In the presence of Gpp(NH)p, SH sites were eliminated and L sites increased, indicating conversion of SH sites to L sites. On the contrary, in the presence of DTNB, L sites were converted to SH sites. These results were obtained at both 37 degrees C and 0 degrees C incubation although the affinity of each site was high at 0 degrees C than at 37 degrees C. These data suggest the interconversion of SH and L sites. The possible existence of two subtypes (GTP-regulated mAChR(SH-L type) and GTP-independent mAChR (H type] is discussed.
Between 1973 and 1981, bilateral total replacement of hip and knee joints was performed in 22 patients with rheumatoid arthritis. During follow-up, 2 patients died of diseases not directly related to the operation. Besides these patients, there were 2 patients who could not be followed up. The remaining 18 patients constituted the subjects for study. We studied the postoperative results, emphasing improvement in the ability to perform everyday activities. Walking ability was improved in 16 patients. There was an increase in the number of patients able to rise from a chair, go up and down stairs, and get in and out of a car, bus or train. Of the 14 married patients (not including 2 patients who were unable to walk and 5 patients over 60 years of age) 7 were able to perform sexual intercourse as well as they had been able to when healthy. The patients who underwent bilateral total replacement of hip and knee joints often presented various problems, for example with regard to indications, the operative technique to use, as well as complications such as heart disease, pulmonary disease, and secondary amyloidosis. We have found, however, that bilateral total replacement of hip and knee joints can accomplish the operative objectives of eliminating pain and improving the quality of daily life in severely handicapped rheumatoid patients.
In this paper, the effect of acute human growth hormone (GH) administration on erythrocyte insulin binding in GH deficient children (N = 6) was studied. Following GH (0.25 U/kg) administration, the blood levels of GH peaked within 4 to 8 h and returned to basal levels 24 h later. However, the changes in somatomedin activity, free fatty acid (FFA), urea, blood glucose and 125I-insulin binding to erythrocyte were observed around 24 h following the injection, and there was a converse relationship between maximum percent 125I-insulin binding (IBmax) and FFA (P less than 0.02). By Scatchard analysis it was found that the decrease in IBmax is mainly due to the change in the number of insulin receptors. These results suggest that GH may possibly affect the insulin binding to erythrocyte indirectly through metabolic changes as a result of hormonal changes in GH deficient children.
This is a report concerning 13 autistic children who have been followed up from their early infancy to adulthood. Some intake variables, such as speech development at the age of 5, were correlated with the outcome status. As a result, we showed that a higher level of speech development at age 5 did not necessarily lead to a better outcome in social adaptability. We showed also that any of the variables we examined, such as the presence of brain organic abnormality, the duration of schooling and the duration of medical treatment, were not factors in determining a good or poor prognosis. We concluded that a rather poor outcome seen in our subjects might be due to the particular situation in Japan throughout this study period, and not a reflection of the real natural history of early infantile autism.
BK virus mutant pm-522, forming small turbid plaques on human cells, can transform rat or hamster cells much more efficiently than the wild-type BK virus (wt-501) does. We compared the nucleotide sequence of wt-501 HindIII C segment with that of pm-522 HindIII-C, which contains the mutation responsible for the altered plaque type and transforming capacity. The difference between the two BK viruses was the local DNA rearrangement (deletions and duplications) that had occurred in the putative control region for early transcription in pm-522 DNA. Whereas wt-501 had three sets of 68-base pair repeats (the central set had a deletion of 18 base pairs) in this region, pm-522 had one set of 68-base-pair units and two sets of shorter 37-base-pair repeats. Three BK virus mutants, forming clear large plaques like those of wt-501 but capable of transforming rat cells, were derived from the recombinant virus carrying the HindIII C segment of pm-522. These mutants had further duplications of short segments originating from the pm-522 sequence in the putative early control region.
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Tissues responses for drugs are often altered by chronic administration of drugs and this alteration is one kind of functional abnormality of the tissues. One mechanism under this functional abnormalities is considered to be in changes in receptors for drugs. In this study, we examined amounts and properties of receptors in sub- and supersensitive states caused by pre-exposure of tissues to drugs and the results obtained were summarized as follows. Long term exposure of tissue to agonists or to conditions which elevate concentration of agonist around the receptor caused reduction in amount of receptor without change in its property. Short term exposure to agonists altered the configuration of the receptor accompanying reduction in sensitivity of the tissue to drugs. But amount of receptor in the tissue was not changed. Heterologous desensitization was observed in some cases by exposure to drugs and no significant change was observed in the receptor of the tissue, qualitatively and quantitatively, indicating dysfunction in the process(es) after activation of the receptor. Denervation and chronic treatments with antagonist and ganglion blocker caused supersensitive state accompanying increase in amount of receptor. But in some cases, qualitative change of receptor, increase in affinity of receptor for agonist, seemed to relate with supersensitive state of tissues.
The response of plasma cyclic AMP to glucagon was investigated in 18 patients with acute liver injury to determine its value as a marker for the severity of the hepatic damage. We also investigated the interrelationship between plasma cyclic AMP response and the hyperglucagonemia often seen in this disease. Plasma cyclic AMP response to glucagon was reduced significantly in patients with acute hepatitis, particularly in severe cases with bridging hepatic necrosis. There was a significant negative correlation between log (peak % cAMP) and prothrombin time (r = -0.715, p less than 0.01), and also total bilirubin (r = -0.819, p less than 0.01). In fatal cases, the early phase of plasma cyclic AMP response after glucagon stimulation was blunted. In patients with acute liver injury, basal IRG levels were significantly high and a significant negative correlation was found between log (peak % cAMP) and basal IRG levels (r = -0.816, p less than 0.01). Our results suggest that the response of plasma cyclic AMP to exogenous glucagon could be useful in evaluating the severity of acute liver injury. The lower cyclic AMP response may be attributed to reduced hepatic reserve and endogenous hyperglucagonemia.
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Cough productive of sputum, exertional dyspnea, and hypoxemia developed in two patients with Graves' disease after six months (patient 1) or three weeks (patient 2) of treatment with propylthiouracil, 300 mg/day. Chest roentgenograms and transbronchial lung biopsy specimens revealed diffuse interstitial pneumonitis. Lymphocyte transformation by phytohemagglutinin was highly stimulated by propylthiouracil. Symptoms and signs improved after cessation of the drug therapy and administration of prednisolone acetate. These cases represent the first report of a complication of diffuse interstitial pneumonitis induced by propylthiouracil.
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Muscarinic cholinergic receptors (mAChR) are degraded on the addition of agonists through energy- and temperature-dependent processes, probably with clustering and endocytosis. Pretreatment of guinea-pig vas deferens with 0.5 mM quinacrine or 5 mM tetracaine, phospholipase A2 (PLase A2) inhibitors, inhibited the ACh-induced degradation of mAChR in the smooth muscle and kept mAChR on the surface membrane, while cocaine and procaine were not effective. On pretreatment with quinacrine or tetracaine the PLase A2 activity in the smooth muscle decreased continuously during culture without change in the contractile response of the tissue. Pretreatment with cocaine and procaine which had no significant effect on the down regulation of mAChR did not inhibit PLase A2 activity. However, activation of PLase A2 by long-term culture of the muscle with ACh and formation of endogenous inhibitor of PLase A2 were not observed under our experimental conditions. The participation of PLase A2 in the agonist-induced degradation of mAChR is discussed in the light of these findings.
Urea-treatment of the microsome fraction of the heart of guinea-pigs caused selective reduction in the apparent affinity of an agonist (carbachol), but not an antagonist (atropine), to muscarinic acetylcholine receptors (mAChR), measured as inhibition of binding of 3H-quinuclidinyl benzilate (3H-QNB). This effect was similar to that of Gpp (NH)p. The effects of urea-treatment and Gpp (NH)p were not additive. On the other hand, treatment of the microsome fraction with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) increased the apparent affinity of agonist, but not antagonist. The effect of DTNB predominated over those of urea-treatment and Gpp (NH)p, when these treatments were combined with DTNB.
The effects of hexamethonium (C6) administration on muscarinic acetylcholine receptors (mACh-R) in the intestine and brain of mice were investigated. Mice were treated with C6 with an osmotic mini-pump (330 mg/kg/day) for one week and then the binding of 3H-quinuclidinylbenzilate (3H-QNB) in the intestine and brain were assayed. This treatment increased the maximum specific binding (Bmax) of 3H-QNB from 160 to 320 fmoles/mg protein in the ileum and from 190 to 340 fmoles/mg protein in the rectum, without affecting the KD values in these regions. On the contrary, C6 treatment did not change the Bmax or KD value in brain tissues. This C6 treatment increased the sensitivity of the contractile response of the intestine to muscarinic agonists, possibly by increasing mACh-R.