Biomedical subjects
Publications and source records attributed to S Katsuki.
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An enzyme-linked immunosorbent assay (ELISA) for measuring human protein C by using two monoclonal antibodies directed toward the heavy chain of protein C is reported. This assay enabled the determination of protein C in concentrations of 10 to 400 ng/ml in less than 3 hours with a single antigen-antibody reaction. Within-run and between-run coefficients of variation were less than 8%. The mean concentrations of protein C in plasma of 42 normal subjects, 24 patients with liver disease, 27 with DIC, 48 with warfarin therapy and 15 with congenital protein C deficiency, were 4.2, 3.0, 2.3, 2.1 and 1.9 micrograms/ml, respectively. The results obtained with the present ELISA correlated well with those of radioimmunoassay (r = 0.935, n = 81) as well as those of Laurell's Rocket method (r = 0.910, n = 81) by using rabbit anti-human protein C serum. The present method was sensitive and specific for measurement of protein C and also PIVKA-protein C in plasma.
In a longitudinal study of a general population in Hisayama, Japan, 339 persons aged 40 years or over at death were autopsied during the period November 1, 1961-October 31, 1971. In 308 of these people, electrocardiograms taken at the periodic examinations were available, and Q.QS items of the Minnesota Code were recorded in 49 persons. The sensitivity of item 1-1 to autopsy-proven old myocardial infarction was 0.32 and the specificity was 0.95. Using the estimated prevalence of old myocardial infarction in this community--77 per 100,000--the proportion of persons without old myocardial infarction among those with item 1-1 in the general population (PF+) was 0.9954 and the proportion of persons with old myocardial infarction among those without item 1-1 (PF-) was 0.0005. The sensitivity of items 1-1 and 1-2 to old myocardial infarction was 0.43 and the specificity was 0.94. PF+ of items 1-1 and 1-2 was 0.9949 and PF- was 0.0005. These large values of PF+ mean that more than 99 per cent of persons with these items are probably false positives if these items are used as a screening test for this disease in the general population of this community, i.e., that these items cannot be defined as a definite myocardial infarction.
2-Chloro-11-(2-dimethyl-aminoethoxy) dibenzo [b, f] thiepin (zotepine) is a new neuroleptic drug which is structurally different from known neuroleptics. Zotepine, chlorpromazine, propericiazine, and cyproheptadine inhibited hyperthermia induced by dosing with fenfluramine in rats in a warm environment (26-28 degrees C). Fenfluramine is known to induce hyperthermia by mediation of central serotonin. Zotepine had a 10 times or greater potency than chlorpromazine, propericiazine and cyproheptadine in inhibiting the hyperthermia. Thioridazine did not inhibit the hyperthermia, whereas haloperidol accelerated the hyperthermia. Zotepine was also the most potent inhibitor of 3H-serotonin binding to rat cortical synaptosomes in vitro. However, cyproheptadine had the strongest anti-serotonin activity in rat fundus preparations, while zotepine and other neuroleptics showed the same order of potency. These results showed that zotepine is a unique neuroleptic with potent central anti-serotonin activity. The central anti-serotonin activity of zotepine is discussed in connection with its lesser extrapyramidal side effects in humans.
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During a ten-year period, from November 1, 1961, to October 31, 1971, 339 residents aged 40 years or over at death were nonselectively autopsied in a Japanese community, Hisayama town (mean autopsy rate: 84%). One or more standard 12-lead ECGs plus V4R and V7 electrocardiograms taken at periodic medical examinations were available for 308 of them. In 46 persons, QS waves were localized in one or more leads from V1 to V4. By transverse sectioning of the hearts, old myocardial infarction extending into the interventricular septum was found in nine of these 46 persons. Frequency of myocardial infarction cases in each category for QS localization was as follows: Lead V1 to V4, three of three; Leads V1 to V3, six of nine; Leads V1 and V2, three of 15; Leads V2 and V3, none of two; Lead V3, none of one; Lead V2, one of eight; and Lead V1, one of 25.
This study of autopsy cases in the general population of the town, Hisayama, describes the incidence and severity of aortic and cerebral atherosclerosis in Japan. Atherosclerosis was more severe in the aorta than in the cerebral arteries of all age groups and its disparity became more conspicuous with age. In hypertensive cases, atherosclerosis was more severe in both the aorta and the cerebral arteries from and beyond the 6th decade of age. The severity of atherosclerosis in the aorta in those with systolic hypertension was lower under the age of 79 and higher after the age of 80 than in diastolic hypertension; the cerebral arteries were afflicted similarly by the two forms of hypertension. The serum cholesterol level correlated better with the severity of aortic than cerebral atherosclerosis.
Sodium (6R,7R)-7-[(Z)-2-(2-amino-4-thiazoyl)-methoxyiminoacetamido]-8-oxo-5-thia-1-azabicyclo[4,2,0] oct-2-ene-2-carboxylate (ceftizoxime sodium), a new semisynthetic cephalosporin derivative, was tested for acute toxicity in various laboratory animal species, nephrotoxicity in rabbits, subacute and chronic toxicity in rats and dogs, and effect on fertility and teratogenicity in rats and rabbits. The i.v. LD50 values of ceftizoxime sodium in mice and rats were around 6000 mg/kg, and no deaths occurred in dogs after the largest dose of 3200 mg/kg. There was no evidence of nephrotoxicity of ceftizoxime sodium in rabbits after an i.v. dose of 1000 mg/kg. Clear-cut changes in subacute and chronic toxicity studies of ceftizoxime sodium were local damage at the injection site and its secondary reactions, although reversible peripheral anemia was observed in one female dog given 1000 mg/kg i.v. In the reproduction studies, ceftizoxime sodium had no adverse effects on fertility or fetal development in rats or rabbits.
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Nitric oxide gas (NO) increased guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue preparations examined. The extent of activation was variable among different tissue preparations and was greatest (19- to 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex, and cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal muscle, adrenal, and epididymal fat. Activation was also observed with partially purified preparations of guanylate cyclase. Activation of rat liver supernatant preparations was augmented slightly with reducing agents, decreased with some oxidizing agents, and greater in a nitrogen than in an oxygen atmosphere. After activation with NO, guanylate cyclase activity decreased with a half-life of 3-4 at 4 degrees but re-exposure to NO resulted in reactivation of preparations. Sodium azide, sodium nitrite, hydroxylamine, and sodium nitroprusside also increased guanylate cyclase activity as reported previously. NO alone and in combination with these agents produced approximately the same degree of maximal activation, suggesting that all of these agents act through a similar mechanism. NO also increased the accumulation of cyclic GMP but not cyclic AMP in incubations of minces from various rat tissues. We propose that various nitro compounds and those capable of forming NO in incubations activate guanylate cyclase through a similar but undefined mechanism. These effects may explain the high activities of guanylate cyclase in certain tissues (e.g., lung and intestinal mucosa) that are exposed to environmental nitro compounds.
1. Cold storage treatment of the guinea-pig taenia caecum had a greater inhibitory effect on the isoprenaline-induced relaxation than that induced by phenylephrine. Prolonged cold storage (12-14 days) almost abolished the effect of isoprenaline but only reduced the phenylephrine effect. The ED50 of cyclic adenosine 3',5'-monophosphate (cyclic AMP) that elicited muscle relaxation was not altered by the prolonged cold storage. 2. After cold storage treatment, tissue cyclic AMP content was decreased; however, isoprenaline still caused a dose-dependent increase in the cyclic AMP level. The threshold dose of isoprenaline for cyclic AMP accumulation was the same in fresh and cold-stored preparations. 3. In the fresh preparation, the onset of the isoprenaline (10(-6)M)-induced relaxation preceded the increase in tissue cyclic AMP. 4. Isoprenaline, phenylephrine, adrenaline and noradrenaline at doses (ED50) sufficient to induce muscle relaxation did not always increase the cyclic AMP level. 5. Similarly, the responses to papaverine and nitroglycerine were not accompanied by an increase in cyclic AMP. 6. The adenylate cyclase and phosphodiesterase (low and high Km) activities of taenia caecum were not attenuated by the prolonged cold storage. 7. Propranolol inhibited both the isoprenaline-induced relazation and cyclic AMP accumulation; however, the pA2 values were significantly different for the two events. 8. Based on these results, both the relaxation and cyclic AMP accumulation caused by isoprenaline are mediated by activation of beta-adrenoceptors but are independent phenomena.
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Sodium nitroprusside, nitroglycerin, sodium azide and hydroxylamine increased guanylate cyclase activity in particulate and/or soluble preparations from various tissues. While sodium nitroprusside increased guanylate cyclase activity in most of the preparations examined, the effects of sodium azide, hydroxylamine and nitroglycerin were tissue specific. Nitroglycerin and hydroxylamine were also less potent. Neither the protein activator factor nor catalase which is required for sodium azide effects altered the stimulatory effect of sodium nitroprusside. In the presence of sodium azide, sodium nitroprusside or hydroxylamine, magnesium ion was as effective as manganese ion as a sole cation cofactor for guanylate cyclase. With soluble guanylate cyclase from rat liver and bovine tracheal smooth muscle the concentrations of sodium nitroprusside that gave half-maximal stimulation with Mn2+ were 0.1 mM and 0.01 mM, respectively. Effective concentrations were slightly less with Mg2+ as a sole cation cofactor. The ability of these agents to increase cyclic GMP levels in intact tissues is probably due to their effects on guanylate cyclase activity. While the precise mechanism of guanylate cyclase activation by these agents is not known, activation may be due to the formation of nitric oxide or another reactive material since nitric oxide also increased guanylate cyclase activity.
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Three agents that activate guanylate cyclase, sodium nitroprusside, nitroglycerin and sodium axide, were examined for their effects on cyclic GMP and cyclic AMP accumulation and muscle motility with several tissues. All of these agents, except nitroglycerin with ventricle preparations, increased cyclic GMP levels and did not alter cyclic AMP in incubations of preparations of bovine tracheal smooth muscle, guinea pig tracheal chains, taenia cecum, atria and ventricle, and rat liver and cerebral cortex. Increases in cyclic GMP with these agents occurred with relaxation of smooth muscle preparations and without alteration in the contractility of atrial preparations. These observations support the hypothesis that cyclic GMP accumulation in smooth muscle may be related to relaxation rather than contraction as proposed previously. Relaxation with these agents is not associated with alterations in cyclic AMP levels. Increases in cyclic GMP levels in atrial preparations can also occur without changes in contractile force or rate of contraction.