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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 199 records · Page 11Linked to original sources

Cerebral infarction due to systemic necrotizing vasculitis in a patient with rheumatic heart disease, subacute bacterial endocarditis and status epilepticus.

Systemic necrotizing vasculitis involving cerebral blood vessels is described in a 30-year-old man with rheumatic heart disease and subacute bacterial endocarditis. Fever, anaemia, splenomegaly and positive blood cultures for Gram-negative bacteria were found on admission. The fever resolved with antibiotic therapy on the third hospital day but he then developed hemiplegia and multifocal seizures. The seizures progressed to uncontrollable status epilepticus accompanied by congestive heart failure and the patient died 20 d after admission. At autopsy, exudative and necrotizing vasculitis involving medium- to small-sized arteries was seen in the brain, the heart and the skeletal muscles. Rheumatic myocarditis and endocarditis and old rheumatic mitral valve deformities were also present. In addition, verrucous endocarditis in the mitral valve and Löhlein's focal glomerulonephritis were noted. We discuss the possible mechanism of the systemic necrotizing vasculitis in relation to rheumatic fever.

Adult

Neurochemical effects following AF64A injection into the basal nuclei of rats.

AF64A, a specific cholinergic neurotoxin, was injected into the basal nuclei of rats. The injected sites were the bilateral nucleus basalis of Meynert (NBM) and the medial septal nucleus (MSN), well known to be the nuclei of origin of the two major cholinergic pathways. The remote effects of injection were estimated by the regional choline acetyltransferase (CAT) activity in the frontal cortex, striatum and hippocampus. The injection of AF64A (1 nmol in 1 microliter) produced a reduction in the CAT activity in each projected site: NBM lesions in the frontal cortex and MSN lesions in the hippocampus after one and three weeks. Twelve weeks after the injection, the reduced CAT activity had returned to normal levels. This neurochemical effect shows plasticity and recovery with time. The injections of small amounts of AF64A (0.2 and 0.1 nmol in 1 microliter) produced no chemical changes after one week.

Acetylcholinesterase

High prevalence of infantile autism in Kurume City, Japan.

We surveyed the prevalence of infantile autism in Kurume City. Children born between 1971 and 1979 ranged in age from 4 to 12 years at the time of the survey. We found 51 cases of infantile autism. In each year group, we determined the ratio of the number of cases of infantile autism to the total number of children. The prevalence ranged from 10.4/10,000 to 17.5/10,000, with a mean prevalence of 15.5/10,000. The sex distribution was 42 males (prevalence of 24.8/10,000) and nine females (prevalence of 5.7/10,000). The results showed a significant sex difference, with a male:female ratio of 4:1 (p less than 0.0005). High prevalence rates of infantile autism in Kurume City were confirmed.

Autistic Disorder

Effects of angiotensin converting enzyme inhibitor and calcium channel blocker on normoxic and hypoxic pulmonary vascular tone in unanesthetized sheep.

We evaluated the effects of captopril and nifedipine on normoxic and hypoxic pulmonary vascular tone in unanesthetized sheep. Infusion of captopril (10 micrograms/kg/min) in normoxia revealed a tendency to increase the mean pulmonary arterial pressure (Ppa) and the pulmonary vascular resistance (PVR) following the systemic vasodilation. A statistically significant increase was reached by 20 minutes. Hypoxia of 10% oxygen in nitrogen produced a prominent pulmonary hypertensive response. Captopril significantly decreased the hypoxic values of Ppa and PVR from 20.3 +/- 1.3 to 17.1 +/- 1.1 mmHg (p less than 0.01) and from 4.31 +/- 0.45 to 3.49 +/- 0.45 mmHg/L/min (p less than 0.01), respectively. Infusion of nifedipine (10 micrograms/kg/min) in normoxia caused an increase in Ppa from 15.5 +/- 0.9 to 18.9 +/- 1.0 mmHg (p less than 0.01), but not in PVR. This elevation in Ppa was considered to be derived from the significant increase in the cardiac output. Nifedipine significantly decreased the hypoxic values of Ppa and PVR from 21.3 +/- 1.5 to 19.3 +/- 1.5 mmHg (p less than 0.05) and from 3.88 +/- 0.30 to 27.3 +/- 0.13 mmHg/L/min (p less than 0.01), respectively. Captopril and nifedipine produced systemic hypotensive responses during both normoxic and hypoxic ventilation. It is concluded that both captopril and nifedipine are potent pulmonary vasodilating drugs in animal subjects with a hypoxic condition and that they might be useful in the clinical vasodilator therapy of hypoxic pulmonary hypertension in man.

Angiotensin-Converting Enzyme Inhibitors

Augmentation and inhibition of beta-adrenergic agonists-stimulated tissue cyclic AMP accumulation by alpha-adrenergic agonists in rat parotid gland.

It was found that phenylephrine and methoxamine had two effects (one was inhibitory and the other was augmentative) on isoproterenol-stimulated cyclic AMP in rat parotid slices. The augmentation was abolished by alpha-adrenergic antagonists or by omission of calcium in the medium. Cyclic AMP accumulation by norepinephrine (NE) was significantly decreased by omission of calcium in the medium. Calmodulin antagonists, trifluoperazine and W-7, decreased NE-induced cyclic AMP accumulation, but another calmodulin antagonist, carmidazolium, did not. Phorbol ester such as 4 beta-phorbol 12-myristate, 13-acetate and phorbol 12, 13-dibutyrate, did not augment the effect of isoproterenol. These results suggest that although the influx of calcium is required in the alpha-adrenergic agonists-induced augmentation, calmodulin and protein kinase C may not be intermediates in this process. Calcium ions (10(-7) and 10(-6) M) slightly increased the activity of adenylate cyclase, but calcium (10(-6)-10(-4) M) dose-dependently inhibited the effect of isoproterenol. Therefore, calcium ions do not participate in the augmentation by directly modulating the activity of adenylate cyclase. The inhibitory effect was not affected by alpha-adrenergic antagonists. The activation of adenylate cyclase by isoproterenol was inhibited by phenylephrine with higher inhibition being obtained in lower concentrations of isoproterenol. Phenylephrine in the presence of isobutylmethylxanthine increased the amount of cyclic AMP and this effect was inhibited by propranolol, but not by phentolamine. [3H]-CGP 12177 binding of the parotid membrane was inhibited by alpha-adrenergic antagonists. These results suggest that the inhibitory effect of phenylephrine and methoxamine may be mediated by beta-adrenergic receptor.

Adrenergic alpha-Agonists

[A study on flomoxef against respiratory infections in the aged].

Flomoxef (FMOX, 6315-S) was used in the treatment of 10 patients (male 8, female 2) with respiratory infections, and clinical responses and side effects of FMOX were evaluated. The mean age of the patients was 68.2 years, and the mean body weight was 45.8 kg; this background of the patients indicates that most of them were elderly, and light in body weight. FMOX was administrated by drip infusion in 1 g doses twice daily in all the cases. The mean duration of FMOX therapy was 14 days, and the mean total dose administered was 28 g. Efficacy rate was 80% in the 10 cases. Adverse reactions were not observed and no abnormalities in laboratory tests were detected. In conclusion, FMOX is an effective antibiotic in the treatment of aged patients with respiratory infections.

Aged

Cloning and sequencing of Serratia protease gene.

The gene encoding an extracellular metalloproteinase from Serratia sp. E-15 has been cloned, and its complete nucleotide sequence determined. The amino acid sequence deduced from the nucleotide sequence reveals that the mature protein of the Serratia protease consists of 470 amino acids with a molecular weight of 50,632. The G+C content of the coding region for the mature protein is 58%; this high G+C content is due to a marked preference for G+C bases at the third position of the codons. The gene codes for a short pro-peptide preceding the mature protein. The Serratia protease gene was expressed in Escherichia coli and Serratia marcescens; the former produced the Serratia protease in the cells and the latter in the culture medium. Three zinc ligands and an active site of the Serratia protease were predicted by comparing the structure of the enzyme with those of thermolysin and Bacillus subtilis neutral protease.

Amino Acid Sequence

Eosinophil responses of permissive and nonpermissive hosts to the young adult worms of Angiostrongylus cantonensis.

Blood and bone marrow eosinophilia was assessed in nonpermissive (guinea pigs) and permissive (rats) hosts following the pulmonary arterial transfers of live or dead young adult worms of Angiostrongylus cantonensis. Guinea pigs showed a marked eosinophilic response to live worms but only a slight response to dead worms. Neither IgE nor haemagglutinating antibodies correlated with the induction of this eosinophilia. In contrast, the rat responded to neither form of the young adult worm. When the guinea pig and the rat were injected with whole worm extract (WWE) of the young adult worms either by an osmotic mini-pump connected to the jugular vein or by intermittent intravenous injections, the former animal showed blood eosinophilia but the latter failed to do so. Guinea pigs also developed blood eosinophilia after continuous exposure to the excretory and secretory products of the young adult worms, administered by the mini-pump. Eosinophil responses to WWE could be induced both in athymic CD-1 (ICR) nude mice and in its heterozygous litter mates, suggesting that T cell-independent mechanism(s) could be involved in the induction of blood eosinophilia in the nonpermissive, mouse host. These data clearly indicate that the eosinophilia-inducing factor(s) and the mechanism of eosinophilia are different in permissive and nonpermissive hosts.

Angiostrongylus

Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis.

The incidence of selective IgA deficiency (SIgAD) was determined in a healthy adult population of 222,597 Japanese volunteer blood donors. Of the blood donors screened, only 0.007% (1:14,840) were found to be IgA-deficient (less than 10 mg/dl) by means of the double diffusion method, while 0.005% (1:18,500) were less than 5 mg/dl, and 0.003% (1:31,800) were less than 1 mg/dl by means of the single radial immunodiffusion method. Statistical analysis of the results clearly showed that the incidence of SIgAD in Japanese blood donors is very much lower than that in blood donors of European ancestry. The Japanese population may occupy a unique position in the ethnical peculiarities. Anti-IgA antibodies were found in 3 (25.0%) of 12 IgA-deficient blood donors whose IgA levels were less than 5 mg/dl, a prevalence rate comparable to that in donors of European ancestry. Although it is difficult to develop a suitable file of IgA-deficient donors in Japan, the establishment of a Rare Donor Registry System on IgA deficiency is a matter of urgency.

Adolescent

Changes in intracellular K+ and Na+ ion concentrations during cell growth and differentiation.

We compared intracellular K+ and Na+ ion concentrations during cell growth and differentiation of a mouse myeloid leukemia M1 cell line. Cells undergoing mitosis had higher K+ concentrations than quiescent cells. Treatment with a K+ channel blocker and furosemide enhanced cell growth and produced a slight increase in the intracellular K+ concentration. Treatment with reagents that reduced the intracellular K+ concentration stopped cell growth. Induction of differentiation in this cell line produced a decrease in the K+ concentration, which always was accompanied by an increase in the Na+ concentration. Treatment with ouabain, which decreased the intracellular K+ concentration, did not, however, induce differentiation in the M1 cell line. The data suggest that cell growth and differentiation in the M1 cells are accompanied by changes in the intracellular K+ and Na+ concentrations but that the changes in the contents of these monovalent cations do not necessarily induce differentiation in this cell line.

Animals

Continuous, low dose of hydralazine, reduces acute hypoxic pulmonary hypertension without a corresponding fall in systemic arterial pressure.

Administration of hydralazine in patients with pulmonary hypertension has been reported to cause excessive systemic vasodilatation, limiting its clinical utility (N Engl J Med 1982; 306: 1326). We studied the effects of hydralazine on hypoxic pulmonary vasoconstriction (HPV) in chronically instrumented sheep and evaluated whether different methods of intravenous administration could prevent severe systemic hypotension. Mean left atrial, pulmonary and systemic arterial pressures (Pla, Ppa and Psa mmHg), cardiac output (CO, l/min, electromagnetic flowmeter) and heart rate were measured continuously. Systemic (SVR) and pulmonary vascular resistances (PVR) were calculated by Psa/CO and (Ppa-Pla)/CO, respectively. Following a 30 min baseline period, we initiated hypoxia with mixture of 10% oxygen in nitrogen. After 20 min of hypoxia we then performed the following two experiments: Group A-Hydralazine (10 micrograms/kg/min) was infused continuously for a further 20 min of hypoxia (n = 6); Group B-Hydralazine (400 micrograms/kg) was administered as a single bolus, followed by an additional 20 min of hypoxia (n = 6). In both Groups A and B, hypoxia produced a prominent pulmonary hypertensive response. Continuous infusion of hydralazine (Group A) significantly decreased the hypoxic values of Ppa and PVR from 25.1 +/- 1.1 to 21.7 +/- 1.6 mmHg (p less than 0.01) and from 4.82 +/- 0.50 to 4.17 +/- 0.40 mmHg/l/min (p less than 0.05), respectively. In Group B, hydralazine as a bolus also significantly decreased HPV, with Ppa dropping from 20.9 +/- 0.9 to 18.3 +/- 1.5 mmHg (p less than 0.05) and PVR falling from 4.98 +/- 0.55 to 4.34 +/- 0.53 mmHg/l/min (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals