Clinical and molecular analyses of neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxia type 1 (SCA1) were performed. In the present study, a Japanese family of AD with an Ala285Val substitution in exon 8 of the presenilin-1 (PS-1) gene was found. This family was characterized by relatively late onset (mean age at 50 years) in familial AD with PS-1 gene mutation and by absence of myoclonus, seizure or paratonia. Magnetic resonance image (MRI) study showed marked linear signal abnormalities in white matter of parietoocctipital lobes, suggesting a presence of cortical amyloid angiopathy of the patient with PS-1 gene mutation. Clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with four different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene were reported. Although features of progressive neurogenic muscular atrophy was common in patients of these families, patients of each family showed characteristic clinical features. Although lower motor sign was evident in all cases, hyperreflexia varied from 0 to 100% among patients with the different mutations, and Babinski sign was not observed in any cases. Bulbar palsy was frequent with a mutation, but not present with another mutation. SOD activity of red blood cells was generally reduced with minor variations. CAG trinucleotide repeat expansion was analyzed in 25 families with hereditary ataxia of Menzel type in the northeast of Japan. Twenty of 38 patients in 12 families had expanded allele for spinocerebellar ataxia type 1 (SCA1). Study of the number of CAG repeats in various tissues showed no differences in the repeat length in lymphocytes, muscle or brain; sperm, however, showed an obvious expansion. This may be a clue to a possible mechanism for the molecular basis of paternal anticipation of the disease. These results suggest that clinical features of some familial cases of neurodegenerative diseases such as AD, ALS, and SCA1 are well correlated with their genetic mutations.
The kidney plays an important role in the pathophysiology of hypertension. Recent studies suggest that glomerular hemodynamics may be critically involved not only in the pathogenesis of hypertension but also in the mode of progression of renal dysfunction. The juxtaglomerular apparatus (JGA), constisting of the glomerular afferent and efferent arterioles and the specialized tubular epithelial cells called the macula densa, plays a central role in the regulation of glomerular hemodynamics and renin release. This article reviews the mechanism by which the JGA controls renin release and glomerular hemodynamics as well as its relevance in the pathogenesis, pathophysiology and treatment of hypertension.
This study was conducted to investigate the effects of interferon (IFN)-γ on normal colonic lamina propria lymphocyte subsets in humans using organ culture method. Lamina propria lymphocyte subsets in normal colonic biopsy tissues receiving 1×105 u/ml of IFN-γ (IFN-γ-treated group) were investigated in comparison with those cultured in medium only (IFN-γ-non-treated group) for 24 hr. CD8-positive cells and IgG, IgAl and 1gM-containing cells were elevated in the IFN-γ-treated group compared with those in the IFN-γ-non-treated group, which was similar to immunological changes in mucosal lesions of inflammatory bowel disease.
We studied the steric course of the reaction catalyzed by the N-ethylmaleimide (NEM) reductase of Yarrowia (Candida) lipolytica (Y. lipolytica), using 4R-[4-2H1]NADPH and 4S-[4-2H1]NADPH as cofactors and N-ethylcitraconimide as substrate. Active substrates and inhibitors of NEM reductase and its subcellular distribution were also investigated to clarify the biochemical properties of this enzyme. NEM reductase catalyzes the reduction of N-ethylmaleimide to N-ethylsuccinimide with NAD(P)H as the cofactor. Several maleimide and cyclopentenone derivatives tested were also active substrates for NEM reductase of Y. lipolytica. Some pyrazolone derivatives, particularly 1-phenyl-5-pyrazolone, were found to be effective inhibitors of NEM reductase. Subcellular localization of NEM reductase was carried out using protoplast formation and differential centrifugation. Ninety-eight percent of the NEM reductase activity was recovered in the cytosolic fraction, indicating that NEM reductase in Y. lipolytica was the cytosolic enzyme. We also determined the stereochemical specificity of the reduction of N-ethylcitraconimide by NEM reductase in Y. lipolytica, showing that 4 Pro-R hydrogen of NADPH was abstracted for enzymatic hydride transfer by NEM reductase, and two hydrogen atoms from NADPH and H2O added to opposite faces of the double bond of N-ethylcitraconimide.
Ebstein's anomaly is a rare congenital cardiac anomaly showing significant clinical manifestations with a high mortality rate in the neonatal period. The prognosis of the patient is essentially determined by the severity in morphological changes, however, high pulmonary vascular resistance in the neonatal period may aggravate tricuspid regurgitation and lead to functional pulmonary atresia. We describe a critically ill neonate with morphologically mild Ebstein's anomaly who was successfully managed with intensive care including isoproterenol administration for functional pulmonary atresia. Isoproterenol is a potent pulmonary vasodilator with inotropic and chronotropic effects, and seemed to decrease the pulmonary vascular resistance allowing increased antegrade blood flow to the pulmonary artery and improved cardiac output. If tachycardia is not present, isoproterenol administration is recommended in critically ill neonates with anatomically mild Ebstein's anomaly and no associated cardiac defects.
We evaluated the neuromuscular reversal with edrophonium using peripheral nerve stimulator and recorder in a patient with malathion intoxication. Edrophonium 10 mg i.v. caused an increase in single twitch tension by 76% of the control during the recovery phase from an acute cholinergic crisis 16 days after ingestion of malathion solution. The present study indicated that edrophonium test seems to be a reliable monitoring in evaluating neuromuscular reversal in the patient with acute malathion insecticide poisoning.
The neuromuscular blocking actions of sisomicin sulfate (SISO), micronomicin sulfate (MCR) and d-tubocurarine (dTc) were studied in 20 rabbits anesthetized with halothane. The i.v. administration of SISO 20-40 mg/kg, MCR 40-80 mg/kg or dTc 0.1-0.3 mg/kg resulted in dose- dependent decreases in twitch tension. The ED50s for SISO, MCR and dTc were 23.5, 58.2 and 0.2 mg/kg, respectively. SISO- and MCR-induced neuromuscular blockade was partially antagonized by neostigmine or by calcium.