Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.

The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.     

Effects of AETT-Induced Neuronal Ceroid Lipofuscinosis on Learning Ability in Rats

Abstract: The behavioral effects of ceroid-lipofuscin accumulation, induced by intraperitoneal administration of acetyl-ethyl-tetramethyl-tetralin (AETT) in Wistar rats for 3 months, were examined in the present studies. A significant increase in neuronal ceroid-lipofuscin was demonstrated neuropathologically as well as morphometrically. Although the AETT-intoxicated rats showed neither alteration of locomotor activity nor shock sensitivity, a significant impairment of learning ability, especially an acquisition trial in passive avoidance tests, was observed. Results of the present studies indicate the possibility that a diffuse lipofuscin accumulation causes a learning impairment in rats. The results also imply the possibility of a significant role of age-related lipofuscin accumulation in the dementing processes of human especially in the elderly.     

Evaluation of therapeutic interventions of sustained monomorphic ventricular tachycardia guided by an electrophysiologic study: a case report

Therapeutic evaluation of sustained monomorphic ventricular tachycardia (VT) using electrophysiologic study (EPS) is presented in a case of refractory VT. A 54-year-old man with a history of recurring syncope underwent coronary angiography which revealed total occlusion of the posterior descending branch of the right coronary artery. Left ventriculography showed a left ventricular aneurysm at the cardiac apex. Ejection fraction of the left ventricle was 36%. He had four VTs of different QRS morphologies in 12 lead electrocardiograms. According to our programmed ventricular stimulations, single or double, and rarely triple, extra stimuli were administered after eight basic stimuli at two basic cycle lengths. Rapid ventricular pacing, up to 210 bpm, was then added. The stimuli were delivered to two different sites in the right ventricle and to at least one site in the left ventricle. When the entire protocol could not induce VT, isoproterenol was given intravenously, and the same protocol was repeated. No drug could prevent VT attacks, even after the surgical resection of two VT foci, VT was still inducible. Postoperative drug therapy could not prevent VT induction in EPS. However, changes in the mode required for VT induction were observed. Among 47 patients with sustained monomorphic VT treated in our hospital, 24 had EPS to evaluate the efficacies of therapeutic interventions, such as drugs and surgery. In 14 patients, no VT was induced by the entire VT induction protocol. Among the remaining 10 patients, four showed changes in the VT induction mode, but VT recurred in their clinical courses even after their treatments.(ABSTRACT TRUNCATED AT 250 WORDS)     

‘Ischemic tolerance’ phenomenon detected in various brain regions

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the ‘ischemic tolerance’ phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of ‘ischemic tolerance’.     

Characterization of enteropathogenic and enteroaggregative Escherichia coli isolated from diarrheal outbreaks.

Virulence characteristics of diarrheal outbreak-associated Escherichia coli O55:NM, O126:NM, and O111:NM were examined. The E. coli O55:NM strains were atypical enteropathogenic E. coli (EPEC), while the E. coli O126:NM and O111:NM strains should be classified as enteroaggregative E. coli (EAggEC). The contributions of EPEC and EAggEC to the human disease burden in Japan might be significantly greater than is currently appreciated.     

Ghrelin: structure and function

Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.     

HLA-DR Antigens in Pemphigus among Japanese

The frequency of HLA-DR4 was significantly increased at P < 0.02 in 37 unrelated pemphigus patients (62.2%), when compared with unrelated 73 healthy controls (30.1%). This antigen was more frequently found in pemphigus foliaceus (70.6%) than pemphigus vulgaris (55.8%).