Effect of dietary lipid peroxides on lymphoid tissues.
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Biomedical subjects
Publications and source records attributed to K Fujimoto.
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Neuronal histamine affects physiological functions of the hypothalamus. To investigate involvement of histamine receptors in feeding, histamine antagonists were infused into the rat third cerebroventricle. All H1- but no H2-antagonists tested, induced transient feeding during the early light when concentration of hypothalamic histamine was highest. No periprandial drinking was observed. Ambulation concomitantly increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early dark or was decreased by alpha-fluoromethylhistidine (alpha-FMH). Bilateral microinjection indicated that the ventromedial hypothalamus, but not the lateral hypothalamus or the paraventricular nucleus, was a main locus for the induction of feeding by an H1-antagonist. The effect was completely abolished when brain histamine was decreased by pretreatment with alpha-FMH. Hypothalamic neuronal histamine suppresses food intake, at least in part, through H1-receptors in the VMH, and diurnal fluctuations of food intake may mirror neuronal histamine level.
In order to examine the role of LTB4, a potent neutrophil chemokinetic and chemotactic factor, in the lung injury induced by Escherichia coli endotoxin, we measured LTB4 in systemic arterial blood plasma and lung lymph in unanesthetized sheep with chronic lung lymph fistulas. E. coli endotoxin (1 microgram/kg) infusion produced a biphasic response. The early period (Phase 1) was a transient pulmonary hypertension. The late period (Phase 2) was a more prolonged period characterized by an increase flow of lung lymph with a high concentration of protein, suggesting increased pulmonary vascular permeability. Peripheral leukocyte counts rapidly decreased during Phase 1 and leukopenia persisted for approximately 5 h. The concentration of LTB4 in arterial plasma and lung lymph significantly increased during Phase 1, and then decreased with a rebound significant increase during Phase 2. That is, LTB4 in plasma and lung lymph showed a biphasic increase after endotoxin infusion. Our data suggest that the elevation of LTB4 is related to the pulmonary leukocyte sequestration in the lung and may contribute to the lung vascular injury induced by endotoxin in unanesthetized sheep.
1. In a double-blind placebo-controlled study of 37 patients with tardive dyskinesia, the therapeutic effect of ceruletide was evaluated. 2. The patients were assigned at random to two groups that received either intramuscular injections of 0.8 micrograms/kg of ceruletide or placebo once weekly for 4 weeks. Conventional neuroleptic medication was not changed 3 weeks prior to and throughout the study period. Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale over an 8-week period. 3. Ceruletide had a more pronounced effect on TD than the placebo however, because of the limited number of subjects examined, the difference between the two groups was not significant. Ceruletide was more effective than placebo in patients under 60 years of age (p less than 0.05) and whose antipsychotic medication was mainly butyrophenones. 4. No serious side effect was noted. 5. The findings suggested that ceruletide therapeutically benefits patients with tardive dyskinesia.
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A chemiluminescence-high performance liquid chromatography (CL-HPLC) system was newly developed and used for the hydroperoxide-specific determination of phosphatidylcholine hydroperoxide (PCOOH) in human plasma. The method involves separation of phosphatidylcholine derivatives from plasma lipids by normal phase HPLC and subsequent detection of hydroperoxide-dependent chemiluminescence (CL) of PCOOH. CL was produced through luminol oxidation during the reaction of the hydroperoxide and cytochrome c-heme. The high specificity for the hydroperoxide allows the sensitive assaying of a large PCOOH range over a concentration range of 50-2,000 pmol of hydroperoxide-O2. Using this method, the occurrence of PCOOH in normal human plasma was strongly suggested and was confirmed quantitatively.
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Recombinant human interleukin-1 alpha augmented resistance of mice to microbial infections caused by Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, Salmonella typhimurium, and Candida albicans. The effective doses of interleukin-1 alpha ranged from 0.01 to 10 micrograms per mouse, depending on the infecting organism, route of administration, and challenge dose. Intravenous interleukin-1 alpha was, dose for dose, more effective than intravenous muramyl dipeptide and lentinan against the P. aeruginosa and K. pneumoniae infections. Augmentation by interleukin-1 alpha of resistance to infection was also observed in P. aeruginosa-infected mice in a state of cyclophosphamide-induced leucopenia. Interleukin-1 alpha may be useful for controlling obstinate infections not curable by antimicrobial agents alone.
We report here the macromolecular dynamics of the cell surface of rat alveolar macrophages during spreading on a substratum, a process that involves the formation of numerous coated pits. We used 'fracture-flip' to prepare high-resolution platinum-shadowed replicas of membrane surfaces. Our observations show the following sequence of events associated with coated pit formation: at 4 degree C the cell surface of macrophages is covered with a moderate density of particulate components, with most ranging from 10 to 25 nm in diameter. These particles appear to be randomly distributed over the cell surface. Incubation of adherent cells at 37 degree C for 15 min results in the formation of large loose clusters (area 0.5-4 micron2) of particles on the adherent surfaces. After incubation of macrophages for 30 min at 37 degree C, these clusters become tighter and eventually form circular depressions (200-300 nm in diameter), which we interpret as part of a process of invagination. After 60 min, the depressions become much steeper. At this time surface particles can be observed on the intervening non-invaginated regions, and the peripheral region of the adherent membrane, as well as the free membrane. Fracture-flip reveals the presence of structures undetected in previous electron-microscopic studies and provides ultrastructural evidence for the clustering of surface macromolecules that is involved in the formation of coated pits.
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Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. The present study aimed to clarify the effects of ginsenoside-Rb1 on feeding behavior and endogenous chemical substances. Rb1 infusion into the rat third cerebroventricle was started at 1930 hr, and ingestive behavior was recorded in a soundproof room illuminated daily from 0800 to 2000 hr. Rb1 at doses of 0.05, 0.10 and 0.20 mumol potently decreased food intake dose-dependently during the first dark period after infusion. Analysis of meal patterns revealed that the suppressive effect was due to decreasing meal size, but not to postprandial intermeal interval and eating speed. Drinking episodes decreased concomitantly with feeding suppression only at the highest dose of 0.20 mumol. Ambulatory activity was not affected in the doses tested. Infusion of Rb1 increased plasma glucose, leaving insulin unaffected. Microinjection of 0.01 mumol Rb1 into the hypothalamic ventromedial nucleus (VMH) decreased food intake, but injection into the lateral hypothalamic area did not. Taking these data together, Rb1 was found to have a suppressive effect on feeding partly through the VMH.
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The present study examined and compared the effects of N-acetylglucosamine and 1-deoxy-N-acetylglucosamine on feeding behavior with those of glucosamine and 1-deoxyglucosamine. Infusion of 12 mu mole N-acetylglucosamine and 24 mu mole 1-deoxy-N-acetylglucosamine into the rat third cerebroventricle did not affect the feeding behavior. However, oral administration of 1200 mumol N-acetylglucosamine elicited feeding and 2400 mumol 1-deoxy-N-acetylglucosamine markedly suppressed feeding. These effects were abolished by truncal vagotomy. Both glucosamine and 1-deoxyglucosamine affected feeding by intra-third cerebroventricular and oral administration. These findings indicate that N-acetyl amino sugars modulate feeding behavior peripherally through the vagal afferent nerve.
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Antitumor activity and the toxicities of 5-fluorouracil (FUra) and its depot form derivatives with different mechanisms such as 5'-DFUR, tegafur and UFT, were compared in mice, and the therapeutic indices were measured. 5'-DFUR was less toxic to immune organs and the functions than those by other fluorinated pyrimidines. The therapeutic indices of 5'-DFUR obtained by using parameters of particular side effects, reduction of the number of GM-CFU in the bone marrow, shrinkage of the thymus, functional disorders in the immune systems, were several times higher than those of tegafur and UFT. On the other hand, there were no marked differences in the intestinal toxicities among the compounds. 5'-DFUR was only about two times less toxic on the intestinal tract than tegafur and UFT when the incidence-of diarrhea and damage to the duodenum were compared. These studies suggest that the difference in the mechanisms converting to FUra is a result of the toxicities causing different extent.