[Hypercholesterolemia and atherosclerosis].
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Animals↗
Biomedical subjects
T Kita
Publications and source records attributed to T Kita.
Long-term effects of a cholesterol-free diet on serum cholesterol levels in Zen monks.
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Adult↗
Immunohistochemical demonstration of a new thiamine diphosphate-binding protein in the rat digestive tract.
We purified a new thiamine diphosphate-binding protein (ThDP-BP), produced an antiserum against it, and examined its immunohistochemical distribution in the rat gastrointestinal tract using the avidin-biotin complex method. Positive staining for ThDP-BP was found in the epithelial glands of the stomach, small intestine and large intestine, and in the nuclei of hepatocytes. Measurement of the content of thiamine and its phosphate esters in extracts from the gastric and intestinal mucosa also indicated the presence of ThDP-BP in the stomach and intestinal mucosa. ThDP-BP may be useful for investigating the absorption and metabolism of the thiamine in metabolic disorders.
Animals↗
Adjuvant effects of antineoplastic prostaglandins to cisplatin in nude mice bearing human ovarian cancer cells.
Effects of antineoplastic prostaglandins (PG) on human ovarian cancer cell growth were examined by using HR cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. With regard to inhibition of cancer cell proliferation in vitro, the effects of delta 7-PGA1 was most marked, followed by that of delta 12-PGJ2, PGJ2 and PGD2. When antineoplastic prostaglandins were administered to nude mice bearing HR cells, tumor growth in groups treated with PGJ2 and delta 12-PGJ2 alone was significantly inhibited 63 days after tumor inoculation, compared to that in an untreated group. Consequently, a significant prolongation of median survival was obtained with delta 12-PGJ2, compared to that in untreated groups and in groups with cisplatin alone. In addition, when prostaglandins were administered together with cisplatin, adjuvant inhibitory effects on the tumor growth were obtained 35, 56 and 63 days after tumor inoculation. Subsequently a significant prolongation of median survival was observed when cisplatin was combined with PGD2 or delta 7-PGA1, compared to the results in groups treated with PGD2 alone, delta 7-PGA1 alone or cisplatin alone. Combination of PGJ2 or delta 12-PGJ2 and cisplatin resulted in a significant decrease of hematocrit and body weight 63 days after tumor inoculation, suggesting a deterioration of the median survival. These results suggest that combination of PGD2 or delta 7-PGA1 with cisplatin may be of clinical use for ovarian cancer resistant to cisplatin.
Animals↗
Probucol and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit--long-term antiatherogenic effect and effects on established plaques.
We performed two studies to investigate the effect of probucol on atherogenesis in vivo in the Watanabe heritable hyperlipidemic (WHHL) rabbit. In the first study (Study A), probucol was administered to 2-month-old WHHL rabbits, to evaluate its long-term effect. When killed at about 1.5 years of age, the percentage area of aorta covered with atherosclerotic plaque in probucol-treated rabbits was markedly less than that seen in non-treated rabbits (23.0 +/- 11.4% vs. 87.7 +/- 8.1%, M +/- S.D., P less than 0.001). In the second study (study B), administration of probucol was commenced with 8-month-old WHHL rabbits to investigate whether the drug was effective for limiting atherosclerosis in rabbits in which plaques had already developed. When killed after 6 months of treatment, the percentage area of aorta covered with plaque was 38.1 +/- 12.1% in treated rabbits and 82.7 +/- 22.6% in non-treated rabbits (P less than 0.02). Microscopic observations of lesions also supported the effect of probucol. Probucol treatment resulted in a change not only in the size but also the composition of lesions. Thus, probucol was effective in preventing atherosclerosis in long-term studies at both early and late stages.
Animals↗
Nicotine-induced sensitization to ambulatory stimulant effect produced by daily administration into the ventral tegmental area and the nucleus accumbens in rats.
Bilateral injections of nicotine (30 micrograms/side) into the ventral tegmental area (VTA) and the nucleus accumbens (NACC) increased the ambulatory activity in rats. Moreover, daily injections of nicotine (10, 20 and 30 micrograms/side) into the VTA and the NACC for 6 successive days produced sensitization to the ambulatory stimulant effect of nicotine. Sensitization produced by daily injections of nicotine (20 micrograms/side) into both the sites was maintained for withdrawal periods of 10 days. Mecamylamine (2 mg/kg, i.p.), SCH23390 (0.05 mg/kg, i.p.) and spiperone (0.1 mg/kg, i.p.) antagonized nicotine-induced sensitization to the ambulatory stimulant nicotine-induced sensitization to the ambulatory stimulant effect produced by daily injections into the VTA. These results suggest that nicotine-induced sensitization to the ambulatory stimulant effect involves the stimulation of the mesolimbic dopaminergic pathway through the nicotinic acetylcholine receptor (nAChR) in the VTA and the NACC.
Animals↗
Effect of aging on macrophage adherence to extracellular matrix proteins.
Fibronectin, type I, type IV and type V collagens were compared for their abilities to promote mouse peritoneal resident macrophage adherence and the effect of aging on macrophage adhesion to these matrix proteins was examined. Adherence of macrophages to fibronectin was remarkable and more than 5-fold compared to type I, type IV or type V collagens. Adherence of macrophages to fibronectin and type I collagen increased during aging. However, no age-related changes were observed in macrophage adherence to type IV and type V collagens. The percent of inhibition of macrophage adherence to fibronectin by arginine-glycine-aspartic acid-serine (RGDS) peptide (58.1 +/- 2.7%) was significantly (P < 0.01) higher than that in cells from young mice (23.1 +/- 5.7%). These data suggest that macrophage attach preferentially to fibronectin and that the ability of macrophage to attach to fibronectin increases during aging. The age-related increase in macrophage attachment to fibronectin is related to the concentration of cell surface receptors of macrophage which recognize RGDS sequence within fibronectin during aging. Adherence of macrophage to fibronectin implies retention of macrophages in subendothelial space. Age-related increase in macrophage ability to attach to fibronectin may be related to atherogenesis during aging.
Aging↗
Modulation of human lymphocyte response to phytohemagglutinin by antineoplastic prostaglandins.
The effects of antineoplstic prostaglandins (PGs) (PGE1, PGE2, PGA1, PGA2, delta 7-PGA1, PGD2, PGJ2 and delta 12-PGJ2) on human peripheral blood lymphocyte (PBL) responses to phytohemagglutinin (PHA) were studied in vitro. All PGs used in this study alone had no mitogenic effect on the PBL. The PBL response to PHA was significantly stimulated at low concentrations (10(-7) and 10(-8) M) of the PGE series while the high concentration (10(-5) M) markedly inhibited the PHA response. PGA1 and PGA2, metabolites of the PGE series, and also delta 7-PGA1 stimulated the PHA response in a dose-dependent manner between 10(-6) and 10(-8) M, and showed a significant stimulatory effect at 10(-6) M while significantly inhibiting the PHA response at 10(-5) M. Similarly, 10(-6) and 10(-7) M (but not 10(-8) M) of PGD2 stimulated significantly the PHA response. PGJ2 and delta 12-PGJ2, which are metabolites of PGD2, also stimulated the PHA response in a dose-dependent manner between 10(-6) and 10(-8) M, and had a significant stimulatory effect at 10(-6) and 10(-7) M. The degree of the stimulatory effect was most marked with the PGD2 series among the antineoplastic PGs examined in this study. On the other hand, PGs (PGF1 alpha and PGF2 alpha) having no antineoplastic effect did not show such effects on the PHA response. These results suggest that antineoplastic PGs may have immunoregulatory effects through negative and positive feedback.
Antineoplastic Agents↗
Decreased arachidonate metabolism in mouse peritoneal macrophages after foam cell transformation with oxidized low-density lipoproteins.
Oxidized low density lipoproteins (LDL) are now considered to be one of the atherogenic lipoproteins in vivo and to play an important role in the pathogenesis of atherosclerosis. We previously demonstrated in mouse peritoneal macrophages that oxidized LDL stimulated prostaglandin (PG) E2 synthesis when incorporated into the cells [Yokode, M. et al. (1988) J. Clin. Invest. 81, 720-729]. In this study, we investigated arachidonate metabolism in macrophages after foam cell transformation. The cells were incubated with 100 micrograms/ml of oxidized LDL for 18 h, then stimulated with zymosan. Lipid-enriched macrophages which had taken up oxidized LDL produced much less eicosanoids, such as PGE2, 6-keto-PGF1 alpha, and leukotriene C4 than control cells. After labeling of the cells with [14C]arachidonic acid, they were stimulated with zymosan and the phospholipase activity was determined. The activity of lipid-enriched cells was about two-thirds of that of control cells. Then we investigated the fatty acid composition of their phospholipid fraction to clarify arachidonic acid content and mobilization. Percent of arachidonic acid of lipid-enriched cells decreased and less arachidonic acid mobilization was observed after stimulation with zymosan. These data suggest that impaired arachidonate metabolism in lipid-enriched macrophages can be explained by their decreased phospholipase activity and changes in their fatty acid composition.
6-Ketoprostaglandin F1 alpha↗
Helicobacter pylori has an ulcerogenic action in the ischemic stomach of rats.
Helicobacter pylori (H. pylori) is now accepted as an important cause of chronic active gastritis. There also seems to be an association between the colonization of H. pylori in the gastric mucosa and peptic ulceration. However, it has not demonstrated that the instillation of H. pylori into the stomach produces the ulcerative gastric lesions in animals or humans. We carried out an experiment to study whether or not H. pylori has an ulcerogenic action in the ischemic stomach of rats, using an ex vivo gastric chamber. The rat stomachs were exposed to 1 ml of H. pylori solution (200 IU of urease/ml) and 1 ml of urea (400 mg/dl) for 60 min after the creation of ischemia in the stomach (by withdrawal of 3 ml of blood). The exposure of the stomach to both H. pylori and urea resulted in severe hemorrhagic gastric mucosal lesions with a marked decrease in potential difference (PD) with a concomitant increase in ammonia concentration in rats with ischemia, whereas gastric lesions and a fall in PD were hardly observed in rats without ischemia. These results have demonstrated that H. pylori has an ulcerogenic action on the stomach subjected to mucosal ischemia.
Animals↗
Probucol pretreatment enhances the chemotaxis of mouse peritoneal macrophages.
To investigate the effects of probucol on macrophage chemotaxis, we preincubated mouse peritoneal macrophages with probucol for 20 hours in vitro and using a modified Boyden chamber system compared their chemotactic responses with those of control macrophages that were preincubated with vehicle. Probucol pretreatment enhanced the macrophage chemotactic responses to zymosan-activated serum, acetylated low density lipoprotein (LDL), and native LDL. Probucol pretreatment also enhanced the basal migration observed when there was no stimulant in the lower chamber of a modified Boyden chamber. The chemoattracting potency of native LDL was weaker than that of zymosan-activated serum in control macrophages; however, both substances became equally potent when the macrophages were preincubated with probucol. The degree of the enhancement to native LDL after probucol preincubation reached fourfold to eightfold. The fashion of the enhanced migration of macrophages to native LDL after preincubation with probucol was predominantly chemotactic rather than chemokinetic. Time-course experiments revealed that it took more than 12 hours of probucol preincubation to show clearly enhanced macrophage chemotaxis to native LDL. Macrophages preincubated with probucol together with cycloheximide showed markedly reduced chemotaxis compared with macrophages preincubated only with probucol. Probucol pretreatment also enhanced macrophage chemotactic responses to high density lipoprotein, oxidized LDL, and lipoprotein-deficient serum.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of reperfusion on left ventricular ejection fraction and volume after acute myocardial infarction.
The effects of reperfusion on left ventricular (LV) function and volume were studied in patients with evolving acute myocardial infarction (AMI). We analyzed the LV ejection fraction and volume in patients who had been admitted within 24 h of the onset of their first AMI with culprit lesion of #6, #7 and #1 (American Heart Association classification). Sixty-five patients (Re group) received successful reperfusion therapy within 6 h after the AMI. The other 60 patients (Oc group), who were admitted from 6 to 24 h after the AMI, received conservative therapy. Patients with re-obstruction of the culprit lesion after reperfusion therapy were excluded from the Re group. Patients with spontaneous recanalization following conservative therapy were excluded from the Oc group. The LV ejection fraction (LVEF), LV end-systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were measured using a modified Dodge's formula by left ventriculography performed 4 weeks after the AMI. LVEF in the Re group was significantly greater than in the Oc group (57 +/- 12 vs 49 +/- 11%) (mean +/- SD, p less than 0.01). LVESVI in the Re group was significantly smaller than in the Oc group (30 +/- 13 vs 38 +/- 16 ml/m2, p less than 0.01). Although LVEDVI was not significantly different between the 2 groups, in patients with a responsible coronary lesion of segment #6, LVEDVI in the Re group was significantly smaller than in the Oc group (67 +/- 14 vs 77 +/- 18 ml/m2, p less than 0.05). Although LVEF and LV volume correlated in both groups, the correlation was weak (r = 0.40-0.42), suggesting that LV volume was not dependent solely on LV functional recovery. The incidence of ventricular aneurysm in the Re group was significantly lower than in the Oc group (15.4 vs 45.0%, p less than 0.01). Multivariate analysis selected reperfusion of the responsible coronary artery as one of the factors significantly associated with a reduction of LVEDVI, LVESVI, an improvement of LVEF, and a decrease in the rate of aneurysm formation. In summary, our results indicated that reperfusion improved EF, reduced LV volume, and decreased the rate of aneurysm formation as compared to non-reperfusion, which suggests that reperfusion therapy is beneficial for both functional recovery and ventricular remodeling.
Adult↗
Emergency coronary angioplasty for acute myocardial infarction--factors affecting acute restenosis in catheterization laboratory and reocclusion during hospitalization.
A total of 107 consecutive patients with acute myocardial infarction underwent emergency coronary angioplasty (PTCA). Restoration of blood flow with TIMI grade III was established by emergency PTCA in 101 patients (94.4%). "Acute restenosis" was defined as a lesion that, when dilated to less than 50%, narrowed again to more than 75% luminar reduction 5 min after the balloon inflation. Acute restenosis occurred in 39 patients (39%). Multivariate analysis selected 3 factors associated significantly with an increased rate of acute restenosis: (1) dissection, (2) small balloon/artery diameter ratio and (3) low systolic blood pressure during PTCA. Reocclusion, which was defined as a total reobstruction of the lesion during hospitalization following emergency PTCA, was examined by predischarge coronary angiography. Acute restenosis correlated significantly with an increase in reocclusion rate. The incidence of documented reocclusion was 12%. Residual stenosis, multivessel disease and irregular dilation correlated significantly with an increased rate of reocclusion. The in-hospital and postdischarge mortalities were 5.6% and 2.1%, respectively. In summary, emergency PTCA produced a high angiographic success rate. Use of adequate balloon size and sufficient dilation correlated significantly with angiographic outcome in emergency PTCA. Patients with acute restenosis, high residual stenosis, irregular dilation, and multivessel disease would have a relatively high risk of reocclusion.
Adult↗
Tolerance to the convulsions induced by daily nicotine treatment in rats.
Development of tolerance to the nicotine-induced convulsions in rats was examined. Acute intraperitoneal (i.p.) administration of nicotine (2.5, 3.75 and 5 mg/kg) produced convulsions in a dose-dependent manner. Mecamylamine (1 mg/kg, i.p.) antagonized the convulsions, but hexamethonium (5 mg/kg, i.p.) did not modify them. Daily nicotine administration (2.5, 3.75 and 5 mg/kg, i.p.) once a day for 6 days developed tolerance to the convulsions induced by nicotine. After the daily administrations of nicotine for 6 days, the effects of a challenge administration of nicotine (2 mg/kg) on the nicotine-induced convulsions were tested on the 7th-day. Further tolerances were also developed by the 7th-day challenge administration. After the 7th-day test, nicotine levels of the brain and blood 15 min after the challenge injection were measured. With nicotine (5 mg/kg once a day)-treatment, nicotine levels of all the brain regions were increased. In contrast, a similar challenge injection had no effect on blood nicotine level. These results indicate that the development of tolerance to the nicotine-induced convulsions is produced relatively earlier and day by day by daily administrations to rats, which is closely related with the increase in brain nicotine level.
Animals↗
Effects of acute administration of nicotine on convulsive movements and blood levels of corticosterone in old rats.
The convulsive movements, blood levels of corticosterone and pharmacokinetics of nicotine after an acute intraperitoneal injection of nicotine (5 mg/kg) were examined in young (6-week-old) and old (2-year-old) rats. In pharmacokinetic study, blood nicotine levels during the elimination phase were significantly higher in old rats than in young rats. However, the duration of convulsions and the elevation of corticosterone levels after the nicotine injection showed significant decreases in old rats compared with those in young rats. These differences of nicotine-induced responses between young and old rats may be involved in the decrease in nicotine sensitivity.
Aging↗
[Vascular proliferation in the stroma of gastric cancer and its significance].
To elucidate vascular characteristics in the stroma of gastric cancer, the morphological and immunohistochemical changes of vascular components were examined in 27 gastric cancers and 7 noncancer gastric tissues including 2 peptic ulcers. In differentiated adenocarcinoma, a large number of blood vessels were observed in vicinity of the cancer glands and type IV collagen (C-IV) was localized around the blood vessels and cancer glands, and ultrastructurally, cytoplasmic organelle and weibel-Palade bodies were encountered in the endothelium. In poorly differentiated adenocarcinoma, a small number of blood vessels were distributed sporadically in the stroma and there were vascular endothelia in which von Willebrand factor (VWF) was localized, and there were much more endothelia in which VWF was not localized compared with differentiated adenocarcinoma. C-IV was localized only around the blood vessels and OKM5 was localized in the endothelia which were distributed in the center of cancer nest in poorly differentiated adenocarcinoma. Ultrastructurally, there were not so many Weibel-Palade bodies in the endothelia without complete basement membrane. The morphological and functional changes of blood vessels were correlated with cancer differentiation and metastasis. These changes may provide biological feature of cancer and may be induced by cancer cells, vascular endothelia and mesenchymal cells.
Adenocarcinoma↗
[Nicotine-induced ambulatory stimulant effect and its reverse tolerance].
Nicotine-induced ambulatory stimulant effect and its reverse tolerance produced by daily administration of nicotine in rats were investigated. Nicotine (0.5 and 1.0 mg/kg, sc) increased the ambulatory activity, which was enhanced by the daily administration of nicotine. Although total ambulatory activity and drinking behavior during 20 h (from 13:00 to 9:00) following daily administration of nicotine (1.0 mg/kg, sc) for 7 successive days decreased, these behaviors returned to the control levels after the nicotine-treatment period. Moreover the periods (tau s) of the ambulatory activity and drinking were not changed by daily injections of nicotine (1.0 mg/kg, sc) for 6 successive days. The enhancement of the ambulatory stimulant effect produced by daily injections of nicotine (0.5 mg/kg) was antagonized by mecamylamine (0.2 mg/kg) and haloperidol (0.05, 0.1 and 0.2 mg/kg), which were subcutaneously administered at 20 min before injections of nicotine. These results suggest that the enhancement of nicotine-induced ambulatory stimulant effect by the daily administration of nicotine is concerned with central dopaminergic stimulation through the nicotinic acetylcholine receptor in the rat brain.
Animals↗
The immunocytochemical localization of tumour necrosis factor and leukotriene in the rat liver after treatment with lipopolysaccharide.
After administration of bacterial lipopolysaccharide, there is an increase in the number of leucocytes which adhere to the endothelial cell surface of the hepatic vessels and pass through the endothelial layer by comparison with controls. There is also marked endothelial cell damage including intracytoplasmic oedema, increased numbers of autophagic vacuoles and dilatation of the intercellular junction in LPS-treated samples. The presence of immunocytochemical products of leukotriene (LTR) and tumour necrosis factor (TNF) was examined using in both LPS-treated and control samples. Immunoreactions of LTR which were seen in specific granules of neutrophils and monocytes attached to the endothelial cell surface may indicate the onset of endothelial cell damage. Positive immunoreactions of TNF on the endothelial cell surface, seen only in LPS-treated samples, indicate that TNF may enhance the passage of blood cells through the endothelia and also increase the endocytotic activity of the liver parenchymal cells, as revealed by the present marker experiment using horseradish peroxidase. Positive reactions of TNF in lysosomes of the endothelial cells suggest that they are able to produce TNF and transport it to the cell surface.
Animals↗