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T Kita

Publications and source records attributed to T Kita.

At least 145 records · Page 8Linked to original sources
PubMed1999

Modulation by endothelin-1 of lipopolysaccharide-induced cyclooxygenase 2 expression in mouse peritoneal macrophages.

We investigated the modulation by endothelin-1 of lipopolysaccharide-induced cyclooxygenase 2 expression and prostaglandin E2 production by mouse peritoneal macrophages. Our previous report showed that endothelin-1 at concentrations above 10(-11) M induced cyclooxygenase 2 expression through mainly endothelin ET(B) receptors and that an endothelin ET(B) receptor-mediated process was not involved in cyclooxygenase 2 activation in macrophages stimulated by lipopolysaccharide for 4 h. In the present study, when macrophages were stimulated by lipopolysaccharide for 12 h in the presence of endothelin-1 (10(-15) to 10(-8) M), cyclooxygenase 2 expression and prostaglandin E2 production were enhanced by 1.2- to 1.6-fold. The endothelin ET(B) receptor selective antagonist, BQ788 (N-cis-2,6-dimethylpiperidino-carbonyl-L-gamma-methyl-leucyl-D-L-m ethoxycarbonyl-tryptophanyl-norleucine), significantly inhibited this synergistic effect of endothelin-1. In addition, the cyclooxygenase 2-selective inhibitor, NS398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide), also suppressed this effect. Western blot analysis showed that the endothelin ET(B) receptor was up-regulated by lipopolysaccharide in a time- and concentration-dependent manner, and that this up-regulation was inhibited by NS398. From these results, we conclude that endothelin-1 promotes lipopolysaccharide-induced cyclooxygenase 2 activation in the delayed phase through endothelin ET(B) receptors up-regulated by lipopolysaccharide.

Animals↗
PubMed1999

Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions.

BACKGROUND: Oxidized LDL (Ox-LDL) seems to play key roles in atherogenesis. Lectinlike Ox-LDL receptor-1 (LOX-1) is a recently identified cell-surface receptor for Ox-LDL. The relationship of this novel receptor for Ox-LDL to atherogenesis, however, has not yet been clarified. In this study, we explored the expression of LOX-1 in the atherosclerotic lesions of human carotid arteries. METHODS AND RESULTS: Using carotid endarterectomy specimens obtained from 21 patients and 2 samples of normal human aortas, we examined LOX-1 expression by reverse transcription-polymerase chain reaction and immunohistochemistry. In aortas without atherosclerosis, LOX-1 expression was undetectable by immunohistochemistry and negligible by reverse transcription-polymerase chain reaction. In carotid arteries, luminal endothelial cells covering early atherosclerotic lesions were more frequently positive for LOX-1 expression than those in advanced atherosclerotic lesions. Endothelial cells in the intimal neovasculature of advanced lesions also expressed LOX-1. In addition, macrophages and smooth muscle cells in the intima of advanced atherosclerotic plaques were positive for LOX-1 expression. CONCLUSIONS: LOX-1 may play important roles in Ox-LDL uptake and subsequent functional alteration in the luminal endothelium in early atherosclerotic lesions and in intimal neovascular endothelial cells in advanced plaques. Furthermore, LOX-1 may also be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages and smooth muscle cells in the atherosclerotic intima.

Aged↗
PubMed1999

Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial events of atherogenesis but does not reduce the size of advanced lesions in apolipoprotein E-deficient mice.

BACKGROUND: Atherosclerosis results from complex inflammatory-fibroproliferative responses. To elucidate the central role of macrophage and macrophage-colony stimulating factor (M-CSF) during atherogenesis, we used a new strategy to administer to adult apolipoprotein E (apoE)-deficient mice a monoclonal antibody (AFS98) raised against c-fms, the receptor of M-CSF. METHODS AND RESULTS: When 6-week-old apoE-deficient mice were fed a high-fat diet and injected with 2 mg of AFS98 intraperitoneally on alternate days for 6 weeks, accumulation of macrophage-derived foam cells in the aortic root was suppressed by 70% compared with that in controls. This preventive effect was associated with neither remarkable decrease of the number of circulating monocytes nor systemic growth retardation. In contrast, when apoE-deficient mice that had been fed a high-fat diet from 6 weeks of age were given AFS98 from 12 to 18 weeks of age, a minimal protective effect on lesion size was observed. CONCLUSIONS: These results suggest that (1) macrophage and M-CSF/c-fms play an essential role in the arterial wall during development of the fatty streak lesion and (2) blockade of the M-CSF/c-fms pathway could act as protection from at least early atherogenesis but could have a less preventive effect on maintenance of the advanced lesions.

Animals↗
PubMed1999

Stimulation of neurotrophic factor secretion from 1321N1 human astrocytoma cells by novel diterpenoids, scabronines A and G.

Glial cells release neurotrophic factors that maintain neurons functionally. When rat pheochromocytoma cells (PC-12) were cultivated with the conditioned medium of human astrocytoma cells (1321N1) incubated with the new diterpenoids, scabronines A and G, isolated from Sarcodon scabrosus, they changed their morphology and there was neurite outgrowth. The scabronines increased the expression of mRNA for nerve growth factor (NGF), and the secretion of NGF from 1321N1 cells in a concentration-dependent manner. However, the enhanced neurite outgrowth produced by the conditioned media was slightly inhibited by NGF neutralizing antibody, and the concentration of NGF released in response to the scabronines was insufficient to cause differentiation. These results suggest that scabronines cause the secretion of other factors together with NGF from 1321N1 cells. The diterpenoids are useful drugs to clarify the mechanism of synthesis and secretion of neurotrophic factors.

Animals↗
PubMed1999

Labeled kynurenine pharmacokinetic modeling studies in gerbils. Nonequilibrium between infused and endogenous kynurenine.

In order to complete pharmacokinetic studies on the central vs. peripheral origin of several tryptophan metabolites, we infused gerbils with labelled kynurenine (2H4 or 15N2). Osmotic minipumps charged with kynurenine solutions were surgically implanted subcutaneously in adult female gerbils (50-60 g). After a variable number of hours, the gerbils were sacrificed and organs taken for determination of labelled/unlabelled kynurenine ratios using mass spectrometric assay of a pentafluorobenzyl derivative as described previously. Surprisingly high ratios of 2H to 1H-kynurenine were measured in the kidney (0.25-0.40) and urine (4.0-8.0), although the ratio of deuterium labelled to endogenous kynurenine remained below detection limits (< 0.05) in serum and other tissues. Infusion of greater quantities of 2H4-kynurenine confirmed these observations in gerbils in which ratios of 2H4-to-1H kynurenine were measurable in serum and tissues. Synthesis and infusion of 15N2-kynurenine demonstrated that these effects were not due to deuterium isotope substitution. The data demonstrate a non-equilibrium between infused and endogenous kynurenine, which is related to differential rates of protein binding and the rapid clearance of free, infused kynurenine by kidney.

Animals↗
PubMed1999

Oral clonidine reduces the requirement of prostaglandin E1 for induced hypotension.

PURPOSE: To determine the effects of preanesthetic oral clonidine on the dose of prostaglandin EI (PGEI) required to produce hypotension during anesthesia. METHOD: Oral placebo, 75 microg or 150 microg clonidine were administered 60 min prior to induction of anesthesia. Anesthesia was maintained with O2:N2O (30:70) and isoflurane 1.0%. After hemodynamic stabilization, an infusion of prostaglandin EI was started (0.05 microg x kg(-1) x min(-1)) and the rate of infusion was adjusted to maintain mean arterial pressure (MAP) between 60-70 mm Hg during operation. RESULTS: Duration of hypotension in placebo, 75 microg and 150 microg preanesthetic oral clonidine treated groups were 132+/-46, 117+/-37 and 129+/-56 min, respectively. The PGEI requirement in each group were 1563+/-180 (28.6+/-3.2), 594+/-197 (10.8+/-3.6) and 283+/-30 (5.5+/-3.6) microg (microg x kg(-1)), respectively. In addition, blood loss in each group were 1461+/-389, 805+/-240 and 931+/-40 ml, respectively. CONCLUSION: Preanesthetic oral clonidine decreased the dose of PGEI required to produce hypotension, and decreased the blood loss during operation.

Administration, Oral↗
PubMed1999

Contribution of endothelin-1 to disruption of blood-brain barrier permeability in dogs.

We examined the effect of intracisternal application of endothelin-1 (ET-1) on the permeability of fluorescein into the cerebrospinal fluid (CSF) in beagle dogs in order to evaluate its role in disruption of blood-brain barrier (BBB) permeability seen in the subarachnoid hemorrhage animal model. Intracisternal application of their autologous blood for producing a canine two-hemorrhage model revealed an enhanced fluorescein permeability into the CSF together with the development of cerebral vasospasm. A single dose of ET-1 (40 pmol/animal) significantly increased penetration of fluorescein compared with that in normal dogs. Although its magnitude was much less than that in the two-hemorrhage model after the first administration of ET-1, the second challenge of the same dose of ET-1 with a 48-h interval produced marked disruption of BBB permeability similar to those in the animal model. Moreover, the ET-1-induced enhancement of fluorescein permeability into the CSF was completely prevented by intracisternal pretreatment with an endothelin ET(A)-receptor selective antagonist, S-0139 (0.03 mg/kg), as were the ET-1-induced cerebral vasoconstriction and behavioral changes as previously reported. Thus, we conclude that ET-1 acting on the adventitial site of brain in dogs contributes to the disruption of BBB permeability via endothelin ET(A)-receptor mediation.

Analysis of Variance↗
PubMed1999

The vast majority of gastric T cells are polarized to produce T helper 1 type cytokines upon antigenic stimulation despite the absence of Helicobacter pylori infection.

Helicobacter pylori infection is associated with chronic infiltration by various cell types, including T cells, whose cytokine production may regulate the inflammatory reaction as well as local immune response to the bacterium. We prospectively analyzed the constituents of the cellular infiltrates and the cytokines produced by T cells in antral biopsies obtained from 73 subjects with and without H. pylori infection, before and after eradication therapy, and compared them with a histological grade of gastritis. We found that T cells predominated in cell number, followed by granulocytes/monocytes and plasma cells in both H. pylori-infected and H. pylori-uninfected subjects. Despite the absence of H. pylori infection, more than 70% of gastric CD4-positive T cells obtained from uninfected tissue produced interferon-gamma (IFN-gamma) in the cytosol. Upon receptor cross-linking of a CD3 and a CD28 molecule, T cells in both infected and uninfected tissue continuously secreted a far greater amount of IFN-gamma than those in peripheral blood mononuclear cell controls for a period of cell culture, whereas the increase in interleukin-4 (IL-4) was very small, and no increase in IL-2 secretion was seen. In H. pylori-infected patients, IFN-gamma secretion was correlated with the grade of mononuclear cell infiltration and decreased to an uninfected control level after eradication therapy. We did not see the effect of eradication on IL-4 secretion. Anti-H. pylori antibody of the IgG2 subclass was remarkably increased in H. pylori-infected subjects. These results together suggest that gastric T cells are already differentiated to produce a large amount of IFN-gamma by a mechanism unrelated to H. pylori infection. H. pylori infection appeared to activate T cells to secrete even more IFN-gamma, which may contribute to maintaining a perpetual inflammation in H. pylori-infected stomach.

Adult↗
PubMed1999

CYP2C19 genotype-related efficacy of omeprazole for the treatment of infection caused by Helicobacter pylori.

OBJECTIVES: Omeprazole is used for the treatment of infection caused by Helicobacter pylori, and it is metabolized by the polymorphic cytochrome P4502C19 (CYP2C19). We have found that the anti-H pylori efficacy by the combination of omeprazole and antibiotics is related to the CYP2C19 genotype. METHODS: One hundred eight patients with cultured H pylori-positive gastritis or peptic ulcer were treated with three regimens: quadruple treatment without proton pump inhibitors (n = 25), dual treatment with omeprazole and amoxicillin (INN, amoxicilline) (n = 26), and triple treatment with omeprazole, amoxicillin, and clarithromycin (n = 57). The CYP2C19 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and the assessment of the eradication of H pylori was based on all negative examinations, including culture, histology, and 13C-urea breath test. RESULTS: The eradication rates for the extensive metabolizers were 50% and 86% for the dual and triple treatments, respectively. In contrast, all of the poor metabolizers treated with omeprazole and antibiotics (n = 15) showed an eradication of H pylori. CONCLUSION: The anti-H pylori effect of dual treatment is highly efficient for CYP2C19 poor metabolizers, which suggests that clarithromycin is not necessary as a first line of therapy for this type of patients. Genotyping can provide a choice for the optimal regimen based on individual CYP2C19 genotype.

Amoxicillin↗
PubMed1999

Effect of Korean red ginseng on psychological functions in patients with severe climacteric syndromes.

OBJECTIVE: To evaluate the degree of psychological dysfunction and levels of stress hormones in postmenopausal women with climacteric syndromes and effect of Korean red ginseng (RG) on them. METHODS: ACTH, cortisol and DHEA-S in peripheral blood from 12 postmenopausal women with climacteric syndromes or 8 postmenopausal women without any climacteric syndrome were measured before and 30 days after treatment with daily oral administration of 6 g RG. Blood samples were collected in the early morning on the bed-rest. In postmenopausal women with climacteric syndromes such as fatigue, insomnia and depression, psychological tests using the Cornell Medical Index (CMI) and the State-Trait Anxiety Inventory (STAI) were performed before and 30 days after treatment with RG. RESULTS: CMI score as well as anxiety (A)-state in STAI score in postmenopausal women with climacteric syndromes was significantly higher than that without climacteric syndrome, while DHEA-S levels in postmenopausal women with climacteric syndromes were about a half of those without climacteric syndrome. Consequently, cortisol/DHEA-S (C/D) ratio was significantly higher in postmenopausal women with climacteric syndromes than in those without climacteric syndrome. When postmenopausal women with climacteric syndromes were treated with daily oral administration of 6 g RG for 30 days, CMI and STAI A-state scores decreased within normal range. Although the decreased DHEA-S levels were not restored to the levels in postmenopausal women without climacteric syndrome, the C/D ratio decreased significantly after treatment with RG. CONCLUSIONS: Improvement of CMI and STAI scores in postmenopausal women suffering climacteric syndromes, particularly fatigue, insomnia and depression, by RG seemed to be brought about in part by effects of RG on stress-related hormones as shown by a decrease in C/D ratio.

Adrenocorticotropic Hormone↗
PubMed1999

Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan.

Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries. Data of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese men and women obtained from a large-scale survey in 1990 were analysed according to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also measured in randomly selected samples and their contribution as a risk factor was estimated especially in postmenopausal women. The subjects in two age groups of men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4-23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older women, respectively. These values are much lower than those in Western populations, the border between the IVth and the top quintile almost corresponding to the average for Americans. Total cholesterol showed a tendency to shift into higher ranges in all age groups in both men and women as BMI increased, with the highest distribution remaining in the range of 160-199 mg/dl (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were still lower than most of the average values in Western populations. The distribution of cholesterol in higher ranges was much greater and the difference according to BMI was smaller in older women than in men. In both men and women, whether younger or older, about 90% of the subjects in the lower quintiles of BMI had triglyceride levels lower than 150 mg/dl. The distribution in the higher range of triglyceride was small in women, not only at younger ages but also in postmenopausal women at the top quintile of BMI. About 85% of the younger women with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The values in postmenopausal women were still higher than in men aged 40-59 years. Shift of the distribution curves of HDL-cholesterol according to BMI was similar in all groups and more remarkable than the change in triglyceride. The average HDL-cholesterol levels at the top quintile were almost comparable to the average values in Western countries; the difference in HDL-cholesterol levels between the two populations can mostly be explained by the difference in BMI. Smokers showed a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL-cholesterol levels, although there was no difference in distribution of BMI between smokers and non-smokers. Relatively low total cholesterol levels even in smokers has probably contributed to the low incidence of IHD in spite of the high frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency to increase after age 40 in women. BMI itself did not have a correlation with serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as total cholesterol increased and the tendency was most remarkable in women around or after the menopause. It was remarkable in older women that as the total cholesterol or apo B level increased there was also an increased prevalence of abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to have a great risk of atherosclerosis regarding the lipid and lipoprotein profile even in the Japanese population.

Adult↗
PubMed1999

Lysophosphatidylcholine activates mitogen-activated protein kinases by a tyrosine kinase-dependent pathway in bovine aortic endothelial cells.

Lysophosphatidylcholine (lyso-PC) is a major component of an atherogenic lipoprotein. In this study, to investigate the involvement of mitogen-activated protein kinases in the signaling pathway by lyso-PC in endothelial cells, we measured the activity of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in bovine aortic endothelial cells. Lyso-PC activated ERK and JNK in a dose-dependent manner. However, the time courses of activation of these kinases were different. ERK and JNK activation by lyso-PC was inhibited by a tyrosine kinase inhibitor, herbimycin A, but not by a protein kinase C (PKC) specific inhibitor. We conclude, therefore, that lyso-PC-mediated ERK and JNK activation is caused by a tyrosine kinase-dependent mechanism, but not conventional types of PKC-dependent mechanisms.

Animals↗
PubMed1999

Oxidized LDL and expression of monocyte adhesion molecules.

Accumulation of substantial numbers of monocyte/macrophages, as well as activated T lymphocytes, in focal areas of arterial intima appears to be a hallmark of atherogenesis. Our report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherogenic lipoproteins, such as oxidized LDL and remnants lipoproteins in diabetic and type III hyperlipidemic patients, can upregulate adhesion molecules for monocytes and T lymphocytes, and growth factors, such as heparin-binding epidermal growth factor-like growth factor and PDGF-A and B chains. Recently we identified the novel receptor for oxidized LDL, named Lox-1. Therefore in this paper we summarize the importance of the interaction between oxidized LDL and its receptor, LOX-1 in terms of early stage of atherogenesis.

Animals↗
PubMed1999

Enhancement of sensitization to nicotine-induced ambulatory stimulation by psychological stress in rats.

1. The authors investigated the influence of psychological stress (PSY-stress) on sensitization to nicotine (0.5 mg/kg, s.c.)-induced ambulatory stimulation. 2. Rats were exposed to the emotional responses of animals which received foot-shock (FS), which they, themselves, did not receive. Ten daily exposures to PSY-stress for 20 min enhanced sensitization to the nicotine-induced ambulatory stimulation compared to that in non-stress rats. 3. However, the increased serum corticosterone levels following nicotine (0.5 mg/kg, s.c.) administered 24 hr after the tenth injection of nicotine in the behavioral study was almost the same in the rats exposed to PSY-stress as compared to non-stress rats. 4. These results suggest that PSY-stress may promote sensitization to nicotine-induced ambulatory stimulation and that the combined effect of PSY-stress and nicotine would facilitate the development of sensitization to nicotine.

Animals↗
PubMed1999

Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer.

This retrospective study of ovarian cancer aimed to elucidate whether expression of apoptosis-related proteins, bcl-2, p53 or MDM-2, is associated with resistance to chemotherapy, especially cisplatin (CDDP) based chemotherapy. Expression of bcl-2, p53 and MDM-2 was assessed by immunohistochemical staining of tumour tissues collected at initial surgery prior to treatment with CDDP-based chemotherapy. Among 66 patients with advanced ovarian cancer with measurable tumour following surgery and evaluable for response to chemotherapy, 42, 45 and 56% were positive for bcl-2, p53 and MDM-2, respectively. Significantly fewer tumours of patients who had a complete response to chemotherapy (CR) showed positivity for bcl-2 (2/20) than for p53 (6/20) and MDM-2 (8/20, P < 0.001). There was an inverse correlation between bcl-2 staining and initial response to chemotherapy, especially in serous and endometrial adenocarcinomas. In patients with stage III-IV, serous or endometrioid adenocarcinomas, significantly poorer survival was seen for those with bcl-2 positive tumours than those with negative bcl-2 staining (P = 0.0064). p53 and MDM-2 were not correlated with initial response to chemotherapy. Multivariate analysis revealed that bcl-2, residual tumour size and histology were significant independent prognostic factors. These results suggest that bcl-2 can be a possible predictor of response to chemotherapy and prognosis in patients with advanced ovarian carcinoma.

Antineoplastic Agents↗
PubMed1999

Bovine milk inhibits both adhesion of Helicobacter pylori to sulfatide and Helicobacter pylori-induced vacuolation of vero cells.

Adhesion of Helicobacter pylori to gastric mucosal cells is an initial important step in colonization and infection. To study adhesion, we investigated whether milk inhibits the adhesion of Helicobacter pylori to sulfatide, an acidic glycosphingolipid that exists in human gastric mucosa and to which Helicobacter pylori adheres. As a measure of functional significance, we also studied whether milk inhibits Helicobacter pylori-induced vacuolation of Vero cells. We used sulfatide-coated polystyrene plates and studied the effect of bovine milk on the adhesion of Helicobacter pylori to sulfatide. We used Vero cells for Helicobacter pylori-induced vacuolation. Bovine milk 100- to 200-fold diluted significantly inhibited both adhesion of Helicobacter pylori to sulfatide and Helicobacter pylori-induced vacuolation in Vero cells. Bovine milk significantly inhibited adhesion of Helicobacter pylori to MKN-45 cells and Lewis b antigen-coated polystyrene plates. In addition, these results suggest that bovine milk contains active substances that inhibit both adhesion of Helicobacter pylori to mucosa and vacuole formation. Bovine milk may have a protective effect on the gastric mucosa in Helicobacter pylori-associated gastritis.

Animals↗
PubMed1999

A sclerosant with astringent properties developed in China for oesophageal varices: comparison with ethanolamine oleate and polidocanol.

BACKGROUND: Xiao zhi ling (XZL), which consists of Chinese nutgalls and aluminium potassium sulphate, is used as a local injection for the treatment of internal haemorrhoids in China. It is also used for endoscopic sclerotherapy of oesophageal varices. To date, however, it has not been compared with other sclerosants with regard to its safety and efficacy. METHODS: In the present study, the effect on the endothelium and the haemolytic and thrombosing effects of XZL were compared with those of 5% ethanolamine oleate and 1% polidocanol, using an endothelial cell line and red blood cells taken from rats and the dorsal marginal ear vein of rabbits. In addition, XZL was injected into the area surrounding varices in rats and its efficacy was studied endoscopically and histologically. RESULTS: Xiao zhi ling reduced the size of varices in rats after causing severe damage in the injected region. Compared with the other two sclerosants, however, XZL had little effect on the endothelium and was the least haemolytic compound. Furthermore, XZL did not cause thrombosis in the injected vein of a rabbit. CONCLUSIONS: These results suggest that XZL is another type of sclerosant with astringent rather than detergent properties. This compound should be used to treat oesophageal varices by paravariceal injection in smaller doses than 5% ethanolamine oleate and 1% polidocanol.

Alum Compounds↗