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991.
Effects of growth hormone (GH) on ghrelin, leptin, and adiponectin in GH-deficient patients 总被引:5,自引:0,他引:5
Edén Engström B Burman P Holdstock C Karlsson FA 《The Journal of clinical endocrinology and metabolism》2003,88(11):5193-5198
Ghrelin is a recently discovered gastric peptide that increases appetite, glucose oxidation, and lipogenesis and stimulates the secretion of GH. In contrast to ghrelin, GH promotes lipolysis, glucose production, and insulin secretion. Both ghrelin and GH are suppressed by intake of nutrients, especially glucose. The role of GH in the regulation of ghrelin has not yet been established. We investigated the effect of GH on circulating levels of ghrelin in relation to its effects on glucose, insulin, body composition, and the adipocyte-derived peptides leptin and adiponectin. Thirty-six patients with adult-onset GH deficiency received recombinant human GH for 9 months in a placebo-controlled study. Body composition and fasting serum analytes were assessed at baseline and at the end of the study. The GH treatment was accompanied by increased serum levels of IGF-I, reduced body weight (-2%) and body fat (-27%), and increased serum concentrations of glucose (+10%) and insulin (+48%). Ghrelin levels decreased in 30 of 36 subjects by a mean of -29%, and leptin decreased by a mean of -24%. Adiponectin increased in the women only. The decreases in ghrelin and leptin correlated with changes in fat mass, fat-free mass, and IGF-I. The reductions in ghrelin were predicted independently of the changes in IGF-I and fat mass. It is likely that the reductions in ghrelin and leptin reflect the metabolic effects of GH on lipid mobilization and glucose production. Possibly, a suppression of ghrelin promotes loss of body fat in GH-deficient patients receiving treatment. The observed correlation between the changes in ghrelin and IGF-I may suggest that the GH/IGF-I axis has a negative feedback on ghrelin secretion. 相似文献
992.
Stig B. Holmberg Peter L. J. Naredi Per G. O. Lindnér Ingvar H. Karlberg Peter L-E. Daneryd Lilian M. Karlsson Anders Pettersson Unne Stenram Larsolof R. Hafström 《Journal of cancer research and clinical oncology》1995,121(8):463-468
Zymosan—a non-specific macrophage-stimulating agent-reduces tumour take in the liver. The mechanism for this effect is not clear, but it may be mediated via the Kupffer cells and prostaglandins. On the other hand, the Prostaglandin-synthesis inhibitor, indomethacin, inhibits tumour growth. Pretreatment with zymosan (3 mg 100 g–1) for 3 days of two different strains of rats, inoculated in the liver with a hepatoma or an adenocarcinoma cell suspension respectively, reduced tumour take and also initial tumour growth. The effect on tumour take and initial growth was inhibited by concomitant administration of indomethacin (0.2 mg 100 g–1). When zymosan was administered after tumour cell inoculation the growth rate of the hepatoma was retarded, but this effect was not abrogated by indomethacin. Pretreatment with indomethacin had no significant effect on tumour take or initial growth. When given after the tumour was established in the liver, indomethacin reduced the growth rate of the hepatoma, but not of the adenocarcinoma. These results suggest that there are different mechanisms for the effects of zymosan on tumour take and on growth of an established tumour. In immunoincompetent nude mice the effect on the hepatoma was similar to the effect in the rat. In vitro both tumours were insensitive to zymosan and indomethacin. This study confirms that pretreatment with a non-specific macrophage stimulator (zymosan) diminishes tumour take and growth in the liver, that the effect of zymosan on tumour take in the liver is abrogated by indomethacin and that the zymosan effect on tumour take in the liver is at least partly mediated by the Kupffer cells and prostaglandins.This study was supported by grants from Swedish Medical Research Foundation (grant no. B94-17X-07184-10C), Assar Gabrielsson's Foundation for Cancer Research and the King Gustaf V Jubilee Clinic Cancer Research Foundation in Gothenburg 相似文献
993.
Quiescence of hematopoietic stem cells and maintenance of the stem cell pool is not dependent on TGF-beta signaling in vivo 总被引:4,自引:0,他引:4
OBJECTIVE: Maintained quiescence of hematopoietic stem cells (HSCs) is of critical importance to prevent premature exhaustion of the stem cell pool under conditions of hematopoietic stress. The growth inhibitory cytokine transforming growth factor beta (TGF-beta) has been shown to play a critical role in maintaining quiescence of HSCs in vitro. Here, we have used conditional knockout mice for the TGF-beta type I receptor (TbetaRI) to ask whether the naturally quiescent state of HSCs in vivo is dependent on TGF-beta signaling and thus whether TGF-beta serves as a protective factor for the stem cell pool during conditions of stress. METHODS: TbetaRI null and control bone marrow chimeras were subjected to repeated treatments with the cell cycle-specific cytotoxic drug 5-fluorouracil (5-FU) and surviving HSCs were assayed by competitive transplantation experiments. Exhaustion of stem cells was provoked by serially transplanting TGF-beta signaling-deficient as well as normal BM cells into lethally irradiated recipients, which were monitored for survival. RESULTS: Surprisingly, we found that TGF-beta receptor-deficient HSCs have similar susceptibility, compared to controls, to repeated 5-FU treatments, indicative of normally maintained quiescence in these cells. Likewise, hematopoietic failure occurred at similar stages in serially transplanted recipients of TbetaRI null and control BM, respectively, demonstrating normal consumption of the stem cell pool during hematopoietic stress. CONCLUSIONS: These findings clearly demonstrate that, despite a key role in vitro, TGF-beta does not provide the necessary signal that induces the quiescent state of HSCs and maintains the stem cell pool in vivo. 相似文献
994.
995.
A G Geiser J J Letterio A B Kulkarni S Karlsson A B Roberts M B Sporn 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(21):9944-9948
The phenotype of the transforming growth factor beta 1 (TGF-beta 1) null mouse has been previously described and is characterized by inflammatory infiltrates in multiple organs leading to a wasting syndrome and death as early as 3 weeks after birth. Since this phenotype occurs in the absence of any detectable pathogen, potential autoimmune disease mechanisms were investigated. We examined major histocompatibility complex (MHC) mRNA expression in tissues of the TGF-beta 1 null mouse and found levels of both the class I and class II MHC mRNA elevated compared to normal or TGF-beta 1 heterozygous littermates. This elevated expression was seen prior to any evidence of inflammatory infiltrates, suggesting a causal relationship between increased MHC expression and activation of immune cell populations. Cell surface expression of MHC molecules was detected by immunohistochemistry and correlated well with mRNA levels. Expression of mRNA for interferon gamma and its receptor was unchanged at the ages when increased MHC expression became apparent. Down-regulation of class I MHC expression by TGF-beta 1 was also demonstrated in vitro in fibroblasts isolated from TGF-beta 1 null mice. These findings suggest that one natural function of TGF-beta 1 is to control expression of both MHC classes. Altered regulation of MHC expression may be a critical step leading to the multifocal inflammation and wasting syndrome seen in the TGF-beta 1 null mouse. These results suggest potential applications for TGF-beta in the management of autoimmune disease, allograft rejection, and other problems associated with altered MHC expression. 相似文献
996.
Karlsson U Bjöersdorff A Massung RF Christensson B 《Scandinavian journal of infectious diseases》2001,33(1):73-74
A clinical case of human granulocytic ehrlichiosis in Scandinavia is presented. The patient developed high fever, myalgia, headache and dyspnoea. Doxycycline treatment resulted in a dramatic improvement. Laboratory confirmation included a fourfold change in anti-Ehrlichia equi IFA titre and a positive PCR confirmed by gene sequence analysis. 相似文献
997.
Dr. med. C. M. Rieder-Nelissen Prof. Dr. med. J. Hasse Dr. R. A. Yeates Dr. E. Sarnow 《Infection》1997,25(3):192-194
Summary In order to investigate the clinical efficacy of the triazole antifungal agent fluconazole (FCA) in the treatment of pulmonary mycosis, in the present study the concentrations of fluconazole in human pulmonary tissue, pericardial fluid and serum were determined at 1, 2, 12 and 13 h after intravenous administration of fluconazole 200 mg. The mean FCA concentrations in the serum were 4.04 mg/l (1 h), 3.82 mg/l (2 h), 2.35 mg/l (12 h) and 2.13 mg/l (13 h). The respective FCA levels in the pulmonary tissue were 4.64 mg/kg, 4.54 mg/kg; 3.50 mg/kg and 3.40 mg/kg and the concentrations in the pericardial fluid were 3.86 mg/l, 3.57 mg/l, 2.35 mg/l and 2.13 mg/l. The FCA concentrations in the pulmonary tissue that were statistically significant higher than the serum concentrations were found at 2 h, 12 h and 13 h after intravenous administration (p<0.05). 相似文献
998.
Human neutrophils have an important role in host defense against microbial infection. At different stages of an infectious process, neutrophils progressively up-regulate receptors and release various effector molecules. These are stored in several distinct types of granules with varying propensity to be secreted. Heparin-binding protein (HBP), also known as CAP37 or azurocidin, is a multifunctional, inactive serine-protease homologue. The present work shows that HBP is released from neutrophils on stimulation with secretagogues that do not trigger the secretion of azurophilic granule content. Therefore, the subcellular localization of HBP was investigated in more detail. Immunofluorescence microscopy revealed that HBP was localized close to the plasma membrane. Further analysis by fractionation of postnuclear supernatants from cavitated neutrophils showed that HBP is stored in azurophilic granules and secretory vesicles but that it is also detected to a minor extent in the plasma membrane. These findings were confirmed by immunoelectron microscopy showing that HBP colocalized with marker proteins of azurophilic granules and secretory vesicles. The presence of HBP in secretory vesicles possibly depends on the stage of cell differentiation, since the promyelocytic cell line HL-60 contains less HBP than mature neutrophils, stored exclusively in the less easily mobilized azurophilic granules. Our findings suggest that HBP can be synthesized or targeted to easily mobilized compartments at a late stage of neutrophil maturation. The ability of neutrophils to secrete HBP from secretory vesicles may be important for proinflammatory functions of this protein, such as the alteration of vascular permeability. 相似文献
999.
In the present study the effect of iodide on thyroid cell growth was investigated in primary suspension cultures of porcine thyroid cells capable of organifying iodide. The addition of a high dose of iodide (10(-4) M) to such cultures caused a marked increase in c-myc mRNA levels, [3H]thymidine incorporation, and mitotic activity. The incorporation of [3H]thymidine started 30-36 h after the addition of iodide. The stimulatory effect was abolished by a simultaneous incubation with methimazole. The concentration dependence of the iodide-induced stimulation of [3H]thymidine incorporation was similar to that of an inhibitory effect on adenylate cyclase activity. W-7, an inhibitor of calmodulin activity, as well as epinephrine, agents that reduce cAMP levels, also stimulated [3H]thymidine incorporation. Moreover, the stimulatory effect of iodide was reduced in the presence of forskolin. The results suggest that an organic form of iodine stimulates thyroid cell growth by reducing cAMP levels and demonstrate the presence of a growth stimulatory pathway in porcine thyroid cells that is independent of exogenous polypeptide growth factors or hormones. 相似文献
1000.
Previous reports dealing with cardiac herniation following intrapericardial pneumonectomy illustrate the critical and often lethal hemodynamic sequelae of this complication. In the case presented here, the first and nearly exclusive sign of cardiac herniation after left-sided pneumonectomy with extensive resection of the pericardium was systemic arterial hypoxemia. Subsequent investigations suggested inter-atrial right-to-left shunt in the presence of a patent foramen ovale, caused by slight right-ventricular outflow obstruction with consecutively reversed pressure relationships at atrial level. This explanation was supported by the operative findings, and reversibility was achieved by pericardial reconstruction with parietal pleura. When the patient died 8 months later due to general progression of a mucoepidermoid carcinoma, autopsy confirmed a large patent foramen ovale. 相似文献