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91.
Gene expression profiling identifies liver X receptor alpha as an estrogen-regulated gene in mouse adipose tissue 总被引:3,自引:0,他引:3
Lundholm L Movérare S Steffensen KR Nilsson M Otsuki M Ohlsson C Gustafsson JA Dahlman-Wright K 《Journal of molecular endocrinology》2004,32(3):879-892
Estrogens reduce adipose tissue mass in both humans and animals. The molecular mechanisms for this effect are, however, not well characterized. We took a gene expression profiling approach to study the direct effects of estrogen on mouse white adipose tissue (WAT). Female ovariectomized mice were treated for 10, 24 and 48 h with 17beta-estradiol or vehicle. RNA was extracted from gonadal fat and hybridized to Affymetrix MG-U74Av2 arrays. 17beta-Estradiol was shown to decrease mRNA expression of liver X receptor (LXR) alpha after 10 h of treatment compared with the vehicle control. The expression of several LXRalpha target genes, such as sterol regulatory element-binding protein 1c, apolipoprotein E, phospholipid transfer protein, ATP-binding cassette A1 and ATP-binding cassette G1, was similarly decreased. We furthermore identified a 1.5 kb LXRalpha promoter fragment that is negatively regulated by estrogen. Several genes involved in lipogenesis and lipolysis were identified as novel targets that could mediate estrogenic effects on adipose tissue. Finally, we show that ERalpha is the main estrogen receptor expressed in mouse white adipose tissue (WAT) with mRNA levels several hundred times higher than those of ERbeta mRNA. 相似文献
92.
Bile acid concentrations in systemic and portal serum in presumably normal man and in cholestatic and cirrhotic conditions 总被引:4,自引:0,他引:4
Total bile acid concentration was determined in systemic and portal serum and in liver tissue from patients with presumably normal liver function, and from patients with extrahepatic cholestasis. Systemic and portal serum bile acids were also determined in patients with alcoholic liver cirrhosis. In 5 patients, in whom a portal catheter was inserted through the umbilical vein, the diurnal variation in systemic and portal serum bile acid concentration was studied. In patients with presumably normal liver function the fasting systemic serum bile acid concentration was 4.8+/-0.5 mumol times 1(-1), and the portal concentration was 12.9+/-1.5 mumol times 1(-1). In cholestasis and liver cirrhosis the systemic and portal bile acid concentration was substantially elevated. The bile acid concentration gradient between systemic serum, portal serum, liver tissue, and hepatic bile was 1:3:80:2600 in the patients with normal liver function. In both the cholestatic and cirrhotic condition the systemic and portal serum bile acid concentration was equilibrated. Postprandially both the systemic and portal bile acid concentration increased, but the gradient between these concentrations was unchanged. The results are compatible with the hypothesis that portal and systemic serum bile acid concentrations are determined by the intestinal absorption rate in subjects with normal liver function and by the hepatic and renal clearance capacity in cholestatic and cirrhotic conditions. 相似文献
93.
A Wennberg A Hyltander A Sj?berg B Arfvidsson R Sandstr?m I Wickstr?m K Lundholm 《Metabolism: clinical and experimental》1992,41(2):165-171
The aim of this study was to evaluate to what extent secondary carnitine deficiency may exist based on the prevalence of subnormal carnitine status in patients with critical illness and abnormal nutritional state. Healthy control patients (n = 12) were investigated and compared with patients with possible secondary carnitine deficiency, ie, patients with overt severe protein-energy malnutrition (PEM, n = 28), postoperative long-term (greater than 14 days) parenteral glucose feeding (250 g glucose/d, n = 7), severe liver disease (n = 10), renal insufficiency (n = 7), and sustained septicemia with increased metabolic rate (n = 8). Nutritional status, energy expenditure, creatinine excretion, and blood biochemical tests were measured in relationship to free and total carnitine concentrations in plasma and skeletal muscle tissue, as well as urinary excretion of free and total carnitine. The overall mortality rate was 48% within 30 days of the investigation in study patients with the highest mortality in liver disease (90%). The hospitalization range was 14 to 129 days in study patients. Most study patients had lost weight (4% to 19%) and had abnormal body composition. Patients with liver disease, septicemia, renal insufficiency, and those on long-term glucose feeding had significantly higher than predicted metabolic rate (+25% +/- 3%), while patients with severe malnutrition had decreased metabolic rate compared with controls. Patients with liver disease had increased plasma concentrations of free (96 +/- 16 mumol/L) and total (144 +/- 27 mumol/L) carnitine compared with controls (45 +/- 3, 58 +/- 7 mumol/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
94.
Microbial translocation and inflammatory response in patients with acute peritonitis 总被引:1,自引:0,他引:1
Osterberg J Ljungdahl M Lundholm M Engstrand L Haglund U 《Scandinavian journal of gastroenterology》2004,39(7):657-664
BACKGROUND: In peritonitis, increased production of cytokines and changes in the splanchnic cellular immune system may cause translocation of bacteria and endotoxins. The aims of this study were to assess the frequency of translocation and relate translocation to the immune response in patients with acute peritonitis. METHODS: Patients with local (LP, n=20) or general peritonitis (GP, n=15) were compared with controls (C, n=12). Blood was obtained preoperatively for cultures, and analyses of endotoxin and cytokines (tumour necrosis factor-alpha, interleukins 6 and 10). Mesenteric lymph nodes (MLNs) were excised for culturing and immunohistochemistry using antibodies CD4, CD8 and CD68. RESULTS: Positive blood and MLN cultures were not obtained in controls. DNA typing proved bacterial translocation in one patient with local and one patient with general peritonitis. Thus translocation was proven to occur in 6% of patients with peritonitis. Endotoxaemia was predominantly found in the GP group. Cytokines increased during peritonitis and more so in patients with GP than in those with LP. More CD8 and CD68 cells were found in MLNs from LP patients than in C patients and more CD4 and CD8 cells in LP patients than in GP patients. There was no significant difference in this regard between the GP and C groups. CONCLUSIONS: Bacterial translocation occurs during acute peritonitis but seems to be fairly infrequent. Peritonitis causes significant inflammatory cellular reactions. 相似文献
95.
Diffuse large cell lymphoma in a patient with hairy cell leukemia: immunoglobulin gene analysis reveals separate clonal origins 总被引:1,自引:0,他引:1
A 75-year-old man with hairy cell leukemia (HCL) was found to have an immunoblastic lymphoma of the small bowel. Immunologic and genotypic characterization of these neoplasms revealed both the HCL and the immunoblastic lymphoma to be of the B cell lineage. The HCL expressed the HCL-associated antigens detected by the monoclonal antibodies HC-1 and HC-2, whereas the immunoblastic lymphoma failed to react with these antibodies. In addition, surface immunoglobulin light chains could not be accurately determined for the hairy cells, whereas the immunoblastic lymphoma was shown to express only kappa immunoglobulin light chains. These immunophenotype differences were compatible with either the clonal evolution of the HCL into the immunoblastic lymphoma or a separate clonal origin for these two neoplasms. An analysis of tumor DNA by Southern blot hybridization revealed different heavy-chain and kappa light-chain gene rearrangements in these two malignancies. Thus the occurrence of the large cell lymphoma most likely represents the emergence of a second clonally unrelated B cell malignancy. 相似文献
96.
Dercksen MW; Weimar IS; Richel DJ; Breton-Gorius J; Vainchenker W; Slaper- Cortenbach CM; Pinedo HM; von dem Borne AE; Gerritsen WR; van der Schoot CE 《Blood》1995,86(10):3771-3782
In the present study, we show by adhesion assays and ultrastructural studies that platelets can bind to CD34+ cells from human blood and bone marrow and that this interaction interferes with the accurate detection of endogenously expressed platelet glycoproteins (GPs). The interaction between these cells was found to be reversible, dependent on divalent cations, and mediated by P-selectin. Enzymatic characterization showed the involvement of sialic acid residues, protein(s). The demonstration of mRNA for the P-selectin glycoprotein ligand 1 (PSGL-1) in the CD34+ cells by polymerase chain reaction (PCR) analysis suggests that this molecule is present in these cells. Under conditions that prevent platelet adhesion, a small but distinct subpopulation of CD34+ cells diffusely expressed the platelet GPIIb/IIIa complex. These cells were visualized by immunochemical studies. Furthermore, synthesis of mRNA for GPIIb and GPIIIa by CD34+ cells was shown using PCR analysis. The semiquantitative PCR results show relatively higher amounts of GPIIb mRNA than of PF4 mRNA in CD34+CD41+ cells in comparison with this ratio in platelets. This finding is a strong indication that the PCR results are not caused by contaminating adhering platelets. MoAbs against GPIa GPIb alpha, GPV, P- selectin, and the alpha-chain of the vitronectin receptor did not react with CD34+ cells. The number of CD34+ cells expressing GPIIb/IIIa present in peripheral blood stem cell (PBSC) transplants was determined and was correlated with platelet recovery after intensive chemotherapy in 27 patients. The number of CD34+CD41+ cells correlated significantly better with the time of platelet recovery after PBSC transplantation (r = .83, P = .04) than did the total number of CD34+ cells (r = .55). Statistical analysis produced a threshold value for rapid platelet recovery of 0.34 x 10(6) CD34+CD41+ cells/kg. This study suggests that if performed in the presence of EDTA the flow cytometric measurement of GPIIb/IIIa on CD34+ cells provides the most accurate indication of the platelet reconstitutive capacity of the PBSC transplant. 相似文献
97.
Transforming growth factor-beta (TGF-beta) and macrophage inflammatory protein-l alpha (MIP-1 alpha) are both well-described inhibitors of committed and multipotential hematopoietic progenitors. The effect of these cytokines; on true stem cell activity in ex vivo culture systems as assayed by murine long-term repopulating activity (LTRA) has not been examined. We studied the stem cell effects of the addition of these cytokines to ex vivo cultures containing interleukin-3 (IL-3), IL- 6, and stem cell factor (SCF), using the murine competitive repopulation assay. We also tested the impact of adding an anti-TGF- beta neutralizing antibody, to ask whether abrogation of autocrine/paracrine TGF-beta may protect or enhance the survival of LTRA during ex vivo culture. TGF-beta 1 had significant suppressive effects on both short- and long-term repopulating activities, and anti- TGF-beta antibody had enhancing effects compared with control cultures containing IL-3, IL-6, and SCF alone. MIP-1 alpha had no significant effects on either short- or long-term repopulating ability. These data suggest that abrogation of TGF-beta during suspension culture may allow enhanced survival or even expansion of primitive cells ex vivo, with implications for many applications, including gene therapy. 相似文献
98.
W Oh DK Stevenson JE Tyson BH Morris CE Ahlfors G Jesse Bender RJ Wong R Perritt BR Vohr KP Van Meurs HJ Vreman A Das DL Phelps T Michael O’Shea RD Higgins 《Acta paediatrica (Oslo, Norway : 1992)》2010,99(5):673-678
Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 ± 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow‐up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow‐up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow‐up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants. 相似文献
99.
Inactivation of factor XIa in human plasma assessed by measuring factor XIa-protease inhibitor complexes: major role for C1-inhibitor 总被引:3,自引:1,他引:2
Wuillemin WA; Minnema M; Meijers JC; Roem D; Eerenberg AJ; Nuijens JH; ten Cate H; Hack CE 《Blood》1995,85(6):1517-1526
From experiments with purified proteins, it has been concluded that factor XIa (FXIa) is inhibited in plasma mainly by alpha 1-antitrypsin (a1AT), followed by antithrombin III (ATIII), C1-inhibitor (C1Inh), and alpha 2-antiplasmin (a2AP). However, the validity of this concept has never been studied in plasma. We established the relative contribution of different inhibitors to the inactivation of FXIa in human plasma, using enzyme-linked immunosorbent assays (ELISAs) for the quantification of complexes of FXIa with a1AT, C1Inh, a2AP, and ATIII. We found that 47% of FXIa added to plasma formed complexes with C1Inh, 24.5% with a2AP, 23.5% with a1AT, and 5% with ATIII. The distribution of FXIa between these inhibitors in plasma was independent of whether FXIa was added to plasma, or was activated endogenously by kaolin, celite, or glass. However, in the presence of heparin (1 or 50 U/mL), C1Inh appeared to be the major inhibitor of FXIa, followed by ATIII. Furthermore, at lower temperatures, less FXIa-C1Inh and FXIa-a1AT complexes but more FXIa-a2AP complexes were formed. These data demonstrate that the contribution of the different inhibitors to inactivation of FXIa in plasma may vary, but C1Inh is the principal inhibitor under most conditions. 相似文献
100.