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121.
Elkins MK Vittinghoff E Baranzini SE Hecht FM Sriram U Busch MP Levy JA Oksenberg JR;San Francisco Primary Infection Group 《Genes and immunity》2005,6(1):66-69
In chronically HIV infected individuals, a number of functional B cell abnormalities have been described. However, the immediate changes that occur in the B cell compartment following viral exposure and how they affect the long-term course of infection are not well understood. We report the longitudinal analysis of B cell repertoires during early infection in untreated and treated individuals receiving highly active antiretroviral therapy (HAART). Analysis was based on IgG heavy chain gene utilization and CDR3 length measurement and relationship with CD4/CD8 counts, viral load, and total serum IgG, and anti-HIV antibodies levels. Repertoires were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. The findings indicate a stable peripheral B cell repertoire during the first 72 weeks following infection, particularly in the HAART treated patients. A modest association between B cell repertoire integrity and viremia levels as well as treatment was detected. 相似文献
122.
Inhibition of poly(ADP-ribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury 总被引:4,自引:0,他引:4
Mota RA Sánchez-Bueno F Saenz L Hernández-Espinosa D Jimeno J Tornel PL Martínez-Torrano A Ramírez P Parrilla P Yélamos J 《Laboratory investigation; a journal of technical methods and pathology》2005,85(10):1250-1262
The severity of acute pancreatitis results from the transmigration and activation of leukocytes within the pancreas and the local synthesis and release of proinflammatory-soluble mediators that transform a local injury into a systemic inflammatory response. Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear DNA-binding protein that has been shown to play a relevant role in cell necrosis and organ failure in various diseases associated with inflammation. Therefore, we set out to investigate whether the genetic deletion of PARP-1 or PARP-2 (a new member of the PARP family) genes, or pharmacological inhibition of PARP activity might affect the development and severity of acute pancreatitis and pancreatitis-associated lung injury. Secretagogue-induced acute pancreatitis was achieved by 12 hourly intraperitoneal injections of cerulein in mice deficient in PARP-1 or PARP-2 genes, and wild-type (WT) littermate mice untreated or treated with PARP activity inhibitors. The severity of pancreatitis was assessed by measurements of serum amylase, lipase, interleukin-1beta and IL-6, pancreatic water content, histologic grading and pancreas myeloperoxidase (MPO) activity. Lung injury was evaluated by quantifying MPO activity and morphological changes. We found that the severity of acute pancreatitis and pancreatitis-associated lung injury was significantly attenuated in mice lacking PARP-1, but not PARP-2, compared with WT mice. Interestingly, administration of PARP inhibitors, 3-aminobenzamide or PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethyacetamide HCl), in WT mice markedly decreased acute pancreatitis severity and pulmonary-associated injury in a larger extension than genetic deletion of PARP-1. Our results support the potential therapeutic application of PARP inhibitors in the development and severity of acute pancreatitis and associated lung injury. 相似文献
123.
Specific allergens enhance elastase release in stimulated neutrophils from asthmatic patients 总被引:12,自引:0,他引:12
Monteseirín J Bonilla I Camacho MJ Chacón P Vega A Chaparro A Conde J Sobrino F 《International archives of allergy and immunology》2003,131(3):174-181
BACKGROUND: The presence of the three forms of IgE receptor - the heterotrimeric high-affinity receptor for IgE (Fc(epsilon)RI), the low-affinity receptor for IgE (Fc(epsilon)RII/CD23) and the Mac-2/IgE-binding protein (epsilonBP) - has been demonstrated on human neutrophils. We have previously shown that specific allergens are able to activate functional responses by neutrophils from allergic patients sensitized to those allergens. Neutrophils are present at the sites of allergic inflammation. The primary (azurophilic) granules of neutrophils contain a variety of enzymes, such as elastase, that might potentiate inflammation. It is not known whether specific allergens are able to elicit elastase release by neutrophils from allergic patients. In addition, we attempted to evaluate the relationship between neutrophil degranulation and lung function of the patients, measured as FEV(1). METHODS: Neutrophils were challenged in vitro with the specific allergens that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Neutrophils from normal subjects were challenged with allergens as control. RESULTS: The in vitro challenge of neutrophils with allergens to which the patients were sensitive elicited a release of elastase by these cells. The in vitro activation of neutrophils was highly allergen specific; allergens other than those accounting for clinical symptoms did not evoke elastase release, and allergens were ineffective on neutrophils from healthy donors. A significant inverse correlation was observed between elastase release and patients' lung function, measured as FEV(1). CONCLUSION: An IgE-dependent mechanism might promote elastase release by neutrophils at allergic sites. There is a significant inverse relationship between levels of elastase released by neutrophils from allergic patients and lung function, as assessed by FEV(1). 相似文献
124.
Ines Santisteban Francisco X. Arredondo-Vega Susan Kelly Marianne Debre Alain Fischer Jean Louis Prignon Bettina Hilman Jane Eldahr David H. Dreyfus Erwin W. Gelfand P. Lynne Howell Michael S. Hershfield 《Human mutation》1995,5(3):243-250
Three new missense mutations (H15D, A83D, and A179D) and a new splicing defect (573 + 1G→A) in the 5′ splice site of intron 5 were among six mutant adenosine deaminase (ADA) alleles found in three unrelated patients with severe combined immunodeficiency disease, the most common phenotype associated with ADA deficiency. When expressed in vitro, the H15D, A83D, and A179D proteins lacked detectable ADA activity. The splicing defect caused skipping of exon 5, resulting in premature termination of translation and a reduced level of mRNA. H15D is the first naturally occurring mutation of a residue that coordinates directly with the enzyme-associated zinc ion. Molecular modeling based on the atomic coordinates of murine ADA suggests that the D15 mutation would create a cavity or gap between the zinc ion and the side chain carboxylate of D15. This could alter the ability of zinc to activate a water molecule postulated to play a role in the catalytic mechanism. A83 and A179 are not directly involved in the active site, but are conserved residues located respectively in a helix 4 and β strand 4 of the α/β barrel. Replacement of these small hydrophobic Ala residues with the charged, more bulky Asp side chain may distort ADA structure and affect enzyme stability or folding.© 1995 wiley-Liss, Inc. 相似文献
125.
In this study we utilized the hamster ovary as a model to investigatethe effects of ovulation induction with gonadotrophin on theactivation of the signal transducer effector system, adenylylcyclase (AC). For this purpose, we prepared membrane particlesfrom the ovary and analysed both gonadotrophin-sensitive ACand non-receptor-mediated activation during a cycle in whichovulation and luteinization were achieved by pregnant maresserum gonadotrophin (PMSG)/human chorionic gonadotrophin (HCG)administration. Results were directly compared with AC activationin similarly prepared membranes obtained at different stagesof the natural unstimulated cycle. AC activity was quantifiedby the direct conversion of ATP substrate into cyclic adenosinemonophosphate (cAMP). Measurements of ovarian weights, serumoestradiol and progesterone concentrations provided a solidbase from which to evaluate the functional status of the ovaryat each time period during the natural and stimulated cycles.We found that ovarian membranes contain functional componentsof the AC system and demonstrated that AC is highly dependenton hormonal changes and the functional state of the ovary. Thus,during the natural cycle, ovarian AC showed relatively constantresponsiveness to follicle-stimulating hormone (FSH) throughoutthe cycle, whereas responsiveness to luteinizing hormone (LH)/HCGreached its peak during the luteal phase. On the other hand,during the stimulated cycle, sensitivity to FSH and LH/HCG variedconsiderably, being absent during the peri-ovulatory period.AC responsiveness to gonadotrophins was only regained 48 h afterovulation. Also during the peri-ovulatory period of the gonadotrophin-inducedcycle, stimulation of ovarian AC with non-hormonal activatorsdeclined. However, the rate of cAMP production in response tothese activators remained very high, indicating that despiterefractoriness to gonadotrophins, ovarian AC retained the capacityto generate cAMP at near maximal efficiency. Basal (non-stimulated)activity, guanine nucleotide activation, hormone responsivenessand stimulation by the non-hormonal activators NaF and forskolinwere all significantly increased in comparison with the naturalcycle. Basal activity alone was 7-fold higher than the activityobserved during the unstimulated cycle. These results suggestthat subsequent to exogenous gonadotrophin administration, thetransmembrane effector AC system must be primed for a higherlevel of activity in the ovarian tissue. This priming of theovarian AC system by exogenous gonadotrophin was also evidentwhen the enzyme was measured under conditions allowing maximalactivity, i.e. in the presence of a combination of NaF and forskolin.Maximal AC activity increased 4- to 5-fold compared with thenatural cycle. We conclude that gonadotrophin administrationinducing ovulation causes profound alterations in the expressionof AC in ovarian membranes. Gonadotrophin treatment increasedthe enzyme activity and induced a temporal desensitization toFSH and LH/HCG in the peri-ovulatory period of the stimulatedcycle. Because the gonadotrophin-sensitive AC system representsthe capacity of FSH and LH/HCG receptors to couple and elicita biological response, our results provide new insights intothe cellular mechanisms that regulate ovarian activity duringinduction of ovulation. 相似文献
126.
Myxoid leiomyosarcoma of the ovary: Analysis of three cases 总被引:2,自引:0,他引:2
Francisco F. Nogales MD Alberto Ayala MD Isabel Ruiz-Avila MD Juan J. Sirvent MD 《Human pathology》1991,22(12):1268-1273
The first three cases of myxoid leiomyosarcoma occurring in the ovary are reported. Two cases in stage III were found in postmenopausal patients and a further case was found in stage I in a 32-year-old. All masses were large and gelatinous with cystic change, necrosis, and hemorrhage, but both uteri and ligaments and contralateral adnexa appeared normal. Microscopically, the tumors showed a predominantly reticular meshwork of elongated cells surrounded by abundant basophilic material. While electron microscopy proved inconclusive due to nondifferentiation, the use of monoclonal antibodies against smooth muscle actin demonstrated a smooth muscle type of differentiation. The differential diagnosis of this rare ovarian condition includes other myxoid ovarian lesions, such as ovarian edema, myxoma, endodermal sinus tumors, and the sarcomatous component of malignant mixed müllerian tumor and carcinosarcoma, as well as lymphovascular tumors. Since mitotic count due to decreased cellular density is unusually low in myxoid leiomyosarcoma, capsular rupture and clinical stage seem to be more reliable prognostic markers. The highly aggressive behavior of myxoid leiomyosarcoma parallels that of typical ovarian leiomyosarcoma. Two of the three patients in this series died of tumor at 13 and 24 months after diagnosis; the other patient is free of disease at 3 years after diagnosis. 相似文献
127.
Cell cycle “checkpoints” help to ensure the integrity of normal cellular functions prior to replicative DNA synthesis and/or
cell division. Cell kinetic abnormalities, particularly arrests at the G1/S and G2/M cell cycle checkpoints, are induced following
exposure to ionizing radiationin vitro. Following irradiation, cellular signaling pathways may lead to G1 arrest and/or apoptosis at the G1/S cell cycle transition
point. Transfection of cyclin D1, a G1/S cyclin, into a rat embryo cells (REC) results in cellular populations that overexpress
cyclin D1, are transformed morphologically, demonstrate an increased incidence of apoptosis, and are tumorigenic in immune-deficient
mice. Despite such phenotypic changes, transfected cell populations maintain the itegrity of the G1 checkpoint following ionizing
radiation. The transfected cells overexpressing Cyclin D1 have a statistically significant increase in the incidence of apoptosis
as compared to parental REC strains or mock-transfected REC. The work provides further evidence of Cyclin D1 playing a critical
role in maintaining the integrity of the G1/S checkpoint, via the activation of apoptotic pathways following exposure to ionizing
radiationin vitro. 相似文献
128.
Significantly reduced expression of the proteoglycan decorin in Alzheimer''s disease fibroblasts 下载免费PDF全文
Enrique Brandan Francisco Melo María García Maribel Contreras 《Journal of clinical pathology》1996,49(6):M351-M356
Aims—To investigate whether proteoglycan synthesis is altered in skin fibroblasts in patients with Alzheimer's disease compared with normal subjects. 相似文献
129.
R D Moore J Hidalgo B W Sugland R E Chaisson 《The New England journal of medicine》1991,324(20):1412-1416
BACKGROUND AND METHODS: We sought to describe the trends in survival from 1983 to 1989 among persons with the acquired immunodeficiency syndrome (AIDS) and to examine the relative effects on the natural history of AIDS of zidovudine use and demographic and clinical characteristics. This longitudinal, observational, population-based study used data from the Maryland Human Immunodeficiency Virus Information System, a data base that links information from the Maryland AIDS Registry with data on public and private health care claims, vital statistics, and hospital, long-term care, and ambulatory care records. RESULTS: The median survival after diagnosis among persons with AIDS (n = 1028) was 140 days longer for those given their diagnoses between 1987 and 1989 than for those given their diagnoses between 1983 and 1985 (450 vs 310 days). Among the 714 persons in whom AIDS was diagnosed after April 1987 (when zidovudine became available), two-year survival was greater among men than women (P less than 0.03), among persons less than 45 years old than among older persons (P less than 0.001), among non-Hispanic whites than among minorities (P less than 0.001), and among persons whose category of human immunodeficiency virus transmission was homosexual contact than among those with heterosexual, transfusion-related, or less common modes of transmission (P less than 0.02). In all the analyses the groups with the longer survival were more likely to have received zidovudine. The median survival among those who received zidovudine was 770 days, as compared with 190 days among those who never received the drug (P less than 0.001). By proportional-hazards analysis, zidovudine therapy was the factor most strongly associated with improved survival. CONCLUSIONS: For Maryland residents with AIDS there has been an improvement in survival since 1987. Zidovudine therapy and perhaps other aspects of care associated with it have contributed substantially to the improved survival. 相似文献
130.
The present paper studies a marker of oxidative stress such as heme oxygenase-1 (HO-1), the main heat shock protein. HO-1 expression was induced in the focal region of the cerebellum following experimental subarachnoid hemorrhage (SAH). Lysed blood was injected into the subarachnoid space or cisterna magna region of adult rats. The experimental groups used were: (1) animals injected with lysed blood alone; (2) animals injected with saline alone; (3) lysed blood plus melatonin (10 mg/kg body weight(BW)); (4) lysed blood plus melatonin (10 mg/kg BW injected 1 h before SAH); (5) lysed blood plus melatonin (5 mg/kg BW injected 1 h before SAH); (6) lysed blood plus vitamin E (Trolox; 30 mg/kg BW injected simultaneously); (7) lysed blood plus vitamin E (30 mg/kg BW injected 1 h before SAH); and (8) lysed blood plus vitamin E (15 mg/kg BW injected 1 h before SAH). Animals were sacrificed 24 h later. Injection of lysed blood induced an overexpression of HO-1. Both, melatonin and vitamin E were able to prevent the expression of the heat shock protein. However, in terms of efficiency, the antioxidant capability of melatonin was clearly higher than that exhibited by vitamin E. The results presented in this study show that antioxidants, especially melatonin, prevent focal regions of injury as assessed by heat shock protein expression in a rat model of SAH. 相似文献