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61.
Short-term hyperglycemia depresses immunity through nonenzymatic glycosylation of circulating immunoglobulin 总被引:7,自引:0,他引:7
Hyperglycemia accompanies a myriad of clinical conditions and causes an acceleration in the nonenzymatic glycosylation (NEG) of proteins. Since many proteins lose function when glycosylated, we assessed the effect of hyperglycemia on the function of immunoglobulin G. Twenty newborn Sprague-Dawley rats underwent splenectomy and 20, splenic mobilization alone. After 3 weeks, all animals received an intraperitoneal injection of Streptococcus pneumoniae. Twelve hours later, ten animals from each group received either control (CIG) or glycosylated (GIG) human immunoglobulin (0.3 gm/kg) intraperitoneally. Asplenic animals receiving GIG lived 28.5 hours vs. 49.6 hours for those receiving CIG (p less than 0.0001). Animals with spleens receiving GIG lived 48.2 hours vs. 51.7 hours for those receiving CIG (p = 0.03). Short-term glycosylation of immunoglobulin causes its inactivation. This may contribute to the increased risk of infection noted in hyperglycemic animals. 相似文献
62.
CT appearance of cervical lipoblastoma 总被引:1,自引:0,他引:1
W C Black J W Burke P S Feldman C M Johnson S Swanson 《Journal of computer assisted tomography》1986,10(4):696-698
We describe a case of lipoblastoma causing respiratory symptoms in an infant, where CT was useful in establishing the diagnosis and demonstrating the extent of involvement so that complete surgical resection could be planned. 相似文献
63.
A case of lymphocytic adenohypophysitis in a postpartum woman who became symptomatic during her 8th month of pregnancy is presented. The clinical presentation, endocrine findings, pathological findings, and operative management are discussed. Transient hypopituitarism is documented. Unlike most previously published cases, this woman had complete recovery of anterior pituitary function. 相似文献
64.
65.
Dolores Acevedo-Garcia Lisa M. Bates Theresa L. Osypuk Nancy McArdle 《Social science & medicine (1982)》2010
Global self-rated health (SRH) is increasingly a key indicator in the assessment of immigrant health. However, evidence of the impact on SRH of generational status, duration of residence in the US, and socioeconomic status (SES) among immigrants and their offspring is limited and inconsistent. We overcome limitations in existing research on this topic by using a uniquely large and diverse data source, the March Annual Social and Economic Supplement of the Current Population Survey (CPS; 2003–2007) (n = 637,209). As a result, we are able to disaggregate results by race/ethnicity, account for country of origin, and consider the role of multiple dimensions of SES. We find that overall first-generation immigrants in the US have lower odds of poor/fair SRH compared to the third-generation. This association is particularly strong for blacks and Hispanics but not significant for Asians. Among first-generation Asians and Hispanics, longer duration of residence is positively associated with poor/fair SRH. Finally, socioeconomic gradients in SRH tend to be less pronounced among the first-generation (versus the third) and, within the first-generation, among recent arrivals (versus those with longer durations). Our results highlight the importance of explicitly accounting for multiple immigration-related variables and their interactions with race/ethnicity and SES. Otherwise, studies may misestimate SRH differences by race/ethnicity and socioeconomic status. The continued growth of the US immigrant population and the second-generation underscore the need to examine patterns in immigrant health systematically. 相似文献
66.
A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases. 总被引:3,自引:0,他引:3
Pavel Sova Xiao-Wei Ren Shaoheng Ni Kathrin M Bernt Jie Mi Nancy Kiviat André Lieber 《Molecular therapy》2004,9(4):496-509
We have constructed a new capsid-modified adenovirus (Ad) vector that specifically replicates in tumor cells and expresses TNF-related apoptosis-inducing ligand (TRAIL). The Ad capsid contains short-shafted fibers derived from Ad serotype 35, which allow for efficient infection of malignant tumor cells, and largely avoids innate toxicity after intravenous application. Replication-dependent homologous recombination in Ad genomes was used to achieve tumor-specific expression of Ad E1a (to mediate viral replication) and TRAIL (to mediate apoptosis and enhance release of progeny virus from infected cells). We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer. Both in vitro and in vivo tumor models showed efficient intratumoral spread of this vector. In a model for metastatic colon cancer, tail vein infusion of Ad5/35.IR-E1A/TRAIL resulted in elimination of preestablished liver metastases. Intravenous injection of this vector caused a transient elevation of serum glutamic pyruvic transaminase in tumor-bearing mice, which we attributed to factors released from apoptotic tumor cells. Liver histology analyzed at day 14 after virus injection did not show signs of hepatocellular damage. This new oncolytic vector represents a potentially efficient means for gene therapy of metastatic cancer. 相似文献
67.
Dorit Naot Usha Bava Brya Matthews Karen E Callon Gregory D Gamble Michael Black Sarah Song Rocco P Pitto Tim Cundy Jill Cornish Ian R Reid 《Journal of bone and mineral research》2007,22(2):298-309
Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease. 相似文献
68.
Nancy S Krieger Kevin K Frick Kelly LaPlante Strutz Anne Michalenka David A Bushinsky 《Journal of bone and mineral research》2007,22(6):907-917
Chronic metabolic acidosis induces net Ca efflux from bone; this osteoclastic bone resorption is mediated by increased osteoblastic prostaglandin synthesis. Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is present in both constitutive (COX-1) and inducible (COX-2) forms. We report here that acidosis increases both osteoblastic RNA and protein levels for COX-2 and that genetic deficiency or pharmacologic inhibition of COX-2 significantly reduces acid-induced Ca efflux from bone. INTRODUCTION: Incubation of neonatal mouse calvariae in medium simulating physiologic metabolic acidosis induces an increase in osteoblastic prostaglandin E2 (PGE2) release and net calcium (Ca) efflux from bone. Increased PGE2 is necessary for acid-induced bone resorption, because inhibition of cyclooxygenase activity with indomethacin significantly decreases not only PGE2 production but also Ca release. Cyclooxygenase is present in both constitutive (COX-1) and inducible (COX-2) forms. Because COX-2 activity has been implicated in several forms of pathological bone resorption, we tested the hypothesis that COX-2 is critical for acid-induced, cell-mediated bone Ca efflux. MATERIALS AND METHODS: To determine the effect of metabolic acidosis on COX-2 RNA and protein, primary cells isolated from neonatal CD-1 mouse calvariae were cultured in neutral (Ntl) or physiologically acidic medium (Met). RNA levels for COX-2 and COX-1 were measured by quantitative real-time PCR. Levels of COX-2 and COX-1 protein were measured by immunoblot analysis. To determine the effect of acidosis on bone Ca efflux in genetically deficient COX-2 mice, mice heterozygous for the COX-2 knockout (strain B6;129S7-Ptgs2(tm1Jed)/J) were used as breeders, and neonatal calvariae were cultured in Ntl or Met. To determine the effects of the specific COX-2 inhibitor, NS398, on acid-induced bone resorption, CD-1 calvariae were incubated in Ntl or Met with or without NS398 (1 microM). Medium PGE2 was assayed by ELISA. RESULTS: Incubation of mouse calvarial cells in Met significantly increased COX-2 RNA and protein levels without a change in COX-1. Increased COX-2 protein levels in response to Met were also observed in cultured calvariae. Acid-induced, cell-mediated Ca efflux from B6;129S7-Ptgs2(tm1Jed)/J calvariae was dependent on genotype. From 0 to 24 h, when physicochemical Ca efflux predominates, Met significantly increased net Ca efflux in all genotypes. After 24 h, when cell-mediated Ca efflux predominates, Met induced greater Ca efflux from (+/+) than from (+/-), and there was no increase from (-/-). In calvariae from CD-1 mice, NS398 significantly inhibited both the acid-induced increase in PGE2 and Ca release. CONCLUSIONS: The specific acid-induced increase in COX-2 RNA and protein levels and the dependency of the increased Ca efflux on COX-2 activity, as determined by both genetic deficiency and pharmacologic inhibition, show that COX-2 is critical for acid-induced, cell-mediated bone resorption. 相似文献
69.
Ana Berta Sousa Ana Medeira Binita M Kamath Nancy B Spinner Isabel Cordeiro 《Revista portuguesa de cardiologia》2006,25(4):447-452
Although most congenital heart defects are isolated abnormalities of embryonic development, with little genetic contribution, a small number are components of syndromes. In such cases, an accurate diagnosis has important implications for individual prognosis and familial genetic counseling. Alagille syndrome (AGS) is a dominantly inherited multisystem developmental disorder, which primarily affects the liver, heart, eyes, skeleton, and face. In recent years, the identification of the AGS gene has drawn attention to the existence of subclinical carriers, and broadened the spectrum of phenotypical variation associated with this syndrome. The authors present a case of mother and son with benign stenosis of the pulmonary artery branches. Subtle facial aspects suggested the diagnosis of AGS, which was confirmed by molecular analysis. Relevant clinical investigations and diagnostic implications are discussed. 相似文献
70.
Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation. 总被引:3,自引:0,他引:3
Robertson Parkman Geoff Cohen Shelly L Carter Kenneth I Weinberg Bernadette Masinsin Eva Guinan Joanne Kurtzberg John E Wagner Nancy A Kernan 《Biology of blood and marrow transplantation》2006,12(9):919-927
Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival. 相似文献