Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CCR5 is the chemokine co-receptor for R5-tropic human immunodeficiency virus type 1 (HIV-1) isolates most often associated with primary infection. We have developed an HIV-1 self-inactivating vector, CAD-R5, containing a CCR5 single-chain antibody (intrabody) gene, which when expressed in T-cell lines and primary CD4+ T cells disrupts CCR5 cell surface expression and provides protection from R5-tropic isolate exposure. Furthermore, CAD-R5 intrabody expression in primary CD4+ T cells supports significant growth and enrichment over time during HIV-1-pulsed dendritic cell-T-cell interactions. These results indicate that CCR5 intrabody-expressing CD4+ T cells are refractory against this highly efficient primary route of infection. CD34+ cells transduced with the CAD-R5 vector gave rise to CD4+ and CD8+ thymocytes in non-obese diabetic (NOD)/ severely combined-immunodeficient (SCID)-human thymus/liver (hu thy/liv) mice, suggesting that CCR5 intrabody expression can be maintained throughout differentiation without obvious cellular effects. CD4+ T cells isolated from NOD/SCID-hu thy/liv mice were resistant to R5-tropic HIV-1 challenge demonstrating the maintenance of protection. Our findings demonstrate delivery of anti-HIV-1 activity through CCR5 intrabodies in primary CD4+ T cells and CD34+ cell-derived T-cell progeny. Thus, gene delivery strategies that provide a selective survival and growth advantage for T effector cells may provide a therapeutic benefit for HIV-1-infected individuals who have failed conventional therapies.
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PMID:T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery. 1673 91

Hyper IgE recurrent infection syndrome (HIES, or Job's syndrome) is a primary immunodeficiency characterized by recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE) levels, and various connective tissue and skeletal system abnormalities including characteristic facies, scoliosis, joint hyperextensibility, retained primary dentition, craniosynostosis, osteopenia, and pathologic fractures. We have identified two patients with aneurysmal coronary artery disease. One was a forty-three-year-old man with HIES and coronary artery aneurysms and ectasia identified on cardiac catheterization following myocardial infarction. The other was a 48-year-old man with coronary artery ectasia-aneurysm identified after cardiac catheterization for evaluation of chest pain. Although connective tissue abnormalities are common in HIES, this is the first report of coronary artery aneurysms in HIES. Further studies are necessary to determine the incidence, pathogenesis, and optimal therapy of these arterial abnormalities in HIES.
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PMID:Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome. 1709 78

Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution syndrome or lipodystrophy, hyperlipidaemia, insulin resistance and diabetes have been extensively reported in subjects treated with new, potent antiretroviral regimens. The potential long-term consequences of HAART-associated metabolic alterations are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving HAART. On the other hand, the use of potent and expensive antiretroviral combinations in developing countries is very restricted and is unlikely to slow the AIDS pandemic, leading to a desperate need for a vaccine. Despite 20 years of effort, it is still a long way off, even also considerable progress has been made in understanding this problem.
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PMID:[HIV infection: emerging issues and new challenges]. 1725 36

Highly active antiretroviral therapy (HAART) has greatly reduced the risk of early death from opportunistic infections and extended the lifespan of people infected with the human immunodeficiency virus (HIV). Thus, many complications and organic damage in the HIV-infected population emerge. Cardiovascular disease as coronary artery disease has become a matter of particular concern. Its incidence is greatly increased in the HIV-infected population over that of people of the same age in the absence of general cardiovascular risk factors. Despite several clinical and laboratory studies in the association between HIV infection and cardiovascular disease, the pathogenic mechanisms of this significant clinical problem are largely unknown and are now under active investigation. Endothelial dysfunction is possibly the most plausible link between HIV infection and atherosclerosis. Increased expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and endothelial adhesion molecule (E-selectin) and inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL-6 has been reported in HIV-positive patients. The effect of HAART on endothelial function in HIV-positive patients is also demonstrated. In this review, we focus on the recent research update of HIV-associated vascular disease and vascular injury. We analyze and discuss the recent clinical and laboratory investigations on the effect of HIV, viral protein, and HAART therapy on endothelial injury and vascular disease; identify the areas of controversy and clinical relevance; and suggest some directions for future research.
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PMID:Current update on HIV-associated vascular disease and endothelial dysfunction. 1737 67

Human immunodeficiency virus (HIV) infection affects multiple organs including the cardiovascular system. Postmortem studies have revealed multiple abnormalities including abnormal coronary artery pathology, arteriopathy/endothelial dysfunction, hyperlipidemia and hypercoagulability prior to the use of protease inhibitors. With the introduction of antiretroviral medications, specifically protease inhibitor therapy, patients with HIV have been further noted to have premature coronary artery disease, hypercoagulability, hyperlipidemia, insulin resistance, fat redistribution syndrome and increased tendency to myocardial infarction. In this article, we report on one patient with HIV disease on protease inhibitor therapy that presented with non-Q-wave myocardial infarction and underwent percutaneous coronary intervention, and was later found to have stent thrombosis. A review of the literature showed no other previous reports of stent thrombosis secondary to acquired hypercoagulability due to protease inhibitor therapy. Possible predictors of stent thrombosis and hypercoagulability are also discussed.
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PMID:HIV disease in thrombocardiology. 1747 40

The objective of this study was to evaluate the scientific evidence on flaxseed, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. Electronic searches were conducted in 9 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion/exclusion criteria are used for selection. Grades were assigned using an evidence-based grading rationale. A review of the literature on flaxseed yielded 13 categories for which flaxseed had been studied in humans, including constipation/laxative, attention-deficit hyperactivity disorder, hyperlipidemia, atherosclerosis/coronary artery disease, breast cancer, cyclic mastalgia (breast pain), menopausal symptoms, hyperglycemia/diabetes, hypertension, lupus nephritis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and prostate cancer. Most of the available evidence investigates the efficacy of alpha-linoleic acid found in flaxseed compared with fish oil, and almost all of the available studies are poor quality. Although flaxseed and flaxseed oil have several promising future uses, the available literature does not support recommendation for any condition at this time.
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PMID:Flax and flaxseed oil (Linum usitatissimum): a review by the Natural Standard Research Collaboration. 1776 Nov 28

The impact of hepatitis C virus (HCV) and other comorbid conditions upon survival is not well quantified in patients on dialysis. We identified HCV-infected and uninfected persons in the USRDS using claims data in 1997-1998 and followed until September 22, 2002 or death. We used Gray's time-varying coefficients model to examine factors associated with survival. Subjects with a renal transplant were excluded. A total of 5737 HCV-infected and 11 228 HCV-uninfected persons were identified. HCV-infected subjects were younger (mean age 57.8 vs 65.3 years), more likely to be male (57.6%vs 49.6%) and black (54.0%vs 36.4%). They were more likely to have a diagnosis of drug (16.5%vs 4.6%) and alcohol use (14.0%vs 3.1%), and to be human immunodeficiency virus (HIV) co-infected (7.4%vs 1.8%) (all comparisons, P < 0.0005). In an adjusted Gray's time-varying coefficient model, HCV was associated with an increased risk of mortality (P < 0.0005). The hazards were highest at the time of HCV diagnosis and decreased to a stable level 2 years after diagnosis. Other factors associated with increased risk of mortality were (P < 0.0005 unless stated) HIV coinfection; diagnosis of drug use (P = 0.001); coronary artery disease (P = 0.006); stroke; diabetes as the primary cause for renal failure; peripheral vascular disease; depression and presence of anaemia. HCV was associated with higher risk of death in patients on dialysis, even after adjusting for concurrent comorbidities. The risk was highest at the time of HCV diagnosis and stabilized over time. Clinical trials of HCV screening and treatment to reduce mortality in this population are warranted.
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PMID:Impact of hepatitis C virus infection and other comorbidities on survival in patients on dialysis. 1787 3

Human immunodeficiency virus (HIV) is now a pandemic. It afflicts multiple organs, including the cardiovascular system. This occurs by direct invasion as well as opportunistic infections complicating acquired immunodeficiency syndrome. The presence of newer highly active antiretroviral therapy has led to longer survival of patients infected with HIV, but the cardiac abnormalities related to HIV have remained less well characterized. It is now evident that cardiac involvement in patients with acquired immunodeficiency syndrome is relatively common. This includes coronary artery disease, dilated cardiomyopathy, pericardial effusion, pulmonary hypertension, and ill effects of highly active antiretroviral therapy in the form of lipodystrophy, lipoatrophy, and dyslipidemia. In fact, HIV can now be viewed as a potential risk factor for coronary artery disease, and the dilemma facing clinicians is how to quantify this risk. Awareness of accelerated coronary artery disease and dilated cardiomyopathy is critical to implement preventive measures early in the course of HIV. However, better guidelines are still needed on the basis of prospective randomized controlled studies involving large populations. In conclusion, this review describes cardiac abnormalities associated with HIV, including possible molecular mechanisms. The co-morbid sequelae, their presentation, and pharmacologic management are also discussed.
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PMID:Cardiovascular manifestations in human immunodeficiency virus-infected patients. 1912 56

Patients with human immunodeficiency virus (HIV) who undergo percutaneous coronary intervention have a substantial risk of subsequent cardiovascular events. However, outcome data from HIV-infected patients who receive drug-eluting stents (DESs) are limited. We hypothesized that HIV-infected patients treated with DESs would have fewer recurrent cardiac events compared with those who receive bare metal stents (BMSs). We evaluated 97 HIV-infected patients and 97 non-HIV control patients who had undergone percutaneous coronary intervention between January 2000 and July 2007. Clinical, laboratory, and angiographic data were obtained by chart review. Major adverse cardiovascular events (MACE), defined as clinically driven coronary revascularization, nonfatal myocardial infarction, and cardiovascular death, were adjudicated by 2 independent physicians. The mean age of the HIV cohort was 53 years, and all patients were men. Compared with non-HIV patients, HIV-infected patients were less likely to have hypertension, diabetes mellitus, and previous coronary artery disease and were more likely to have been treated with longer stent length and more stents. During a mean follow-up of 3.1 years, patients who received a DES had a lower rate of MACE compared with those who had received a BMS, regardless of HIV status. After multivariate adjustment for baseline characteristic differences, non-HIV-DES patients had 65% fewer MACE and HIV-DES patients had 60% fewer MACE compared with non-HIV-BMS patients. In conclusion, these data suggest that treatment with DESs in the HIV population is safe and efficacious.
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PMID:Comparison of outcomes using bare metal versus drug-eluting stents in coronary artery disease patients with and without human immunodeficiency virus infection. 1957 50

The inherent complexity of biomedical systems is well recognized; they are multi-scale, multi-science systems, bridging a wide range of temporal and spatial scales. This article reviews the currently emerging field of multi-scale modelling in computational biomedicine. Many exciting multi-scale models exist or are under development. However, an underpinning multi-scale modelling methodology seems to be missing. We propose a direction that complements the classic dynamical systems approach and introduce two distinct case studies, transmission of resistance in human immunodeficiency virus spreading and in-stent restenosis in coronary artery disease.
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PMID:Multi-scale modelling in computational biomedicine. 2002 13


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