Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Recently, encouraging AIDS vaccine trials in macaques have implicated cytotoxic T lymphocytes (CTLs) in the control of the simian human immunodeficiency virus SHIV89.6P that induces acute CD4(+) T cell depletion. However, none of these vaccine regimens have been successful in the containment of replication of the pathogenic simian immunodeficiency viruses (SIVs) that induce chronic disease progression. Indeed, it has remained unclear if vaccine-induced CTL can control SIV replication. Here, we show evidence suggesting that vaccine-induced CTLs control SIVmac239 replication in rhesus macaques. Eight macaques vaccinated with DNA-prime/Gag-expressing Sendai virus vector boost were challenged intravenously with SIVmac239. Five of the vaccinees controlled viral replication and had undetectable plasma viremia after 5 wk of infection. CTLs from all of these five macaques rapidly selected for escape mutations in Gag, indicating that vaccine-induced CTLs successfully contained replication of the challenge virus. Interestingly, analysis of the escape variant selected in three vaccinees that share a major histocompatibility complex class I haplotype revealed that the escape variant virus was at a replicative disadvantage compared with SIVmac239. These findings suggested that the vaccine-induced CTLs had "crippled" the challenge virus. Our results indicate that vaccine induction of highly effective CTLs can result in the containment of replication of a highly pathogenic immunodeficiency virus.
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PMID:Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial. 1521 Jul 46

With the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection has become a chronic disease with more frequent end-stage organ failures. As a result, the question of transplantation in HIV patients is raised more often. However, some of the HAART regimen medications require elimination or metabolism via the P-glycoprotein (P-gp) and multidrug-resistant protein (MRP) transporters or via the cytochrome P450 enzyme system. Since these transporters and enzymes are also responsible for the clearance of immunosuppressive drugs, drug-drug interactions are likely to occur. Indeed, profound drug-drug interactions between protease inhibitors and immunosuppressive drugs have been observed and they required reductions in drug dosage. In contrast, HAART using nucleoside or nonnucleoside reverse transcriptase inhibitors without the use of protease inhibitors has been shown to produce less significant drug-drug interactions. It is thus crucial to take into account those potential pharmacokinetic and/or pharmacodynamic drug-drug interactions in order to avoid drug toxicity or a lack of efficacy. The aim of this work was to review and synthesize the international literature on this field in order to give practical recommendations on how to manage immunosuppressive drugs in HIV patients who get transplanted and on how to handle HAART therapy in transplant-recipient patients who get infected with HIV.
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PMID:Antiretroviral and immunosuppressive drug-drug interactions: an update. 1556 42

Human intravenous immunoglobulins (hIVIgs) are used in two broad categories of diseases: immunodeficiency and autoimmunity. Among the immune-mediated diseases hIVIgs are of benefit in idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and dermatomyositis. Chronic idiopathic pericarditis (CIP) is a chronic disease of unknown origin characterized by recurrent episodes of pericardial inflammation. The cause of the recurrence is unknown, although in some cases it may be traced to a viral infection and to the presence of antimyocardial antibodies. Since a viral infection can induce an autoimmune process through a mechanism of molecular mimicry, and since the optimal therapy for prevention of the recurrences has not been established, we reasoned that treatment with hIVIgs could be beneficial in our patients unresponsive to previous immunosuppressive therapies. We describe four patients affected by CIP treated with monthly high-dose hIVIgs (0.4 g/kg daily for 5 consecutive days) for five times followed by administration every 2 months. Three of the four patients could permanently discontinue steroid therapy and are still in remission after years of follow-up. Our experience suggests that hIVIgs therapy may be a useful and safe treatment for CIP in steroid-dependent patients.
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PMID:Efficacy of intravenous immunoglobulin in chronic idiopathic pericarditis: report of four cases. 1567 54

Serbia and Montenegro is an intermediate TB burden country with 21/100,000 populations sputum smear-positive pulmonary TB incidence rate of 37/100,000 in total. The aim of this article was to explain how the well known rule: "There is as much TB as much we look for it" applies in Serbian settings at the beginning of the 21th century, in the light of Global Partnership to Stop TB: the first target, case detection rate of 70% by 2005. To achieve the target, each physician must be aware that there are persons at higher risk for developing TB and that they must be detected by primary health care facilities or special institutions. Immunodeficiency due to any reason, chronic disease or condition, and especially recent M. tuberculosis infection, make infected persons more liable to develop TB. Apart from TB patients traces contact following the "stone-in-the-pond" principle, with long-term routine in Serbia, it is necessary to perform a screening of symptomatics, in defined risk groups: refugees and internally displaced people in collective 'centers (700,000 or 10% of Serbian population), mentally disabled persons in asylums, Roma (Gypsies) in slams (450,000), prisoners and elderly under protection and care of collective institutions. The screening is based on examination of symptomatics. Radiographs are useful, but bacteriological diagnostic is the golden standard in TB diagnosis. Mass radiography is not recommended due to cost/effect ratio. Cured TB patients might contribute to TB detection rate increase, especially in risk groups. Population education on TB symptoms is in progress.
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PMID:[Active case detection for tuberculosis in risk groups in Serbia]. 1568 27

Costs for preterm and critically ill neonates in a neonatal intensive care unit (NICU) can be astronomical related to the number of inpatient day's accrued and professional ancillary fees. NICU births are often associated with maternal risk factors such as previous preterm or low birth weight delivery, maternal infections, chronic disease states, substance abuse and/or human immunodeficiency virus (HIV) infection. Accordingly, Johns Hopkins HealthCare provides a disease management approach for the prevention of NICU births through "Partners With Mom." This maternity disease management program identifies pregnant women that could potentially generate high-dollar claims. The mission of the program is to reduce hospital/NICU admissions related to pregnancy complications and improve maternal/neonatal outcomes. If an NICU birth does occur, multiple avenues are pursued to control costs. By working in concert with Partners With Mom, the NICU Disease Management Program utilizes a multifaceted approach by tracking maternal risk factors, optimizing levels of required inpatient neonatal care and pursuing other avenues of revenue enhancement.
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PMID:Decreasing NICU Costs in the managed care arena: the positive impact of collaborative high-risk OB and NICU disease management programs. 1593 Oct 48

Clinical practice guidelines for the management of acute sinusitis in children have been published by the American Academy of Pediatrics. Of note is that in this document, a brief discussion of chronic disease concluded that the pathogenesis and management are essentially unknown. Although there are insufficient data in the literature to develop evidence-based clinical guidelines, a careful review of the literature and clinical experience of experts who manage pediatric chronic sinusitis is presented in an effort to develop specific recommendations and to offer practical treatment options. Factors associated with chronic sinusitis should be addressed individually and include recurrent viral upper respiratory infections, allergic and nonallergic rhinitis, ciliary dyskinesia, cystic fibrosis, immunodeficiency, and anatomic abnormalities. Bacteriology includes the 3 pathogens associated with acute disease i.e., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis but with chronic sinusitis also includes Staphylococcus aureus, anaerobic bacteria, and fungi. Medical interventions discussed include endoscopic sinus surgery, saline nasal irrigation, intranasal decongestant therapy, intranasal steroids, and oral antibiotics. Clinical ranking without regard to side effects and cost suggests that endoscopic sinus surgery and antral irrigation have the highest probability of substantial symptom improvement. Other issues discussed include identification and management of gastroesophageal reflux disease (GERD), allergy, and immune deficiency.
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PMID:Chronic sinusitis in children. 1601 92

Clinical tuberculosis (TB), whether noncavitary or cavitary, is the late stage of a chronic disease process, since Mycobacterium tuberculosis is a slowly growing organism. Our studies have shown that the profiles of antigenic proteins expressed by the in vivo bacteria that elicit antibodies differ in cavitary and noncavitary TB. To gain insight into antigenic proteins expressed during incipient, subclinical TB, an expression library of M. tuberculosis genomic DNA was screened with sera obtained during subclinical TB from guinea pigs infected with aerosols of M. tuberculosis H37Rv. One of the proteins recognized by antibodies elicited during subclinical TB infection of guinea pigs is the 309-kDa PPE55 (Rv3347c) protein. Genomic hybridization studies suggest that the PPE55 gene is specific to the M. tuberculosis complex and is present in a majority of clinical isolates tested. Antibodies to the C-terminal, approximately 100-kDa fragment of PPE55 (PPE-C) were detectable in sera from 29/30 (97%) human immunodeficiency virus-negative/TB-positive (HIV(-) TB(+)) patients and 17/24 (71%) HIV(+) TB(+) patients tested but not in sera from purified-protein derivative-positive healthy controls, suggesting that the in vivo expression of PPE55 protein correlates with active M. tuberculosis infection. Anti-PPE-C antibodies were also detected in retrospective sera obtained months prior to manifestation of clinical TB from 17/21 (81%) HIV(+) TB(+) individuals tested, providing evidence that the protein is expressed during incipient, subclinical TB in HIV-infected humans. Thus, PPE55 is a highly immunogenic protein that may be useful for differentiating between latent TB and incipient, subclinical TB.
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PMID:Immunogenicity of the Mycobacterium tuberculosis PPE55 (Rv3347c) protein during incipient and clinical tuberculosis. 1604 Oct 15

The sequence diversity of human immunodeficiency virus type 1 (HIV-1) represents a major obstacle to the development of an effective vaccine, yet the forces impacting the evolution of this pathogen remain unclear. To address this issue we assessed the relationship between genome-wide viral evolution and adaptive CD8+ T-cell responses in four clade B virus-infected patients studied longitudinally for as long as 5 years after acute infection. Of the 98 amino acid mutations identified in nonenvelope antigens, 53% were associated with detectable CD8+ T-cell responses, indicative of positive selective immune pressures. An additional 18% of amino acid mutations represented substitutions toward common clade B consensus sequence residues, nine of which were strongly associated with HLA class I alleles not expressed by the subjects and thus indicative of reversions of transmitted CD8 escape mutations. Thus, nearly two-thirds of all mutations were attributable to CD8+ T-cell selective pressures. A closer examination of CD8 escape mutations in additional persons with chronic disease indicated that not only did immune pressures frequently result in selection of identical amino acid substitutions in mutating epitopes, but mutating residues also correlated with highly polymorphic sites in both clade B and C viruses. These data indicate a dominant role for cellular immune selective pressures in driving both individual and global HIV-1 evolution. The stereotypic nature of acquired mutations provides support for biochemical constraints limiting HIV-1 evolution and for the impact of CD8 escape mutations on viral fitness.
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PMID:Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution. 1622 47

Simian immunodeficiency virus (SIV) is known to result in an asymptomatic infection of its natural African monkey host. However, some SIV strains are capable of inducing AIDS-like symptoms and death upon experimental infection of Asian macaques. To further investigate the virulence of natural SIV isolates from African monkeys, pig-tailed (PT) macaques were inoculated intravenously with either of two recently discovered novel lentiviruses, SIVlhoest and SIVsun. Both viruses were apparently apathogenic in their natural hosts but caused immunodeficiency in PT macaques. Infection was characterized by a progressive loss of CD4(+) lymphocytes in the peripheral blood and lymph nodes, generalized lymphoid depletion, a wasting syndrome, and opportunistic infections, such as Mycobacterium avium or Pneumocystis carinii infections. However, unlike SIVsm/mac infection of macaques, SIVlhoest and SIVsun infections in PT macaques were not accompanied by high viral loads during the chronic disease stage. In addition, no significant correlation between the viral load at set point (12 weeks postinfection) and survival could be found. Five out of eight SIVlhoest-infected and three out of four SIVsun-infected macaques succumbed to AIDS during the first 5 years of infection. Thus, the survival of SIVsun- and SIVlhoest-infected animals was significantly longer than that of SIVagm- or SIVsm-infected macaques. All PT macaques maintained strong SIV antibody responses despite progression to SIV-induced AIDS. The development of immunodeficiency in the face of low viremia suggests that SIVlhoest and SIVsun infections of macaques may model unique aspects of the pathogenesis of human immunodeficiency virus infection in humans.
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PMID:Immunodeficiency in the absence of high viral load in pig-tailed macaques infected with Simian immunodeficiency virus SIVsun or SIVlhoest. 1625 39

This case report describes an atypical case of duodenal leishmaniasis in an elderly patient not infected with human immunodeficiency virus. Investigation of this 84 year old woman with a constitutional syndrome and dysphagia revealed anaemia of chronic disorder, a high erythrocyte sedimentation rate, and polyclonal hypergammaglobulinaemia. Abdominal ultrasonography revealed thickening of the stomach wall, which was seen to be inflamed during gastroscopy. Duodenal histology revealed numerous leishmania amastigotes within macrophages. This was confirmed by bone marrow biopsy and leishmania serology. This case report stresses the importance of atypical symptoms and the unusual location of visceral leishmaniasis, not only in immunodepressed patients, but also in elderly immunocompetent patients.
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PMID:Unusual duodenal presentation of leishmaniasis. 1631 55


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