UMLS:C0021051 - FACTA Search

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

Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1993, Zimbabwe's blood service revised its notification system to protect the confidentiality of blood donors found to be positive for human immunodeficiency virus (HIV) or another sexually transmitted disease (STD). In the past, such donors were referred back to their physicians, many of whom were unable or unwilling to discuss STDs; other donors had no personal physician. Now, donors who test positive for HIV, syphilis, or gonorrhea are informed by mail they have an unspecified infection and offered follow-up and counseling services from an organization or doctor (who also receive letters) of their choice. However, some nongovernmental organizations to which infected donors are referred report that less than half present for counseling. Common reasons include a reluctance to go to a site perceived as an AIDS center, fears of an HIV diagnosis, concerns about encountering a counselor they know personally, difficulties related to travel or limited clinic hours, and problems with the postal service. Still in need of clarification is Zimbabwe's policy toward young blood donors. Many countries seek out school-age donors because of their presumed lower risk of infection; however, when these young people test positive, ethical dilemmas emerge about parental notification and consent for counseling. Finally, to reduce the misuse of blood donation services for HIV testing, measures are needed to improve the availability of HIV screening.
...
PMID:Testing positive. Counselling blood donors. 1229 30

We have investigated the capacity of two human immunodeficiency virus type 1-derived lentivectors, differing in the presence of a 118-bp pol fragment containing the cPPT/CTS element, to transduce human normal primary cells of different hematopoietic lineages. Infection of resting monocytes with a high multiplicity of infection (MOI > 10) revealed that the lentivirus carrying the pol fragment (cPPT) is effective, transducing 75% of cells compared with 36% for the no-cPPT vector. Even at low MOIs (< or =1) the cPPT vector still shows a better transduction efficiency than the no-cPPT vector. Moreover, transduction does not require dendritic cell differentiation. In contrast, infection of nonactivated T lymphocytes showed that both vectors, tested at high MOIs, can transduce a small, although measurable, percentage of cells (up to 10%), which may correspond to G(1a) "activated" cells as detected by simultaneous staining of DNA and RNA, in our cultures in the presence of medium alone. Furthermore, we show that the sole addition of interleukin 2 or interleukin 15 represents a full proliferative signal under our conditions and permits high transduction efficiency (up to 30% with the cPPT vector and 15% with the no-cPPT vector). Still higher transduction of T lymphocytes can be achieved after stimulation with phytohemagglutinin and interleukin 2 (up to 78% with the cPPT vector vs. 42% with the no-cPPT vector). Finally, both viruses do not transduce either resting or proliferating tonsillar B lymphocytes.
...
PMID:A human immunodeficiency virus type 1 pol gene-derived sequence (cPPT/CTS) increases the efficiency of transduction of human nondividing monocytes and T lymphocytes by lentiviral vectors. 1239 13

Since the onset of the AIDS epidemic, some 20 million people have died and the estimate is that today close to 40 million are living with type 1 human immunodeficiency virus (HIV)/AIDS. About 14 thousands people are infected worldwide daily with this disease. Still, only a few pharmaceuticals are available for AIDS chemotheraphy. Some pharmaceuticals act against the virus before the entrance of the HIV into the host cells. One of these targets is the glucosidase protein. This class of enzymes has been recently explored because the synthesis of viral glycoproteins depends on the activity of enzymes, such as glucosidase and transferase, for the elaboration of the polysaccharides. In this work we study several glucosidase inhibitors. The DFT method is used to compute atomic charges and the ligand/receptor interaction was simulated with docking software. Analysis of the interactions of the proposed pharmaceutical, a pseudodisaccharide, with the Thermotoga maritima 4-alpha-glucanotransferase in complex with modified acarbose, the scores from docking as well as the graphical superposition of all the ligands, suggest that our molecular designed pseudo-disaccharide may be a potent glucosidase inhibitor.
...
PMID:Computer-aided molecular design of novel glucosidase inhibitors for AIDS treatment. 1521 6

Although human immunodeficiency virus type 1 (HIV-1) RNA is the acknowledged "gold standard" marker for monitoring disease activity in patients receiving highly active antiretroviral therapy (HAART), it remains unaffordable in resource-constrained settings. The present study investigated two commercially available kits for the detection of HIV-1 viral load markers as more affordable alternatives to HIV-1 RNA quantitation. The greatly improved heat-denatured, signal-boosted HiSens HIV-1 p24 Ag Ultra kit (Perkin-Elmer) and the ExaVir Load Quantitative HIV-RT kit (Cavidi Tech AB) were compared with the Amplicor HIV-1 Monitor (version 1.5) assay (Roche Molecular Systems Inc.). A total of 117 samples containing HIV-1 subtype C were analyzed by all three methodologies. Eighty-nine of these samples represented serial measurements from 20 patients receiving HAART. The remaining samples analyzed were from a group of treatment-naive patients. The association between the p24 antigen assay and the RNA assay was fairly strong (R(2) = 0.686). The association between the reverse transcriptase (RT) quantitation assay and the RNA assay was strong (R(2) = 0.810). Both alternative assays seemed most useful for the serial monitoring of patients receiving HAART (n = 89 plasma samples from 20 patients), as all assays showed a statistically significant downward trend over time, with the trend being either linear or curvilinear. In addition, all three assays showed negative correlations with the CD4 count (CD4 count versus RNA load, r = -0.336 and P = 0.001; CD4 count versus p24 antigen level, r = -0.541 and P < 0.0001; CD4 count versus RT level, r = -0.358 and P = 0.0006). Still of major concern are both the lack of sensitivity and the wide degrees of variability of both assays. However, both assays provide a less expensive alternative to the Roche viral load assay and demonstrate the same trends during treatment.
...
PMID:Evaluation of two commercially available, inexpensive alternative assays used for assessing viral load in a cohort of human immunodeficiency virus type 1 subtype C-infected patients from South Africa. 1569 92

Autosomal-recessive Schimke immuno-osseous dysplasia (SIOD) characterized by spondyloepiphyseal dysplasia, focal-segmental glomerulosclerosis (FSGS), T-cell immunodeficiency and facial dysmorphism is caused by defects in the SMARCAL1 gene. The gene product is involved in the transcriptional regulation of other genes. A 12-year-old boy of consanginous Turkish descent developed disproportionate short stature from spondyloepiphyseal dysplasia at the age of 6 and nephrotic syndrome at the age of 10 years. Renal biopsy revealed FSGS, the kidney function was normal, T-lymphocytes were diminished without infectious complications, and he has had no cerebral ischemia. Analysis of the patient's SMARCAL1 gene revealed a novel homozygous C1798T transition leading to a R561C substitution. The parents and two healthy sisters were found to be heterozygous. A younger brother, who is also homozygous for the mutation, is clinically asymptomatic and has no proteinuria at the age of 18 months. Still, his CD4 cells are diminished. For SMARCAL1 mutations a clear genotype-phenotype correlation has been reported: severe SIOD with in utero or early-childhood onset leading to end-stage renal disease within a few years is caused by nonsense, frame shift or splice mutations. Many patients die from infections and cerebrovascular insults during childhood. Mild SIOD manifests later and progresses more slowly without infectious or cerebral vascular complications--the underlying defect being missense mutations in all three patients reported so far. The novel R561C missense mutation in our patient with mild SIOD is additional evidence for the genotype-phenotype correlation reported for SMARCAL1 mutations.
...
PMID:R561C missense mutation in the SMARCAL1 gene associated with mild Schimke immuno-osseous dysplasia. 1623 66

For a brief period, modern medical science was considered to have relegated infectious disease to that of a minor clinical challenge. However, several infectious diseases have emerged or re-emerged in recent years, raising epidemiological concerns, as well as issues over the availability of effective measures of control and treatment. Invariably, these infectious agents have been studied carefully in relation to the safety of blood products, often resulting in concern and action. Emerging diseases arise from many sources. Some are the result of viruses crossing the species barrier from animals to humans. In addition, combinations of these newly identified viruses may make each more difficult to treat, as in the case of human immunodeficiency virus and hepatitis C virus coinfection. Still others can arise from completely new biological mechanisms, such as the prion disease variant Creutzfeldt-Jacob disease, which has spread from infected cattle to humans, particularly in the United Kingdom. The emergence of new viruses and new disease sources has had a significant impact on coagulation factor therapies and blood donation policies. We must deal with these multiple threats and their potential to compromise the safety of our blood supply.
...
PMID:Hemophilia therapy and blood-borne pathogen risk. 1680 29

The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 bears the epitopes of two broadly neutralizing antibodies (Abs), 2F5 and 4E10, making it a target for vaccine design. A third Ab, Fab Z13, had previously been mapped to an epitope that overlaps those of 2F5 and 4E10 but only weakly neutralizes a limited set of primary isolates. Here, libraries of Fab Z13 variants displayed on phage were engineered and affinity selected against an MPER peptide and recombinant gp41. A high-affinity variant, designated Z13e1, was isolated and found to be approximately 100-fold improved over the parental Fab not only in binding affinity for the MPER antigens but also in neutralization potency against sensitive HIV-1. Alanine scanning of MPER residues 664 to 680 revealed that N671 and D674 are crucial for peptide recognition as well as for the neutralization of HIV-1 by Z13e1. Ab competition studies and truncation of MPER peptides indicate that Z13e1 binds with high affinity to an epitope between and overlapping with those of 2F5 and 4E10, with the minimal peptide epitope WASLWNWFDITN. Still, Z13e1 remained about an order of magnitude less potent than 4E10 against several isolates of pseudotyped HIV-1. The sum of our molecular analyses with Z13e1 suggests that the segment on the MPER of gp41 between the 2F5 and 4E10 epitopes is exposed on the functional envelope trimer but that access to the specific Z13e1 epitope within this segment is limited. Thus, the ability of MPER-bearing immunogens to elicit potent HIV-1-neutralizing Abs may depend in part on recapitulating the particular constraints that the functional envelope trimer imposes on the segment of the MPER to which Z13e1 binds.
...
PMID:An affinity-enhanced neutralizing antibody against the membrane-proximal external region of human immunodeficiency virus type 1 gp41 recognizes an epitope between those of 2F5 and 4E10. 1728 72

Current vaccine efforts to elicit cross-reactive neutralizing antibodies (NAbs) against human immunodeficiency virus (HIV) focus on the engineering of soluble mimetics of the trimeric HIV Env glycoprotein (commonly termed gp140 immunogens). Such immunogens are thought to be more effective than previously tested monomeric gp120 immunogens at eliciting cross-reactive NAbs. Still, the breadth of neutralizing antibody responses elicited by gp140 immunogens is narrow. Understanding why antibodies elicited by gp140 immunogens fail to neutralize a wide range of heterologous primary HIV isolates is necessary for improving the design of such immunogens. We previously reported that antibodies elicited in macaques by SF162 Env-derived gp140 immunogens fail to neutralize several heterologous "neutralization-resistant" primary HIV type 1 isolates, such as JRFL, ADA, and YU2. Here we show that by replacing the V1 region of Env on these heterologous viruses with that of SF162, we render them highly susceptible to neutralization by the SF162gp140-elicited antibodies. We observed that viral neutralization was mediated not only by vaccine-elicited anti-V1 but also by anti-V3 antibodies and antibodies directed against as yet unidentified Env regions, depending on the heterologous Env background. Our study indicates that common neutralization epitopes are differentially exposed on diverse primary HIV isolates and that the V1 loop contributes to this differential exposure. Therefore, the antibody responses elicited by soluble gp140 immunogens will have to overcome several distinct obstacles in order to neutralize diverse primary HIV isolates.
...
PMID:The first hypervariable region of the gp120 Env glycoprotein defines the neutralizing susceptibility of heterologous human immunodeficiency virus type 1 isolates to neutralizing antibodies elicited by the SF162gp140 immunogen. 1800 32

Human genomic instability syndromes affect the nervous system to different degrees of severity, attesting to the vulnerability of the CNS to perturbations of genomic integrity and the DNA damage response (DDR). Ataxia-telangiectasia (A-T) is a typical genomic instability syndrome whose major characteristic is progressive neuronal degeneration but is also associated with immunodeficiency, cancer predisposition and acute sensitivity to ionizing radiation and radiomimetic chemicals. A-T is caused by loss or inactivation of the ATM protein kinase, which mobilizes the complex, multi-branched cellular response to double strand breaks in the DNA by phosphorylating numerous DDR players. The link between ATM's function in the DDR and the neuronal demise in A-T has been questioned in the past. However, recent studies of the ATM-mediated DDR in neurons suggest that the neurological phenotype in A-T is indeed caused by deficiency in this function, similar to other features of the disease. Still, major issues concerning this phenotype remain open, including the presumed differences between the DDR in post-mitotic neurons and proliferating cells, the nature of the damage that accumulates in the DNA of ATM-deficient neurons under normal life conditions, the mode of death of ATM-deficient neurons, and the lack of a major neuronal phenotype in the mouse model of A-T. A-T remains a prototype disease for the study of the DDR's role in CNS development and maintenance.
...
PMID:The neurological phenotype of ataxia-telangiectasia: solving a persistent puzzle. 1845 74

Human cytomegalovirus (CMV) infection (CMVI) results in lethal risks at the immunodeficiency status, including the HIV co-infection. Carboxy-mimickers of the polymeric backbone of nucleic acids, potential agonists and antagonists of the virus genome were developed as promising candidates for the antiviral protective agents. In parallel with stimulation of antiviral immunity the mimickers derived membrane potent compounds (MPC), were shown to be able to prevent directly and efficiently the cell infection by various strains of the human immunodeficiency virus (HIV) [Antibiotics and Chemother 2003; 48: 2:29-41; 5:7-15]. The paper presents new data and discussion of the results on investigation of the MPC, modified by the previously designed adamantane or norbornene and by the recently applied sulfoacidic pharmacophores in the experimental model of CMVI in vitro (human diploid fibroblast cells). Eight substances with various ratios of theabove mentioned cage-hydrocarbon and/or anion pharmacophores in the macromolecule were tested and active MPC modifications were detected which efficiently inhibited the CMVI with high indexes of selectivity up to 250, 4286 and 7500 in prophylactic, therapeutic and viricidal experimental schemes respectively. Modulating influence of the lipotropic (cage-hydrocarbon) pharmacophores on the anti-CMV activity was observed only in the viricidal and prophylactic experimental schemes, in which the lipid membranes of the cells and/or virus envelopes were involved. Still, the dominant role in the antiviral activity of MPC in all the experimental schemes was played by the sulfoacid-anionic chemical structure modulation. By increasing the density of the negative charge of the macromolecules to the levels comparable with the charge of the genome molecules, theanionic modification evidently amplified the potential of the antagonistic competition of the synthetic MPC with the virus genome, thus impairing the virus-specific interactions. The most promising compounds AS-688 and AS-678/-679 were selected for further investigation of the mechanisms of the anti-CMV and anti-HIV activity.
...
PMID:[Antiviral activity of polycarboxylic substances modified by cage hydrocarbon and sulfoacid pharmacophors against cytomegalovirus infection in vitro]. 1922 17

<< Previous 1 2 3 4 Next >>