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)

The rare human genetic disorder ataxia-telangiectasia (A-T) has multiple consequences including a variable degree of immunodeficiency. Khanna and co-workers (Khanna, K. K., Yan, J., Watters, D., Hobson, K., Beamish, H., Spring, K., Shiloh, Y., Gatti, R. A., and Lavin, M. F. (1997) J. Biol. Chem. 272, 9489-9495) evaluated signaling in Epstein-Barr virus (EBV) immortalized A-T lymphoblastoid cell lines (LCLs), derived from the B cells of A-T patients. They showed that A-T lymphoblastoid cells lack signaling through the B cell antigen receptor and concluded that the fault in A-T encompasses intracellular signaling in B cells. However, it is established that EBV latent membrane protein 2A (LMP2A) blocks signaling in EBV-bearing cells by interaction with cellular tyrosine kinases. To test whether the reported fault in A-T B cells was not inherent in A-T but the result of influence of wild-type EBV, we derived A-T LCLs with wild-type or LMP2A-deleted EBV and studied signaling in these cells in response to cross-linking the B cell antigen receptor. We report that intracellular calcium mobilization and tyrosine phosphorylation in LMP2A-depleted LCLs derived from A-T patients is indistinguishable from that in LMP2A-depleted LCLs derived from normal controls. Further, signaling is blocked similarly in A-T and normal lymphoblastoid cells bearing wild-type EBV. In conclusion there is no evidence of any defect in B cell receptor signal transduction in A-T B cells.
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PMID:Signal transduction through the B cell antigen receptor is normal in ataxia-telangiectasia B lymphocytes. 1173 29

The authors describe two children with Kikuchi necrotizing lymphadenitis, the main manifestations of which were cervical lymphadenopathy, fatigue, and fever. The diagnosis was based on histopathologic findings after open biopsy. Results of serologic studies, immunoperoxidase staining for Epstein-Barr virus (EBV) latent membrane protein, in situ hybridization for Epstein-Barr encoded RNAs, and polymerase chain reaction amplification of EBV Epstein-Barr nuclear antigen-1 (EBNA) DNA suggested that EBV was the causative agent in both patients. The disease was mild and subsided after complete surgical resection in one patient, with a follow-up of 1 year. In the other patient, a short course of corticosteroids led to complete clinical remission within 2 months, but the child still has biologic signs of persistent EBV infection. He experienced relapse with a large cervical mass and fever 28 months after the initial onset. Histologic findings were identical to those at initial presentation. Symptoms again resolved spontaneously within 2 weeks, but the follow-up was short (12 mos) and the child's EBNA antibodies are still absent. No evidence of immunodeficiency was found in either child. The cause of Kikuchi disease is unknown, but a viral or postviral hyperimmune reaction has been proposed. Malignant lymphoma and systemic lupus erythematosus are differential diagnoses. Early recognition of Kikuchi disease minimizes potentially harmful and unnecessary investigations and treatments. These findings add Kikuchi disease to the protean manifestations of chronic EBV infection.
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PMID:Epstein-Barr virus-associated Kikuchi disease in two children. 1184 3

Infection of chicken embryo fibroblasts by avian reovirus induces an increase in the permeability of the host plasma membrane at late, but not early, infection times. The absence of permeability changes at early infection times, as well as the dependence of late membrane modification on both viral protein synthesis and an active exocytic route, suggest that a virus-encoded membrane protein is required for avian reovirus to permeabilize cells. Further studies revealed that expression of nonstructural p10 protein in bacterial cells arrested cell growth and enhanced membrane permeability. Membrane leakiness was also observed following transient expression of p10 in BSC-40 monkey cells. Both its permeabilizing effect and the fact that p10 shares several structural and physical characteristics with other membrane-active viral proteins indicate that p10 is an avian reovirus viroporin. Furthermore, the fusogenic extracellular NH(2)-terminal domain of p10 appears to be dispensable for permeabilizing activity, because its deletion entirely abolished the fusogenic activity of p10, without affecting its ability to associate with cell membranes and to enhance membrane permeability. Similar properties have reported previously for immunodeficiency virus type I transmembrane glycoprotein gp41. Thus, like gp41, p10 appears to be a multifunctional protein that plays key roles in virus-host interaction.
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PMID:Modification of late membrane permeability in avian reovirus-infected cells: viroporin activity of the S1-encoded nonstructural p10 protein. 1189 56

A 42-year-old man with acquired immunodeficiency syndrome developed a mass of the right parotid gland and multiple hepatic masses. Hematoxylin-eosin-stained sections of the parotid lesion showed a diffuse infiltrate of large mononuclear cells with vesicular nuclei and prominent nucleoli, consistent with a non-Hodgkin lymphoma. Immunohistochemical stains demonstrated expression of the T-cell markers CD3 and UCHL-1, as well as latent membrane protein 1 and T-cell intracellular antigen 1. Flow cytometry showed surface expression of CD2, CD3, CD7 (dim), CD8, and CD56. CD5 was not expressed. Molecular evaluation by polymerase chain reaction demonstrated monoclonal rearrangement of the T-cell receptor gamma gene. Epstein-Barr virus early RNA and human immunodeficiency virus RNA were demonstrated by in situ hybridization. To our knowledge, this is the first reported case of T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus. After 2 separate chemotherapy regimens, the patient achieved clinical remission for 1(1/2) years; he then developed progressive pulmonary lesions and died.
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PMID:Natural killer-like T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus. 1203 70

Part of the genome of the human immunodeficiency virus type 1 (HIV-1) encodes for a short membrane protein Vpu, which has a length of 81 amino acids. It has two functional roles: (i) to downregulate CD4 and (ii) to support particle release. These roles are attributed to two distinct domains of the peptide, the cytoplasmic and transmembrane (TM) domains, respectively. It has been suggested that the enhanced particle release function is linked to the ion channel activity of Vpu, with a slight preference for cations over anions. To allow ion flux across the membrane Vpu would be required to assemble in homooligomers to form functional water-filled pores. In this study molecular dynamics simulations are used to address the role of particular amino acids in 4, 5, and 6 TM helix bundle structures. The helices (Vpu(6-33)) are extended to include hydrophilic residues such as Glu, Tyr, and Arg (EYR motif). Our simulations indicate that this motif destabilizes the bundles at their C-terminal ends. The arginines point into the pore to form a positive charged ring that could act as a putative selectivity filter. The helices of the bundles adopt slightly higher average tilt angles with decreasing number of helices. We also suggest that the helices are kinked. Conductance measurements on a peptide (Vpu(1-32)) reconstituted into lipid membranes show that the peptide forms ion channels with several conductance levels.
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PMID:Bundles consisting of extended transmembrane segments of Vpu from HIV-1: computer simulations and conductance measurements. 1204 68

Previous estimates of rates of synonymous (d(S)) and nonsynonymous (d(N)) substitution among Neisseria meningitidis gene sequences suggested that the surface loops of the variable outer membrane protein PorB were under only weak selection pressure from the host immune response. These findings were consistent with studies indicating that PorB variants were not always protective in immunological and microbiological assays and questioned the suitability of this protein as a vaccine component. PorB, which is expressed at high levels on the surface of the meningococcus, has been implicated in mechanisms of pathogenesis and has also been used as a typing target in epidemiological investigations. In this work, using more precise estimates of selection pressures and recombination rates, we have shown that some residues in the surface loops of PorB are under very strong positive selection, as great as that observed in human immunodeficiency virus-1 surface glycoproteins, whereas amino acids within the loops and the membrane-spanning regions of the protein are under purifying selection, presumably because of structural constraints. Congruence tests showed that recombination occurred at a rate that was not sufficient to erase all phylogenetic similarity and did not greatly bias selection analysis. Homology models of PorB structure indicated that many strongly selected sites encoded residues that were predicted to be exposed to host immune responses, implying that this protein is under strong immune selection and requires further examination as a potential vaccine candidate. These data show that phylogenetic inference can be used to complement immunological and biochemical data in the choice of vaccine candidates.
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PMID:Phylogenetic evidence for frequent positive selection and recombination in the meningococcal surface antigen PorB. 1227 Aug 95

Haemophilus ducreyi is the etiologic agent of chancroid, a sexually transmitted disease that increases the rate of transmission of human immunodeficiency virus. Chancroid ulcerations are difficult to distinguish from those produced by syphilis and herpes. Diagnosis based solely on clinical grounds is inaccurate, and culture is insensitive. Highly sensitive PCR has largely superseded culture as the preferred method of laboratory diagnosis; however, neither culture nor PCR is feasible where chancroid is endemic. We developed a rapid (15-min) diagnostic test based on monoclonal antibodies (MAbs) to the hemoglobin receptor of H. ducreyi, HgbA. This outer membrane protein is conserved in all strains of H. ducreyi tested and is required for the establishment of experimental human infection. MAbs to HgbA were generated and tested for cross-reactivity against a panel of geographically diverse strains. Three MAbs were found to be unique and noncompetitive and bound to all strains of H. ducreyi tested. Using an immunochromatography format, we evaluated the sensitivity and specificity of the test using geographically diverse strains of H. ducreyi, other Haemophilus strains, and other bacteria known to superinfect genital ulcers. All H. ducreyi strains were positive, and all other bacteria were negative, resulting in a specificity of 100%. The minimum number of CFU of H. ducreyi detected was 2 x 10(6) CFU, and the minimum amount of purified HgbA protein detected was 8.5 ng. Although this level of sensitivity may not be sufficient to detect H. ducreyi in all clinical specimens, further work to increase the sensitivity could potentially make this a valuable bedside tool in areas where chancroid is endemic.
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PMID:Development of a rapid immunodiagnostic test for Haemophilus ducreyi. 1235 68

Chemokine receptors are membrane proteins that play an important role in inflammation and the cellular entry of human immunodeficiency virus type I (HIV-1). Understanding the structure-function relationship of chemokine receptor-ligand interactions and developing novel strategies to control these interactions have important implications for therapeutic intervention of human diseases such as HIV-1 infection. This article reviews the work carried out in our laboratory in molecular modeling and site-directed mutagenesis of chemokine receptor-ligand interactions and chemical synthesis of chemokine-derived peptide agonists and antagonists. These studies demonstrate a paradigm for exploring and controlling membrane protein-protein interactions.
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PMID:Structure, function and modulation of chemokine receptors: members of the g-protein-coupled receptor superfamily. 1237 58

A characteristic 30-base pair (bp) deletion (del) in the 3' end of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene, coding for the C-terminal NF-kappa B activation domain, has been identified in various lymphoproliferative disorders and nasopharyngeal carcinomas. In the single report to date of human immunodeficiency virus primary brain lymphomas (HIV-PBLs), del-LMP1 was noted in seven cases out of nine. The present study was designed to identify this deletion in a series of 31 diffuse large B-cell HIV-PBLs, with the aim of determining its possible oncogenic action. The presence of EBV was confirmed by EBER mRNA in situ hybridization. After genomic extraction from frozen tissue, two 20-base oligonucleotide primers flanking the site of the 30-bp deletion were used. DNA sequencing of the polymerase chain reaction (PCR) products confirmed an identical segment spanning 30-bp and 69-bp, frequently associated with mutational hotspots in 19 cases (61%). A role for del-LMP1 in the oncogenic potential of EBV in systemic proliferations is a matter of debate. Its high incidence suggests that the oncogenic mechanism of LMP1 in the brain might differ significantly from that in systemic lymphoid proliferations, and might be enhanced by HIV infection.
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PMID:High frequency of a 30-bp deletion of Epstein-Barr virus latent membrane protein 1 gene in primary HIV non-Hodgkin's brain lymphomas. 1244 63

To determine the prevalence rates and serovar distribution of Chlamydia trachomatis cervical infections in Cuban women, two different groups were selected. Group I consisted of 60 human immunodeficiency virus (HIV-1) seropositive women from different regions of Cuba and group II of 60 randomly selected women HIV seronegative and apparently healthy. C. trachomatis was detected in cervical scrapes by mean of nested polymerase chain reaction (PCR) specific for major out membrane protein. The overall prevalence rate of C. trachomatis in cervical scrapes determined by nested PCR was 10% in group I and the estimated prevalence was 6.6% for group II; 83.3% of HIV seropositive women with C. trachomatis infection reported history of pelvic inflammatory disease followed by cervicitis (50%). The control group C. trachomatis-infected women referred a history of cervicitis in 75% of cases. Other reports in the latter group included infertility and pelvic inflamatory disease in 50%. The present study is the first report of C. trachomatis prevalence in Cuba. It showed that there was not significantly difference in the prevalence rate of C. trachomatis between both groups.
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PMID:Prevalence of Chlamydia trachomatis in human immunodeficiency virus-infected women in Cuba. 1256 68


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