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)

Forty-two Tanzanian patients with genital warts were treated with 0.5% podophyllotoxin solution (Wartec) for 3 days. Thirteen patients (30.9%) were cured and a further 7 patients (16.7%) had more than 50% of lesions cleared at 6 weeks, while 19 patients were resistant to treatment. Three patients had a recurrence of lesions after an initial response. Thirty-three patients were tested for serological evidence of infection with human immunodeficiency virus (HIV) and 15 (45.5%) patients were shown to be HIV-1 antibody positive. The response to treatment was analysed in relation to HIV antibody status. The cure rate was significantly higher in HIV seronegative patients (8/18 = 44.4%) compared to HIV seropositive patients (1/15 = 6.7%) (P = 0.018). We conclude that podophyllotoxin treatment provides a useful non-hospital based treatment for genital warts, but HIV infection appears to contribute to the failure of treatment for genital warts.
Int J STD AIDS
PMID:Response to podophyllotoxin treatment of genital warts in relation to HIV-1 infection among patients in Dar es Salaam, Tanzania. 777 23

Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains in vivo produced cytokines and inflammatory mediators, including a factor that induces IgG2b production of lipopolysaccharide (LPS) preactivated murine B lymphocytes. In order to determine the mechanism by which RA-SF acts on LPS activated mouse B cells, CBA/N mice were used as an experimental model. The X-linked immunodeficiency of these mice is caused by a point mutation in the Bruton's tyrosine kinase (btk) gene. We have earlier shown that RA-SF can reconstitute the CBA/N B cell deficiency in vitro and in vivo, with regard to IgG2b production after LPS stimulation. Since transforming growth factor (TGF)-beta has been suggested to be a switch factor for IgG2b, we aimed at investigating the role of TGF-beta in our experimental system. We found that TGF-beta could not mimic the effect of RA-SF on CBA spleen cells. A small increase of IgG2b secretion was observed with spleen cells from normal CBA mice, whereas Ig secretion of all isotypes was suppressed in CBA/N spleen cells treated with TGF-beta at any concentration. Neutralizing antibodies against TGF-beta suppressed the response of CBA B cells, whereas the response by CBA/N B cells was enhanced by the same antibody preparation. Here we also show that the abnormal B cell responsiveness to TGF-beta, typical of CBA/N, co-segregates with the btk mutation in male (CBA x CBA/N)F2 spleen cells. This was determined by allele specific PCR recognizing the identified base substitutions of the btk gene, typical of the two strains. We propose that RA-SF contains a factor, separate from TGF-beta, that is involved in the differentiation of IgG2b expressing cells.
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PMID:Differential sensitivity to transforming growth factor (TGF)-beta of CBA and of CBA/N B cells demonstrates that the IgG2b inducing factor in synovial fluid from rheumatoid arthritis patients is not identical to TGF-beta. 779 24

Recent epidemiologic, immunologic, and pathophysiologic data suggest that female genital schistosomiasis, a special form of urinary schistosomiasis due to infection with the trematode Schistosoma haematobium, may be a risk factor for human immunodeficiency virus (HIV) in the 44 African countries where these infections coexist. Eggs of the parasite are found in the organs of the female genital tract (vagina, vulva, and cervix), as well as in urine. Epidemiologists have estimated that 90 million Africans are infected with S. haematobium and that 35-100% of so infected women of childbearing age suffer intermittently from genital lesions caused by eggs sequestered within the epithelium. Lesions associated with this disease tend to be multiple and bleed easily, spontaneously or on contact. Women heavily infected with S. haematobium or S. mansoni show a decrease in the number of circulating CD4+ T cells and NK cells; moreover, a cross-reactivity between HIV-1 virion infectivity factor and a surface antigen to S mansoni has been shown. The eroded, friable epithelium of women with genital schistosomiasis provides HIV with access to deeper cell layers; moreover, the abundance of CD4+ cells and macrophages within the confines of the granuloma makes rapid binding of HIV more likely than is the case with other sexually transmitted diseases. The greatest increase in HIV prevalence in the past decade has occurred in Uganda, Kenya, Malawi, and the Central African Republic--countries with S. haematobium rates of about 70%. In addition, the HIV prevalence rate in areas highly endemic for this parasite is 1.2-1.7 times greater in women than men. Needed, to confirm this association, are correlation studies of increases in HIV prevalence over time in women 15-30 years of age and rates of genital schistosomiasis.
Int J STD AIDS
PMID:Female genital schistosomiasis as a risk-factor for the transmission of HIV. 781 59

Government and media education has promoted the use of condoms in an attempt to reduce the spread of the human immunodeficiency virus (HIV). Condoms have been identified, in vitro, as an effective barrier to HIV and a large heterosexual study has shown there was no transmission of infection in those couples systematically using condoms. Safer sex knowledge and practice and HIV knowledge were assessed in 584 individuals, 16-74 years old, attending a London genitourinary medicine (GUM) clinic via a self-administered, anonymous questionnaire. Over 80% were heterosexual, 64% had attended a GUM clinic before, 60% had a history of sexually transmitted infection. Over 80% were aware of the protective effect of condoms and the risks of intravenous drug use; 66% of geographical risk factors; 49% of the risks of anal sex; and 53% perceived masturbation as safer. Only 10.4% always used condoms; over 50% gave no reason for non-use. Use was not increased in higher risk respondents nor in those with good safer sex/HIV knowledge, nor was there any sex difference. Although knowledge of some aspects of safer sex was good, anal sex risks, geographical sex risks, and alternative safer sexual practices were less well known. In addition, condom use was disappointingly low, even in the presence of good safer sex knowledge, awareness of high risk behavior and despite intense media health education. As a result of this survey educational input was increased, allowing an interaction which is lacking in media campaigns, and a variety of condoms were introduced in an attempt to increase use. Re-audit will be important in assessing the effects of such changes. Pre-adolescent targeting before sexual patterns are learned may be useful. Further research into this difficult area is essential.
Int J STD AIDS
PMID:Audit of patients' knowledge of their oral contraceptive pill. 781 61

The protein-tyrosine kinase gene Itk is expressed preferentially in T lymphoid cells of the mouse and is induced by IL-2. A related gene, Btk, is expressed in the murine B lymphoid and myeloid lineages. Because mutations in Btk and the corresponding human gene are associated with X-linked immunodeficiency syndromes, it was of interest to map Itk and its human counterpart. By Southern blot analysis of DNA from the progeny of two multilocus crosses, murine Itk was mapped to Chromosome 11. By fluorescence in situ hybridization, human ITK was mapped to 5q32-q33. Murine Itk and its human homologue lie within regions of conserved synteny that include several growth factor and growth factor receptor genes. This region in humans is frequently deleted in the myelodysplastic syndrome, suggesting possible involvement of ITK in this disorder.
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PMID:Mapping of the gene for the tyrosine kinase Itk to a region of conserved synteny between mouse chromosome 11 and human chromosome 5q. 782 87

The defective gene responsible for the recessively inherited immunodeficiency X-linked agammaglobulinemia (XLA) has been shown to encode a cytoplasmic protein tyrosine kinase of the Src family designated Btk (Bruton's tyrosine kinase). To facilitate the search for germline mutations of the Btk gene, we have characterized its genomic structure. Eighteen introns were positioned within the approximately 37 kb gene. Each of the exon/intron boundaries were defined and sequenced, and all but two conform to consensus sequences. We have utilized the genomic organization of Btk and the intervening sequence data to design an assay for amplifying each of the 19 exons from XLA patient DNA for single strand conformation polymorphism (SSCP) analysis. By using this method we have identified mutations in 12 of 14 unrelated affected males: seven different base substitutions and two small deletions. Two of the mutations described in exon 15 of the kinase domain were found in more than one patient and may represent a mutation hot spot. Exon scanning has proven to be a valuable method for identifying the patient mutations in genomic DNA without the use of cDNA. The mutations are easily confirmed with direct sequencing of the amplified exons. This approach will greatly benefit XLA family studies involving carrier detection and prenatal diagnosis. In addition, the mutations identified may reveal residues involved in the specific protein interactions necessary in the B-cell developmental pathway, of which Btk is an integral component.
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PMID:Genomic organization of the Btk gene and exon scanning for mutations in patients with X-linked agammaglobulinemia. 788 Mar 20

Since 1981 the number of persons infected with HIV has increased steadily. There are an estimated 13 million HIV infected persons worldwide, with 5000 additional persons becoming infected with HIV each day. The global spread of AIDS has not been stopped. Even though there have been marked reductions in high-risk practices among older homosexual and bisexual men in developed countries, HIV transmission continues among young homosexual and bisexual men and intravenous (IV) drug users. HIV transmission among women and heterosexual men, especially Blacks and Hispanics, is increasing at a faster rate than other groups. In developing countries, heterosexually transmitted HIV infections are the norm. 66% of all HIV infected persons are from sub-Saharan Africa. Presence of other sexually transmitted diseases, particularly genital ulcers, facilitates HIV transmission and accounts for most cases in developing countries. 24% of US urban young heterosexuals have more than 1 sexual partner and 40% of them never use condoms with primary or secondary partners. Exchange of sex for money or drugs (e.g., cocaine) fuels the heterosexual transmission of HIV. At this time of crisis, priorities and control efforts must be reevaluated. The focus should be shifted from AIDS (the most severe stage of immunodeficiency) to HIV infection. This will allow the reinforcement of the public message that prevention of HIV infection prevents AIDS. The highest global priority should be on prevention of sexual transmission of HIV and STDs. Thus, better strategies for STD treatment need to be developed, and women need to be empowered to exert more control over barrier methods and other risk-reduction strategies. Other guiding principles must be HIV prevention among drug users; prevention programs which are planned, evaluated, and revised based on surveillance data and other studies; and comprehensive and forceful global leadership to convey, at least, a sense of urgency about the spread of HIV.
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PMID:Preventing HIV: have we lost our way? 791 Mar 19

In order to better understand the genomic diversity and molecular phylogeny of the human retroviruses, the plasmas from 250 Zairean patients collected in 1969 were tested for antibodies to human T-cell lymphoma and human immunodeficiency viruses (HTLV or HIV) using ELISA and confirmatory Western blots and for viral nucleic acids by reverse transcriptase-directed PCR (RT-PCR). Interestingly, none of the patients was confirmed positive for HIV, even though this region is now endemic for HIV-1. However, 74 (30%) and 3 (1%) of the samples were positive for antibodies to HTLV-I and II, respectively. Forty-four of 74 (59%) Western blot-positive Zairean samples were RT-PCR positive for HTLV-I, while 1 of 3 (33%) of HTLV-II-seropositive samples was RT-PCR positive. On the contrary, none of the Western blot-negative or indeterminate samples were RT-PCR positive for either HTLV-I or HTLV-II. We have cloned and sequenced 140 bp of the pol gene flanked by SK110/SK111 from 8 HTLV-I- and 1 HTLV-II-positive archival samples from Zaire. The HTLV-I isolates from Zaire cluster together as a phylogenetic group, diverging from the prototype Japanese HTLV-I (ATK) by a range of 1.4 to 3.6%. Their close homology to some African STLV-I isolates suggests relatively recent interspecies transmission. The Zairean HTLV-II isolate is closely grouped with the HTLV-II substrain of isolates found in Paleo-Amerindians of the New World, making it unlikely that it represents an endemic African strain.
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PMID:Serological and nucleic acid analyses for HIV and HTLV infection on archival human plasma samples from Zaire. 791 21

Splenectomy has been reported to alter inconsistently the CD4 lymphocyte numbers in patients infected with the human immunodeficiency virus (HIV). To further assess the effect of splenectomy we have retrospectively examined the charts of 10 patients who were infected with HIV and who had undergone splenectomy. There was a significant increase in the mean CD4 numbers following splenectomy (mean increase of 326/microliters, or 2.1-fold, P = 0.0009), the total lymphocyte numbers (mean increase of 1.55/ml, or 2.2-fold, P = 0.001) and in the CD8 lymphocyte count (mean increase of 968/microliters, or 2.3-fold, P = 0.014). No significant difference was observed in the percentage CD4 lymphocytes (P = 0.95) or in the CD4:CD8 lymphocyte ratio (P = 0.76). In two patients, symptoms suggestive of impaired immune function developed post-splenectomy, at a time when their CD4 lymphocyte numbers were markedly higher than their pre-splenectomy values. One developed oral candidiasis (CD4 960/microliters, percentage CD4 32%), and in one patient a 7 kg weight loss was associated with recurrent mouth ulcers (CD4 680/microliters, percentage CD4 7%). We conclude that the total CD4 count increases significantly after splenectomy while the percentage CD4 lymphocyte count and CD4:CD8 lymphocyte ratio do not. Our data suggest that the CD4 lymphocyte count overestimates the immune function in these patients, although our findings are not conclusive.
Int J STD AIDS
PMID:CD4 lymphocyte numbers after splenectomy in patients infected with the human immunodeficiency virus. 791 47

X-linked agammaglobulinemia (XLA) is an inherited human immunodeficiency disease, characterized by an arrest in B-cell development, which results in a dramatic decrease in immunoglobulin production. The gene product defective in XLA has been identified as a cytoplasmic protein tyrosine kinase, named Bruton's tyrosine kinase (Btk). The dramatic XLA phenotype indicates a critical role for Btk in the regulation of B-cell development. However, neither external stimuli leading to Btk activation nor any of its in vivo substrates have thus far been identified, and the mechanism of disease induction remains unexplained. We report here that stimulation of the B-cell antigen receptor (membrane immunoglobulin) on mature B-cells induces tyrosine phosphorylation of Btk in vivo, accompanied by an increase in its kinase activity in vitro. These results place Btk in the B-cell receptor signal transduction pathway, which is known to be essential in driving B-cell differentiation.
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PMID:B-cell antigen receptor stimulation activates the human Bruton's tyrosine kinase, which is deficient in X-linked agammaglobulinemia. 792 28


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