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

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heterosexual transmission of human immunodeficiency virus (HIV) in New York City is principally a phenomenon of the urban inner city, where a large number of infected current or former drug addicts live in close social and sexual contact with inner-city women. These women are at high risk for sexual acquisition of HIV. Evidence of heterosexual transmission is already apparent in the high levels of infection in STD (sexually transmitted disease) clinics and has been noted in a New York State Department of Health study showing that 1 of every 61 women who gave birth in New York City was infected. This problem will increase and will be associated with the derivative problems of pediatric acquired immunodeficiency syndrome (AIDS). Intense targeted counseling, education, and voluntary testing of inner-city populations, combined with additional drug treatment resources, are essential if the rate of heterosexual transmission is to be decreased.
...
PMID:Heterosexual HIV transmission. 252 May 42

Sera from 260 men from Denmark and elsewhere attending two Copenhagen sauna clubs for homosexual men during nine months of 1982-1983 were investigated for markers for syphilis, hepatitis A and B, and human immunodeficiency virus (HIV). Five per cent (12 men) had active syphilis, and another 35% (92) had a history of and/or serologic markers for syphilis. Ninety-four men (36%) were positive for antibodies to hepatitis A virus, ten (4%) were positive for hepatitis B surface antigen (HBsAg), and 153 (59%) were positive for antibodies to HBsAg. Antibodies to HIV were found in 45 (20%) of the 220 men investigated for this marker. Markers for hepatitis A and B and for syphilis were more frequent in the HIV antibody-positive individuals, but the association was significant only for markers for hepatitis B (relative risk = 2.0). Thus STD markers had little predictive value for seropositivity for antibodies to HIV. Among 37 men investigated more than once, a seroconversion rate of 3% per month for antibodies to HIV was found, but this estimate must be taken with reservation. The rate of seropositivity for antibodies to HIV among men from Denmark was 23%, and three (8%) of the 40 HIV-positive Danish men developed the acquired immunodeficiency syndrome (AIDS) during the four years following the initial investigation. This study shows that by 1982-1983 HIV had spread considerably in the Danish high-risk group, although there were only seven reported cases of AIDS in the country at that time.
...
PMID:Sexually transmitted diseases, antibodies to human immunodeficiency virus, and subsequent development of acquired immunodeficiency syndrome. Visitors of homosexual sauna clubs in Copenhagen: 1982-1983. 335 36

Bruton's tyrosine kinase (BTK) is a nonreceptor tyrosine kinase critical for B cell development and function. Mutations in BTK result in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Using a random mutagenesis scheme, we isolated a gain-of-function mutant called BTK* whose expression drives growth of NIH 3T3 cells in soft agar. BTK* results from a single point mutation in the pleckstrin homology (PH) domain, where a Glu is replaced by Lys at residue 41. BTK* shows an increase in phosphorylation on tyrosine residues and an increase in membrane targeting. Transforming activity requires kinase activity, a putative autophosphorylation site, and a functional PH domain. Mutation of the SH2 or SH3 domains did not affect the activity of BTK*. Expression of BTK* could also relieve IL-5 dependence of a B lineage cell line. These results show that transformation activation and regulation of BTK are critically dependent on the PH domain.
...
PMID:Activation of Bruton's tyrosine kinase (BTK) by a point mutation in its pleckstrin homology (PH) domain. 753 39

Risk factors for postcoital bleeding were examined in 475 women who were enrolled in a study of heterosexual transmission of human immunodeficiency virus (HIV). In bivariate analyses, history of sexually transmitted diseases (STDs; P = .03), HIV infection (P = .008), and dyspareunia or pain during intercourse (P = .0001) were significant risk factors. In multivariate analysis, the two latter factors remained significant (for HIV, odds ratio [OR] = 2.1, P = .02, 95% confidence interval [CI] = 1.1-4.0; for dyspareunia, OR = 3.5, P < .001, 95% CI = 1.8-6.6), as did the interaction term of STD history and heavy smoking (OR = 2.4, P = .02, 95% CI = 1.2-5.0). Pain during intercourse was the strongest predictor of postcoital bleeding but may be part of the same phenomenon. Similarly, because this study relied on cross-sectional data, the direction of the causal pathway linking HIV to postcoital bleeding cannot be established. However, these data suggest that smoking, a modifiable risk factor, may increase risk of postcoital bleeding and contribute to susceptibility for HIV and other STDs.
...
PMID:Risk factors for postcoital bleeding among women with or at risk for infection with human immunodeficiency virus. 864 35

Bruton's tyrosine kinase (Btk) has been identified as the protein responsible for the primary immunodeficiency X-linked agammaglobulinemia (XLA) and has been described as a new member of Src-related cytoplasmic protein tyrosine kinases. We have recently characterized the structure of the entire gene encoding Btk and developed a polymerase chain reaction (PCR)-based assay to detect germline mutations within it. In this report we describe six mutations, five of which are novel, of the Btk gene in patients with XLA and demonstrate the inheritance pattern of the defect within the families of the affected individuals. The mutations found include two nonsense and two missense mutations, a single base deletion at an intron acceptor splice site, and a 16-bp insertion. A single strand conformation polymorphism was also found in the 5' end of intron 8 with the same assay. This technique has provided a powerful tool for direct analysis of the Btk gene for the diagnosis of XLA and carrier detection. The identification of new mutations may eventually reveal the role of Btk in the signaling pathways involved in B-cell development.
...
PMID:Characterization of germline mutations of the gene encoding Bruton's tyrosine kinase in families with X-linked agammaglobulinemia. 762 83

X-linked agammaglobulinemia, a B cell immunodeficiency, is caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The absence of a functional Btk protein leads to a failure of B cell differentiation and antibody production. B cell receptor stimulation leads to the phosphorylation of the Btk protein and it is, therefore, likely that Btk is involved in B cell receptor signaling. As a nonreceptor tyrosine kinase, Btk is likely to interact with several proteins within the context of a signal transduction pathway. To understand such interactions, we have generated glutathione S-transferase fusion proteins corresponding to different domains of the human Btk protein. We have identified a 120-kD protein present in human B cells as being bound by the SH3 domain of Btk and which, after B cell receptor stimulation, is one of the major substrates of tyrosine phosphorylation. We have shown that this 120-kD protein is the protein product of c-cbl, a protooncogene, which is known to be phosphorylated in response to T cell receptor stimulation and to interact with several other tyrosine kinases. Association of the SH3 domain of Btk with p120cbl provides evidence for an analogous role for p120cbl in B cell signaling pathways. The p120cbl protein is the first identified ligand of the Btk SH3 domain.
...
PMID:The protein product of the c-cbl protooncogene is phosphorylated after B cell receptor stimulation and binds the SH3 domain of Bruton's tyrosine kinase. 762 18

X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency resulting from mutations in the gene for a cytoplasmic protein tyrosine kinase (Btk). We have utilised reverse-transcription-based PCR in combination with the chemical cleavage and mismatch technique (CCM) to screen for Btk mutations in 42 unrelated patients having classical XLA or 'leaky' XLA-like phenotypes. A variety of mutations, including point mutations, large deletions and splicing defects were detected using this strategy. In total, 20 mutations were found in these patients. All the mutations were different with the exception of three unrelated patients who all showed the same Arg-->His amino acid substitution (R641H) at a highly-conserved residue in the kinase domain. We have also used structural modelling of the Btk kinase domain to predict how two different amino acid substitution mutations at highly-conserved residues are likely to affect the Btk kinase activity.
...
PMID:Identification of Btk mutations in 20 unrelated patients with X-linked agammaglobulinaemia (XLA). 763 20

To investigate the role of B cells in the development of experimental Staphylococcus aureus-induced arthritis, we used X-linked immunodeficiency (xid) mice that carry a Bruton's tyrosine kinase mutation affecting the function of B cells. NFR/N.xid and congenic NFR/N mice were inoculated i.v. with a toxic syndrome toxin-1 producing S. aureus LS-1 strain. B cell-deficient NFR/N.xid mice developed less frequent (p < 0.01) and less severe (p < 0.01) arthritis than NFR/N mice did. These clinical findings were corroborated by histopathologic evaluation, indicating that NFR/N.xid mice had significantly lower (p < 0.01) erosivity of the disease. Interestingly, infected NFR/N.xid mice showed decreased bacterial burden in blood, joints, and other organs compared with the control mice. Serologic studies displayed poor B cell responses to staphylococcal cell walls, toxic shock syndrome toxin-1, and ssDNA, accompanied by a low level of Igs in infected NFR/N.xid mice. More importantly, xid defect affected cytokine profile. The in vitro experiments showed that the lymphocytes from NFR/N.xid mice had low IL-6, but high IFN-gamma production upon stimulation with staphylococcal cell walls compared with NFR/N mice. Furthermore, the in situ hybridization technique revealed the relative increase of IFN-gamma, but marked decrease of IL-1 beta mRNA expression in spleens of infected NFR/N.xid mice. No significant difference in IL-4, IL-10, and TNF-alpha mRNA expression was found between both strains. Our findings demonstrate that B cells may, directly or indirectly, contribute to the pathogenesis of septic arthritis. The results indicate that increased IFN-gamma production along with low IL-6 and IL-1 beta synthesis found in xid mice may provide a more favorable outcome of S. aureus arthritis.
...
PMID:Mice with the xid B cell defect are less susceptible to developing Staphylococcus aureus-induced arthritis. 763 57

The small intestine is a common site of involvement in patients infected with the human immunodeficiency virus (HIV). Although there are numerous mechanisms by which small intestinal disease may occur in HIV infected patients, the resulting clinical manifestations of these disorders are remarkably similar and include the development of diarrhoea, weight loss and nutrient deficiencies. In fact, the original designation of AIDS in African countries as the 'slim disease' underlines the importance of small intestinal involvement (most likely secondary to parasitic infections) which commonly occurs in Third World Countries. The current review will provide a clinically oriented overview of small intestinal disease in patients infected with HIV. Because specific data on treatment of small intestinal diseases in AIDS is often lacking, some presented information is based on the author's experience and opinions.
Int J STD AIDS
PMID:Small intestinal manifestations of HIV infection. 764 15

X-linked agammaglobulinemia is a primary inherited immunodeficiency resulting in a lack of or dramatic reduction in the number of mature B lymphocytes and, thus, greatly reduced levels of serum immunoglobulin. The defect results from mutations in the gene for Bruton's tyrosine kinase (Btk). Using rabbit antisera generated against Btk, we have demonstrated an increase in the level of in vitro kinase activity present in anti-Btk immunoprecipitates from B cells following stimulation with anti-immunoglobulin antibody. This increase in immune complex kinase activity is detectable 1 to 2 min following stimulation and remains elevated for over 30 min. A similar increase was not seen with two late pre-B cell lines investigated in the same way. This stimulation of activity may suggest a role for Btk in signalling through the B cell receptor or associated proteins, in mature B cells.
...
PMID:The protein defective in X-linked agammaglobulinemia, Bruton's tyrosine kinase, shows increased autophosphorylation activity in vitro when isolated from cells in which the B cell receptor has been cross-linked. 773 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---