Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human papillomavirus infection represents the most common mucocutaneous viral infection, and 3% to 5% of all patients have clinically evident warts. Human papillomavirus infections of the genital tract are one of the most common sexually transmitted viral infections in the United States. Data from STD clinics and private physicians' offices reveal that genital warts, one manifestation of genital HPV infection, have been diagnosed more frequently in recent years. With the use of a variety of diagnostic techniques, asymptomatic HPV infection has been identified in men and women and is probably much more common than is clinically apparent infection.
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PMID:Epidemiology of human papillomavirus infections. 164 1

The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.
Int J STD AIDS 1990 Sep
PMID:Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine. 196 87

Antibodies against thymus epithelial cells (anti-TEC) and the basal cell layer (BCLA) of squamous epithelia have been described in association with HDV-related chronic liver disease (CLD). Data are lacking on their presence during nAnB virus infection. Sera from 51 patients with nAnB post-transfusion hepatitis, including acute and chronic cases diagnosed during a prospective study on candidates for cardiac surgery, and 167 with various forms of CLD were tested for the presence of anti-TEC and BCLA using indirect immunofluorescence on human thymus and rat forestomach sections. Both antibodies mainly occurred in nAnB, HDV and cryptogenic CLD (anti-TEC: 51%, 47% and 42%; BCLA: 29%, 38% and 31%, respectively). The prevalence of anti-TEC in nAnB CLD turned out to be higher than that recorded in alcoholic, HBV-related, autoimmune, liver and kidney microsomal antibody positive CLD and primary biliary cirrhosis (p ranging from less than 0.03 to less than 0.0004). Two monoclonal antibodies (Mabs) to cytokeratins gave a pattern superimposable on that of spontaneous anti-TEC (both Mabs) and BCLA (only one). Antibodies against epithelial constituents, presumably targeting cytokeratin-associated antigens, occur not only in HDV CLD, as previously reported, but also in nAnB CLD, where they might represent a diagnostic aid, due to the unavailability of reliable serological markers of nAnB infection. The close similarity of anti-TEC and BCLA status between nAnB and cryptogenic CLD suggests a nAnB etiology of at least a proportion of chronic liver patients at present scored as cryptogenic.
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PMID:Serum antibodies to thymus epithelial cells in non-A, non-B and cryptogenic chronic liver disease. 247 4

Immunologists working in the field of autoimmunity tend to concentrate all their efforts on the elucidation of possible malfunctions of the immune system, particularly pathologic changes of immune regulation. Also in the OS model various groups of investigators emphasized this approach, although it was already clear early in the history of this model that SAT has a multigenic background. The fact that this disease cannot be transferred into normal, histocompatible animals without an appropriate non-MHC linked genetic background was a strong indication that detailed studies of thyroid-associated factors may be warranted for the elucidation of the pathogenesis of this disease and perhaps also its human counterpart, Hashimoto thyroiditis. Since several reviews on the immunologic aspects in the OS model have been published in recent years we have in this communication attempted to discuss the - mostly still rudimentary - findings concerning the target organ itself, including morphological changes before the beginning of infiltration, the analysis of Tg, the altered thyroid function before onset of SAT, the results of cross-breeding studies of OS and inbred normal chickens in respect to the susceptibility of the offspring for the transfer of SAT, the possible role of a virus infection and the aberrant expression of MHC class II antigens on TEC. Cross-breeding studies revealed that most probably a single gene is responsible for the primary altered thyroid function and at least 3 genes code for the susceptibility of the OS thyroid gland to the autoimmune attack. It is not yet clear for which of the above-mentioned observations each of these genes is responsible and what is/are the initial triggering mechanism(s). Ongoing studies in our laboratory concentrate on this question, specifically the potential role of endogenous viruses in this process.
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PMID:The role of genetically-determined primary alterations of the target organ in the development of spontaneous autoimmune thyroiditis in obese strain (OS) chickens. 346 60

Sixty-five medical personnel thought to be exposed to hepatitis-B-surface antigen (HBs) positive material by accidental needle stick were treated with 4 ml hepatitis B-immunoglobulin (SRK, Swiss Red Cross). The prophylaxis was started as soon as possible, mostly within an hour or two. 56 patients were followed up with clinical and serological tests at monthly intervals for 9 months. In individuals exposed to HBs-antigen negative material, signs of HBV-infection could be detected only in one. In 36 cases potentially infectious material proved to be HBs-Ag positive. Six of the medical personnel (16.7%) had signs of hepatitis B-virus infection. One individual (2.8%) developed clinical hepatitis type B. Three (8.3%) converted to active hepatitis B markers (anti-HBs and/or anti-HBc) without clinical symptoms. Two of four who already had anti-HBs before exposure developed antibodies to HBc afresh at three- and six-month intervals. These serological conversions and the one case of clinical hepatitis developed despite the fact that HB-Ig was given in nearly all cases within one hour of exposure. The incubation period was 5-8 months. It is concluded that even rapid prophylaxis with HB-Ig after needle stick exposure does not afford 100% protection. It is urged that any passive prophylaxis with HB-Ig in exposed personnel should be complemented by active hepatitis B immunization.
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PMID:[Can prevention of hepatitis B following exposure to hepatitis virus be improved by immediate administration of HB immune serum?]. 687 37

AIDS is not merely a new viral disease, or an unprecedented variety of acquired immune deficiency. It is an STD equally transmitted by blood and birth, it has for the last eleven years, baffled all the assault attempted by the most competent researchers, it is lethal in the vas majority of cases, it has reached a planetary dimension. Its prevention interferes as well with more than one religion's prescriptions and will undoubtedly interfere with sexual fulfillment. Finally, it reminds us that what we call ethics is fragile, that it is actually based on an agreement and that it can be drastically modified if a majority of citizens are under threat.
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PMID:[AIDS: ethical drift]. 782 91

Monoclonal mouse IgG3 antibody (ABL 364) against the carbohydrate Le(y) antigen enhanced infection in vitro with HTLV-1 and with HIV-1 when propagated in both transformed and normal lymphocytes. Enhancement was independent of complement, occurred with both lymphocytes and monocytes as target cells, and did not use either L(ey) epitopes on target cells for cross-linkage of virus to the cell or the Fc part of the antibody as a ligand for any cellular receptor. For enhancement to occur, binding of anti-Le(y) antibody to virus was required to take place before virus binding to its specific receptor with no indication of any alternative pathway of infection, as evidenced by abrogation of enhancement by anti-CD4 MAb or soluble recombinant CD4, and also the inability of anti-Le(y) MAb to mediate HIV infection of HSB-2 cells in which HTLV-1/HIV pseudovirus infection was enhanced. While F(ab)2 fragments of ABL 364 also enhanced infection, a human/mouse chimeric antibody and a fully humanized antibody had no enhancing effect on free virus infection. We suggest that binding of anti-Le(y) ABL 364 or its F(ab)2 fragment induced a conformational change in the gp120 oligomers facilitating the process of infection, and that this function was abrogated by the IgG1 Fc of the chimeric and the humanized antibodies. The observations indicate that the non-paratope domains of antiviral antibodies can influence their function as neutralizing or enhancing for infection.
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PMID:Enhancement of retroviral infection in vitro by anti-Le(y) IgG: reversal by humanization of monoclonal mouse antibody. 790 6

A study of simian T-cell lymphoma/leukemia virus infection, conducted on 747 nonhuman primates belonging to 14 different species in Central and Western Africa, indicated that 4 species (Cercopithecus aethiops, Erythrocebus patas, Papio doguera, and Cercopithecus mona pogonias) had a high prevalence of seropositivity to simian T-cell lymphoma/leukemia virus type I (STLV-I). The other nonhuman primate species, however, had negative or low levels of anti-HTLV-I antibodies. STLV-I pol and env DNA was detected in 12 of 12 different animals among the seropositive species. However, STLV-I pX DNA could be detected in only 10 of 12 animals. Comparative phylogenetic analyses based on 140 bp sequence of the pol gene indicate that these STLV-I isolates were 0-9% divergent from each other and were 3.5-7% divergent from the prototype related human retrovirus HTLV-I (ATK). The West African STLV-I isolates formed a unique phylogenetic cluster as did most of the Central African STLV-I isolates, save for STLV-I (Tan 90). The phylogenetic data indicate that cross species transmission of HTLV-I and STLV-I continued to occur long after their ancestral strain separated from the progenitor to HTLV-II. Comparative amino acid analyses indicated that there was marked conservation of the TAX protein regardless of host species, while the pol and REX proteins exhibited increasing levels of diversity.
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PMID:Seroepidemiologic, molecular, and phylogenetic analyses of simian T-cell leukemia viruses (STLV-I) from various naturally infected monkey species from central and western Africa. 825 65

We investigated the prevalence of human immunodeficiency viruses-1 and 2 (HIV-1 and HIV-2), human T-lymphotropic virus type I and II, hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus among intravenous drug users (IVDU) in Hiroshima, Japan, where little is known about their present levels. From June to December 1993, serum samples were collected from 47 IVDU and 98 alcoholics in Hiroshima, Japan, and examined for markers of virus infection. The prevalence of antibody to HCV (anti-HCV) and/or HCV-RNA was significantly higher in IVDU than alcoholics (74.5% vs 20.4%, 44.7% vs 10.2% respectively, P < 0.001). In contrast, the prevalence of antibody to hepatitis B surface antigen and/or core antigen (anti-HBs and/or anti-HBc) showed no significant difference between the 2 groups (57.4% vs 66.3%). HIV-1 infection was found in one (2.1%) IVDU and genome analysis indicated that it was subtype B according to Myers' classification. Thus, an extremely low level of HIV infection and a high level of HCV infection was found in IVDU. Careful follow-up of this group is thought to be needed to minimize an outbreak of HIV-1 infection in Japan.
Int J STD AIDS
PMID:Prevalence of blood-borne viruses among intravenous drug users and alcoholics in Hiroshima, Japan. 884 4

X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of B lymphocytes due to an arrest in B lymphocyte development, is caused by mutations in the gene encoding Btk (Bruton tyrosine kinase). The BTK gene has been cloned and the genomic organization determined. BTK codes for 19 exons and is expressed in all hematopoietic cell lineages but is selectively down-regulated in T lymphocytes and plasma cells. The different Btk domains include PH, TH, SH3, SH2, and the kinase (SH1) domains. Btk, a cytoplasmic protein tyrosine kinase, is involved in cell signaling, although the precise pathway remains elusive. Mutation analysis has been performed in 236 families representing 282 patients. Mutations are scattered throughout the gene and consist of missense, nonsense, and splice site mutations as well as deletions and insertions. The major consequence of nonfunctional Btk appears to be a delay or block of the development of pro-B cells to pre-B cells and then to mature lymphocytes. Because IgG is actively transported across the placenta, affected newborns have normal levels of serum IgG at birth followed by gradually decreasing IgG levels and development of hypogammaglobulinemia and increased susceptibility to infections. Bacterial infections are the most common clinical manifestation. Resistance to viral infection is intact, except for an unusual susceptibility to infections with enteroviruses that may result in vaccine-related paralytic poliomyelitis or a dermatomyositis-meningoencephalitis syndrome. The diagnosis of XLA is based on the presence of lymphoid hypoplasia, markedly reduced serum levels of all 3 major classes of immunoglobulins, failure to make antibody to antigenic stimulation, and almost complete absence of B lymphocytes in the peripheral blood. Carrier detection and prenatal diagnosis are possible. The prophylactic infusion of high-dose intravenous immunoglobulin (IVIG) and the use of antibiotics have markedly improved the long-term prognosis of patients with XLA.
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PMID:X-linked agammaglobulinemia. A clinical and molecular analysis. 898 47


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