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

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

To investigate the clinical and serological responses to an inactivated influenza vaccine (split-virion A/Singapore/6/86-like strains H1N1 (15 ug HA), A/Beijing/353/89-like H3N2 (15 ug HA) and B/Yamagata/16/88-like strain (15 ug HA): MFV-JECT, Merieux, UK) in persons with HIV infection, diabetes, obstructive lung diseases, elderly adults and healthy volunteers. Forty-nine HIV-infected persons received 2 doses of the vaccine at one-month intervals; 34 healthy volunteers, 30 elderly persons, 29 with insulin and non-insulin diabetes and 14 with obstructive airways diseases were vaccinated with one single dose between October 1992 to January 1993. Serological testing of antibody responses was done using haemagglutination assay. Beta2-microglobulin in HIV-infected persons was measured using radioimmunodiffusion between 1st and 2nd dose. Fructosamine levels in diabetic persons were assessed for diabetic control and peak expiratory flow rate (PEFR) was self monitored in persons with lung diseases. All groups apart from the elderly filled in a symptom score chart for the first 5 days following vaccination. A 4-fold rise in titre equal to or more than 1:64 to all the 3 antigens occurred in 20 (58.8%) of healthy volunteers compared with 13 (44.8%) diabetics, 5 (35.7%) with lung diseases, 10 (33.3%) elderly and 13 (26.5%) with HIV infection. A significant correlation of serological response to number of CD4 count in persons with HIV infection was noted (H1N1 P=0.0013, H3N2 P=0.025, BYAM P=0.0018). Mean beta2-microglobulin levels did not change significantly post 1st and 2nd vaccination. Mean fructosamine level did not change significantly. There was no significant change in PEFR. The vaccine was well tolerated. Persons with HIV infection and low CD4 count do not serologically respond well to influenza vaccine even with 2 doses compared to the other 4 groups. The other 4 groups had adequate protective serologic responses. The vaccine was well tolerated in all groups.
Int J STD AIDS 1997 Dec
PMID:Clinical and serological responses to an inactivated influenza vaccine in adults with HIV infection, diabetes, obstructive airways disease, elderly adults and healthy volunteers. 943 53

Nine populations (Germans, Turks, Moroccans, Ovambos, Ugandans, Chinese, Japanese, Papuans, and Australian Aborigines) were investigated using six microsatellite systems (HumCD4, Hum F13B, HumFES/FPS, HumTH01, HumVWA, and D21S11), so-called STRs (short tandem repeats). Allele frequency data and sequencing results were used to compare the population genetic diversity among these populations. The genetic differences varied depending on the STR applied. According to the systems investigated, we defined three categories of STR microvariation: LOMs (low microvariation systems), INMs (intermediate microvariation systems), and HIMs (high microvariation systems). LOMs (STRs: CD4, FES, F13B, TH01) are characterised by a number of repeats between 5-15 and a stable repeat sequence. INMs and HIMs each showed an increasing number of repeats and additional sequence variation in the repeat motifs. The rate of new mutations was associated with the extent of microvariation. The reconstruction of phylogenetic trees led to a clustering in an early split of the African populations followed by further branching of the Asian/Melanesian and the Caucasian groups.
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PMID:Population genetic diversity in relation to microsatellite heterogeneity. 948 77

We set out to quantify the changes in HIV-related morbidity and mortality associated with the clinical use of antiretroviral therapy via prospectively collected patient-related events (admissions, bed days, deaths, WHO stage 3 and 4 events and drug costs) on all HIV patients known to the Regional Infectious Disease Unit (RIDU) from 1 January 1987 to 31 December 1996. The introduction of zidovudine monotherapy in 1987 for those with AIDS was associated with a subsequent decline of inpatient activity for 2 years: in 1989 there was a 23% reduction in bed days but only a 6% reduction in admissions. A further dramatic decline of patient-related events in those with AIDS was noted during 1996 following the introduction of combination therapy, a 39% reduction in admissions, 44% reduction in bed days, 54% reduction in stage 4 events, 33% reduction in WHO stage 3 events and 40% reduction in the death rate. Reductions were also observed for patients without AIDS including a 42% reduction in the rate of patients developing AIDS. Similar reductions were noted when the patients were classified by immunological instead of clinical status although data for 1997 suggest an increase in patient-related activity for those with CD4 counts >200 cells/microl possibly as a result of low levels of anti-HIV therapy. The introduction of combination therapy for HIV has to date led to a minimum saving of one inpatient bed per 100 patient years which helped defray the cost of combination therapy. Although we cannot imply causality from an observational study, dramatic reductions in patient-related activity were associated with the introduction of combination therapy into clinical practice. The ultimate extent and duration of this effect cannot as yet be predicted and caution is required since similar reductions were noted with zidovudine therapy which were unfortunately time limited.
Int J STD AIDS 1998 Feb
PMID:Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients. 950 72

We conducted a small exploratory study to assess whether testosterone therapy is an effective treatment for clinical symptoms characteristic of hypogonadism in eugonadal men with AIDS. Treatment consisted of 12 weeks of bi-weekly intramuscular injections of testosterone cypionate. Twenty-three men enrolled in the study; mean age was 37 and 44% were ethnic minorities. All had an AIDS diagnosis and the mean CD4 cell count was 150 cells/mm3. All baseline serum testosterone levels were within the laboratory reference range and above 500 ng/dl. Diminished libido was an inclusion criterion, plus each patient had at least one additional symptom (low mood, low energy, loss of appetite and/or weight). Nineteen men completed the trial and a majority of patients responded with regard to libido (89%), mood (67%), energy (71%), and appetite (67%) as rated by the Clinical Global Impressions Scale. With the exception of appetite, self and clinician rated measures showed significant improvement in all symptom domains. Among the 14 study completers with significant weight loss, the average weight gain was 2.3 kg, with a 1.8 kg increase in body cell mass and no change in body fat. These results suggest that testosterone is as effective in treating these symptoms in eugonadal men with AIDS as we have found in our research with hypogonadal HIV+men.
Int J STD AIDS 1998 Jan
PMID:Testosterone therapy for clinical symptoms of hypogonadism in eugonadal men with AIDS. 951 14

The expression of a transgene coding for a chimeric molecule, containing the cytoplasmic and transmembrane domains of the beta1-integrin chain and the extracellular domain of the T-cell differentiation antigen CD4, was targeted to the mouse mammary gland by the mouse mammary tumor virus (MMTV) promoter. The chimera does not interact with the extracellular ligands; however, its expression in cultured cells was shown to interfere with focal adhesion kinase (FAK) phosphorylation following ligation of endogenous beta1-integrin. Therefore, expression of the transgenic protein on the cell surface should uncouple adhesion from intracellular events associated with the beta1-cytoplasmic domain and thus perturb beta1-integrin functions. Although most of the transgenic females were able to lactate, their mammary glands had a phenotype clearly distinct from that of wild-type mice. At mid-pregnancy and the beginning of lactation, transgenic glands were underdeveloped and the epithelial cell proliferation rates were decreased, while the apoptosis levels were higher than in wild-type glands. In lactation, the amounts of the whey acidic protein (WAP) and beta-casein gene transcripts were diminished, and the basement membrane component, laminin and the beta4-integrin chain accumulated at the lateral surface of luminal epithelial cells, revealing defects in polarization. Our observations prove that in vivo, beta1-integrins are involved in control of proliferation, apoptosis, differentiation and maintenance of baso-apical polarity of mammary epithelial cells, and therefore are essential for normal mammary gland development and function.
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PMID:Perturbation of beta1-integrin function alters the development of murine mammary gland. 954 27

beta2 integrin molecules are involved in a multitude of cellular events, including adhesion, migration, and cellular activation. Here, we studied the influence of beta2 integrins on interleukin-2 (IL-2)-mediated signal transduction in human CD4(+) T cell lines obtained from healthy donors and a leukocyte adhesion deficiency (LAD) patient. We show that IL-2 induces tyrosine phosphorylation of a 125-kDa protein and homotypic adhesion in beta2 integrin (CD18)-positive but not in beta2-integrin-negative T cells. EDTA, an inhibitor of integrin adhesion, blocks IL-2-induced tyrosine phosphorylation of the 125-kDa protein but not other proteins in beta2-integrin-positive T cells. Likewise, a beta2 integrin (CD18) antibody selectively inhibits induction of the 125-kDa phosphotyrosine protein, whereas cytokine-mediated tyrosine phosphorylation of other proteins is largely unaffected. Immunoprecipitation experiments indicate that the IL-2-induced 125-kDa phosphotyrosine protein is the focal adhesion kinase-related protein B (fakB). Thus, IL-2 induces strong tyrosine phosphorylation of fakB in beta2-integrin-positive but not in beta2-integrin-negative T cells, and CD18 mAb selectively blocks IL-2-induced fakB-tyrosine phosphorylation in beta2-integrin-positive T cells. In parallel experiments, IL-2 does not induce or augment tyrosine phosphorylation of p125(FAK). In conclusion, our data indicate that IL-2 induces beta2-integrin-dependent signal transduction events involving the tyrosine kinase substrate fakB.
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PMID:Interleukin-2 induces beta2-integrin-dependent signal transduction involving the focal adhesion kinase-related protein B (fakB). 961 21

In order to clarify the transmission process of human immunodeficiency virus type 1 (HIV-1) through the epithelial cell barrier, HeLa cells susceptible and non-susceptible to HIV-1 were cloned and designated as P6 HeLa and N7 HeLa cells, respectively. P6 HeLa cells could be infected with the LAI strain of HIV-1 and mediated HIV-1 transcytosis. In contrast, N7 HeLa cells exhibited neither HIV-1 infection nor transcytosis. CD4 and galactosylceramide as the receptors for HIV-1 were not detected on P6 HeLa cells, although an anti-CD4 monoclonal antibody (mAb) blocked HIV-1 infection. Since HIV-1-infected P6 HeLa cells exhibited no fusion and survived, we speculated that the P6 HeLa cells expressed molecules other than CD4 which facilitated HIV-1 infection. Two mAbs (A-14 ITK and C57 a9-9) which inhibited the HIV-1 infection of P6 HeLa cells were generated. Each mAb recognized distinct molecule(s) as shown by Western blotting. Transcytosis by the P6 HeLa cells was inhibited by C57 a9-9 but not by A-14 ITK or anti-CD4 mAb. Both infection and transcytosis may be responsible for HIV-1 transmission through epithelial cells in a complex manner. Although infection and transcytosis occurred via different mechanisms, the molecule(s) recognized by C57 a9-9 mAb may be associated with both processes.
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PMID:Human immunodeficiency virus type 1 (HIV-1) infection and transcytosis activity of a HIV-1 susceptible clone from HeLa cell. 962 19

In early HIV disease, immunodeficiency is characterized by the inability of CD4+ T cells to produce a critical cytokine, IL-2, and to express the receptor for IL-2 (IL-2R) in response to antigenic or mitogenic stimulation. The shared common gamma-chain (gamma(c)) of IL-2R and its associated Janus kinase, JAK3, are indispensable for normal T cell function. Here, we show that the inhibition of IL-2R expression and proliferation induced by ligation of CD4 by HIV envelope glycoprotein, gp120, is correlated with inhibition of expression and activation of JAK3. Stimulation through the gamma(c)-related cytokine receptors restores JAK3 expression and activation and rescues CD4-mediated T cell unresponsiveness. Collectively, these data argue that inhibition of JAK3 expression and activation may, in part, explain the T cell dysfunction seen in early HIV disease. In addition, rescue from gp120-mediated T cell unresponsiveness by activation of JAK3 suggests a novel therapeutic approach for enhancing immune function in HIV disease.
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PMID:Cutting edge: JAK3 activation and rescue of T cells from HIV gp120-induced unresponsiveness. 963 77

Human immunodeficiency virus (HIV) infection is considered to influence the pathogenesis of human papillomavirus (HPV)-associated diseases. It is not clear whether this occurs directly through molecular interactions between viral genes and/or indirectly through effects on the immune functions. In the present study we compared molecular characteristics of penile condylomas from immunocompetent and HIV-positive individuals. Using polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR techniques we determined some characteristics of local immune responses and transcriptional activity of both viruses. Our findings revealed that HIV-seropositivity was accompanied by multiple HPV infection and a CD4-count-dependent appearance of oncogenic HPV-types. HIV infection also changed the patterns of HPV transcription favouring transcription of early genes such as E7. Apparently, HIV infection influences local immunity by altering HPV transcription and by systemic immunodeficiency.
Int J STD AIDS 1998 May
PMID:Systemic immunosuppression by HIV infection influences HPV transcription and thus local immune responses in condyloma acuminatum. 963 4

TcRzeta/CD3 ligation initiates a signaling cascade involving CD4/CD8-p56(lck), p59(fyn), and ZAP-70, as well as lymphoid downstream proteins VAV, SLP-76, and FYB/SLAP. A current question concerns the nature of the downstream binding partner(s) of FYB in T cells. In this study, using a two-hybrid screen with FYB as bait, we have identified eight clones, four of which correspond to the recently published lymphoid protein SKAP55, and two which correspond to a related protein with some 44% homology to SKAP55 (termed SKAP55-related protein, SKAP55R). The SKAP55 clones showed only minor differences (two substitutions and one residue deletion) from SKAP55. SKAP55R has the same overall structure as SKAP55 except for the presence of a unique N terminus with a well-defined coiled-coil domain. Both SKAP55 and SKAP55R were found to bind FYB through their SH3 domains and to act as substrates for the FYN kinase in T cells. Furthermore, immunofluorescence confocal microscopy showed that FYB and SKAP55 colocalize in the perinuclear region of cells. SKAP55 also colocalizes with another FYB binding protein, SLP-76. Taken together, these observations demonstrate that FYB is part of an interactive matrix with SKAP55 and a SKAP55-related protein.
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PMID:FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells. 967 55


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