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)

Infection of C57BL/6 mice with LP-BM5 murine leukemia virus (MuLV) leads to the development of murine acquired immunodeficiency syndrome (MAIDS) characterized by abnormal lymphoproliferation, hypergammaglobulinemia and severe immunodeficiency. Progression of MAIDS is delayed in X chromosome-linked immunodeficient (XID) mice, which have an abnormality of Bruton's tyrosine kinase (Btk) and lack functionally mature B cells including CD5+ B cells. In this study, we report the following four major findings. (i) Susceptibility to disease induction is not reconstituted by transfer of CD5+ B cells to XID mice. (ii) Spleen cells from asymptomatic XID mice are able to transmit MAIDS to wild-type mice. (iii) MAIDS can be transmitted to XID mice with the transfer of B cells, but not T cells, from C57BL/6 mice with MAIDS. (iv) Cells which undergo massive lymphoproliferation in XID mice with MAIDS by cell transfer are of host origin, but are not from the donor. We suggest from these results that a B cell subpopulation that is impaired in XID mice plays an important role in the initiation of MAIDS.
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PMID:The xid mutation plays an important role in delayed development of murine acquired immunodeficiency syndrome. 904 55

Utilizing a prospective study of health service activity for HIV/AIDS, 2 estimates of hospital costs of care analysed with reference to gender, risk activity, immunological and clinical staging (1987 definition of AIDS) were undertaken. Utilizing combined costs per life year (based on hospital and hospice activity but not primary and community care) the ratio of costs for CD4 < 200 and CD4 > 200 was for most risk groups between 2-5:1 whilst for AIDS: pre-AIDS it was between 3.6-8.3:1 except for homosexuals where it was 12.6:1. A comparison of the standard hospital costs for infectious diseases with the published accounts for clinical AIDS care in Lothian suggests a 3-4-fold underestimate in the costs of providing a comprehensive health care service.
Int J STD AIDS 1997 Jan
PMID:The cost of health care for HIV-positive patients. 904 82

Whilst interest in the Internet is increasing there has been very little information to date on health-related resources. This review provides a personal selection of some initial sites together with brief descriptions of their contents in the areas of general medicine, infectious diseases, travel-related medicine and HIV/AIDS.
Int J STD AIDS 1997 Feb
PMID:The Internet and medicine: related sites including HIV/AIDS. 906 4

A cross-sectional study of a cohort of 49 male human immunodeficiency virus (HIV)-infected intravenous drug users attending the Infectious Diseases Unit of the National University of Malaysia during 1991-94 yielded a clinical profile of these patients. The mean age of respondents was 33.2 years and the mean duration of intravenous drug use was 12.7 years. On average, these men had known of their HIV-positivity for 53.2 weeks. Intravenous drug use was the only reported HIV risk factor in 34 men (69%). Clinical symptoms at intake included fatigue (49%), weight loss (47%), night sweats (31%), fever (14%), and diarrhea (6%), while clinical findings included hepatomegaly (57%), lymphadenopathy (35%), and oral thrush (29%). Anemia (82%), leucocytosis (53%), hypoalbuminemia (43%), hyperglobulinemia (88%), elevated liver enzymes and hyponatremia (57%) were frequent laboratory findings. The prevalences of hepatitis B virus, cytomegalovirus, and toxoplasma infection were 12.1%, 72.7%, and 59%, respectively. A total of 91 diagnoses were made in these 49 patients: most common were pneumonia, tuberculosis, bacteremia, infective endocardiditis, mycotic aneurysm, and psychiatric disorders. The mean duration of known progression to acquired immunodeficiency syndrome (AIDS) in the 7 patients at this stage was 391 days. Pneumocystis carinii pneumonia was the most common AIDS-defining illness. Three months into the study, 19 men (57%) had defaulted, reflecting the difficulties of involving drug addicts in research and intervention projects. Moreover, 16 patients (33%) were first confirmed HIV-positive at presentation to the hospital, suggesting that many drug users' HIV status remains unknown until they develop symptoms requiring hospital care.
Int J STD AIDS 1997 Feb
PMID:A study of Malaysian drug addicts with human immunodeficiency virus infection. 906 11

The demonstration that RNA can be cleaved by cis ribozyme (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Ribozymes are effective for modulation of gene expression because of their simple structure, site-specific cleavage activity, and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against myriad genes, including oncogenes (ras, BCR-ABL) and drug resistance genes (MDR-1, c-fos). These ribozymes have cleaved the target RNAs in culture system and developed to the in vivo system. We reported that fos ribozyme has altered the expression of c-fos and DNA repair genes in drug resistance cancer cells, and reversed the sensitivity to cisplatin. Furthermore, we have developed high efficiency by the transfer system in vivo.
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PMID:[Reversal of drug resistance in human cancer cells by anti-oncogenes]. 906 74

A prospective study of health service and hospice resource utilization (average length of stay or ALOS, discharge rate, bed day use, outpatient consultation) analysed with reference to gender, risk activity, immunological and clinical staging (1987 definition of AIDS) for the financial year 1992-93 was undertaken at the Regional Infectious Disease Unit (RIDU), City Hospital, Edinburgh, Scotland where 72% of 513 patients were infected via injection drug use. Not surprising therefore overall, drug users were the heaviest users of the inpatient facilities (74% of the discharges and 65% of the bed days) although homosexuals had the highest discharge rate (114 per 100 person years) and rate of bed day use (1654 days per 100 person years). Immunodeficiency (CD4 count < 200 cells/ul) and a clinical diagnosis of AIDS were both associated with greater inpatient and outpatient resource use compared to those without immunodeficiency (CD4 count > or = 200 CD4 cells/ul) or AIDS. Gender effects were complex; the ALOS for women was increased for all risk groups whatever the CD4 count whilst there was no consistent trend of more resource use for women by risk group. Drug users were the heaviest overall users of the local hospice (84% of all admissions, 83% of the bed days and a discharge rate of 76.4 per 100 person years), more than double the rates experienced by the other risk groups. Thus both clinical and immunological staging (AIDS or a CD4 count < 200 cells/ul) were associated with increased resource use in HIV infection and estimates of resource use for AIDS need to be increased by around one-third to take into account hospice use. Despite the preponderance of drug users in Edinburgh, comparisons with other centres did not reveal increased resource use.
Int J STD AIDS 1997 Apr
PMID:Hospital and hospice resource use of HIV-positive patients in Edinburgh. 914 56

The demonstration tha RNA can be cleavaged by cis-ribozyme(catalytic RNAs, RNA enzyme) has potentially important therapeutic implications. Ribozymes are effective for modulation of gene expression because of their simple structure, site-specific cleavage activity and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against myriad genes, including oncogenes (ras, BCR-ABL) and drug resistance genes(MDR-1, c-fos, DHFR). These ribozymes have cleaved the target RNAs in culture system(in vitro) and developed in vivo system. We reported that anti-fos ribozyme has altered the expression of c-fos and DNA repair genes in cisplatin-resistance cancer cells, and reversed the sensitivity to ciaplatin. Furthermore, we have developed high efficiency by the transfer system using an electroporation in vivo.
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PMID:[Circumventing multidrug resistance in human cancer by anti-ribozyme]. 915 62

Central venous catheters (CVCs) for patients with AIDS are at risk of a number of complications including bacterial infections. A 6-year retrospective review was undertaken of the records of the 33 patients (42% infected by injection drug use (IDU)) who received intravenous therapy both in hospital and at home via CVCs. Twenty-eight per cent of 53 insertions suffered a complication, the commonest of which was a pneumothorax (8%). The post insertion complication rate was 0.98/100 catheter days (cd). Thrombotic occlusion (0.15/100 cd) was the commonest non septic event while sepsis was overall the commonest event (0.69/ 100 cd) of which half were considered serious (0.33/100 cd). The most frequently isolated organisms were Staphylococci spp. (71%). The median time to an exit site infection was 59 days and to serious catheter sepsis 86 days. Infection did not differ significantly with age, gender, transmission risk activity or catheter type although Portacaths had the lowest rate of infection (0.33/100 cd). The median survival of the 53 CVCs was 88 days although if the temporary catheters were excluded it was 118 days. Kaplan-Meier estimates of survival analysis revealed 55%, 32% and 19% of all the CVCs surviving 3, 6 and 12 months respectively. Our experience suggests that home intravenous therapy and previous IDU does not preclude the use of CVCs although further research is needed on reducing the infection-related complications of such therapy.
Int J STD AIDS 1997 Jul
PMID:Central venous catheters in patients with AIDS. 922 87

Rho small GTPases regulate a variety of cellular signaling pathways involved in cell growth and transformation. In this study, we examined potential roles for Rho in adhesion-dependent and -independent pathways regulating apoptosis. Rho GTPases are specifically inactivated by exoenzyme C3 (C3) of Clostridium botulinum. Using a novel Sindbis virus-based gene expression system, we created a double subgenomic recombinant (dsSIN:C3) capable of expressing active C3 in intact cells. Infection of L929 fibroblasts with dsSIN:C3 caused essentially complete ADP-ribosylation of intracellular Rho within 1 h. dsSIN:C3-infected cells also became rounded within 1-2 h and detached by 5 h post-infection. Infection of L929 in suspension with dsSIN:C3 disrupted the ability for normal cellular attachment and spreading. Infection of primary cell explants of chicken embryo fibroblasts (CEF) and rat aortic smooth muscle cells (RSM) with dsSIN:C3 caused cytoskeletal effects similar to those seen in L929. We also observed that C3 markedly decreased the basal phosphorylation state of focal adhesion kinase (FAK). Most intriguingly, we found that dsSIN-based expression of C3 or loss of function mutants of Rho could each induce apoptosis and, in RSM, this effect was observed to be adhesion-independent. Rho GTPases, therefore, appear to regulate signal pathways that are required for cell survival and growth that are separate from, but likely overlap with, Rho-dependent pathways involved in cellular adhesion.
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PMID:Inactivation of the small GTPase Rho disrupts cellular attachment and induces adhesion-dependent and adhesion-independent apoptosis. 939 76

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


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