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 by human immunodeficiency virus type 2 (HIV-2) has not previously been described in North or East Africa. We examined over 1200 sera of high-risk individuals from three North/East African countries for antibodies to HIV-2. Results indicated that 17 were repeatedly reactive by ELISA; 4 were confirmed by Western blot. Of the 4 confirmed, 2 produced strong reactions to the envelope antigens of HIV-2 but not of HIV-1. One of these subjects was a foreigner from Senegal who was tested while in Egypt and one was a Djiboutian prostitute who was infected presumably prior to October 1987. We conclude that HIV-2 has been introduced into this region and that specific testing of selected individuals for HIV-2 is warranted.
Int J STD AIDS 1990 Jan
PMID:Serological evidence for human immunodeficiency virus type 2 in east Africa. 209

The BCR/ABL gene, formed by the Philadelphia chromosome translocation (Ph1) of human chronic myelogenous leukemia, encodes an altered ABL gene product, P210. P210 is strongly implicated in the malignant process of chronic myelogenous leukemia, but it precise role is unknown. Infection of long-term bone marrow cultures enriched for B-lymphoid cell types with a Moloney murine leukemia virus retroviral vector containing the BCR/ABL cDNA resulted in clonal outgrowths of immature B-lymphoid cells which expressed abundant P210 kinase activity. Surprisingly, infection of long-term myeloid lineage-enriched cultures also resulted in clonal outgrowths of immature B-lymphoid cells. The P210-expressing lymphoid cell lines resulting from either type of culture were resistant to the lethal effects of corticosteroids. These findings indicate that high levels of P210 expressed from a Moloney murine leukemia virus long terminal repeat preferentially stimulate the growth of immature B-lineage cells, and this effect is apparent even in myeloid lineage-enriched cultures, in which few if any lymphoid cells can be detected prior to infection.
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PMID:Selective transformation of primitive lymphoid cells by the BCR/ABL oncogene expressed in long-term lymphoid or myeloid cultures. 326 66

During the clinical trials 8,861 patients have been treated with ciprofloxacin worldwide. 3,822 of the therapeutic courses were valid for analysis of efficacy according to FDA standards. The following dosages were usually administered: UTI: 100 to 500 mg twice daily orally or 100 mg twice daily intravenously; RTI: 250 to 1000 mg twice daily orally or 200 mg twice daily intravenously; septicemia: 200 mg intravenously twice daily; gonorrhea: 250 to 500 mg single tablet orally; all other infections: 500 to 1000 mg twice daily orally or 200 mg twice daily intravenously. Ciprofloxacin was administered to 762 courses of lower RTI, 88 courses of upper RTI, 108 courses of bacteremia, 766 courses of skin structure infection, 142 courses of bone and joint infections, 149 courses of intra-abdominal infections, 33 courses of gastrointestinal infections, 1,633 courses of UTI, 49 courses of pelvic infections, 279 courses of STD, mainly gonorrhea, and three courses of meningitis. The clinical response was resolution in 76%, improvement in 18% and failure in only 6%. Bacteriologic response by all sites evaluable: pathogens were eradicated from 74%, markedly reduced in 2%, persisted in 10%. Relapse occurred in 4% and reinfection was observed in another 6%. The overall response was favourable for 90% of the patients. Drug safety was established on a data base of 8,861 courses worldwide. The following side-effects according to COSTART terminology were observed: digestive 5%, metabolic nutritional 4.6%, central nervous 1.6%, skin 1.4%, hemic and lymphatic 1%, cardiovascular 0.4%, body as a whole 0.4%, urogenital 0.3%, special senses 0.3%, musculo-skeletal 0.1%, respiratory 0.08%. Several courses had more than one reaction. Thus the total incidence of side-effects for the treated patient population was 10.2%. Ciprofloxacin is a highly effective drug and a breakthrough in several areas of medical interest. It is relatively safe and side-effects are usually mild or moderate in intensity and transient.
Infection 1988
PMID:Worldwide clinical data on efficacy and safety of ciprofloxacin. 328 11

We examined patients attending an STD clinic (Department of Dermatology, Lasarettet, Lund). Chlamydia trachomatis was demonstrated in 26% of 2021 male patients by culture from the urethra (using cyclo-heximide-treated McCoy cells). The corresponding figure for Neisseria gonorrhoeae was 15%. Both organisms were found in 5% of the patients. In women, culture from the cervix demonstrated C. trachomatis in 16% of 1039 patients. N. gonorrhoeae was found in 14%, and both organisms in 4% of the patients. Men with chlamydial urethritis were more frequently found to have a watery discharge than those with gonococcal urethritis. They also had fewer leucocytes in smears from the urethra. Treatment with different tetracyclines gives good therapeutic results in both men and women infected with C. trachomatis. In contact-tracing, 53% of 95 male partners and 65% of 103 female partners were found to harbour C. trachomatis. About 50% of these contacts were free of symptoms. This indicates the importance of contact-tracing in genital chlamydial infection.
Infection 1982
PMID:Diagnosis and treatment of chlamydial venereal disease. 708 80

The study was conducted at three urban adolescent clinics administered by the Denver Department of Health and Hospitals.The population was derived predominantly from inner city, low-income adolescents 12-18 years old during the period of May 1989 to January 1990. A questionnaire regarding sexual and STD history, contraceptive use, and substance use was administered to each patient. Specimens for laboratory studies included collection of vaginal fluid swabs for pH determination and wet mount microscopy; sequential cervical swabs for testing for Neisseria gonorrhea, Chlamydia trachomatis, and HPV DNA; and endocervical swabs and ectocervical scrapes for cytology. A total of 634 were included. The population was ethnically mixed: 167 (26%) were Black, 287 (45%) were Hispanic, 174 (28%) were White, 1 (0.2%) was Asian, and 3 (10.5%) were of other ethnic groups. The mean age was 16.8 years, with a range of 12-18 years. Cervical HPV infection was the most prevalent STD in the population, detected in 99 (15.6%) subjects, followed by infection with C. trachomatis in 69 (11.0%), N. gonorrhea in 45 (7.1%), and T. vaginalis in 34 (5.3%). Overall, 188 (30.3%) subjects had any of the 4 STDs detected. The most prevalent, higher-risk HPV types were 16/18, either as single or mixed infections, which were detected in 46 (7.2%) patients. Infection with HPV types 31/33/35 or 6/11 occurred in an additional 31 (4.9%) and 23 (3.6%) subjects, respectively. Overall, 152 (24%) patients had any manifestation of genital HPV infection, 23 (15%) with clinically apparent infection (external genital warts), an additional 54 (36%) with cytologically apparent infection (low-grade squamous intraepithelial lesions or LSIL) without warts, and 69 (49%) with subclinical cervical infection (with neither warts nor LSIL). The relative risk of cervical HPV DNA for those with 2 or more partners was 2.7 (p 0.001). By multivariate analysis, the independent predictors of cervical HPV DNA included the number of lifetime sexual partners (2 or more partners: OR, 1.9) and current genital warts (OR, 5.1).
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PMID:Spectrum of genital human papillomavirus infection in a female adolescent population. 748 7

Mutants and fusion products of the c-abl gene were used to define some of the molecular requirements for rapid plasmacytoma (PC) and pre-B-lymphoma induction in pristane-treated N-myc transgenic BALB/c mice. A-MuLV induced PCs in 21 of 25 mice with a mean post-pristane latency period of 46 +/- 9 days, compared to 134 +/- 25 days in controls exposed to pristane alone. delta XB, a mutant of type IV c-abl with a deletion of the SH3 domain, was equally effective in inducing PCs in 7 of 7 mice with a latency period of 49 +/- 7 days, indicating that gag sequences are not required for rapid PC induction. The delta XB delta Nar mutant that carried a large C-terminal deletion in addition showed only a negligible activity, if any, suggesting that PC acceleration requires the C-terminal domain in the same way as lymphoid transformation and in contrast to fibroblast transformation. BCR-ABL fusion constructs encoding an 185-kDa protein as in acute leukemia, or a 210-kDa protein as in chronic myelocytic leukemia (CML), did not accelerate pristane-induced PC development in the N-myc transgenic mice, in contrast to their known ability to immortalize lymphoid cells in vitro. Only one of 14 non-transgenic littermates developed a pre-B lymphoma after A-MuLV infection, and none of 10 normal littermates infected with delta XB virus developed a construct-carrying tumor. This result suggests that PC acceleration is due to co-operative interaction of the N-myc transgene and activated abl. Infection of N-myc transgenic bone marrow or spleen cells with A-MuLV in vitro led to the outgrowth of pre-B lymphomas after transplantation to pristane-treated BALB/c recipients. The lymphoma-inducing activity of A-MuLV depends on its high titer, since diluted A-MuLV or the lower-titered delta XB induced only PCs under the same conditions. The v-abl, delta XB and BCR-ABL-carrying viruses generated immortalized lymphoblastoid lines in vitro, regardless of the presence of the N-myc transgene, suggesting that lymphoid transformation is a direct function of appropriate abl sequences in contrast to PC acceleration.
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PMID:Molecular requirements for rapid plasmacytoma and pre-B lymphoma induction by Abelson murine leukemia virus in myc-transgenic mice. 801 9

All laboratory tests performed and medical reports received in South Australia in 1990-1991 and screening results for Chlamydia trachomatis at the central STD clinic from 1988-1991 were analysed to clarify the epidemiology of genital chlamydial infection. From 70,494 laboratory tests in 1990-1991, 2449 (3.5%) infections were detected of which 2431 (99%) were also reported by clinicians. Infections were detected in 1335 (6.4%) of 21,004 patients (71% of 29,401 attendees) screened at the central STD clinic from 1988 to 1991. STD clinic yields suggest a male:female ratio of 1.08:1 (95% confidence intervals = 1.05:1-1.11:1), with 46% of infections in males and 67% of infections in females being asymptomatic. For both males and females, infection rates were highest in 15-19-year-olds and decreased with increasing age, but were not independently related to marital status. The statewide epidemiological pattern was probably distorted in medical reports because of selection biases in testing (89% of tests performed by non-STD clinicians were on females) which resulted in decreased detection in asymptomatic females, symptomatic and asymptomatic males, married persons and unmarried young persons 15-19-year-old females and 15-24-year-old males) by private practitioners. A cost-effective method for increased detection of chlamydial infection in undertested groups (particularly of asymptomatic unmarried males aged 15-24) will be required to control transmission of chlamydial infection in South Australia. Increased detection in young married persons is also desirable.
Int J STD AIDS
PMID:The epidemiology of genital chlamydial infection in South Australia. 839 99

Infection with Toxoplasma gondii is the most common parasitic infection worldwide with an estimated prevalence of 1-2 billion people. The risk of developing severe toxoplasmosis is higher for immunocompromised individuals and fetuses of mothers who have acquired a primo-infection. The current therapy of choice for toxoplasmosis is the synergistic combination of pyrimethamine and sulphadiazine. This therapy is highly effective but its use is complicated in immuno-compromised individuals due to adverse secondary effects. In addition, since pyrimethamine is potentially teratogenic, its use is not recommended during early pregnancy. Clindamycin, a lincosaminide, in combination with pyrimethamine has been shown to be an acceptable therapeutic alternative in patients who are unable to tolerate pyrimethamine plus sulphadiazine. In the search for new, effective compounds with less adverse or toxic effects, recent efforts have focused on the new macrolides and the azalides. Here, the results of the investigations and, in particular, the theoretical considerations for the potential use of azithromycin in the therapy of toxoplasmosis in immunocompromised individuals are reviewed.
Int J STD AIDS 1996
PMID:The potential role of azithromycin in the treatment of prophylaxis of toxoplasmosis. 865 22

The case records of consecutive patients admitted to a specialist HIV/AIDS inpatient unit between 1989 and 1993 with pyrexia of undetermined origin (PUO) were reviewed in order to determine the eventual diagnosis. Seventy-nine episodes occurred in 75 patients; 52 patients had a prior AIDS defining diagnosis. CD4+ lymphocyte counts ranged widely, 0-0.79 (median = 0.04) x 10(9)/l. Infections were found in 63 episodes (79%), including mycobacterial infection in 41 episodes (53%) and bacterial infection in 12 episodes (15%). Tumours were found in 6 episodes (8%), 5 of these were lymphoma. Factitious fever accounted for 2 episodes (3%) and connective-tissue disease for 1 episode (1%); no definite diagnosis was reached in 7 episodes (9%). PUO in HIV positive patients is commonly due to infection or tumour. Unexplained fever in this patient group should not be ascribed to HIV infection itself and should be vigorously investigated to find a cause.
Int J STD AIDS
PMID:Pyrexia of undetermined origin in patients with human immunodeficiency virus infection and AIDS. 879 78

Blastic transformation of chronic myelogenous leukemia (CML) is characterized by the presence of nonrandom, secondary genetic abnormalities in the majority of Philadelphia1 clones, and loss of p53 tumor suppressor gene function is a consistent finding in 25-30% of CML blast crisis patients. To test whether the functional loss of p53 plays a direct role in the transition of chronic phase to blast crisis, bone marrow cells from p53+/+ or p53-/- mice were infected with a retrovirus carrying either the wild-type BCR/ABL or the inactive kinase-deficient mutant, and were assessed for colony-forming ability. Infection of p53-/- marrow cells with wild-type BCR/ABL, but not with the kinase-deficient mutant, enhanced formation of hematopoietic colonies and induced growth factor independence at high frequency, as compared with p53+/+ marrow cells. These effects were suppressed when p53-/- marrow cells were coinfected with BCR/ ABL and wild-type p53. p53-deficient BCR/ABL-infected marrow cells had a proliferative advantage, as reflected by an increase in the fraction of S+G2 phase cells and a decrease in the number of apoptotic cells. Immunophenotyping and morphological analysis revealed that BCR/ABL-positive p53-/- cells were much less differentiated than their BCR/ABL-positive p53+/+ counterparts. Injection of immunodeficient mice with BCR/ABL-positive p53-/- cells produced a transplantable, highly aggressive, poorly differentiated acute myelogenous leukemia. In marked contrast, the disease process in mice injected with BCR/ABL-positive p53+/+ marrow cells was characterized by cell infiltrates with a more differentiated phenotype and was significantly retarded, as indicated by a much longer survival of leukemic mice. Together, these findings directly demonstrate that loss of p53 function plays an important role in blast transformation in CML.
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PMID:Blastic transformation of p53-deficient bone marrow cells by p210bcr/abl tyrosine kinase. 891 57


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