Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
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This is a study of Lesotho's proposal to United Nations agencies for financial assistance to build a medical school and a 600- bed referral teaching hospital. To qualify for such assistance, a feasibility study was prepared that included data from Lesotho's Ministries of Planning, Finance and Health on the following: 1) demography, including fertility; 2) health status and major health problems; 3) health facilities and health service utilization; 4) health manpower; and 5) health service organization, financing and cost. Lesotho's population was 1.37 million in 1981 growing at 2.3% per year. 13% of the population was urban, living in Maseru, the capital. Infant and child mortality rates are 116/1000 and 15.6/1000 while maternal mortality rates are 3.7/1000. The leading causes of death for children are malnutrition, acute respiratory and infectious diseases, gastrointestinal diseases and congenital anomalies. While adults are dying from tuberculosis, heart disease, injuries, burns and digestive diseases. Even though Lesotho's climate and high altitude insulate it from many diseases, there is concern over the high incidence of pulmonary tuberculosis, sexually transmitted diseases (STD's) and respiratory infections. In 1980 1/3 of the population has access to hospital care. Maseru had 40% of the hospital beds, yet only 4.4% of the population. In 1982 there were 1536 health workers employed by the Ministry of Health, of these 41 were doctors, 175 nurses and 132 nursing assistants. Instead of building a new medical school, Lesotho accepted renovating the existing general hospital, converting it into a national referral center, while introducing more specialties at 20% of the $US60 estimated for a new medical school. Recommendations to the government also included: 1) special programs aimed at reducing and controlling tuberculosis and STD's; 2) establishing and strengthening primary health care programs; and 3) decreasing long hospital stays. (author's modified).
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PMID:Getting the best value for money in health care. 261 Aug 47

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

The relatively high numbers of patients with IDU-related HIV in Scotland has resulted in considerable management difficulties not previously experienced by other medical units. Chronic physical ill health in drug users is becoming commoner with the advent of HIV and other centres are now experiencing the type of problems that the Regional Infectious Disease Unit (RIDU) in Edinburgh has faced over the last 10 years. Very little has been published concerning the difficulties of managing patients who use drugs and have a physical illness in medical units in the UK. This paper presents examples of common problems together with the RIDU's experience of management in the hope that it will help others to deliver effective and efficient physical and mental health care to patients with drug problems.
Int J STD AIDS
PMID:Injection drug use-related HIV healthcare--problems and management in Edinburgh. 764 22

The English-speaking Caribbean is in transition toward communicable disease health patterns seen in the more developed world. Structural adjustment policies in recent years have weakened control measures, such as water supply and sanitation, as illustrated by recent outbreaks of typhoid fever in Jamaica (1990-1991), increased malaria incidence in Suriname and Guyana (with temporary importation into southern Trinidad in 1991), an upswing in tuberculosis in some countries, and the occurrence of cholera outbreaks in Belize, Suriname, and Guyana. The emergence of epidemic cholera throughout most of Latin America in 1991, and Caribbean mainland countries in 1992, aroused concern. Deteriorating socioeconomic conditions and the consequent communicable disease risk underscored the absence of communicable disease control in the Caribbean Cooperation in Health (CCH) strategy which was adopted in 1986 by the countries of the Caribbean Community. The Caribbean Epidemiology Center (CAREC) offered the following analysis: At least four out of seven CCH priorities already directly address critical aspects of communicable disease control, and therefore the question arises whether communicable disease control should be recognized as an explicit CCH priority. Beyond cholera and the diseases already represented in the CCH strategy, there are only a few other communicable diseases that warrant specific attention at this time: tuberculosis; leprosy, which CAREC member countries may want to eradicate; and leptospirosis, a zoonosis (communicable disease of animals transmissible to humans) thought to be the most frequent disease of this type in the Caribbean. These three conditions are insufficient to justify a distinct communicable disease grouping within CCH. However, if all communicable diseases of public health importance were to be grouped together (AIDS/STD, vaccine-preventable diseases, food- and waterborne diseases, vector-borne diseases), such a group would be important enough to justify a distinct priority category, with several major subcategories.
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PMID:Communicable disease control as a Caribbean public health priority. 801 35

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

Studies in various regions of the world have shown that women infected with HIV-1 are at increased risk for cervical human papillomavirus (HPV) infection as well as for cervical cancer precursor lesions. HIV infection and cervical cancer are both widespread in West Africa, but little is known about the relationship between HPV and HIV-2, the predominant type of HIV in the general population of many West African countries. The authors report findings from their collection of cervical samples for cytology and HPV analysis from 93 women presenting to the University of Dakar Infectious Disease Service; 18 women infected with HIV-1, 17 with HIV-2, and 58 HIV seronegative controls. Compared to those without HIV infection, HIV seropositive women were 13.1 and 11.0 times more likely to have HPV detected using Southern transfer hybridization and the polymerase chain reaction, respectively. The detection of high and intermediate risk HPV types was significantly associated with HIV-1 and HIV-2 infection. Among HPV-positive women, those infected with HIV were more likely to harbor high-risk HPV types. HIV-1 and HIV-2 seropositive women were 23.3 and 9.3 times more likely to have a cytological diagnosis of dysplasia, respectively, than were HIV-seronegative women. Biopsy-proven cervical intraepithelial neoplasia (CIN) 3 was found in one woman with HIV-1 and invasive cancer was found in one woman with HIV-2. It remains unclear, however, whether HIV-1 and HIV-2 confer similar risks of developing CIN 2-3 and the potential of invasive cervical cancer.
Int J STD AIDS
PMID:Cervical intraepithelial neoplasia and human papillomavirus infection among Senegalese women seropositive for HIV-1 or HIV-2 or seronegative for HIV. 806 Oct 90

This article presents an overview of the use of mathematical models to study the demographic impact of STDs. Written for the nonmathematician, the article introduces the basic concepts of mathematical epidemiology for infectious diseases, such as the mass-action principle, the threshold density concept, and the basic reproductive rate. Described are the main features that characterize the epidemiology of STDs and those features that differentiate them from other directly transmitted diseases, such as measles, rubella, and others. Also presented are major findings concerning the importance of sexual behavior on the dynamics of STD transmission, and the numerical analysis of the demographic impact on gonococcal and HIV infections using a mathematical model. The epidemiology of these two STDs is explored, as well as how the growth rate of the population can influence the epidemiology of these STDs. Finally, the authors demonstrate how, under some circumstances, early treatment of gonorrhea can reduce the demographic impact of HIV in regions most affected by both diseases.
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PMID:The impact of HIV and other STDs on human populations. Are predictions possible? 810 29


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