HIV testing in the insurance industry--the gap between theory and practice.
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Biomedical subjects
Publications and source records attributed to L London.
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During the period of current political transition, concern for the future of South Africa's health services have led to increased interest in different models for the provision and financing of health care. These debates have included an examination of the concept of Managed Care and the ideas of Health Maintainance Organization. Progressive trade unions, particularly, have been faced with the prospect of promoting private sector health care if they are directly to meet their members health needs, while at the same time seeking an equitable health care system for a future democratic South Africa. The Ray Alexander Workers Clinic is presented as a model of a worker-based health service which attempts to address this contradiction. Important lessons for a future National Health Service may be learnt. The role of worker control and cost containment are emphasized and implications for integration into State Services and relationships to social services for the broader community are explored. An argument is made that worker-based health services offer excellent possibilities for integration in a future National Health Service in South Africa that is centred on a Primary Health Care approach.
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Despite the high incidence of cancer of the uterine cervix among black South African women, many do not have access to cytological screening services. Data describing Papanicolaou smear coverage and factors related to coverage are presented from 9 surveys of rural women workers in the food canning and processing industry in the Cape. Adequacy of Pap smear coverage was assessed according to whether the respondent had ever previously had a Pap smear, or had had one in the 3 years preceding the survey. From the 3 surveys with the greatest generalisability, only 49-65% of workers reported adequate Pap smear coverage. Knowledge about Pap smears was lacking. At the same time, of those women with adequate coverage, many appeared to be receiving unnecessary routine Pap smears. It appears that the policy which makes the availability of Pap smears dependent upon acceptance of contraceptive services is responsible for both the lack of Pap smear coverage and the over-provision of smears in this group of women. An urgent review of state Pap smear policy is required and a coherent community-based educational programme to facilitate the prevention of cervical cancer should be implemented as soon as possible.
Despite the recognition that occupational dermatitis is extremely common, few data exist on the prevalence of skin disorders in South African industry. A cross-sectional prevalence study among 686 female workers in a canning factory in the western Cape showed high rates of dermatoses--in particular, chronic paronychia, intertrigo and dermatitis of the hands. A statistically significant association was found between exposure to 'wet work' in the industry and the prevalence of chronic paronychia and intertrigo. Age was also found to be associated with these dermatoses, irrespective of duration of service. The prevalence of dermatitis of the hands was increased among high-exposure workers, but not significantly. Dermatoses are an important occupational hazard in the canning industry, and there is a need for improved preventive measures.
If reports from the Workmen's Compensation Commissioner are compared with international figures, dermatitis in South African industry appears to be underestimated. Compensation for occupational dermatitis in South Africa relies on the presence of a positive patch test. A prevalence study at a canning factory in the western Cape showed high rates of dermatoses. No association could be shown between dermatitis, intertrigo or chronic paronychia and patch-test positivity. It is argued that patch-test positivity is purely coincidental to the dermatoses and that patch testing has little role to play where the majority of occupational dermatoses are irritant in nature. Reform of the system of compensation for occupational skin disorders is urgently needed and should be integrated in workplace-based preventive and curative programmes.
Primary prevention is the mainstay of management of occupational dermatoses. Despite the high rates of dermatoses found in a study of 686 female workers in a canning factory in March 1990, use of protective gloves was extremely low, even though there was evidence that they prevented acute paronychia and intertrigo. Reasons associated with low glove use were unavailability, discomfort and workers' failure to perceive a protective role for gloves. Difficulties with replacement of damaged gloves were an important cause of unavailability. Domestic and other non-occupational exposure at the workplace appeared to be unimportant in the development of dermatoses. Important preventive interventions are possible in the industry to reduce the rates of dermatoses among the workforce.
Agrichemicals are used extensively in agriculture in South Africa and throughout the world and may present serious health hazards. A review is made of their acute, sub-acute and chronic health effects with attention to the teratogenic and carcinogenic potential. Assessment of agrichemical toxicity is critically discussed. The limited data available on agrichemical poisoning in South Africa suggest that agrichemical poisoning is significantly under-reported and is potentially a major public health problem. Implications for the development of health policy affecting farm workers are outlined.
Transcriptional regulation of the human c-myc gene, an important aspect of cellular differentiation, occurs in part at the level of transcript elongation. In vivo, transcriptional arrest, due to either pausing or termination, occurs near the junction between the first exon and first intron and varies with the growth state of the cell. We have tested the transcription of c-myc templates in HeLa nuclear extracts. We did not observe significant arrest under standard conditions, but we found that a considerable fraction of transcription complexes stopped at the c-myc TII site (just past the first exon-intron junction) when the KCl concentration was raised to 400 mM during elongation. Transcriptional arrest at TII also was observed at KCl concentrations as low as 130 mM and when potassium acetate or potassium glutamate was substituted for KCl. Under these conditions, arrest occurred at the TII site when transcription was initiated at either the c-myc P2 promoter or the adenovirus 2 major late promoter. Further, the TII sequence itself, in forward but not reverse orientation, was sufficient to stop transcription in a HeLa nuclear extract. By separating the TII RNA from active transcription complexes by using gel filtration, we found that arrest at TII at 400 mM KCl resulted in transcript release and thus true transcriptional termination. The efficiency of termination at TII depended on the growth state of the cells from which the extracts were made, suggesting that some factor or factors control premature termination in c-myc.
The t(14;18) of human follicular B cell lymphoma translocates the Bcl-2 gene into the Ig H chain locus and markedly deregulates Bcl-2 expression. We sought to determine if Bcl-2 could be directly implicated in a growth-factor pathway. Consequently, we introduced a retrovirus containing the murine Bcl-2 gene (N2-M-Bcl-2) or the parental retrovirus (N2) into a series of factor-dependent hemopoietic cell lines. Overexpressed Bcl-2 resulted in no long term IL-2, IL-3, or IL-6 independent clones, indicating that Bcl-2 could not spare the need for a specific ligand-receptor interaction. However, Bcl-2 did extend the short term survival of IL-3-dependent cell lines after factor deprivation. Although viable, IL-3-deprived pro B lymphocytes (FL5.12) bearing N2-M-Bcl-2 were in Go, and deregulated Bcl-2 did not obviously influence cell-cycle progression. Bcl-2 predominant effects were to delay the onset of cell death and to modestly augment viable cell growth in the first 48 h after IL-3 deprivation. This death sparing was associated with increased levels of Bcl-2 RNA and protein in factor-deprived cells possessing N2-M-Bcl-2. This result was not restricted to prolymphocytes because an IL-3-dependent mast cell line (32D) as well as a promyeloid line (FDC-P1) demonstrated the same response to Bcl-2. Moreover, the effect was not limited to the IL-3/IL-3R signal transduction pathway in that promyeloid cells maintained in granulocyte-macrophage-CSF or IL-4 displayed a similar response. Yet, Bcl-2-enhanced cell survival was not universal as an IL-2-dependent T cell line, and an IL-6-dependent myeloma line demonstrated no consistent effect upon IL withdrawal. Thus, Bcl-2 appears to interfere with cell death but in a cell type and/or factor-restricted fashion.
We characterized the basis for the follicular lymphoproliferation in transgenic mice bearing a Bcl-2-immunoglobulin (Bcl-2-Ig) minigene representing the t(14;18) of human follicular lymphoma. Discriminatory S1 nuclease protection assays revealed that the Bcl-2-Ig transgene was overexpressed relative to endogenous mouse Bcl-2 in spleen and thymus. Western (immunoblot) analysis demonstrated the overproduction of the human 25-kilodalton Bcl-2 protein, which arose from the transgene, in spleen, thymus, and the expanded B-cell subset. Despite the generalized lymphoid pattern of deregulation, two-color flow cytometry and density gradient centrifugation indicated that the expanded lymphocytes were predominantly small, resting B cells coexpressing B220, immunoglobulin M (IgM), IgD, Ia, and kappa. Cell cycle analysis confirmed that about 97% of these expanded B cells reside in G0/G1. An extensive characterization of transgenic lines revealed a fourfold excess of IgM-IgD-expressing B cells in spleen and dramatically increased numbers in bone marrow. While resting, these cells proliferated in response to lipopolysaccharide and anti-IgM and demonstrated normal B-cell colony formation in soft agar. Moreover, these B cells, which demonstrated an extended survival in vitro even in the absence of stroma, were also resting in G0, yet were capable of proliferative responses. These findings provide consistent evidence that the accumulation of B cells after Bcl-2 overproduction is secondary to prolonged cell survival and not increased cell cycling. This suggests a unique role for Bcl-2 as a proto-oncogene that enhances cell survival independent of promoting cell division.
The mechanisms responsible for regulating the growth and differentiation of pluripotent stem cells involve the complex interaction of a series of specific and nonspecific growth factors and signals. In this report, colony-stimulating factor (CSF)-dependent clonal cell lines, recombinant and/or purified CSFs, and clonal assays were used to investigate the mechanism of interleukin 4 (IL-4)-induced modulation of CSF-dependent cell growth. IL-4 inhibits in a dose-dependent fashion either the interleukin 3 (IL-3)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced growth of the myelomonocytic progenitor cell line, FDC-P1. This inhibitory effect of IL-4- on IL-3- or GM-CSF-induced cell growth was verified using normal bone marrow cells. Our data supports the hypothesis that IL-4 is acting directly on the progenitor cell and not indirectly through the action of accessory cells. Further, because the inhibitory effect of IL-4 is selective and does not affect all CSF-dependent cell lines, other factors, including the maturational state or the lineage of the cell may be important in dictating an effect, if any, mediated by IL-4.
Tuberculosis remains a serious public health problem in South Africa. Current control policy in industry relies on passive case-finding and regards industrial workers as at low risk. Analysis of tuberculosis among a canning factory population in the Boland demonstrated high rates of pulmonary tuberculosis, comparable to the high rates in the community, and an absence of the 'healthy worker effect'. Black men were at particular risk. An argument is made for a review of current practices in tuberculosis control based on a sound knowledge of risk profiles for particular industries.
Hematopoietic cell development is regulated by a series of growth factors that are progressively restricted in their biological activity. IL-3 is a multi-lineage growth factor that supports the growth and differentiation of progenitor cells belonging to multiple lineages. However, the mechanism by which IL-3 induces proliferation and differentiation of these cells is not completely understood. In this report, we have used two IL-3-dependent cell lines, FDC-P1 (a myeloid progenitor) and F15.12 (a lymphoid progenitor) to investigate IL-3-mediated growth and differentiation. When either FDC-P1 or FL5.12 cells are deprived of IL-3, greater than 90% of all cells accumulate in the G0 phase of the cell cycle. Upon readdition of IL-3, the cells will reenter the active phases of the cell cycle. Therefore, IL-3 can act as both a competence (G0----G1) factor, and a progression (G1----M) factor for hematopoietic precursor clones. FDC-P1 cells can also proliferate in response to granulocyte/macrophage colony-stimulating factor (G/M-CSF) and IL-4 (B cell stimulatory factor 1 [BSF-1]). However, resting (G0) FDC-P1 cells have lost their ability to grow in response to both G/M-CSF and IL-4, even though both factors can induce a G0----G1 transition. Therefore, G/M-CSF or IL-4 behave as progression factors among certain IL-3-responsive clones, and in those cases only in defined points in the cell cycle. Both IL-4 and G/M-CSF can maintain long-term growth of FDC-P1 cells. Upon removal of factor for 24 h, these clones accumulate in the G1 phase of the cell cycle and do not appear to enter G0 even after 36 h of factor deprivation. Therefore, cells maintained in G/M-CSF or IL-4 have altered growth requirements compared with the IL-3-dependent lines from which they were derived. The ability of various hematopoietic growth factors to regulate cell cycle progression in IL-3-dependent cell lines is dependent not only upon the lineage from which these cells were derived, but also the phase of the cell cycle in which those cells reside. The consequences of these interactions dictate the manner by which various clones will respond to CSFs and whether the cells will grow and/or differentiate.
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We report that resting human peripheral blood natural killer (NK) cells proliferate in response to recombinant interleukin 2 (rIL 2), and addition of irradiated lymphoblastoid B cells significantly increase their proliferative response. Interaction of IL 2 with the Tac IL 2 receptor expressed on activated NK cells is necessary to maintain continued growth of these cells. Experiments in which NK cell mitosis is prevented by colchicine show that the majority of peripheral blood NK cells are induced into the first cell cycle over a 6-day culture period in the presence of rIL 2. The addition of the irradiated lymphoblastoid B cell line, Daudi, to colchicine blocked cultures does not increase the proportion of cells entering cell cycle in response to rIL 2 alone. In limiting dilution analysis, only 1/1700 B73.1+ cells grow clonally in response to rIL 2. The frequency of clonal growth of NK cells in response to irradiated Daudi cells alone is minimal, whereas the addition of irradiated Daudi cells to rIL 2 stimulated cultures resulted in a 10-fold increase in clonal frequency compared with the cultures in rIL 2 alone. Therefore, Daudi cells may act by maintaining continuous proliferation of the NK cells originally responsive to IL 2. Unlike NK cells, only a minimal proportion of peripheral blood T cells proliferate in response to IL 2. These IL 2 responsive T cells are characterized by a lower bouyant density than the majority of peripheral blood T cells. These results indicate physiologic differences between peripheral blood resting NK and T cells in their ability to be induced to cycle. IL 2 is a growth factor for both cell types, but although the presence of the growth factor is sufficient for quiescent NK cells to be induced into cycle, T cells require antigenic or other mitogenic stimuli to respond to IL 2. The small proportion of light density IL 2 responsive T cells might represent in vivo activated T cells.