The type-A horizontal cell: GABAergic characteristics and role in development of the outer plexiform layer

Morphological analysis of neonatal rabbit retina suggests that the type-A horizontal cell acts as the pioneer cell for development of the OPL. It is the first mature element of the OPL, and it forms the infrastructure upon which the OPL accrues. The role of type-A horizontal cells in influencing postnatal development of the OPL was examined.^ GABAergic characteristics of the type-A horizontal cell were defined. The type-A horizontal cell was found to possess two more GABAergic characteristics in addition to those previously demonstrated, during a short period in early postnatal development: endogenous stores of GABA and the GABA precursor, glutamate. Lesioning the type-A horizontal cell resulted in their permanent loss in addition to the disappearance of cone terminals and a dramatic increase in rod terminals within the OPL. Thus the type-A cells are not a necessary prerequisite for positioning the OPL in postnatal development, but may be necessary for establishment of the normal photoreceptor mosaic.^ Since type-A horizontal cells possess a number of GABAergic qualities during the period of cone photoreceptor cell differentiation, and there are reports of GABA's trophic action in other developing neuronal systems; the role that GABAergic type-A horizontal cells play in directing photoreceptor differentiation was examined.^ Disrupting effects of GABA-A receptor antagonists indicate that type-A horizontal cells act as postsynaptic targets for the growing cone terminals of photoreceptor cells. These trophic or synaptic interactions may involve GABA-A receptors activated by GABA released from horizontal cells. These findings are consistent with the hypothesis that type-A horizontal cells act as pioneering cells in directing the postnatal development of the OPL.^ These studies offer an in depth analysis of the structural and chemical relationship between type-A horizontal cells and other elements of the OPL from which the roles of type-A horizontal cells and the GABA system in development can be defined. They contribute to our knowledge of both structural and GABAergic mechanisms involved in central nervous system development. ^

Analysis of participation in the federally mandated coal workers' health surveillance program

The Federal Coal Mine Health and Safety Act of 1969 required that periodic chest radiographs be offered to underground coal miners to protect the miners from the development of Coal Workers' Pneumoconiosis (CWP) and progression of the disease to progressive massive fibrosis (PMF). These examinations are administered by the National Institute for Occupational Safety and Health (NIOSH) through the Coal Workers' Health Surveillance Program (CWHSP). The mine operator is required to provide each miner with the opportunity to have the chest radiograph at no cost to the miner.^ Three rounds of examinations have been conducted since 1969 and the fourth is underway. The decrease in participation over rounds is of great concern if the incidence and progression of CWP are to be understood and controlled.^ This study developed rates of participation for each of 558 West Virginia underground coal mines who submitted or had NIOSH assigned plans for making chest radiographs available during the third round, July 1978 through December 1980. These rates were analyzed in relation to desired levels of participation and to reinforcing, predisposing and enabling factors presumed to affect rates of participation in disease prevention and surveillance programs.^ Two reinforcing factors, size of mine and inclusion of the mine in the National Coal Study (NCS) epidemiology research program, and the enabling factor, use of an on-site radiograph facility, demonstrated highly significant relationships to participation rates.^ The major findings of the study were: (1) Participation in the CWHSP is even lower than previously estimated; (2) CWHSP program evaluation is not systematic and program data base is not complete and comprehensive; and (3) NIOSH program policy is not clear and administration of the CWHSP is fragmented and lacks adequate fiscal and personnel resources. ^

COSTS AND EFFECTS OF ARKANSAS' LONG-TERM CARE DEMONSTRATION PROJECT (MEDICAID, CHANELLING, COMMUNITY ASSESSMENT)

The purpose of this study was to assess the impact of the Arkansas Long-Term Care Demonstration Project upon Arkansas' Medicaid expenditures and upon the clients it serves. A Retrospective Medicaid expenditure study component used analyses of variance techniques to test for the Project's effects upon aggregated expenditures for 28 demonstration and control counties representing 25 percent of the State's population over four years, 1979-1982.^ A second approach to the study question utilized a 1982 prospective sample of 458 demonstration and control clients from the same 28 counties. The disability level or need for care of each patient was established a priori. The extent to which an individual's variation in Medicaid utilization and costs was explained by patient need, presence or absence of the channeling project's placement decision or some other patient characteristic was examined by multiple regression analysis. Long-term and acute care Medicaid, Medicare, third party, self-pay and the grand total of all Medicaid claims were analyzed for project effects and explanatory relationships.^ The main project effect was to increase personal care costs without reducing nursing home or acute care costs (Prospective Study). Expansion of clients appeared to occur in personal care (Prospective Study) and minimum care nursing home (Retrospective Study) for the project areas. Cost-shifting between Medicaid and Medicare in the project areas and two different patterns of utilization in the North and South projects tended to offset each other such that no differences in total costs between the project areas and demonstration areas occurred. The project was significant ((beta) = .22, p < .001) only for personal care costs. The explanatory power of this personal care regression model (R('2) = .36) was comparable to other reported health services utilization models. Other variables (Medicare buy-in, level of disability, Social Security Supplemental Income (SSI), net monthly income, North/South areas and age) explained more variation in the other twelve cost regression models. ^

The relationship between calcium and fluoride intake, pregnancy and lactation and the risk of height loss in white women

This study was designed to investigate the effect of calcium and fluoride intake, and parity and lactation on the risk of spinal osteoporosis. Height loss was used as a surrogate measure for spinal fractures by taking advantage of documented changes in height found during the 25-year follow-up of the Charleston Heart Study cohort. Women who had lost 2-4" in height or who had no change in height during the follow-up period were defined as case and comparison subjects respectively. Calcium intake when the subjects were "about 25" and in the recent past, average intake of fluoride over 25 years, and parity and history of breastfeeding were ascertained by questionnaire from 54 case and 77 comparison subjects. Low calcium intake in the past decreased the risk of height loss (age-adjusted OR = 0.3, 95%CI: 0.1-0.96) although several potentially important confounding variables could not be adjusted for. There was no association between risk of height loss and present calcium intake (OR = 0.8, 95%CI: 0.3-2.6 for low versus high intake) after adjustment for past calcium intake. High fluoride intake decreased the risk of height loss (adjusted OR = 0.4, 95%CI: 0.1-1.2). The effect of fluoride or calcium intake in the present was modified by the level of the other nutrient. Compared to a low intake of both calcium and fluoride, a high intake of one increased the risk of height loss (crude OR = 3.3 for high fluoride/low calcium, crude OR = 6.0 for high calcium/low fluoride) although a high intake of both was slightly protective (crude OR = 0.7). It is estimated that a "high" nutrient intake in this population was greater than 850mg/day for calcium and 2mg/day for fluoride. After adjustment for age, increasing parity decreased the risk of height loss in women who had never breastfed (OR = 0.2, 95%CI: 0.01-1.7 for 4 or more children). Women who had breastfed were also at lower risk of height loss than nulliparous women (OR = 0.3, 95%CI: 0.1-1.2 for 4 or more children) although at any level of parity, breastfeeding women had a greater risk of height loss than did non-breastfeeding women. ^

The impact of social support networks on compliance with hypertensive therapeutic regimens among noninstitutionalized black adults

A conceptual framework based on the Health Belief Model was proposed which identified those factors most significant in the prediction of compliance behavior. The hypothesized model was applied to analyze the effects of sociodemographic characteristics, self-assessed health status, and social support networks on compliance with antihypertensive regimens, focusing on black adults.^ The study population was selected from the National Health and Examination Survey II (NHANES II) which produced a sample of 3,957 eligible persons 35-74 years of age.^ The study addressed the following research questions: (a) what is the relationship between demographic variables and self-assessed health status, (b) what is the relationship between social support network and self-assessed health status, (c) what is the compliance, (d) what factors, e.g., demographic characteristics, social support network, self-assessed health status, are most related to compliance, and (e) does the effect of these factors on compliance differ between black and white adults?^ The results of the study found that blacks: (a) had poorer health than whites, and education and income were significantly related to self-assessed health status, (b) the stronger social support networks of blacks, the better their health status, and (c) older blacks and those in poorer health were more likely to comply with recommended treatment. The hypothesized conceptual model for the prediction of compliance behavior was partially substantiated for both blacks and whites.^ Implications for the application of the conceptual model are also discussed. ^

Potential roles for bcl-2 in the pathogenesis, progression, and treatment of prostate cancer

The most common molecular alterations observed in prostate cancer are increased bcl-2 protein expression and mutations in p53. Understanding the molecular alterations associated with prostate cancer are critical for successful treatment and designing new therapeutic interventions. Hormone-ablation therapy remains the most effective nonsurgical treatment; however, most patients will relapse with hormone-independent, refractory disease. This study addresses how hormone-ablation therapy may increase bcl-2, develops a transgenic model to elucidate the role of bcl-2 multistep prostate carcinogenesis, and assesses how bcl-2 may confer resistance to cell death induction using adenoviral wild-type p53 gene therapy. ^ Two potential androgen response elements were identified in the bcl-2 promoter. Bcl-2 promoter luciferase constructs were transfected into the hormone- sensitive LNCaP prostate cell line. In the presence of dihydrotestosterone, the activity of one bcl-2 promoter luciferase construct was repressed 40% compared to control cells grown in charcoal-stripped serum. Additionally, it was demonstrated that both bcl-2 mRNA and protein were downregulated in the LNCaP cells grown in the presence DHT. This suggests that DHT represses bcl-2 expression through possible direct and indirect mechanisms and that hormone-ablation therapy may actually increases bcl-2 protein. ^ To determine the role of bcl-2 in prostate cancer progression in vivo, probasin-bcl-2 mice were generated where human bcl-2 was targeted to the prostate. Increased bcl-2 expression rendered the ventral prostate more resistant to apoptosis induction following castration. When the probasin-bcl-2 mice were crossed with TRAMP mice, the latency to tumor formation was decreased. The expression of bcl-2 in the double transgenic mice did not affect the incidence of metastases. The double transgenic model will facilitate the study of in vivo effects of specific genetic lesions during the pathogenesis of prostate cancer. ^ The effects of increased bcl-2 protein on wild-type adenoviral p53-mediated cell death were determined in prostatic cell lines. Increased bcl-2 protected PC3 and DU145 cell lines, which possess mutant p53, from p53-mediated cell death and reductions in cell viability. Bcl-2 did not provide the same protective effect in LNCaP cell line, which expresses wild-type p53. This suggests that the ability of bcl-2 to protect against p53-mediated cell death is dependent upon the endogenous status of p53. ^