Insulin influences astroglial morphology and glial fibrillary acidic protein (GFAP) expression in organotypic cultures.

Variations in the levels and timing of exposure to insulin-related peptides influence the phenotypic appearance of astroglia present in organotypic cultures of the E17 mouse cerebellum as well as the expression of glial fibrillary acidic protein (GFAP) mRNA and its encoded protein. The morphology of GFAP-immunoreactive cells was influenced by the levels of insulin added in an age-specific manner. Fetal radial glia were selectively and significantly (P less than 0.001) increased by high (10 micrograms/ml) insulin levels, comprising the majority of the GFAP-positive cells seen. In contrast, there was an almost complete reversal of this pattern elicited by low (10 pg/ml) insulin levels, where GFAP-positive cells appeared undifferentiated and epithelioid (P less than 0.001). In newborn cultures, on the other hand, the morphological responses to both high and low levels of insulin were considerably attenuated and involved radial glia primarily, whose numbers were significantly increased by the high insulin levels. Exposure to high levels of insulin was accompanied by an increase in GFAP mRNA expression, as determined by non-isotopic (biotin) in situ hybridization histochemistry, and intense GFAP immunoreactivity, while low insulin levels elicited minimal expression of both message and protein product. In view of the critical interdependence of developing neurons and radial glia with respect to neuronal migration and the differentiation of neurons and astroglia, the responses observed suggest developmentally regulated mechanisms by which insulin-related peptides themselves may influence directly and indirectly both neuronal and astroglial differentiation.

Characteristics of hospitalizations of HIV-infected patients: an analysis of data from the 1994 healthcare cost and utilization project.

Hospitals are significant resources for care of HIV/AIDS patients. Previous studies that have attempted to identify and track the characteristics of these patients and their hospitalizations have been limited in their ability to produce national estimates of patient use of such resources. This study, using data from the Healthcare Cost and Utilization Project (HCUP-3) attempted to characterize and estimate the cost of hospital usage by HIV/AIDS patients. We estimate that in 1994 approximately 188,506 admissions of HIV/AIDS patients occurred with an average charge of $19,244 U.S. per admission, for an estimated total cost of $3.63 billion. Compared with non-HIV-infected patients, HIV/AIDS patients tended to be male (75.83% versus 41.49%), a member of a minority group (53.51% versus 20.77%), hospitalized in a private, nonprofit, urban teaching hospital with a longer average length of stay (10.27 versus 5.52 days), and to have a higher in-hospital mortality (11.45% versus 2.58%). Approximately half of the hospital charges (47%) for these admissions were absorbed by Medicaid, and 25% by private insurance. The remainder of the charges were borne by the patients themselves. The results presented here for 1994 predate the widespread use of protease inhibitor/ highly active antiretroviral therapy (HAART), thus making this study an important benchmark for the delineation of the effects of HAART and any other future developments in HIV therapy on the characteristics of HIV/AIDS patient resource use on a national level. This study further demonstrates that HCUP is a powerful tool for the estimation and costing of hospital resource use.

Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain.

The rodent and primate basal forebrain is a target of a family of endogenous peptide signaling molecules, the neurotrophins--nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3--and of the gonadal steroid hormone estrogen, both of which have been implicated in cholinergic function. To investigate whether or not these ligands may act on the same neurons in the developing and adult rodent basal forebrain, we combined autoradiography with 125I-labeled estrogen and either nonisotopic in situ hybridization histochemistry or immunohistochemistry. We now report colocalization of intranuclear estrogen binding sites with the mRNA and immunoreactive protein for the low-affinity nerve growth factor receptor, which binds all three neurotrophins, and for the cholinergic marker enzyme choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6). Colocalization of estrogen and low-affinity nerve growth factor receptors implies that their ligands may act on the same neuron, perhaps synergistically, to regulate the expression of specific genes or gene networks that may influence neuronal survival, differentiation, regeneration, and plasticity. That cholinergic neurons in brain regions subserving cognitive functions may be regulated not only by the neurotrophins but also by estrogen may have considerable relevance for the development and maintenance of neural substrates of cognition. If estrogen-neurotrophin interactions are important for survival of target neurons, then clinical conditions associated with estrogen deficiency could contribute to the atrophy or death of these neurons. These findings have implications for the subsequent decline in those differentiated neural functions associated with aging and Alzheimer disease.