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Biomedical subjects

B L Lewis

Publications and source records attributed to B L Lewis.

At least 19 recordsLinked to original sources
PubMed2000

Ventral tegmental area afferents to the prefrontal cortex maintain membrane potential 'up' states in pyramidal neurons via D(1) dopamine receptors.

The electrophysiological nature of dopamine actions has been controversial for years, with data supporting both inhibitory and excitatory actions. In this study, we tested whether stimulation of the ventral tegmental area (VTA), the source of the dopamine innervation of the prefrontal cortex, would exert different responses depending on the membrane potential states that pyramidal neurons exhibit when recorded in vivo, and whether VTA stimulation would have a role in controlling transitions between these states. Prefrontal cortical neurons have a very negative resting membrane potential (down state) interrupted by plateau depolarizations (up state). Although the up state had been shown to be dependent on hippocampal afferents in nucleus accumbens neurons, our results indicate that neither hippocampal nor thalamic inputs are sufficient to drive up events in prefrontal cortical neurons. Electrical VTA stimulation resulted in a variety of actions, in many cases depending on the neuron membrane potential state. Trains of stimuli resembling burst firing evoked a long-lasting transition to the up state, an effect blocked by a D(1) antagonist and mimicked by chemical VTA stimulation. These results indicate that projections from the VTA to the prefrontal cortex may be involved in controlling membrane potential states that define assemblies of activable pyramidal neurons in this region.

Animals↗
PubMed1999

Modulation of cell firing in the nucleus accumbens.

Pennartz et al. have proposed that functions of the nucleus accumbens (NA) are subserved by the activity of ensembles of neurons rather than by an overall neuronal activation. Indeed, the NA is a site of convergence for a large number of inputs from limbic structures that may modulate the flow of prefrontal cortical information and contribute to defining such ensembles, as exemplified in the ability of hippocampal input to gate cortical throughput in the nucleus accumbens. NA neurons exhibit a bistable membrane potential, characterized by a very negative resting membrane potential (down state), periodically interrupted by plateau depolarizations (up state), during which the cells may fire in response to cortical inputs. A dynamic ensemble can be the result of a distributed set of neurons in their up state, determined by the moment-to-moment changes in the spatial distribution of hippocampal inputs responsible for transitions to the up state. Ensembles may change as an adaptation to the contextual information provided by the hippocampal input. Furthermore, for dynamic ensembles to be functionally relevant, the model calls for near synchronous transitions to the up state in a group of neurons. This can be accomplished by the cell-to-cell transfer of information via gap junctions, a mechanism that can allow for a transfer of slow electrical signals, including "up" events between coupled cells. Furthermore, gap junction permeability is tightly modulated by a number of factors, including levels of dopamine and nitric oxide, and cortical inputs, allowing for fine-tuning of this synchronization of up events. The continuous selection of such dynamic ensembles in the NA may be disputed in schizophrenia, resulting in an inappropriate level of activity of thalamocortical systems.

Afferent Pathways↗
PubMed1995

Use of surgical intrauterine insemination to manage infertility in a colony of research German shepherd dogs.

A colony of German shepherd dogs with inherited ventricular arrhythmias and sudden death had infertility that was resolved by intrauterine insemination. Mating of German shepherd males to related German shepherd females (40 cycles) by vaginal artificial insemination resulted in a low pregnancy rate of 35% and a small median litter size of 3.5. When these same German shepherd males were bred to female beagles by vaginal artificial insemination, the pregnancy rate of 100% (P = 0.02) and median litter size of 7.0 were significantly (P = 0.04) greater. Therefore, inadequate fertility existed when the German shepherds were mated. Because matings between these dogs were necessary, surgical intrauterine insemination of fresh semen was instituted in eight German shepherd females over nine cycles. In bypassing the cervix with this method, German shepherd fecundity increased significantly, with a pregnancy rate of 100% (P = 0.002) and median litter size of 8.0 (P = 0.001). Surgical intrauterine insemination may be an important method for management of canine infertility in the research environment.

Animals↗
PubMed1990

Adaptation of an enzymatic cycling assay for NADP(H) measurement to the COBAS-FARA centrifugal analyzer.

NADP(H) measurements by enzymatic amplification are described in which the interface step between cycling (glucose-6-phosphate and glutamic dehydrogenases) and indicator (6-phosphogluconic dehydrogenase) enzymes has been reconfigured, permitting the entire operation to run as a continuous assay on a centrifugal fast analyzer. This is accomplished by using the sequential load feature of the analyzer and incorporating either sodium dodecyl sulfate (SDS) or SDS and hydrogen peroxide as kill reagents to replace the thermal step (destruction of cycle enzymes by boiling). The ability of SDS to render a cycle inoperative during the run time of the indicator enzyme depends on the inherent resistivity and absolute amount of its enzyme proteins to this surfactant. Criteria used to judge the efficacy of a potential kill reagent are based on the sample blank time-response curve and the cycle product recovery by the indicator enzyme. Various other enzyme cycling systems which can be fitted to the centrifugal fast analyzer are highlighted.

Centrifugation↗
PubMed1986

Acquisition of small rural hospitals by multihospital systems.

The occurrence of multihospital systems, two or more hospitals owned, leased, or managed by a separate organization, represents a note-worthy change in the way health care is organized today. The impact of this for small rural hospitals, however, has only been studied indirectly or anecdotally. This investigation, using data from national surveys, systematically documents and analyzes this trend and discusses its potential impact. By 1983 almost one quarter of all small rural hospitals were affiliated with multihospital systems. This growth occurred primarily over the last few years, and was accompanied by a rapid surge in the involvement of for-profit systems. This contrasts sharply with traditional rural hospital care which had been provided primarily by nonprofit or religious institutions. There also were differences in the form of affiliation the hospitals had with their parent organizations, with the most recent movement toward management contracts. Differential changes also occurred in the patterns of affiliation by geographic region.

Catchment Area, Health↗
PubMed1986

A taxonomic analysis of multihospital systems.

Research to date on multihospital systems has proved largely uninformative, in part because similarities and differences among these organizations have not been addressed systematically. Through numeric classification, this article identifies populations of multihospital systems that share similar organizational attributes. Drawing on McKelvey's classification theory, 16 organizational characteristics of 160 multihospital systems are analyzed using a series of taxonomic techniques, including cluster analysis, multiple discriminant analysis, and analysis of coefficients of variation. Fifteen distinct subgroups of systems are identified and described, and their implications for organization research discussed.

Catholicism↗
PubMed1985

Differential proliferative responses of cultured Schwann cells to axolemma and myelin-enriched fractions. II. Morphological studies.

Axolemma-enriched and myelin-enriched fractions were prepared from bovine CNS white matter and conjugated to fluorescein isothiocyanate (FITC). Both unlabelled and FITC-labelled axolemma and myelin were mitogenic for cultured rat Schwann cells. Treatment of Schwann cells with the FITC-labelled mitogens for up to 24 h resulted in two distinct morphological appearances. FITC-myelin-treated cells were filled with numerous round, fluorescent-labelled intracellular vesicles, while FITC-axolemma-treated cells appeared to be coated with a patchy, ill-defined fluorescence, primarily concentrated around the cell body but extending onto the cell processes. These observations were corroborated under phase microscopy. Electron microscopy revealed multiple, membrane-bound, membrane-containing phagosomes within myelin-treated cells and to a far lesser extent in axolemma-treated cells. The effect on the expression of the myelin-mediated and axolemma-mediated mitogenic signal when Schwann cells were treated with the lysosomal inhibitors, ammonium chloride and chloroquine, was evaluated. The mitogenicity of myelin was reduced 70-80% by these agents whereas the mitogenicity of axolemma was not significantly altered under these conditions. These results suggest that axolemma and myelin stimulate the proliferation of cultured Schwann cells by different mechanisms. Myelin requires endocytosis and lysosomal processing for expression of its mitogenic signal; in contrast, the mitogenicity of axolemma may be transduced at the Schwann cell surface.

Animals↗
PubMed1985

Toward an empirical classification of hospitals in multihospital systems.

Inconsistency and lack of utility in multihospital systems research is often attributable to misspecification of the unit of analysis and lack of generalizability of research findings. The typical, system-level focus takes an "organizations are all alike" approach that masks potentially important variation among constituent hospitals in systems. This article develops and validates a multivariate, empirical typology of hospitals affiliated with multihospital systems. The objective of the typology is to identify prevalent types of system hospitals that share similar organizational and operational characteristics. Three hundred and sixty-six hospitals affiliated with secular, not-for-profit multihospital systems were subjected to cluster analysis within and across affiliation categories (owned, leased, and contract managed). Findings indicate that the population of hospitals in not-for-profit systems is organizationally heterogeneous but that distinct groupings of hospitals, based largely on size and affiliation status, occur within this population. Homogeneous groupings of hospitals were tested for differences in governance and performance characteristics. Although these clusters differ only slightly in their governance characteristics, they do manifest several differences in performance characteristics. Implications and applications of these findings are discussed.

Contract Services↗
PubMed1984

Cyclic AMP and calcium as potential mediators of stimulation of cultured Schwann cell proliferation by axolemma-enriched and myelin-enriched membrane fractions.

The roles of cyclic AMP and calcium in the transduction of the mitogenic effects of central nervous system axolemma and myelin-enriched fractions on cultured Schwann cells were examined. Cyclic AMP levels were not elevated in axolemma or myelin-stimulated Schwann cells, but were increased when stimulated with cholera toxin, an adenyl cyclase activator. The mitogenicity of axolemma and myelin was markedly reduced by 2.5 mM citrate, a calcium chelator, and 10 uM trifluoroperazine, an inhibitor of calmodulin. Treatment of Schwann cells with several tumor-promoting phorbol esters caused significant enhancement of the mitogenicity of the axolemma and myelin preparations. These data suggest that the mitogenic effects of axolemma and myelin are not mediated by cyclic AMP, but may be mediated by calcium ions.

Animals↗
PubMed1984

Differential proliferative responses of cultured Schwann cells to axolemma- and myelin-enriched fractions. I. Biochemical studies.

Cultured rat Schwann cells were treated for 72 h with axolemma- and myelin-enriched fractions prepared from rat brainstem. [3H]Thymidine was added to the cultures 48 h before the termination of the experiment. Although, both fractions produced a dose-dependent uptake of label into Schwann cells, the shape of the dose response curves and rates at which [3H]thymidine was incorporated were different. The axolemma-enriched fraction produced a sigmoid dose response curve with a Hill coefficient of 2.05. The dose response curve for myelin rose sharply and saturated at a level that was approximately 50% of the maximal response observed with axolemma. Schwann cells that had been treated with axolemma exhibited little change in the rate of [3H]thymidine incorporation from 36-72 h after the addition of the membranes. In contrast, Schwann cells accumulated label three times faster during the 48-72-h period following the addition of myelin to the cultures when compared with the rate during the preceding 12-h interval. Furthermore, the mitogenic activity of the myelin-enriched fraction was decreased by the addition of ammonium chloride, a lysosomal inhibitor, whereas the activity of the axolemmal fraction was not impaired.

Animals↗
PubMed1984

The financial characteristics of hospitals under for-profit and nonprofit contract management.

In this assessment of the financial characteristics of a large sample of contract-managed hospitals compared with traditionally managed hospitals, emphasis was given to differences between hospitals managed by for-profit and nonprofit organizations and between hospitals before and after they were contract managed. Our findings suggest higher profitability for hospitals managed by nonprofit organizations in light of their poor profitability prior to contract management and better activity ratios for for-profit managed hospitals. These and other findings are discussed in terms of their implications for both hospital administrators and researchers.

Capital Expenditures↗
PubMed1984

Hospital contract management: a descriptive profile.

Despite the dramatic growth in hospital contract management in the last decade, research only recently has begun to provide insights into the structure, operation, and effectiveness of these arrangements. Two descriptive questions regarding hospital contract management are addressed in an effort to increase correspondence between theoretical and evaluative research in this area: (1) how do contract-managed hospitals differ from traditionally managed hospitals? and (2) how do contract-managed hospitals differ from each other? Principal discriminating variables in the analyses are hospital size, control, urban-rural location, region, management organization control, and management organization size. Results of the analysis on a sample of 406 contract-managed hospitals and 401 unaffiliated hospitals reveal important differences between contract-managed and traditionally managed hospitals as well as among contract management organizations. These findings are discussed in terms of their implications for future research and performance evaluations on contract management arrangements.

Contract Services↗
PubMed1983

Further studies on the mitogenic response of cultured Schwann cells to rat CNS axolemma-enriched fractions.

Axolemma-enriched fractions isolated from rat CNS stimulated cultured Schwann cells to divide without changing their morphology. Fluorescent activated cell sorter analysis of the axolemma-stimulated cells demonstrated an approximate 3-fold increase in the number of Schwann cells in the S-phase of the cell cycle. This increase correlated well with increases in the number of [3H]thymidine-labeled nuclei observed by light level radioautography. The membrane-bound mitogen was relatively heat-stable, but trypsin-sensitive, and was inactivated both by lipid extraction and sonication. Liver plasma membranes did not increase the mitotic index over that of untreated cells, indicating the axolemma-induced mitosis was not a general response to exogenous membranes. Increasing serum concentrations in the presence of a constant level of axolemma did not change the mitotic index, suggesting that the axolemma did not cause mitosis by removal of an inhibitory factor in serum. Potential mitogens such as gangliosides, myelin basic protein, heparin, an axolemmal lipid extract, and cGMP had no effect on the cultured Schwann cells. The characteristics of the axolemma-related mitogenic factor are discussed relative to other known mitogens for cultured Schwann cells.

Animals↗
PubMed1982

Family functioning as a mediating variable affecting psychosocial adjustment of children with cystic fibrosis.

Family functioning was examined as a mediating variable affecting adjustment in children with cystic fibrosis. Three groups of children (cystic fibrosis, asthma, and healthy control subjects) were initially compared on two dimensions of adjustment: self-concept and frequency of behavior problems. The families of these children were compared according to functional level of "cohesion" and "adaptability" (assessed by an as yet unvalidated family functioning measure). No significant difference was found between the groups in family functioning or children's self-concept. The two groups of chronically ill children did have significantly higher frequencies of behavior problems than had the healthy children. When there was statistical control for effects related to family functioning, however, this difference was not significant. Family functioning was found to be a better predictor of child adjustment than was the presence of illness. These results are consistent with recent research suggesting that children with cystic fibrosis adjust in basically healthy ways and that any deficits result more from mediating factors. In this study family functioning was found to be an important mediating factor in this process.

Asthma↗