PubMed Health⌕ Search

Biomedical subjects

J C Hershey

Publications and source records attributed to J C Hershey.

At least 19 recordsLinked to original sources
PubMed2001

Revascularization in the rabbit hindlimb: dissociation between capillary sprouting and arteriogenesis.

OBJECTIVE: Animal models of hindlimb ischemia are critical to our understanding of peripheral vascular disease and allow us to evaluate therapeutic strategies aimed to improve peripheral collateral circulation. To further elucidate the processes involved in revascularization following ischemia, we evaluated the temporal association between tissue ischemia, vascular endothelial cell growth factor (VEGF) release, angiogenesis (capillary sprouting), arteriogenesis (growth of the larger muscular arteries), and reserve blood flow (functional collateral flow). METHODS: New Zealand White rabbits (male 3-4 kg) were evaluated at specific days (0, 5, 10, 20 or 40) following femoral artery removal for measurement of hindlimb blood flow, skeletal muscle lactate production and VEGF content, capillary density (a marker of angiogenesis), and angiographic score (a marker of arteriogenesis). RESULTS: Maximal capillary sprouting occurred within 5 days of femoral artery removal and was temporally associated with reduced resting hindlimb blood flow, increased lactate release and detectable levels of skeletal muscle VEGF. The growth of larger angiographically visible collateral vessels occurred after 10 days and was not temporally associated with ischemia or skeletal muscle VEGF content, but did coincide with a large functional improvement in the reserve blood flow capacity of the limb. CONCLUSIONS: Following femoral artery removal in the rabbit, the time course of angiogenesis and arteriogenesis were clearly distinct. Tissue ischemia and/or VEGF may stimulate capillary sprouting, but this response does not translate to a significant improvement in collateral flow. The growth and development of the larger collateral vessels was correlated with a large functional improvement in collateral flow, and occurred at a time when VEGF levels were undetectable.

Analysis of Variance↗
PubMed2000

Determinants of priority for risk reduction: the role of worry.

One hundred twenty-two members (experts) of the Society for Risk Analysis completed a mailed questionnaire and 150 nonexperts completed a similar questionnaire on the World Wide Web. Questions asked included those about priorities on personal and government action for risk reduction, badness of the risk, number of people affected, worry, and probabilities for self and others. Individual differences in mean desire for action were largely explained in terms of worry. Worry, in turn, was largely affected by probability judgments, which were lower for experts than for nonexperts. Differences across risks in the desire for action, within each subject, were also determined largely by worry and probability. Belief in expert knowledge about the risk increased worry and the priority for risk reduction. A second study involving 91 nonexperts (42 interviewed and 49 on the Web) replicated the main findings for nonexperts from the first study. Interviews also probed the determinants of worry, attitudes toward government versus personal control, and protective behaviors.

Adolescent↗
PubMed1998

Phosphorylation of the rRNA transcription factor upstream binding factor promotes its association with TATA binding protein.

rRNA synthesis by RNA polymerase I requires both the promoter selectivity factor 1, which is composed of TATA binding protein (TBP) and three TBP-associated factors, and the activator upstream binding factor (UBF). Whereas there is strong evidence implicating a role for phosphorylation of UBF in the control of growth-induced increases in rRNA transcription, the mechanism of this effect is not known. Results of immunoprecipitation studies with TBP antibodies showed increased recovery of phosphorylated UBF from growth-stimulated smooth muscle cells. Moreover, using an immobilized protein-binding assay, we found that phosphorylation of UBF in vivo in response to stimulation with different growth factors or in vitro with smooth muscle cell nuclear extract increased its binding to TBP. Finally, we demonstrated that UBF-TBP binding depended on the C-terminal 'acidic tail' of UBF that was hyperphosphorylated at multiple serine sites after growth factor stimulation. Results of these studies suggest that phosphorylation of UBF and subsequent binding to TBP represent a key regulatory step in control of growth-induced increases in rRNA synthesis.

Animals↗
PubMed1997

Expression of the smooth muscle myosin heavy chain gene is regulated by a negative-acting GC-rich element located between two positive-acting serum response factor-binding elements.

To identify cis- and trans-acting factors that regulate smooth muscle-specific gene expression, we studied the smooth muscle myosin heavy chain gene, a rigorous marker of differentiated smooth muscle. A comparison of smooth muscle myosin heavy chain promoter sequences from multiple species revealed the presence of a highly conserved 227-base pair domain (nucleotides -1321 to -1095 in rat). Results of a deletion analysis of a 4.3-kilobase pair segment of the rat promoter (nucleotides -4220 to +88) demonstrated that this domain was necessary for maximal transcriptional activity in smooth muscle cells. Gel-shift analysis and site-directed mutagenesis demonstrated that one true CArG and another CArG-like element contained within this domain were both recognized by the serum response factor and were both required for the positive activity attributable to this domain. Additional studies demonstrated that mutation of a GC-rich sequence within the 227-base pair conserved domain resulted in a nearly 100% increase in transcriptional activity. Gel-shift analysis showed that this GC-rich repressor element was recognized by both Sp1 and Sp3. These data demonstrate that transcriptional control of the smooth muscle myosin heavy chain gene is highly complex, involving both negative and positive regulatory elements, including CArG sequences found in the promoters of multiple smooth muscle differentiation marker genes.

Animals↗
PubMed1997

Undercontribution bias in health care spending account decisions.

Results from this work describe 239 responses to a mailed survey regarding employee benefits decisions at a large eastern university. The primary objective of this work is to test for an undercontribution bias in health care financing decisions. The results establish the existence of an undercontribution bias in both actual employee decisions and hypothetical flexible spending account contribution decisions. We describe this bias within the context of related biases including loss aversion, mental accounting, status quo and omission biases. Surprisingly, we find a significant order effect in this study and posit that preference construction in this context is an active, reference-dependent process. In addition, results from this work demonstrate the endogenous nature of health care flexible spending account expenditures. The results have important implications both for the descriptive framework of and the normative solution to the flexible spending account contribution decision.

Community Participation↗
PubMed1996

Cognitive processes and the decisions of some parents to forego pertussis vaccination for their children.

Public health analyses suggest that, in spite of the possibility that pertussis vaccine may cause rare cases of neurological injury, catastrophic risks to individual children are lower if they are vaccinated. A number of parents, however, choose not to vaccinate their children. The purpose of this study was to investigate the decision processes of some parents who choose to vaccinate and some parents who choose not to do so. Surveys were mailed to 500 randomly selected subscribers of Mothering magazine. Two hundred and ninety-four completed questionnaires were returned (59%). In addition to well-recognized factors in vaccination decisions, perceived dangers of the vaccine, and of the disease and susceptibility to the disease, several cognitive processes not previously considered in vaccination decision studies were found to be important predictors in this population of parents: perceived ability to control children's susceptibility to the disease and the outcome of the disease; ambiguity or doubts about the reliability of vaccine information; a preference for errors of omission over errors of commission; and recognition that if many other children are vaccinated, the risk to unvaccinated children may be lowered. Although perhaps most cases of undervaccination for pertussis reflect more general problems of health care access, some parents choose to forego vaccination for their children for other reasons. Traditional risk-benefit arguments alone will be unlikely to persuade these parents to reassess their decisions. Efforts to increase childhood vaccination must incorporate an understanding of the cognitive processes that help drive these decisions.

Adult↗
PubMed1996

Individual choice in spending accounts. Can we rely on employees to choose well?

Flexible spending accounts (FSA) represent a current health care financing tool that may become an important component of incremental health care reform. Because FSAs require employees to make financial contributions based on anticipated health care needs, contribution decisions are likely to be subject to many of the errors made in other insurance decisions. The authors analyzed the benefits selections, benefits forms completion, and FSA contribution levels of approximately 9,500 employees of the University of Pennsylvania from 1987 to 1992. Default and repeat choice trends characterize the completion of benefits forms and the reselection of health insurance options by employees. Despite the economic benefits of contributing to an FSA, only 14% of employees contributed in any one year and 73% never made a contribution. Multivariate models of these contributions fail to demonstrate the importance of what ought to be relevant influences in contribution decisions (for example, age, income, family status, or underlying health insurance). Whereas most FSA decisions are characterized by default contributions of $0, employees who contribute in one year are most likely to contribute exactly the same amount the next year, even when other circumstances change. The pervasiveness of these patterns raises concerns that health care reform plans that rely on financial incentives at the consumer level--for example, proposed medical saving accounts--will be inefficient.

Choice Behavior↗
PubMed1996

Measuring hospital outcomes from a buyer's perspective.

This study reports lessons learned from a project to develop a flexible, generalizable, and valid method for corporate buyers of hospital care that would permit them to use available secondary data to rate the outcomes quality of all hospitals in a local market area. As hospitalization insurance has moved from coverage that applied equally to all licensed hospitals to arrangements which selected a certain preferred hospital or hospitals and rejected others, the need to determine the quality of different hospitals (as well as what they would cost the insurer or buyer) has become apparent. The product of this project was the development and demonstration of a set of rating methods that build on the strengths available in large hospital discharge data bases, such as (but by no means limited to) that of the Pennsylvania Health Care Cost Containment Council (PHC4). These measures, or others developed using these methods, deal with uncertainty in the data--its diagnosis and treatment--in a conceptually valid and practically useful way, illustrate a process that might be used in the general development of quality measures, and provide a useful critique of some other measures.

Commerce↗
PubMed1996

Genetic screening for reproductive planning: methodological and conceptual issues in policy analysis.

OBJECTIVES: This paper explores several critical assumptions and methodological issues arising in cost-effectiveness analyses of genetic screening strategies in the reproductive setting. METHODS: Seven issues that arose in the development of a decision analysis of alternative strategies for cystic fibrosis carrier screening are discussed. Each of these issues required a choice in technique. RESULTS: The presentations of these analyses frequently mask underlying assumptions and methodological choices. Often there is no best choice. In the case of genetic screening in the reproductive setting, these underlying issues often touch on deeply felt human values. CONCLUSIONS: Space limitations for published papers often preclude explaining such choices in detail; yet these decisions determine the way the results should be interpreted. Those who develop these analyses need to make sure that the implications of important assumptions are understood by the clinicians who will use them. At the same time, clinicians need to enhance their understanding of what these models truly mean and how they address underlying clinical, ethical, and economic issues.

Cystic Fibrosis↗
PubMed1995

Angiotensin II-induced hypertrophy of rat vascular smooth muscle is associated with increased 18 S rRNA synthesis and phosphorylation of the rRNA transcription factor, upstream binding factor.

Hypertrophy of vascular smooth muscle cells (VSMC) is an important adaptive response of hypertension. Drug intervention studies have implicated a role for angiotensin II (A-II) in the mediation of VSMC hypertrophy in vivo, and A-II is a potent hypertrophic agent for VSMC in culture. Our laboratory has previously shown that A-II-induced hypertrophy of cultured VSMC is due in part to generalized increases in protein synthesis and increased content of rRNA. The aim of the present study was to determine if A-II stimulates rRNA gene synthesis and whether the rRNA transcription factor, upstream binding factor (UBF), is involved. Nuclear run-on analysis demonstrated that A-II induced a greater than 5-fold increase in rRNA gene synthesis within 6 h of stimulation. A-II also stimulated a rapid increase in UBF phosphorylation as well as nucleolar localization, but no changes in the content of UBF. Phosphoamino acid analysis showed that phosphorylation occurred only on serine residue(s). Results demonstrate that increased transcription of ribosomal DNA contributes to the A-II-induced increase in protein synthesis and VSMC hypertrophy, and suggest that an important regulatory event in this pathway may be the phosphorylation and/or nucleolar localization of UBF.

Angiotensin II↗
PubMed1995

Why some health policies don't make sense at the bedside.

Cost-effectiveness analysis and other forms of decision analysis are becoming more common in the medical literature and are increasingly influential in the development of health policy. Nevertheless, many clinicians find it difficult to apply policies developed from these analyses to individual encounters with patients. We examine the assumptions behind these analyses and argue that the perspective they embody can make clinical strategies appear to be less risky in theory than they are at the bedside. We believe that this problem underlies the intuitive concern many physicians have about policy analyses and calls into question the value of these analyses in shaping clinical practice. These analyses aggregate the benefits and burdens of alternative interventions across different individual persons. Thus, overall population risk appears blunted, as it would in a diversified portfolio of stocks that react differently to financial forces or in a herd of cattle that react differently to veterinary interventions. The assumptions behind these analyses make sense if aggregate outcome is what matters, but not if one cares about each individual investment or animal. Because such aggregation tends to understate individual risk, when applied to human health policy, it may misrepresent the interests of patients and cannot be assumed to provide useful guidelines for decision making at the bedside.

Cost-Benefit Analysis↗
PubMed1994

The influence of sympathoadrenal activation on skeletal muscle oxygen extraction during endotoxemia.

We have previously shown a direct relationship (r = .97) between the fall in arterial blood pressure and the increase in skeletal muscle oxygen extraction (MVO2) during canine endotoxemia. Since it is well known that hypotension activates the sympathetic system, the primary aim of these experiments was to determine if the increase in MVO2 during endotoxemia is a result of elevated levels of catecholamines due to increased sympathetic neural and/or humoral activity (sympathoadrenal system). Canine gracilis muscles were vascularly isolated and perfused in situ at a constant flow (6-7 ml/min/100 g). Endotoxemia was induced by a 30 min intravenous infusion of Escherichia coli endotoxin (2 mg/kg), which induced a 50% reduction in arterial pressure. Perfusion pressure, mean arterial pressure, and arteriovenous oxygen difference (a-v O2) were continuously measured. We found 1) no significant difference between the amount of O2 extracted by an innervated or a denervated muscle during endotoxemia; 2) the intra-arterial infusion of norepinephrine or epinephrine into a denervated gracilis muscle (plasma molar concentrations of; 10(-11), 10(-9), 10(-7), and 10(-5) failed to increase MVO2 to the level observed during endotoxemia; 3) pretreatment of a muscle with propranolol to block skeletal muscle beta-adrenergic receptors, did not suppress the endotoxin-induced rise in MVO2. We concluded that the increase in MVO2 seen after the administration of endotoxin is not due to either increased sympathetic nerve activity or elevated levels of circulating catecholamines. We speculate that the increased MVO2 during endotoxemia is caused by nonadrenergic mediators released by endotoxin rather than the hypotensive stimulus.

Adrenal Cortex↗
PubMed1993

Variation in physicians' decision-making thresholds in management of a sexually transmitted disease.

OBJECTIVE: To gain insight into the variation in physicians' clinical decisions and further understand the factors that influence physicians' thresholds for testing and treating. DESIGN: Written clinical scenarios were mailed to two groups of physicians who were asked to provide probability estimates of syphilis, how these estimates might change with new information, and when a diagnostic test would be ordered or treatment begun. A model was then used to calculate the probabilities at which physicians ordered tests or initiated treatment. PARTICIPANTS: Group 1 comprised 126 board-certified internists from metropolitan Philadelphia responding from a sample of 360 such physicians randomly selected from a directory. Group 2 consisted of 31 experts in sexually transmitted disease responding from a sample of 50 experts selected by the authors. MEASUREMENTS AND MAIN RESULTS: Experts were willing to obtain a serologic screening test at a lower likelihood of syphilis (0.013%) than were internists (0.034%), and they were willing to obtain a lumbar puncture at a lower likelihood of neurosyphilis (0.165%) than were internists (0.393%). The difference in the groups' thresholds to begin neurosyphilis treatment was not significant. A multivariate model showed that group differences were created by individual characteristics (years in practice, subspecialty board certification, and full-time nonacademic practice) that were associated with higher thresholds for serologic screening. CONCLUSIONS: There are differences in the diagnostic testing practices for syphilis between national experts and internists. Although status in one of these groups alone did not predict the threshold for obtaining syphilis tests, certain individual characteristics were predictive. Examination of physician characteristics helps to explain the variation observed in their practice patterns, and determination of physicians' thresholds aids in analyzing these variations.

Clinical Laboratory Techniques↗