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Biomedical subjects

J S Larson

Publications and source records attributed to J S Larson.

At least 19 recordsLinked to original sources

Medicine, government, and the human genome.

The sequencing of the human genome represents the most important scientific discovery of out age. What can the medical community expect from government in applying the new technology? The major government initiative, the Human Genome Project, is due to be completed in 2005 but a number of important issues remain. Genetic therapy promises to be the most significant use of the new technology, developing new drugs and treatment for the genetic components of disease. However, genetic enhancement is a controversial area involving moral, legal, and ethical issues. Government policy will have to respond to these issues as well as to important developments in the private sector. Ultimately, the public good will have to be protected as scientific discoveries advance the frontiers of medicine.

Federal Government↗

The conceptualization of health.

The meaning of health is complex and subject to change. In this article, four conceptual models of health are presented to summarize the current meanings for health. The medical model is the most widely used definition in the United States, but the World Health Organization model has gained in popularity during the past several decades. In addition, there are other newer models--the wellness model and the environmental model--that are adding new meanings to the definition of health. By understanding and combining these different meanings, the prospects for improving medical outcomes and the quality of care are enhanced. This conceptual work is a prelude to improving health status assessment in a variety of contexts.

Environmental Health↗

Early extubation after abdominal aortic reconstruction.

OBJECTIVE: To assess the safety of early (<2 hrs) extubation after elective infrarenal aortic surgical procedures. DESIGN: A retrospective chart review of 192 consecutive elective infrarenal aortic surgical procedures from January 1990 to March 1994 at Mayo Clinic Scottsdale was undertaken. MEASUREMENTS AND MAIN RESULTS: Combined general and epidural anesthesia was used extensively (187 patients; 97.4%). Early extubation was accomplished in 166 (86.5%) patients. Time to extubation was dependent on clinical factors and not by protocol. All early extubations occurred in the operating room or recovery room with a median time from skin closure of 12 minutes. Ten patients were extubated from 2 to 12 hours after the procedure, 14 patients more than 12 hours after the procedure, and 2 patients were not extubated and subsequently expired. Of the 166 patients extubated within 2 hours, 8 (4.8%) required reintubation. Factors found univariantly to be significantly associated with failure of early extubation include obesity, abnormal chest x-ray postoperatively, prior myocardial infarction, and prior coronary revascularization (p < 0.05). CONCLUSION: Early extubation (<2 hrs) after elective infrarenal aortic procedures may be performed safely and should be undertaken unless clinical features suggest failure of extubation.

Aged↗

A BRCA1 mutant alters G2-M cell cycle control in human mammary epithelial cells.

Mutations in BRCA1 increase the risk of breast and ovarian cancer. Although the mechanism by which mutant BRCA1 alters growth regulation is unknown, the COOH terminus of BRCA1 appears to play a critical role. To examine this, we introduced a vector expressing BRCA1 COOH-terminal residues 1293-1863 (CT-BRCA1) into nontumorigenic human breast epithelial cells. Overexpression of CT-BRCA1 led to a reduction in the doubling time (from 64 to 44 h) and a decreased reliance on growth factors, suggesting that this CT-BRCA1 may function in a dominant-negative manner. Expression of CT-BRCA1 induced alterations in cell cycle control, mainly in G2-M, including a loss of G2-M block by colchicine. These results suggest that one function of BRCA1-related growth control occurs by governing checkpoint(s) between DNA replication and mitosis.

BRCA1 Protein↗

The MOS 36-item short form health survey. A conceptual analysis.

The SF-36 is a practical and widely-tested instrument for measuring health status and medical outcomes. This article is not a critique of the SF-36, rather, it underscores its viability as an instrument for measuring physical and mental health and well-being. The article is a conceptual analysis of the SF-36, from the viewpoint of four models of health: medical, World Health Organization, wellness, and environmental. All four models suggest that the SF-36 be expanded to include other dimensions of health, especially mental and social. Specific dimensions to be included are: incidents of morbidity, satisfaction with quality of life, absence of mental disorders, social adjustment, social support, higher states of functioning, and adjustment to the environment. The end result of the suggested additions would be an instrument with greater conceptual meaning, for use in medical outcomes studies or surveys of the general population.

Evaluation Studies as Topic↗

In vitro activation of purified human heat shock factor by heat.

A major regulatory step in the heat-induced transcription of heat shock protein (hsp) genes in eukaryotes is the activation of heat shock factor (HSF). In metazoans and Schizosaccharomyces pombe, HSF is present in unstressed cells but is unable to bind to its target DNA sequence element, the heat shock element (HSE). Heat induction of the DNA binding activity of HSF is a critical component required for activation of heat shock genes. Inactive HSF in extracts of non-heat shocked human cells can be heated in vitro to activate HSF, suggesting the factors required to sense temperature and activate HSF are soluble factors [Larson, J. S., Schuetz, T. J., & Kingston, R. E. (1988) Nature 335, 372-375]. We utilized the ability to purify human HSF in the active form to characterize further the in vitro activation of HSF. Here we have developed a procedure to deactivate the DNA binding ability of HSF. When purified and deactivated HSF is heated, the DNA binding ability of HSF is activated. This activation occurs most efficiently at 43 degrees C (heat shock temperature), but, in contrast to activation in the crude system, some activation of HSF is observed at 37 degrees C (non-heat shock temperature). We show that purified and deactivated HSF is similar to natural inactive HSF in both size and shape. Thus, the monomer to trimer transition that activates HSF can occur in a temperature-dependent fashion in the absence of other proteins. It is possible that these biochemical properties of HSF contribute to the ability of HSF to respond to heat in vivo.

Animals↗

Comparing drugs for short-term sedation.

Selected benzodiazepines and a phenol derivative are reviewed in relation to their appropriateness as short-term sedatives in settings such as noninvasive and invasive medical procedures. Terminating sedation with flumazenil is also a focus of interest.

Anesthesia↗

Predictors of international health status.

This study presents a new measure of health status, called the Health Status Scale (HSS). The HSS is composed of five indicators: three measuring adult mortality and two measuring mental and social health. The scale is created to conform to the World Health Organization (WHO) definition of health as including physical, mental, and social components. The scale is used as the dependent variable in a regression equation, using six common predictors of health status. The predictors relate to health personnel, nutrition, and health facilities. The results of the regression analysis indicate that health facilities are the most significant predictors of health status, using the HSS. Their significance may be due to the relationship between adult mortality and the absence of facilities to treat chronic disease in adults.

Data Collection↗

Activation in vitro of sequence-specific DNA binding by a human regulatory factor.

The human heat-shock factor (HSF) regulates heat-shock genes in response to elevated temperature. When human cells are heated to 43 degrees C, HSF is modified post-translationally from a form that does not bind DNA to a form that binds to a specific sequence (the heat-shock element, HSE) found upstream of heat-shock genes. To investigate the transduction of the heat signal to HSF, and more generally, how mammalian cells respond at the molecular level to environmental stimuli, we have developed a cell-free system that exhibits heat-induced activation of human HSF in vitro. Comparison of HSF activation in vitro and in intact cells suggests that the response of human cells to heat shock involves at least two steps. First, an ATP-independent, heat-induced alteration of HSF allows it to bind the HSE; the temperature at which activation occurs in vitro implies that a human factor directly senses temperature. Second, HSF is phosphorylated. It is possible that similar multi-step activation mechanisms play a role in the response of eukaryotic cells to a variety of environmental stimuli, and that these mechanisms evolved to increase the range and flexibility of the response.

Cell-Free System↗

Evaluation of coagulation studies from heparinized arterial lines with use of Lab-Site high-pressure tubing.

Heparinized arterial catheters are commonly used in critically ill patients to monitor pressures and to collect blood for laboratory analysis. To remove the heparinized fluid used to keep these lines patent large volumes of blood are often withdrawn and discarded or calculations of tube volume must be made. Repeated violation of stopcocks may lead to contamination and infection of arterial lines. In addition, discarded blood has become an increasing concern as a source of infection for health care personnel. This study evaluates the efficacy of noncompliant arterial line tubing that contains two polymer sampling ports permanently placed at prefixed distances such that if blood is withdrawn to the distal port, undiluted arterial blood can then be withdrawn from the proximal port. Blood from arterial lines that consisted of 20-gauge catheters connected to Lab-Site tubing was withdrawn in the method suggested by the manufacturer with no removal or wasting of excess blood from the system. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) studies performed on this sample were compared with those performed on a simultaneously drawn venous sample. Regression analysis showed a correlation coefficient of 0.966 for PT and 0.935 for aPTT, demonstrating an excellent correlation for the technique. The average arterial PT was 0.12 seconds less than venous control and the average arterial aPTT was 0.49 seconds greater than control. Neither of these differences was significant. We conclude that this type of high-pressure tubing allows accurate blood samples to be obtained from arterial lines without the necessity of precise calculations or blood wastage.

Blood Coagulation Tests↗