PubMed Health⌕ Search

Biomedical subjects

K M Conrad

Publications and source records attributed to K M Conrad.

32 records · Page 2Linked to original sources
PubMed1994

Angiotensin II stimulates sis-inducing factor-like DNA binding activity. Evidence that the AT1A receptor activates transcription factor-Stat91 and/or a related protein.

Recent studies on cytokine and growth factor stimulated signal transduction have defined a direct pathway (Stat91) linking cell surface receptors to target genes in the nucleus. The Stat91 pathway regulated c-fos gene transcription involves activation by tyrosine phosphorylation of the DNA binding factor SIF (sis-inducing factor) in the cytoplasm, its nuclear translocation, and interaction with the regulatory element SIE (sis-inducing element). SIF is a complex of proteins containing members of the STAT family of transcription factors. We determined whether angiotensin II (AII), which acts as a growth factor in many cell types, could activate the Stat91 pathway. We used neonatal rat cardiac fibroblasts expressing G-protein linked AII receptors and CHO-K1 cells expressing stably transfected angiotensin type 1A (AT1A) receptors to address this question. Angiotensin II induced SIF-like activity in both cell types, with initial induction at 15-30 min, maximal around 2-3 h, and undetectable at 6 h. Cytoplasmic and nuclear fractions from cells exposed to AII contained DNA binding activity to SIE. The SIF activity was insensitive to protein synthesis inhibitors and sensitive to the tyrosine kinase inhibitor genistein. Stat91 or a related protein was identified as a component of the AII-induced SIF complex and increased levels of this tyrosine-phosphorylated protein were found in nuclear extracts of cells treated with AII. This is the first evidence that a seven transmembrane, G-protein-coupled receptor, namely AT1A, activates the Stat91-nuclear signaling pathway.

Angiotensin II↗
PubMed1994

Angiotensin II-induced protein tyrosine phosphorylation in neonatal rat cardiac fibroblasts.

Angiotensin II has been demonstrated to act as a growth factor in rat cardiac fibroblasts. However, the signaling events that lead to fibroblast cell growth in response to angiotensin II remain to be elucidated. This study was designed to determine whether angiotensin II stimulated tyrosine phosphorylation of proteins in cardiac fibroblasts. Immunoblot analysis demonstrated rapid tyrosine phosphorylation of distinct substrates of 125, 95, 46-60, and 44 kDa in response to 10 nM angiotensin II. Tyrosine phosphorylation was maximal at 5 min and persisted for at least 180 min. Additional tyrosine-phosphorylated proteins of 185, 145, and 85 kDa were detected in response to 10 ng/ml platelet-derived growth factor BB. A cluster of 75-80-kDa proteins were phosphorylated in response to angiotensin II, phorbol ester, and platelet-derived growth factor. Angiotensin II-induced tyrosine phosphorylation was unaffected by phorbol ester-sensitive protein kinase C down-regulation and could be partially blocked by pertussis toxin pretreatment. Angiotensin II stimulation resulted in increased cytosolic tyrosine kinase activity which was recovered by immunoprecipitation. Immunoblot analysis demonstrated tyrosine phosphorylation of p44MAPK, and, in addition, we demonstrated for the first time tyrosine phosphorylation of p125FAK, p46SHC, and p56SHC in response to angiotensin II. The finding that angiotensin II and platelet-derived growth factor stimulated tyrosine phosphorylation of p46SHC and p56SHC suggested that this protein may serve as a common tyrosine kinase substrate in the mitogenic signaling cascade induced by G-protein-coupled receptors and growth factors and is consistent with the hypothesis that angiotensin II-induced tyrosine phosphorylation is involved in mitogenic signaling pathways in neonatal rat cardiac fibroblasts.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Musculoskeletal injuries in the fire service: views from a focus group study.

1. The focus group is a qualitative data collection method involving carefully planned small group discussions designed to obtain perceptions on a defined area of interest. Focus groups can be used by occupational health nurses for gathering ecologically based, in-depth needs assessment information from workers prior to program planning. 2. Occupational health nurses can be guided in their needs assessments by an ecological framework that considers the person, workplace, and situational factors that contribute to occupational health problems. 3. A focus group study of fire chiefs and firefighters used an ecological framework to elicit participants' perceptions of the factors that contribute to musculoskeletal injury and the preventive strategies that would be acceptable to them. Participants shared their insights, motivations, and feelings about the factors, thus suggesting concepts and hypotheses to be explored further. 4. The occupational health nurse needs to consider the differing meanings that management and workers attach to an occupational health problem.

Fires↗
PubMed1994

A case management tool for occupational health nurses: development, testing, and application.

1. Case management is a process of coordinating an individual client's health care services to achieve optimal, quality care delivered in a cost effective manner. The case manager establishes a provider network, recommends treatment plans that assure quality and efficacy while controlling costs, monitors outcomes, and maintains a strong communication link among all the parties. 2. Through development of audit tools such as the one presented in this article, occupational health nurses can document case management activities and provide employers with measurable outcomes. 3. The Case Management Activity Checklist was tested using data from 61 firefighters' musculoskeletal injury cases. 4. The activities on the checklist are a step by step process: case identification/case disposition; assessment; return to work plan; resource identification; collaborative communication; and evaluation.

Adult↗
PubMed1993

Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts.

Angiotensin II has been reported to be a hormonal stimulus of cardiac growth, a response that may involve myocyte hypertrophy as well as growth of nonmyocytes. This study was designed to determine whether neonatal rat cardiac fibroblasts have an angiotensin II receptor that is coupled with hypertrophic and/or proliferative growth. Competitive radioligand binding studies showed that cardiac fibroblasts have a single class of high-affinity (IC50, 1.0 nM) angiotensin II binding sites (Bmax, 778 fmol/mg protein) that are sensitive to the competitive nonpeptide AT1 receptor antagonist losartan (IC50, 13 nM). Other angiotensin peptides competed for [125I]angiotensin II binding in the following rank order: angiotensin II > angiotensin III > angiotensin I > > [des-Asp1-des-Arg2]angiotensin II. A nonhydrolyzable analogue of guanosine triphosphate increased the dissociation rate of bound [125I]angiotensin II and decreased hormone binding to the receptor at equilibrium. The angiotensin II receptor was coupled with increases in intracellular calcium. Incorporation of precursors into protein, DNA, and RNA in response to angiotensin II was determined. In serum-deprived cultures, a 24-hour exposure to 1 microM [Sar1]angiotensin II increased rates of phenylalanine, thymidine, and uridine incorporation by 58%, 103%, and 118%, respectively. These increases were blocked by the noncompetitive AT1 receptor antagonist EXP3174. After 48 hours, [Sar1]angiotensin II increased total protein and DNA of cardiac fibroblasts by 23% and 15%, respectively, with no change in the protein/DNA ratio. [Sar1]Angiotensin II increased cell number by 138% after a 24-hour exposure, without affecting cell area. In summary, cardiac fibroblasts have G protein-linked AT1 receptors that are coupled with proliferative growth. These results suggest that angiotensin II-induced cardiac hypertrophy is, in part, secondary to stimulated increases in nonmyocyte cellular growth.

Angiotensin II↗
PubMed1993

Factors associated with male workers' engagement in physical activity: white collar vs. blue collar workers.

The purpose of this study was to identify factors associated with male workers' participation in different kinds of physical activity, noting differences between white collar and blue collar workers. This study examined the variables, perceived health status, self efficacy, perceived barriers, age, education, income, and job category (Pender, 1987) for their association with physical activity. Self efficacy and perceived health status were the cognitive-perceptual factors that predicted physical activity. Job category (e.g., blue collar vs. white collar) was found to be a highly significant predictor of physical activity. Comparing physical job requirements with the individual worker capacity can suggest to the occupational health nurse physical fitness programs that are most appropriate for individual workers.

Adult↗
PubMed1992

Why children start smoking cigarettes: predictors of onset.

We review findings from 27 prospective studies of the onset of cigarette smoking conducted since 1980. Almost 300 measures of predictors of smoking onset were examined, and 74% of them provided multivariate support for predictors of onset derived from theory and previous empirical findings. Expected relationships were strongly supported for (a) socioeconomic status, with students with compromised status being more likely to try smoking; (b) social bonding variables, particularly peer and school bonding, with less support for family bonding; (c) social learning variables, especially peer smoking and approval, prevalence estimates, and offers/availability, with less consistent support for parent smoking and approval; (d) refusal skills self efficacy; (e) knowledge, attitudes and intentions, with the expected stronger predictions from intentions than from attitudes than from knowledge; and (f) broad indicators of self-esteem. The few investigators who analyzed their data separately by age, gender, or ethnicity found many differences by these factors, though there were too few of them to detect any pattern with confidence. Though the 27 studies are far from perfect, we believe that they confirm the importance of many well-accepted predictors and raise some questions about others. In particular, family smoking, bonding and approval each received unexpectedly low support. It is not clear whether this lack of support reflects reality as it has always been, is due to a changing reality, reflects developmental changes, either in the age of subjects or the stage of onset, or is due to poor measurement and too few tests. Future prospective studies need to be theory-driven, use measures of known reliability and validity, report analyses of scale properties, and use statistical methods appropriate to the hypotheses or theories under study. Finally, we encourage more investigations of the potentially different predictors of transitions to experimental or regular cigarette smoking. This will require multi-wave studies and careful measurement of changes in smoking behavior.

Adolescent↗
PubMed1992

Detection of angiotensin I and II in cultured rat cardiac myocytes and fibroblasts.

Angiotensin II (ANG II) is a stimulus for positive chronotropic and inotropic effects, protein synthesis, and hypertrophic growth in cardiac tissue. These short- and long-term effects of ANG II are mediated through specific plasma membrane receptors. Indirect evidence suggests that ANG II synthesized in the myocardium may be important in regulating cardiac function. The cell types in the myocardium that produce components of the renin-angiotensin system have not been determined. In this study, we evaluated whether cultured cardiomyocytes and fibroblasts obtained from ventricles of neonatal rat hearts were capable of synthesizing ANG I and II. Both cardiomyocytes and fibroblasts were found to have immunofluorescent staining for ANG I, ANG II, and angiotensin-converting enzyme (ACE). The amounts of ANG I and II in cell extracts and conditioned media obtained from cardiomyocytes and fibroblasts were quantified by radioimmunoassay. The amounts of ANG I and II detected in cardiomyocyte cultures (1.48 x 10(6) cells/dish) were 32.2 +/- 16.2 (n = 4) and 6.2 +/- 2.9 (n = 4) ng/10(6) cells, respectively. The amounts of ANG I and II detected in the media conditioned by a 48-h exposure to cardiomyocytes were 5.2 +/- 1.2 (n = 3) and 2.1 +/- 1.2 (n = 3) ng/10(6) cells, respectively. The amounts of ANG I and II detected in fibroblast cultures (5.38 x 10(6) cells/dish) were 34.8 +/- 4.9 (n = 4) and 8.0 +/- 3.5 (n = 4) ng/10(6) cells, respectively. The amounts of ANG I and II obtained from media conditioned by a 48-h exposure to fibroblasts were 4.7 +/- 0.6 (n = 4) and 3.3 +/- 2.1 (n = 4) ng/10(6) cells, respectively. The identity of the radioimmunoassayable materials as ANG I and II peptides was confirmed in cardiomyocytes using an in vitro bioassay based on displacement of 125I-ANG II from receptor binding sites in cardiac membranes prepared from neonatal pig heart. Identification of ANG I and II and ACE in vitro in cultures of cardiac myocytes and fibroblasts supports the hypothesis that there is an intracardiac renin-angiotensin system that produces these peptides.

Angiotensin I↗
PubMed1992

Angiotensin-II-binding sites on hepatocyte nuclei.

Angiotensin-II (Ang II) stimulates gene expression and cell growth in several cell types. Studies that have shown localization of Ang II to nuclei of myocytes and hepatic nuclear Ang II binding suggest that these actions may be mediated by nuclear receptors. We characterized Ang II binding to rat liver nuclei, which were free of plasma membrane based on enzyme analysis and electron microscopy. At 18 C, specific binding of 0.1-0.3 nM [125I]Ang II to nuclei and nuclear envelopes reached equilibrium by 2 h. Unlabeled Ang II inhibited [125I]Ang II binding to nuclei with an IC50 of 1.4 +/- 0.2 nM (+/- SE; n = 6). In half of the nuclear preparations, a lower affinity site (IC50, 50.4 +/- 23.6 nM), which accounted for 7-32% of specific Ang II binding, was detected by Scatchard analysis. Results similar to these were obtained with nuclear envelopes. Other Ang peptides competed for binding in the rank order: Ang III (IC50, 2.1 nM) greater than Ang I (IC50, 33) greater than [Des-Phe8]Ang II (IC50, 362) greater than [Des-Asp1-Des-Arg2]Ang II (IC50, 736). Losartan (DuP 753), an AT1 receptor antagonist, inhibited binding (IC50, 10.9 +/- 0.9 nM), whereas the AT2 receptor antagonist PD123177 did not. The pH optimum for binding to nuclear envelopes was 7, with binding more sensitive to low (5 and 6) than high (8 and 9) pH. Nonhydrolyzable GTP analogs accelerated displacement of bound [125I]Ang II by 10(-5) M Ang II. Differences were noted in pH sensitivity, time course, binding affinity for Ang I, II, and III, and rate of dissociation between nuclei or nuclear envelopes and plasma membrane Ang II binding. These results suggest that nuclear envelopes have a G-protein-coupled Ang II-binding site, which belongs to the AT1 class of Ang II receptors, with properties different from the plasma membrane receptor.

Angiotensin II↗
PubMed1990

Effect of worksite health promotion programs on employee absenteeism. A comparative analysis.

Employee absenteeism is an important economic variable that needs to be examined by occupational health nurses when evaluating worksite health promotion programs. Two of the three Blue Cross and Blue Shield Plan studies suggested that their programs acted to contain absenteeism among program participants. The worksite programs that met with success tended to be comprehensive and to have strong management support. Strengths of the three studies included the use of comparison groups and pretest measures of absenteeism in the analyses. Limitations included selection bias, subject dropout over time, limited monitoring of the program process, and the use of an analysis method that did not consider the statistical characteristics of the absenteeism variable.

Absenteeism↗
PubMedDate not supplied

Do blue-collar workers perceive the worksite health climate differently than white-collar workers?

A mail survey was distributed to a random sample of 497 both blue- and white-collar workers employed at a large manufacturing company to measure dimensions of worksite health climate: organizational and interpersonal support, and health norms. Statistically significant differences were observed for nearly all aspects of the dimensions with white-collar workers having more positive perceptions than blue-collar workers. The study suggests that future research explore how these perceptions may be enhanced and what role they may play in promoting worker health.

Adult↗
PubMedDate not supplied

Threats to internal validity in worksite health promotion program research: common problems and possible solutions.

Reviews of the research on worksite health promotion programs reveal that most studies are limited in their ability to draw clear inferences about program effects because the studies employed flawed research designs and/or analyses. Conclusions are often drawn about program effectiveness with little consideration given to alternative explanations for the findings. In an effort to promote improved research, this article uses the Cook and Campbell delineation of threats to valid causal inference to illustrate how the threats can operate in worksite health promotion program research as well as how they can be examined and controlled. Researchers, even those attempting to conduct true experiments, must consider the existence of all plausible threats to validity and control or rule them out before valid causal inferences can be drawn. The theoretical and design issues involved in worksite health promotion program research are presented, followed by a discussion of threats to internal validity.

Data Collection↗
PubMedDate not supplied

Musculoskeletal injury: ergonomics and physical fitness in firefighters.

As a means of reducing the increasing incidence of musculoskeletal injuries in firefighters, the authors offer a framework for a program that would integrate hazard control and health promotion approaches. Particular focus is placed on the role of ergonomics and physical fitness factors in preventing these injuries.

Ergonomics↗