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Biomedical subjects

S Lehr

Publications and source records attributed to S Lehr.

13 recordsLinked to original sources
PubMed1999

Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro.

Grb2-associated binder-1 (Gab-1) has been identified recently in a cDNA library of glioblastoma tumors and appears to play a central role in cellular growth response, transformation, and apoptosis. Structural and functional features indicate that Gab-1 is a multisubstrate docking protein downstream in the signaling pathways of different receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR). Therefore, the aim of the study was to characterize the phosphorylation of recombinant human Gab-1 (hGab-1) protein by EGFR in vitro. Using the pGEX system to express the entire protein and different domains of hGab-1 as glutathione S-transferase proteins, kinetic data for phosphorylation of these proteins by wheat germ agglutinine-purified EGFR and the recombinant EGFR (rEGFR) receptor kinase domain were determined. Our data revealed similar affinities of hGab-1-C for both receptor preparations (KM = 2.7 microM for rEGFR vs 3.2 microM for WGA EGFR) as well as for the different recombinant hGab-1 domains. To identify the specific EGFR phosphorylation sites, hGab-1-C was sequenced by Edman degradation and mass spectrometry. The entire protein was phosphorylated by rEGFR at eight tyrosine residues (Y285, Y373, Y406, Y447, Y472, Y619, Y657, and Y689). Fifty percent of the identified radioactivity was incorporated in tyrosine Y657 as the predominant peak in HPLC analysis, a site exhibiting features of a potential Syp (PTP1D) binding site. Accordingly, GST-pull down assays with A431 and HepG2 cell lysates showed that phosphorylated intact hGab-1 was able to bind Syp. This binding appears to be specific, because it was abolished by changing the Y657 of hGab-1 to F657. These results demonstrate that hGab-1 is a high-affinity substrate for the EGFR and the major tyrosine phosphorylation site Y657 in the C terminus is a specific binding site for the tyrosine phosphatase Syp.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Adrenaline inhibits depolarization-induced increases in capacitance the presence of elevated [Ca2+]i in insulin secreting cells.

Cell capacitance (Cm), cell conductance (Gm), access conductance (Ga) and membrane voltage (Vm) were measured simultaneously in insulin secreting cells using the dual frequency method. Depolarization and stimulation of the cells with secretagogues increased Cm. EGTA abolished the increase in [Ca2+]i and prevented the rise of Cm. Adrenaline inhibited the augmentation of Cm without lowering [Ca2+]i. In pertussis toxin pretreated cells adrenaline had no effect. Thus, stimulation of insulin secretion is accompanied by an increase in Cm. Inhibition of exocytosis by adrenaline occurs even in the presence of elevated [Ca2+]i, i.e. at a more distal step of exocytosis.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Reemployment of patients with surgical salvage of open, high-energy tibial fractures: an outcome study.

Between January 1, 1988, and December 31, 1990, 36 patients with 37 type III high-energy open tibial shaft fractures were treated at Lehigh Valley Hospital. Patients with primary amputations were excluded. All patients with high-energy open tibial fractures with an intact posterior tibial nerve, protective sensations of the plantar surface of the foot, and warm ischemia time of less than 6 hours were considered salvageable. A retrospective review of the charts was completed. Twenty-eight patients with 29 fractures were interviewed for work status, an average of 39 months after treatment. Twenty-five patients with 25 fractures were working at the time of the accident. Three patients with four fractures were not working at the time of the accident. Nineteen of 25 patients (76%) returned to work. Sixteen of 25 patients (64%) returned to work at a similar level of manual labor. The average delay between injury and return to work was 11 months (range, 3-18 months). Two of the 36 patients (5.5%) required secondary amputations. Twenty-five of 28 patients (89%) interviewed reported one or more subjective complaints. The two amputees reported no subjective complaints.

Adolescent↗
PubMed1996

Adrenaline-, not somatostatin-induced hyperpolarization is accompanied by a sustained inhibition of insulin secretion in INS-1 cells. Activation of sulphonylurea K+ATP channels is not involved.

Adrenaline and somatostatin inhibit insulin secretion via pertussis toxin (PTX)-sensitive mechanisms. Since glucose-stimulated release involves inhibition of ATP-sensitive K+ (K+ATP) channels and activation of Ca2+ influx, we took advantage of the glucose-sensitive, insulin-secreting cell line INS-1 to investigate whether inhibitors of insulin release modulate membrane voltage and K+ATP channel activity in cell-attached patch-clamp experiments. We found that adrenaline, through alpha2-adrenoceptors, and somatostatin counteracted glucose-induced depolarization and action potentials. As expected, these effects were mediated via PTX-sensitive G proteins since PTX pretreatment of the cells eliminated the effects of adrenaline and somatostatin on membrane voltage. When INS-1 cells were activated by adding both the K+ATP channel inhibitor tolbutamide and the adenylyl cyclase activator forskolin, adrenaline and somatostatin still repolarized the plasma membrane. Single-channel measurements in the cell-attached mode revealed that tolbutamide closed a 40 to 70 pS K+ channel which was neither reopened by adrenaline nor by somatostatin. In parallel cell preparations, insulin secretion was measured by radioimmunoassay. Insulin release induced by glucose, forskolin and tolbutamide was abolished by adrenaline. In contrast, somatostatin attenuated insulin secretion by only 30%. After comparing the potency of adrenaline and somatostatin on membrane voltage and on insulin secretion, it is concluded that the repolarizing effect of adrenaline on membrane voltage is not sufficient to explain its potent inhibitory effect on insulin secretion.

Adenosine Triphosphate↗
PubMed1996

Effects of glucose, forskolin and tolbutamide on membrane potential and insulin secretion in the insulin-secreting cell line INS-1.

Membrane voltages (Vm) of INS-1 cells, an insulin-secreting cell line, were measured mostly using the cell-attached mode of the patch-clamp method. The cell-attached configuration allowed the cell to be kept intact. Measurement of Vm was possible because seal resistances were very high and because the membrane obviously had a sufficiently high conductance (probably via K+ channels). Resting Vm was -80 +/- 1 mV (n = 42) and was mainly determined by sulphonylurea-sensitive K+ATP channels since tolbutamide depolarized the plasma membrane in a concentration-dependent manner and generated action potentials at 50 and 100 micromol/l. D-Glucose, tested between 0.5 and 16.7 mmol/l, also depolarized the plasma membrane in a concentration-dependent manner and induced action potentials at concentrations higher than 5.6 mmol/l. Similarly, forskolin (5 micromol/l) depolarized the cells and increased the frequency of Ca2+-mediated action potentials. Insulin secretion was measured from cells growing in culture dishes, by radioimmunoassay. Glucose doubled secretion in INS-1 cells, whereas tolbutamide had no significant effect on secretion in the presence of 0.5 mmol/l and 16. 7 mmol/l glucose. At 3 mmol/l glucose, tolbutamide increased insulin release slightly. Forskolin elevated secretion twofold at a low glucose concentration. In contrast, when glucose or tolbutamide were added together with forskolin secretion was potentiated five- to tenfold. These results show that glucose induces membrane activation in INS-1 cells. Furthermore, the potent effect of tolbutamide, i.e. to depolarize the plasma membrane without inducing insulin release, leads to the conclusion that effects distal to depolarization are pivotal for secretion in INS-1 cells.

Action Potentials↗
PubMed1993

Factors associated with use of safer sex practices among college freshmen.

The purpose of this exploratory study was to examine the relationship of knowledge of AIDS, misconceptions about AIDS, knowledge of safer sex practices, perceived susceptibility, and future time perspective to the practice of safer sex behaviors in 352 single, sexually active, college freshmen. Data were analyzed using stepwise multiple regression analysis and discriminant analysis. There were too few black females for analysis. Future time perspective explained the most variance in safer sex practices for black males. Knowledge of AIDS, perceived susceptibility, misconceptions about AIDS, knowledge of safer sex practices, and future time perspective did not explain a significant amount of variance in use of safer sex practices for either white males or females. However, perceived susceptibility and future time perspective differentiated sexually active from nonsexually active white males and females.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Knowledge of AIDS and safer sex practices among college freshmen.

We assessed knowledge of the acquired immunodeficiency syndrome (AIDS) and of safer sex practices among college freshmen. A second purpose of the study was to assess this knowledge among black as well as white students. Students attending classes at three private colleges in a large southern city were asked to participate in the study. Respondents completed the modified AIDS information survey, the knowledge of safe sex practices questionnaire, and a demographic data sheet. A total of 689 questionnaires were received from single college freshmen. The results indicated that respondents were knowledgeable about the cause and transmission of AIDS but were less knowledgeable about medical aspects. Most knew that condoms are effective in preventing the spread of AIDS, but fewer could differentiate between the effectiveness of latex and nonlatex condoms. These findings are useful to health educators in improving AIDS education programs.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Impact of minimal injuries on a level I trauma center.

Overtriage (i.e.; transport of patients with minimal injuries to a trauma center) has been accepted as necessary to avoid missing clinically significant injuries. We reviewed our experience with 344 patients (ISS less than or equal to 4) who were admitted to a level I trauma center during a 2-year period. The trauma team was activated for 209 patients (TA), and emergency department referrals accounted for 135 (ED). One hundred seventy-three patients (TA = 64%, ED = 36%) met American College of Surgeons' Committee on Trauma (ACSCOT) field triage criteria (FTC). Mechanism of injury, especially ejection from a motor vehicle, was the most frequently utilized FTC indicator. We found no differences between the TA and ED groups relative to Trauma Score, Glasgow Coma Scale score, Injury Severity Score, length of stay, or ICU days. Mean total costs were higher for the TA group than for the ED group. The TA group had a higher nursing acuity level than the ED group. Compliance with FTC yields an inherent overtriage of minimally injured patients; however, noncompliance with FTC compounds the overtriage rate. Failure to comply with FTC is costly, labor intensive, and may represent misuse of the trauma system. We propose continual re-education of prehospital personnel, increased responsibility of all hospitals in the trauma center catchment area, and protocols for "downstaging" trauma resuscitation in minimally injured patients.

Adult↗
PubMedDate not supplied

Group dynamics within long-term continuing education programs.

Nursing educators have responded to the need for continuing education by developing a variety of programs ranging in length from half-day seminars to several months of intensive study. Although books and articles have been written about nurses returning to school for baccalaureate degrees and the ensuing expectations, changes, and needs involved in this process, the literature revealed little information on how students, families, and faculty "live" a long-term continuing education (CE) experience. This article will examine the evolution of students into well-defined groups. The stages of group process, development of norms, assumption of roles within the groups, and factors related to conflicts are discussed. Methods used to reduce conflict and facilitate the movement of the groups to the resolution stage are presented in order to assist instructors involved in long-term CE programs.

Adult↗
PubMedDate not supplied

Measurement of safe sex behavior in adolescents and young adults.

The aim of this project was to develop an instrument to measure use of safe sex practices among adolescents and to conduct initial evaluation of the psychometric properties of the instrument. The Safe Sex Behavior Questionnaire (SSBQ) was designed to measure the frequency of use of safe sex practices and was assessed for content validity, reliability, and construct validity through a series of tests. The content validity index computed for the SSBQ was 98%. Initial reliability computed for sums of items of the total scale was .82 among 89 college freshmen. Using a second sample of 531 subjects, the SSBQ was factor-analyzed separately for males and females and five similar factors emerged for each gender. Reliability coefficients for sums of salient items for each factor ranged from .52 to .85. Using a third sample of 174 subjects, construct validity was assessed by correlating the SSBQ with measures of general assertiveness and general risk-taking. The resulting correlations were appreciable and in the predicted directions, thus providing support for the construct validity of the instrument.

Acquired Immunodeficiency Syndrome↗