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Biomedical subjects

P Bishop

Publications and source records attributed to P Bishop.

At least 19 recordsLinked to original sources
PubMed2001

DNA binding properties of basic helix-loop-helix fusion proteins of Tal and E47.

The basic helix-loop-helix (bHLH) transcription factor Tal has been shown to form heterodimers with the ubiquitously expressed bHLH transcription factor E47 and thereby modulate gene expression. The absence of homodimeric Tal-DNA complexes had been attributed to the inability of Tal to homodimerize, but subsequent studies have shown that the bHLH region of Tal does homodimerize. In order to correlate the contributions of both the basic region and the helix-loop-helix (HLH) domain to the lack of DNA binding by Tal homodimers, mutant and fusion proteins based on Tal and E47 were designed and synthesized. Size-exclusion chromatography established that all mutant and fusion proteins were dimeric. Point mutations were made within the basic region of Tal based on residues within E47 that are essential for DNA binding, but an affinity for DNA was not observed. Even complete replacement of the basic region in Tal with the basic region of E47, in an E47-Tal fusion protein, did not confer DNA binding upon the protein. However, when the dimerization domain in Tal was replaced with its E47 counterpart, in a Tal-E47 fusion protein, sequence specific DNA binding was observed with an apparent dissociation constant of 3.6 x 10(-9) M2. Furthermore, circular dichroism studies showed that the basic region of Tal in the Tal-E47 fusion protein underwent a random coil to helix transition in the presence of a specific DNA probe. These experimental observations indicate that the inability of Tal homodimers to recognize DNA stems from a misalignment of its basic region with respect to the HLH domain, rather than an intrinsic inability of the Tal basic region to bind DNA.

Amino Acid Sequence↗
PubMed2000

Reduced growth rate accompanied by aberrant epidermal growth factor signaling in drug resistant human breast cancer cells.

We examined transforming growth factor (TGF) alpha, epidermal growth factor (EGF) and EGF receptor (EGFR) expression and signaling in three drug resistant MCF-7 human breast cancer sublines and asked whether these pathways contribute to the drug resistance phenotype. In the resistant sublines, upregulation of both TGFalpha and EGFR mRNA was observed. In an apparent contrast with upregulated growth factor and receptor gene expression, the drug resistant sublines displayed a reduced growth rate. Defects in the EGFR signaling pathway cascade were found in all examined drug resistant sublines, including altered EGF-induced Shc, Raf-1, or mitogen-activated protein kinase phosphorylation. Induction of c-fos mRNA expression by EGF was impaired in the sublines compared to parental MCF-7 cells. In contrast, the induction of the stress-activated protein kinase activity was similar in both parental and drug resistant cells. Evaluating the link between the reduced growth rate and drug resistance, serum starvation experiments were performed. These studies demonstrated that a reduced proliferative activity resulted in a marked reduction in sensitivity to cytotoxic agents in the parental MCF-7 cells. We propose that the altered EGFR levels frequently observed in drug resistant breast cancer cells are associated with perturbations in the signaling pathway that mediate a reduced proliferative rate and thereby contribute to drug resistance.

Anisomycin↗
PubMed2000

Estrogen and substrate metabolism: a review of contradictory research.

The increasing number of females participating in physical activity has heightened our awareness of changes in the menstrual cycle which often accompany physical activity. As such, there has been a considerable amount of research investigating the relationships between menstrual cycle changes and bone mineral density, performance, ventilation and substrate metabolism. A number of researchers have concluded that there may be enhanced fat metabolism in eumenorrhoeic versus amenorrhoeic females, or in the follicular phase versus the luteal phase of the menstrual cycle, due to the theoretical estrogen level in eumenorrhoeic versus amenorrhoeic females or the luteal phase versus the follicular phase. However, a definite relationship between resting estrogen level and substrate metabolism has not been clearly established. In addition, the mechanisms which may be responsible for the effect of estrogen on substrate metabolism have not been addressed. It appears that the effects of estrogen on metabolism may be via the effect of estrogen on glucogenic hormones or lipolytic enzymes. Therefore, the primary purpose of this review is to explore the effects of estrogen on substrate metabolism. Menstrual cycle physiology and possible mechanisms for the effects of estrogen on metabolism, as well as previous research on estrogen and metabolism in rats and humans, will be discussed.

Amenorrhea↗
PubMed1999

Synchronous and metachronous gastric adenocarcinoma: case report and literature review.

Whilst synchronous adenocarcinoma of the stomach is well documented, metachronous primary disease is exceedingly rare. We report a man with a family history of colonic and gastric cancer, who underwent a resection of a Duke's C adenocarcinoma of the rectum, aged 56 years, and a proximal partial gastrectomy for synchronous stage 1 gastric adenocarcinomas of the lesser curve, aged 61 years. Nine years later, a metachronous gastric primary was discovered in the gastric remnant, necessitating total gastrectomy. Total gastrectomy is the operation of choice for synchronous gastric primaries as it ensures clearance and prevents metachronous growth. However, it may not be appropriate for all gastric cancer as operative morbidity and mortality are increased, and because synchronicity and metachronicity of gastric cancer are uncommon. Moreover, there are no consistent data to demonstrate a survival advantage for total compared with partial gastrectomy for operable gastric cancer. If, after partial gastrectomy, synchronous disease is detected in the resected specimen (as in this reported case), endoscopic surveillance for metachronous disease is advised, since this may be amenable to surgical cure.

Adenocarcinoma↗
PubMed1998

Protein and platelet interactions with thermally denatured fibrinogen and cross-linked fibrin coated surfaces.

In this work the hypothesis that a mature, cross-linked fibrin clot, pre-formed on a biomaterial, may be relatively nonthrombogenic was investigated. A cross-linked fibrin layer was formed on polyethylene which had been precoated with thermally denatured fibrinogen. Plasma protein adsorption and platelet interactions with the cross-linked fibrin and denatured fibrinogen surfaces were investigated. The adsorption of albumin, fibrinogen, and fibronectin from plasma was measured. For all three proteins, the cross-linked fibrin surface exhibited much higher levels of adsorption than either the thermally denatured fibrinogen or the polyethylene surface. Vroman peaks were observed for fibrinogen and fibronectin on polyethylene but not on the cross-linked fibrin and thermally denatured fibrinogen materials. In dilute plasma the thermally denatured fibrinogen surface showed considerable resistance to protein adsorption. However, at plasma concentrations greater than about 5% normal, this protein resistance was apparently lost. Platelet interactions (adhesion and release of granule constituents from adherent platelets) using suspensions of washed platelets in the presence of red cells were investigated at shear rates of 50, 300, and 525 s(-1) using a cone and plate apparatus. The levels of platelet adhesion on the different surfaces were in the order: adsorbed fibrinogen > cross-linked fibrin > thermally denatured fibrinogen = polyethylene. Platelets on the cross-linked fibrin surface also showed high levels of release indicating significant platelet activation. Scanning electron microscopic observations were in agreement with the platelet adhesion and release data, showing only a few (but well-spread) adherent platelets on the cross-linked fibrin surface.

Adsorption↗
PubMed1997

Validity of a heart rate monitor during work in the laboratory and on the Space Shuttle.

Accurate heart rate measurement during work is required for many industrial hygiene and ergonomics situations. The purpose of this investigation was to determine the validity of heart rate measurements obtained by a simple, lightweight, commercially available wrist-worn heart rate monitor (HRM) during work (cycle exercise) sessions conducted in the laboratory and also during the particularly challenging work environment of space flight. Three different comparisons were made. The first compared HRM data to simultaneous electrocardiogram (ECG) recordings of varying heart rates that were generated by an ECG simulator. The second compared HRM data to ECG recordings collected during work sessions of 14 subjects in the laboratory. Finally, ECG downlink and HRM data were compared in four astronauts who performed cycle exercise during space flight. The data were analyzed using regression techniques. The results were that the HRM recorded virtually identical heart rates compared with ECG recordings for the data set generated by an ECG simulator. The regression equation for the relationship between ECG versus HRM heart rate data during work in the laboratory was: ECG HR = 0.99 x (HRM) + 0.82 (r2 = 0.99). Finally, the agreement between ECG downlink data and HRM data during space flight was also very high, with the regression equation being: Downlink ECG HR = 1.05 x (HRM) -5.71 (r2 = 0.99). The results of this study indicate that the HRM provides accurate data and may be used to reliably obtain valid data regarding heart rate responses during work.

Adult↗
PubMed1997

Impact of body size on women's military obstacle course performance.

The United States Military Academy uses an Indoor Obstacle Course Test (IOCT) to assess military-relevant physical fitness. There are both anaerobic and aerobic fitness components to this test. Recent attention has been focused on the apparent difficulty of heavier female cadets to succeed on the IOCT. The purpose of this study was to use allometric scaling to examine the effects of body weight (BW), fat-free mass (FFM), percent body fat (%BF), and fat mass (FM) on IOCT performance for female cadets. The sample included 38 female cadets who successfully completed the IOCT. Performance was defined by the time, T, to complete the entire course. FFM was determined via a three-site skinfold test. Allometric modeling was used to determine the exponent in the following index: T*BW2 such that the independent contributions of body size are partialled out. This analysis was used for all four independent variables simply by substituting BW with the other independent variables. The following exponents were found to be significant (p < 0.05): 0.45 +/- 0.13 for %BF and 0.24 +/- 0.12 for FM indicating that these independent variables play a significant role in female performance on the IOCT. For example, if a female cadet could decrease her %BF from 20% to 18%, which would be decrement of ten percent, then her estimated decrease in IOCT time is 4%. In addition, a trend (p = 0.06) was found for FFM meaning that as FFM increases, T decreases. We conclude that, among USMA female cadets, small decreases in %BF may be significantly advantageous to IOCT performance.

Adult↗
PubMed1996

Type VI collagen is present in human and bovine vitreous.

BACKGROUND: Heterotypic (mixed) collagen fibrils that contain collagen types II, IX and V/XI have previously been identified in vitreous gel. The purpose of this study was to determine whether vitreous gel also contains type VI collagen microfibrils, as they are widely distributed in other tissues where they may play an important structural role. METHODS: Bovine and human vitreous gel was analysed by rotary shadowing electron microscopy after bacterial collagenase digestion and gel filtration chromatography. Bovine vitreous was extracted in 4 M guanidine hydrochloride, and following isopycnic centrifugation fractions were analysed by western blotting. RESULTS: Type VI collagen microfibrils were identified by electron microscopy in human and bovine vitreous. Type VI collagen was identified by western blot analysis. CONCLUSION: Type VI collagen is present in vitreous and may participate in the structural assembly of the vitreous gel.

Animals↗