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Education ?

Medical School Score
Southern Illinois University (1992)

Awards & Distinctions ?

American Board of Emergency Medicine

Publications & Research

Dr. Chapman has contributed to 16 publications.
Title A Comparison of Complete Mitochondrial Genomes of Silver Carp Hypophthalmichthys Molitrix and Bighead Carp Hypophthalmichthys Nobilis: Implications for Their Taxonomic Relationship and Phylogeny.
Date November 2010
Journal Journal of Fish Biology

Based upon morphological characters, Silver carp Hypophthalmichthys molitrix and bighead carp Hypophthalmichthys nobilis (or Aristichthys nobilis) have been classified into either the same genus or two distinct genera. Consequently, the taxonomic relationship of the two species at the generic level remains equivocal. This issue is addressed by sequencing complete mitochondrial genomes of H. molitrix and H. nobilis, comparing their mitogenome organization, structure and sequence similarity, and conducting a comprehensive phylogenetic analysis of cyprinid species. As with other cyprinid fishes, the mitogenomes of the two species were structurally conserved, containing 37 genes including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA (tRNAs) genes and a putative control region (D-loop). Sequence similarity between the two mitogenomes varied in different genes or regions, being highest in the tRNA genes (98.8%), lowest in the control region (89.4%) and intermediate in the protein-coding genes (94.2%). Analyses of the sequence comparison and phylogeny using concatenated protein sequences support the view that the two species belong to the genus Hypophthalmichthys. Further studies using nuclear markers and involving more closely related species, and the systematic combination of traditional biology and molecular biology are needed in order to confirm this conclusion.

Title Mechanisms of Pre-apoptotic Calreticulin Exposure in Immunogenic Cell Death.
Date March 2009
Journal The Embo Journal

Dying tumour cells can elicit a potent anticancer immune response by exposing the calreticulin (CRT)/ERp57 complex on the cell surface before the cells manifest any signs of apoptosis. Here, we enumerate elements of the pathway that mediates pre-apoptotic CRT/ERp57 exposure in response to several immunogenic anticancer agents. Early activation of the endoplasmic reticulum (ER)-sessile kinase PERK leads to phosphorylation of the translation initiation factor eIF2alpha, followed by partial activation of caspase-8 (but not caspase-3), caspase-8-mediated cleavage of the ER protein BAP31 and conformational activation of Bax and Bak. Finally, a pool of CRT that has transited the Golgi apparatus is secreted by SNARE-dependent exocytosis. Knock-in mutation of eIF2alpha (to make it non-phosphorylatable) or BAP31 (to render it uncleavable), depletion of PERK, caspase-8, BAP31, Bax, Bak or SNAREs abolished CRT/ERp57 exposure induced by anthracyclines, oxaliplatin and ultraviolet C light. Depletion of PERK, caspase-8 or SNAREs had no effect on cell death induced by anthracyclines, yet abolished the immunogenicity of cell death, which could be restored by absorbing recombinant CRT to the cell surface.

Title A Suite of Parallel Vectors for Baculovirus Expression.
Date November 2006
Journal Protein Expression and Purification

The expression of proteins using recombinant baculoviruses is a mature and widely used technology. However, some aspects of the technology continue to detract from high throughput use and the basis of the final observed expression level is poorly understood. Here, we describe the design and use of a set of vectors developed around a unified cloning strategy that allow parallel expression of target proteins in the baculovirus system as N-terminal or C-terminal fusions. Using several protein kinases as tests we found that amino-terminal fusion to maltose binding protein rescued expression of the poorly expressed human kinase Cot but had only a marginal effect on expression of a well-expressed kinase IKK-2. In addition, MBP fusion proteins were found to be secreted from the expressing cell. Use of a carboxyl-terminal GFP tagging vector showed that fluorescence measurement paralleled expression level and was a convenient readout in the context of insect cell expression, an observation that was further supported with additional non-kinase targets. The expression of the target proteins using the same vectors in vitro showed that differences in expression level were wholly dependent on the environment of the expressing cell and an investigation of the time course of expression showed it could affect substantially the observed expression level for poorly but not well-expressed proteins. Our vector suite approach shows that rapid expression survey can be achieved within the baculovirus system and in addition, goes some way to identifying the underlying basis of the expression level obtained.

Title Differential Effects of Etomoxir Treatment on Cardiac Na+-k+ Atpase Subunits in Diabetic Rats.
Date February 2003
Journal Molecular and Cellular Biochemistry

Etomoxir, an inhibitor of mitochondrial carnitine palmitoyltransferase-1, is known to attenuate the changes in myosin isoforms and sarcoplasmic reticular function that occur in diabetic rat hearts. In the present study, we tested the hypothesis that etomoxir also prevents the diabetes-induced depression of sarcolemmal (SL) Na+-K+ATPase activity by differentially affecting its alpha and beta-subunit levels. Streptozotocin-induced diabetes was associated with a decreased in alpha2-, alpha3-subunit levels, whereas the alpha1-and beta1-subunits were unchanged. Treatment of diabetic rats for 4 weeks with etomoxir (8 mg/kg/day) increased the alpha1-subunit levels, but failed to prevent the decrease in alpha2- and alpha3-subunit levels. In euglycemic control rats, etomoxir increased the alpha1-subunit protein level per g heart weight, but did not alter the alpha2-, alpha3- and beta1-subunit levels. The large decrease in Na+-K+ ATPase activity per g heart weight in diabetic rats was prevented by etomoxir, which suggests that the increased alpha1-subunit levels seen with this drug compensated for the decreased alpha2- and alpha3-subunit levels. The SL yield was also increased by etomoxir in euglycemic rats in proportion to the higher alpha1-subunit level, which resulted in an unchanged alpha1-content when expressed per mg SL protein; however, the alpha2- and beta1-subunit levels were reduced (p < 0.05). The depressed alpha2- and beta3 subunit levels of diabetic rats were associated with reduced mRNA abundance. However, no increase in alpha1-subunit mRNA abundance was seen in the etomoxir treated rats, which suggests that possibly post-transcriptional mechanisms are occurring in these hearts.

Title Changes in the Expression of Cardiac Na+-k+ Atpase Subunits in the Um-x7.1 Cardiomyopathic Hamster.
Date August 2000
Journal Life Sciences

Previous studies have shown that cardiac Na+ -K+ ATPase activity in the UM-X7.1 hamster strain is decreased at an early stage of genetic cardiomyopathy and remains depressed; however, the mechanism for this decrease is unknown. The objective of the present study was to assess whether changes in the expression of cardiac Na+-K+ ATPase subunits in control and UM-X7.1 cardiomyopathic hamsters are associated with alterations in the enzyme activity. Accordingly, we examined sarcolemmal Na+-K+ ATPase activity as well as protein content and mRNA levels for the alpha1, alpha2, alpha3 and beta1-subunit of the Na+-K+ ATPase in 250-day-old UM-X7.1 and age-matched, control Syrian hamsters; this age corresponds to the severe stage of heart failure in the UM-X7.1 hamster. Na+-K+ ATPase activity in UM-X7.1 hearts was decreased compared to controls (9.0 +/- 0.8 versus 5.6 +/- 0.8 micromol Pi/mg protein/hr). Western blot analysis revealed that the protein content of Na+-K+ ATPase alpha1- and beta1-subunits were increased to 164 +/- 27% and 146 +/- 22% in UM-X7.1 hearts respectively, whereas that of the alpha2- and alpha3-subunits were decreased to 82 +/- 5% and 69 +/- 11% of control values. The results of Northern blot analysis for mRNA levels were consistent with the protein levels; mRNA levels for the alpha1- and beta1-subunits in UM-X7.1 hearts were elevated to 165 +/- 14% and 151 +/- 10%, but the alpha2-subunit was decreased to 60 +/- 8% of the control value. We were unable to detect mRNA for the alpha3-subunit in either UM-X7. 1 or control hearts. These data suggest that the marked depression of Na+-K+ ATPase activity in UM-X7.1 cardiomyopathic hearts may be due to changes in the expression of subunits for this enzyme.

Title A Three-coil Comparison for Mr Angiography.
Date May 2000
Journal Journal of Magnetic Resonance Imaging : Jmri

The purpose of this work was to compare intracranial magnetic resonance angiography (MRA) image quality using three different radiofrequency coils. The three coil types included a reduced volume quadrature birdcage coil with endcap, a commercially available quadrature birdcage head coil, and a four-element phased-array coil. Signal-to-noise ratio (SNR) measurements were obtained from comparison studies performed on a uniform cylindrical phantom. MRA comparisons were performed using data acquired from 15 volunteers and applying a thick-slab three-dimensional time-of-flight sequence. Analysis was performed using the signal difference-to-noise ratio, a quantitative measure of the relative vascular signal. The reduced-volume endcap and phased-array coils, which were designed specifically for imaging the intracranial volume of the head, improved the image SNR and vascular detail considerably over that obtained using the commercially available head coil. The endcap coil configuration provided the best vascular signal overall, while the phased-array coil provided the best results for arteries close to the coil elements.

Title Accuracy, Clinical Correlation, and Patient Acceptance of Two Handheld Prothrombin Time Monitoring Devices in the Ambulatory Setting.
Date October 1999
Journal The Annals of Pharmacotherapy

OBJECTIVE: To evaluate the accuracy, clinical correlation, ease of use, and patient acceptance of the Coaguchek and the ProTime Microcoagulation System as compared with standard laboratory methods for prothrombin time determination. METHODS: A total of 30 prothrombin times, expressed as international normalized ratios (INRs), were determined by each handheld device for comparison with standard laboratory testing. Accuracy was evaluated by calculating the absolute difference for each pair of INR values. Clinical correlation was defined as an INR obtained by the handheld monitor that would have resulted in the same therapeutic decision as the INR obtained by the standard laboratory method. Subjects were surveyed to determine which method of INR determination they preferred and their reasons for that preference. RESULTS: Accuracy was superior with the Coaguchek monitor. The absolute difference (mean +/- SD) in the laboratory and Coaguchek INRs was 0.28+/-0.23 (p = 0.96). The absolute difference (mean +/- SD) in the laboratory and the ProTime Microcoagulation System INRs was 0.56+/-0.34 (p < 0.001). For clinical correlation, two out of 24 (8.3%) INRs with the Coaguchek were sufficiently different from the laboratory INR to have resulted in a different therapeutic decision, compared with 12 out of 24 (50%) with the ProTime Microcoagulation System (p < 0.005). Of subjects surveyed, 77.8% preferred the finger stick method. CONCLUSIONS: The Coaguchek was superior to the ProTime Microcoagulation System in accuracy, clinical correlation, and ease of use. The study also showed that patients preferred capillary blood sampling by finger puncture over venipuncture for INR monitoring.

Title Expression of Gi-2 Alpha and Gs Alpha in Myofibroblasts Localized to the Infarct Scar in Heart Failure Due to Myocardial Infarction.
Date August 1999
Journal Cardiovascular Research

OBJECTIVE: Patients surviving large transmural myocardial infarction (MI) are at risk for congestive heart failure with attendant alteration of ventricular geometry and scar remodeling. Altered Gi-2 alpha and Gs alpha protein expression may be involved in cardiac remodeling associated with heart failure, however their expression in scar tissue remains unclear. METHODS: MI was produced in Sprague-Dawley rats by ligation of the left coronary artery. Gi-2 alpha and Gs alpha protein concentration, localization and mRNA abundance were noted in surviving left ventricle remote to the infarct, in border and in scar tissues from 8 week post-MI hearts with moderate heart failure. RESULTS: We observed a 4.5- and 5.0-fold increase in immunoreactive Gi-2 alpha protein concentration occurs in the border and scar regions vs. control values, respectively, in 8-week post-MI rat hearts. Similarly, immunoreactive Gs alpha protein concentration was increased 3.4- and 8.2-fold, respectively, in these tissues vs. controls. Double-fluorescence labeling and phenotyping studies revealed that both Gi-2 alpha and Gs alpha proteins were localized to myofibroblasts in the infarct scar and to viable myocytes bordering the scar. Northern analysis revealed that the Gi-2 alpha/GAPDH ratio was increased in both viable and scar regions (1.24- and 1.85-fold respectively) from experimental hearts when compared to sham-operated control values when compared to noninfarcted left ventricle, the value of this ratio in scar tissue was elevated approximately 1.5 fold. The Gs alpha/GAPDH ratio was significantly increased (1.28-fold) only in the scar region vs. control. CONCLUSION: Our results indicate a marked increase in the expression of Gi-2 alpha and Gs alpha from myofibroblasts of the infarct scar as well as remnant myocytes bordering the scar in 8-week post-MI rat hearts. We suggest that these changes may be associated with ongoing remodeling in the infarct scar in chronic post-MI phase of this experimental model.

Title Alterations of Heart Function and Na+-k+-atpase Activity by Etomoxir in Diabetic Rats.
Date May 1999
Journal Journal of Applied Physiology (bethesda, Md. : 1985)

To examine the role of changes in myocardial metabolism in cardiac dysfunction in diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to induce diabetes and were treated 2 wk later with the carnitine palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8 mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart rate, left ventricular systolic pressure, and positive and negative rate of pressure development and an increase in end-diastolic pressure. The sarcolemmal Na+-K+-ATPase activity was depressed and was associated with a decrease in maximal density of binding sites (Bmax) value for high-affinity sites for [3H]ouabain, whereas Bmax for low-affinity sites was unaffected. Treatment of diabetic animals with etomoxir partially reversed the depressed cardiac function with the exception of heart rate. The high serum triglyceride and free fatty acid levels were reduced, whereas the levels of glucose, insulin, and 3,3',-5-triiodo-L-thyronine were not affected by etomoxir in diabetic animals. The activity of Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax (per g heart wt) for both low-affinity and high-affinity binding sites in control and diabetic animals was increased by etomoxir treatment. Etomoxir treatment also increased the depressed left ventricular weight of diabetic rats and appeared to increase the density of the sarcolemma and transverse tubular system to normalize Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization may represent an important signal for improving the depressed cardiac function and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose utilization.

Title Polarographic Needle Electrode Measurements of Oxygen in Rat Prostate Carcinomas: Accuracy and Reproducibility.
Date September 1995
Journal International Journal of Radiation Oncology, Biology, Physics

PURPOSE: The oxygenation status of tumors may be important for predicting tumor response to therapy. Previous studies with the anaplastic (R3327-AT) and well-differentiated (R3327-H) Dunning rat prostate tumors using indirect assays of tumor oxygenation indicated the relative hypoxic and radioresistant nature of the anaplastic tumor. We now report direct measurements of oxygen in these tumors made with the pO2 histograph to determine: (a) whether a significant difference in oxygenation status could be detected between them: (b) whether sequential measurements on the same tumor gave similar values; and (c) whether tumor oxygenation correlated with tumor volume. METHODS AND MATERIALS: R3327-AT and R3327-H tumors were grown in Fischer X Copenhagen rat to volumes of 1.0-7.0 cm3. Electrode measurements (100-200) were made in tumors in anesthetized animals along two parallel tracks. Repeat measurements were made at 1-5 days along different parallel tracks. Oxygen partial pressures of muscle tissue were measured and served as a normal tissue control. Statistical analyses were applied to determine whether tumor oxygen levels were different between the two tumor histologies, whether sequential measurements in the same tumor were reproducible, and whether tumor oxygenation correlated with tumor volume. RESULTS: The average median pO2 of the well-differentiated (n = 15) and the anaplastic (n = 15) tumors was 6.0 mmHg (SE +/- 1.3) and 2.2 mmHg (SE +/- 0.3), respectively. The average median pO2 of normal rat muscle (n = 15) was 23.6 mmHg (SE +/- 2.0). These values represent highly significant differences in oxygen concentration between the two tumors and rat muscle. The differences in average mean pO2 values were also highly significant. Repeat measurements in the same tumors on different days gave average median values of 4.7 and 2.2 mmHg in the R3327-H (n = 15) and R3327-AT (n = 15) tumors, respectively. For these repeat measurements, median pO2 values decreased in 15 and increased in 15 tumors, and were not significantly different from the first measurements. The average differences observed in median pO2 were 37% (SE +/- 7) and 58% (SE +/- 10) for the R3327-H and R3327-AT tumors, respectively. No significant correlation was observed between pO2 levels and the tumor volumes investigated in this study. CONCLUSIONS: The median pO2 values of the anaplastic Dunning tumors were significantly lower than those of the well-differentiated tumors (p < 0.001). Oxygen levels in both tumors were significantly lower than those measured in normal rat muscle (p < 0.00005). Repeat measurements of median pO2 in the same tumors were not significantly different for either tumor model (p > 0.5). The changes observed in pO2 distributions within individual tumors from day to day may indicate true dynamics of its oxygenation status and/or the limits of electrode measurements, by sampling along only two insertion sites. The electrode measurements of pO2 in these tumor models are reproducible and confirm previously detected oxygenation differences between the anaplastic and well-differentiated tumors.

Title Conservative Management of an Ovarian Polyembryoma.
Date May 1994
Journal Obstetrics and Gynecology

BACKGROUND: Polyembryomas are rare, immature germ cell malignancies characterized by numerous embryo-like bodies in association with mature and immature teratoma structures and primitive embryonic tissue. The purpose of this paper is to present a patient in whom surgical staging and postoperative serial tumor markers and imaging studies were used to determine management. CASE: A 43-year-old woman with a stage IA polyembryoma was followed with serial alpha-fetoprotein and hCG assays, as well as serial abdominal and pelvic computed tomography (CT) scans, following surgical staging and a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Chemotherapy was not given because the patient's tumor markers declined steadily into the normal range and imaging studies revealed no evidence of recurrent disease. CONCLUSION: Women with polyembryomas surgically staged and confined to one ovary may be followed with serial tumor markers and diagnostic imaging techniques to avoid aggressive cytotoxic chemotherapy.

Title Failure of Gas Bladder Inflation in Striped Bass: Effect on Selenium Toxicity.
Date July 1992
Journal Archives of Environmental Contamination and Toxicology

Young striped bass (Morone saxatilis) with uninflated gas bladders were less sensitive to selenate and more sensitive to selenite exposure than normally developing striped bass in 96-hour acute toxicity tests. Gas bladder inflation failure is a common problem in the culture of striped bass and some other species, and care should be taken to avoid the use of fish with uninflated gas bladders in research.

Title Alterations in Cardiac Contractile Proteins Due to Oxygen Free Radicals.
Date July 1991
Journal Biochimica Et Biophysica Acta

In view of the potential role of free radicals in the genesis of cardiac abnormalities under different pathophysiological conditions and the importance of contractile proteins in determining heart function, this study was undertaken to examine the effects of oxygen free radicals on the rat heart myofibrils. Xanthine plus xanthine oxidase (X + XO) which is known to generate superoxide anions (O2-) and hydrogen peroxide (H2O2), an activated species of oxygen, was found to decrease Ca(2+)-stimulated ATPase activity, increase Mg(2+)-ATPase activity and reduce sulfhydryl (SH) group contents in myofibrils; these effects were completely prevented by superoxide dismutase (SOD) plus catalase (CAT). Both H2O2 and hypochlorous acid (HOCl), an oxidant, produced actions on cardiac myofibrils similar to those observed by X + XO. The effects of H2O2 and HOCl were prevented by CAT and L-methionine, respectively. N-ethylmaleimide (NEM) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), inhibitors of SH groups, also produced effects similar to those seen with X + XO. Dithiothreitol (DTT), a well known sulfhydryl-reducing agent, prevented the actions of X + XO, H2O2, HOCl, NEM and DTNB. These results suggest that marked changes in myofibrillar ATPase activities by different species of oxygen free radicals may be mediated by the oxidation of SH groups.

Title Modification of Cardiac Adrenergic Receptors by Oxygen Free Radicals.
Date April 1991
Journal The American Journal of Physiology

To examine the effects of oxygen free radicals on alpha- and beta-adrenergic receptors, rat heart crude membranes were incubated with xanthine plus xanthine oxidase, H2O2, or H2O2 plus Fe2+. The assay of beta-adrenergic receptors involving [3H]dihydroalprenolol (DHA) binding revealed that the maximal number of binding sites (Bmax) and dissociation constant (Kd) were increased by xanthine plus xanthine oxidase. H2O2 increased the Kd value for [3H]DHA binding. When a hydrophilic ligand, [3H]CGP-12177, was used for the beta-adrenergic receptor assay, an increase in Kd value without any changes in Bmax value was evident on treating the membranes with xanthine plus xanthine oxidase. The assay of alpha-adrenergic receptors involving [3H]prazosin binding showed a decrease in the number of binding sites and an increase in Kd value only after a prolonged period of incubation. Both H2O2 and H2O2 plus Fe2+ increased the Kd value for [3H]prazosin without changes in Bmax. Changes in both alpha- and beta-adrenergic receptors similar to those with crude membranes were also seen by employing the purified heart sarcolemmal membranes. These data indicate that adrenergic receptors in the sarcolemmal membranes are modified by oxygen free radicals.

Title Dantrolene Sodium in the Treatment of Malignant Hypertension.
Date December 1982
Journal South African Medical Journal = Suid-afrikaanse Tydskrif Vir Geneeskunde
Title A Hydrodynamical Model of Bordered Pits in Conifer Tracheids.
Date September 1977
Journal Journal of Theoretical Biology

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