Medical Specialties Commons^™

Let-7 Expression Defines Two Differentiation Stages Of Cancer, Scott Shell, Sun-Mi Park, Amir Reza Radjabi, Robert Schickel, Emily Kistner, David Jewell

Dartmouth Scholarship

The early phases of carcinogenesis resemble embryonic development, often involving the reexpression of embryonic mesenchymal genes. The NCI60 panel of human tumor cell lines can genetically be subdivided into two superclusters (SCs) that correspond to CD95 Type I and II cells. SC1 cells are characterized by a mesenchymal and SC2 cells by an epithelial gene signature, suggesting that SC1 cells represent less differentiated, advanced stages of cancer. miRNAs are small 20- to 22-nucleotide-long noncoding RNAs that inhibit gene expression at the posttranscriptional level. By performing miRNA expression analysis on 10 Type I and 10 Type II cells, we have determined …

Walking Age Does Not Explain Term Versus Preterm Difference In Bone Geometry, Haifa Abou Samra, Bonny Specker

Ethel Austin Martin Program Publications

OBJECTIVE: To elucidate the relationship between bone geometry and onset of walking in former term and preterm children.
STUDY DESIGN: We conducted a cross-sectional study of 128 preschool children aged 3 to 5 years who underwent peripheral quantitative computerized tomography measures of bone size at the distal tibia. Linear models were developed, stratifying by sex, to determine whether bone differences between children born term and preterm were caused by differences in walking age.
RESULTS: Children with a history of preterm birth walked later than children born at term (12.4 +/- 0.5 versus 10.9 +/- 0.2 months; P = .004); however, …

Gangliocytic Paraganglioma: Case Report And Review Of The Literature, Agnes Witkiewicz, Avi Galler, Charles Yeo

Department of Surgery Faculty Papers

Gangliocytic paraganglioma is a rare tumor, which occurs nearly exclusively in the second portion of the duodenum. Generally, this tumor has a benign clinical course, although rarely, it may recur or metastasize to regional lymph nodes. Only one case with distant metastasis has been reported. We present a case of duodenal gangliocytic paraganglioma treated first by local resection followed by pylorus-preserving pancreaticoduodenectomy. Examination of the first specimen revealed focal nuclear pleomorphism and mitotic activity, in addition to the presence of three characteristic histologic components: epithelioid, ganglion, and spindle cell. In the subsequent pancreaticoduodenectomy specimen, there was no residual tumor identified …

Quality Of Weight Loss Advice On Internet Forums, Kevin O Hwang, Kiran Farheen, Craig W Johnson, Eric J Thomas, Ann S Barnes, Elmer V Bernstam

Faculty, Staff and Student Publications

BACKGROUND: Adults use the Internet for weight loss information, sometimes by participating in discussion forums. Our purpose was to analyze the quality of advice exchanged on these forums.

METHODS: This was a retrospective analysis of messages posted to 18 Internet weight loss forums during 1 month in 2006. Advice was evaluated for congruence with clinical guidelines; potential for causing harm; and subsequent correction when it was contradictory to guidelines (erroneous) or potentially harmful. Message- and forum-specific characteristics were evaluated as predictors of advice quality and self-correction.

RESULTS: Of 3368 initial messages, 266 (7.9%) were requests for advice. Of 654 provisions …

Energizing Mirna Research: A Review Of The Role Of Mirnas In Lipid Metabolism, With A Prediction That Mir-103/107 Regulates Human Metabolic Pathways, Bernard R. Wilfred, Wang-Xia Wang, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: (1) adipocyte biochemistry and cell fate determination; (2) regulation of metabolic biochemistry in invertebrates; and (3) regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon …

Relationships Between Scores On The Jefferson Scale Of Physician Empathy, Patient Perceptions Of Physician Empathy, And Humanistic Approaches To Patient Care: A Validity Study., Karen M. Glaser, Fred W. Markham, Herbert M. Adler, Patrick R. Mcmanus, Mohammadreza Hojat

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Empathy is the backbone of a positive physician-patient relationship. Physician empathy and the patient's awareness of the physician's empathic concern can lead to a more positive clinical outcome.

MATERIAL/METHODS: The Jefferson Scale of Physician Empathy (JSPE) was completed by 36 physicians in the Family Medicine residency program at Thomas Jefferson University Hospital, and 90 patients evaluated these physicians by completing the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE), and a survey about physicians' humanistic approaches to patient care.

RESULTS: A statistically significant correlation was found between scores of the JSPE and JSPPPE (r=0.48, p

CONCLUSIONS: These findings …

Survival After Bidirectional Cavopulmonary Anastomosis: Analysis Of Preoperative Risk Factors., Mark A. Scheurer, Elizabeth G Hill, Nagavardhan Vasuki, Scott Maurer, Eric M. Graham, Varsha Bandisode, Girish S. Shirali, Andrew M. Atz, Scott M. Bradley

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Prognostic factors for survival after bidirectional cavopulmonary anastomosis for functionally single ventricle are not well defined. We analyzed preoperative hemodynamic and echocardiographic data to determine risk factors for death or transplantation at least 1 year after bidirectional cavopulmonary anastomosis.

METHODS: Data for all patients who underwent bidirectional cavopulmonary anastomosis before 5 years of age at our institution from September 1995 through June 2005 were analyzed. Available preoperative echocardiograms and catheterizations were reviewed. Survivors were compared with those who died or underwent transplantation. Bivariable associations between demographic and clinical risk factors and survival status (alive without transplantation vs dead or …

Neural Reprogramming In Retinal Degeneration, Robert E Marc, Bryan W Jones, James R Anderson, Krista Kinard, David W Marshak, John H Wilson, Theodore Wensel, Robert J Lucas

Faculty, Staff and Student Publications

PURPOSE: Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration.

METHODS: Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP.

RESULTS: After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion …

Mechanisms Of Perceptual Learning Of Depth Discrimination In Random Dot Stereograms, Liat Gantz, Saumil S Patel, Susana T L Chung, Ronald S Harwerth

Faculty, Staff and Student Publications

Perceptual learning is a training induced improvement in performance. Mechanisms underlying the perceptual learning of depth discrimination in dynamic random dot stereograms were examined by assessing stereothresholds as a function of decorrelation. The inflection point of the decorrelation function was defined as the level of decorrelation corresponding to 1.4 times the threshold when decorrelation is 0%. In general, stereothresholds increased with increasing decorrelation. Following training, stereothresholds and standard errors of measurement decreased systematically for all tested decorrelation values. Post training decorrelation functions were reduced by a multiplicative constant (approximately 5), exhibiting changes in stereothresholds without changes in the inflection points. …

Neuropathological Findings Processed By Artificial Neural Networks (Anns) Can Perfectly Distinguish Alzheimer's Patients From Controls In The Nun Study, Enzo Grossi, Massimo P. Buscema, David Snowdon, Piero Antuono

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover …

Meeting Report: The Role Of Environmental Lighting And Circadian Disruption In Cancer And Other Diseases, Richard G. Stevens, David E. Blask, George C. Brainard, Johnni Hansen, Steven W. Lockley, Ignacio Provencio, Mark S. Rea, Leslie Reinlib

Department of Neurology Faculty Papers

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have …

Azithromycin In The Extremely Low Birth Weight Infant For The Prevention Of Bronchopulmonary Dysplasia: A Pilot Study, Hubert O. Ballard, Michael I. Anstead, Lori A. Shook

Pediatrics Faculty Publications

BACKGROUND: Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (< or = 1000 grams) population.

METHODS: Infants < or = 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA.

RESULTS: A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and …

The Flagellum Of Pseudomonas Aeruginosa Is Required For Resistance To Clearance By Surfactant Protein A, Shiping Zhang, Francis X. Mccormack, Roger C. Levesque, George A. O'Toole, Gee W. Lau

Dartmouth Scholarship

Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa …

Concave Pit-Containing Scaffold Surfaces Improve Stem Cell-Derived Osteoblast Performance And Lead To Significant Bone Tissue Formation., Antonio Graziano, Riccardo D'Aquino, Maria Gabriella Cusella-De Angelis, Gregorio Laino, Adriano Piattelli, Maurizio Pacifici, Alfredo De Rosa, Gianpaolo Papaccio

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Scaffold surface features are thought to be important regulators of stem cell performance and endurance in tissue engineering applications, but details about these fundamental aspects of stem cell biology remain largely unclear.

METHODOLOGY AND FINDINGS: In the present study, smooth clinical-grade lactide-coglyolic acid 85:15 (PLGA) scaffolds were carved as membranes and treated with NMP (N-metil-pyrrolidone) to create controlled subtractive pits or microcavities. Scanning electron and confocal microscopy revealed that the NMP-treated membranes contained: (i) large microcavities of 80-120 microm in diameter and 40-100 microm in depth, which we termed primary; and (ii) smaller microcavities of 10-20 microm in diameter …

Acute Proximal Hamstring Rupture, Steven B. Cohen, James Bradley

Department of Orthopaedic Surgery Faculty Papers

Hamstring strain is common in athletes, and both diagnosis and surgical treatment of this injury are becoming more common. Nonsurgical treatment of complete ruptures has resulted in complications such as muscle weakness and sciatic neuralgia. Surgical treatment recently has been advocated to repair the complete rupture of the hamstring tendons from the ischial tuberosity. Surgical repair involves a transverse incision in the gluteal crease, protection of the sciatic nerve, mobilization of the ruptured tendons, and repair to the ischial tuberosity with the use of suture anchors. Reports in the literature of surgical treatment of proximal hamstring rupture are few, and …

Time-Kill And Synergism Studies Of Ceftobiprole Against Enterococcus Faecalis, Including Beta-Lactamase-Producing And Vancomycin-Resistant Isolates, Cesar A Arias, Kavindra V Singh, Diana Panesso, Barbara E Murray

Faculty, Staff and Student Publications

Ceftobiprole (BAL9141) is an investigational cephalosporin with broad in vitro activity against gram-positive cocci, including enterococci. Ceftobiprole MICs were determined for 93 isolates of Enterococcus faecalis (including 16 beta-lactamase [Bla] producers and 17 vancomycin-resistant isolates) by an agar dilution method following the Clinical and Laboratory Standards Institute recommendations. Ceftobiprole MICs were also determined with a high inoculum concentration (10(7) CFU/ml) for a subset of five Bla producers belonging to different previously characterized clones by a broth dilution method. Time-kill and synergism studies (with either streptomycin or gentamicin) were performed with two beta-lactamase-producing isolates (TX0630 and TX5070) and two vancomycin-resistant isolates …

Importance Of The Ebp (Endocarditis- And Biofilm-Associated Pilus) Locus In The Pathogenesis Of Enterococcus Faecalis Ascending Urinary Tract Infection, Kavindra V Singh, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: We recently demonstrated that the ubiquitous Enterococcus faecalis ebp (endocarditis- and biofilm-associated pilus) operon is important for biofilm formation and experimental endocarditis. Here, we assess its role in murine urinary tract infection (UTI) by use of wild-type E. faecalis OG1RF and its nonpiliated, ebpA allelic replacement mutant (TX5475).

METHODS: OG1RF and TX5475 were administered transurethrally either at an ~1 : 1 ratio (competition assay) or individually (monoinfection). Kidney pairs and urinary bladders were cultured 48 h after infection. These strains were also tested in a peritonitis model.

RESULTS: No differences were observed in the peritonitis model. In mixed UTIs, …

Acquisition Of A Natural Resistance Gene Renders A Clinical Strain Of Methicillin-Resistant Staphylococcus Aureus Resistant To The Synthetic Antibiotic Linezolid, Seok-Ming Toh, Liqun Xiong, Cesar A Arias, Maria V Villegas, Karen Lolans, John Quinn, Alexander S Mankin

Faculty, Staff and Student Publications

Linezolid, which targets the ribosome, is a new synthetic antibiotic that is used for treatment of infections caused by Gram-positive pathogens. Clinical resistance to linezolid, so far, has been developing only slowly and has involved exclusively target site mutations. We have discovered that linezolid resistance in a methicillin-resistant Staphylococcus aureus hospital strain from Colombia is determined by the presence of the cfr gene whose product, Cfr methyltransferase, modifies adenosine at position 2503 in 23S rRNA in the large ribosomal subunit. The molecular model of the linezolid-ribosome complex reveals localization of A2503 within the drug binding site. The natural function of …

Surgical Versus Nonsurgical Treatment For Lumbar Degenerative Spondylolisthesis., James N Weinstein, Jon D Lurie, Tor D Tosteson, Brett Hanscom, Anna N A Tosteson, Emily A Blood, Nancy J O Birkmeyer, Alan Hilibrand, Harry Herkowitz, Frank P Cammisa, Todd J Albert, Sanford E Emery, Lawrence G Lenke, William A Abdu, Michael Longley, Thomas J Errico, Serena S Hu

Rothman Institute Papers

BACKGROUND: Management of degenerative spondylolisthesis with spinal stenosis is controversial. Surgery is widely used, but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials.

METHODS: Surgical candidates from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a randomized cohort or an observational cohort. Treatment was standard decompressive laminectomy (with or without fusion) or usual nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) bodily pain and physical function scores (100-point scales, …

Dermatology 75 Years Ago., Lawrence Parish, Joseph A Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

It seems that the practicing dermatologist in 2007 is being attacked on all fronts. The Food and Drug Administration has mandated a cumbersome program for monitoring isotrentinoin usage, its analogue barely comes under scrutiny. iPledge is just a plain nightmare. The acumen of the board certified dermatologist is being challenged by Maintenance of Certification proposals because other specialties are doing it; yet, the neighborhood pharmacist is unhampered in dispensing all sorts of advice about treatment. The insurance clerk thrives on denying medication, prescribed by the physician, using flawed reasoning or else suggesting that a ten days’ supply of medicine should …

A Review Of The Association Between Congestive Heart Failure And Cognitive Impairment., Michael B. Cohen, Paul J. Mather

Division of Cardiology Faculty Papers

Heart failure is a growing epidemic with an estimated 5 million Americans suffering from this condition. Several clinical trials have demonstrated a high correlation between congestive heart failure (CHF) and cognitive impairment. The severity of cognitive impairment correlates positively with the degree of CHF. The underlying mechanism for cognitive impairment remains unclear but appears to be related to cerebral hypoperfusion and impaired cerebral reactivity with selective impairment of verbal memory and attention domains. Furthermore, cognitive dysfunction represents one aspect of frailty, a novel concept that encompasses a range of clinical conditions that results in functional impairment in patients with heart …

Clinical Implication Of Genome-Wide Profiling In Diffuse Large B-Cell Lymphoma And Other Subtypes Of B-Cell Lymphoma., Javeed Iqbal, Shantaram Joshi, Kavita N. Patel, Sofi I. Javed, Can Kucuk, Afeera Aabida, Francesco D'Amore, Kai Fu

Journal Articles: Pathology and Microbiology

The differentiation of lymphoid cells is tightly regulated by transcription factors at various stages during their development. During the maturation processes, different genomic alterations or aberrations such as chromosomal translocation, mutation and deletions may occur that can eventually result in distinct biological and clinical tumors. The different differentiation stages create heterogeneity in lymphoid malignancies, which can complicate the diagnosis. The initial diagnostic scheme for lymphoid diseases was coined by Rappaport followed by Revised European and American Classification of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely …

A Pilot Study Of Atomoxetine In Young Children With Attention-Deficit/Hyperactivity Disorder., Christopher J. Kratochvil, Brigette S. Vaughan, Michelle L. Mayfield-Jorgensen, John S. March, Scott H. Kollins, Desiree W. Murray, Hima Ravi, Laurence L. Greenhill, Lisa A. Kotler, Natalya Paykina, Patricia Biggins, Julie Stoner

Journal Articles: Psychiatry

OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of atomoxetine during acute treatment of attention-deficit/hyperactivity disorder (ADHD) in 5 and 6 year olds.

METHOD: Twenty two children (male n = 19, 86%) with ADHD were treated with atomoxetine for 8 weeks in a three-site, open-label pilot study. Dosing was flexible, with titration to a maximum of 1.8 mg/kg per day. Parent education on behavior management was provided as part of each pharmacotherapy visit.

RESULTS: Subjects demonstrated a mean decrease of 20.68 points (SD = 12.80, p < 0.001)) on the ADHD Rating Scale-IV (ADHD-IV-RS) total score, 10.18 (SD = 7.48, p < 0.001) on the inattentive subscale and 10.50 (SD = 7.04, p < 0.001) on the hyperactive/impulsive subscale. Clinical Global Impression-Severity (CGI-S) was improved in 82% of the children (95% CI, 66-98%) and Children's Global Assessment (CGAS) scores improved 18.91 points on average (SD = 12.20, p < 0.001). The mean final dose of atomoxetine was 1.25 mg/kg per day (SD = 0.35 mg/kg per day). Mood lability was the most commonly reported adverse event (n = 12, 54.5%). Eleven subjects (50%) reported decreased appetite and a mean weight loss of 1.04 kg (SD = 0.80 kg) (p < 0.001) was observed for the group. Vital sign changes were mild and not clinically significant. There were no discontinuations due to adverse events or lack of efficacy.

CONCLUSION: Atomoxetine was generally effective for reducing core ADHD …

Chronic Disease Prevention In Adolescence, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Ambulatory Care Adverse Events And Preventable Adverse Events Leading To A Hospital Admission, Donna M Woods, Eric J Thomas, Jane L Holl, Kevin B Weiss, Troyen A Brennan

Faculty, Staff and Student Publications

BACKGROUND: Most healthcare in the US is delivered in the ambulatory care setting, but the epidemiology of errors and adverse events in ambulatory care is understudied.

METHODS: Using the population-based data from the Colorado and Utah Medical Practices Study, we identified adverse events that occurred in an ambulatory care setting and led to hospital admission. Proportions with 95% CIs are reported.

RESULTS: We reviewed 14,700-hospital discharge records and found 587 adverse events of which 70 were ambulatory care adverse events (AAEs) and 31 were ambulatory care preventable adverse events (APAEs). When weighted to the general population, there were 2608 AAEs …

Sociodemographic Characteristics And Diabetes Predict Invalid Self-Reported Non-Smoking In A Population-Based Study Of U.S. Adults, Monica A. Fisher, George W. Taylor, Brent J. Shelton, Sara M. Debanne

Markey Cancer Center Faculty Publications

BACKGROUND: Nearly all studies reporting smoking status collect self-reported data. The objective of this study was to assess sociodemographic characteristics and selected, common smoking-related diseases as predictors of invalid reporting of non-smoking. Valid self-reported smoking may be related to the degree to which smoking is a behavior that is not tolerated by the smoker's social group.

METHODS: True smoking was defined as having serum cotinine of 15+ng/ml. 1483 "true" smokers 45+ years of age with self-reported smoking and serum cotinine data from the Mobile Examination Center were identified in the third National Health and Nutrition Examination Survey. Invalid non-smoking was …

Management Of Morel-Lavallee Lesion Of The Knee: Twenty-Seven Cases In The National Football League, Samir G. Tejwani, Steven B. Cohen, James P. Bradley

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The Morel-Lavallee lesion is a closed degloving injury most commonly described in the region of the hip joint after blunt trauma. It also occurs in the knee as a result of shearing trauma during football and is a distinct lesion from prepatellar bursitis and quadriceps contusion.

PURPOSE: To review the authors' experience with Morel-Lavallee lesion of the knee in the elite contact athlete to construct a diagnostic and treatment algorithm.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: Twenty-seven knees in 24 players were identified from 1 National Football League team's annual injury database as having sustained a …

Oocyte Cytoplasmic Maturation: A Key Mediator Of Oocyte And Embryo Developmental Competence., A J Watson

Obstetrics & Gynaecology Publications

Efforts have intensified to successfully mature and inseminate oocytes in vitro and then culture ensuing embryos to transferable stages from a large number of mammalian species. Success varies, but generally even for the most successful species it is only possible to obtain a maximum of a 40 to 50% development of zygotes to the blastocyst stage. Reduced oocyte developmental competence is suggested as a primary reason for the reduced potential of in vitro-produced embryos. The vast majority of in vitro-matured oocytes are meiotically competent; however, many do not attain an optimal oocyte diameter before insemination. Variations in oocyte in vitro …

Colon Carcinoma Cells Harboring Pik3ca Mutations Display Resistance To Growth Factor Deprivation Induced Apoptosis., J. Wang, Karen Kuropatwinski, Jennie Hauser, Michael R. Rossi, Yunfei Zhou, Alexis Conway, Julie L.C. Kan, Neil W. Gibson, James K.V. Willson, John K. Cowell, Michael G. Brattain

Journal Articles: Eppley Institute

PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is mutated in a variety of human cancers. We screened the colon cancer cell lines previously established in our laboratory for PIK3CA mutations and found that four of them harbored gain of function mutations. We have now compared a panel of mutant and wild-type cell lines for cell proliferation and survival in response to stress. There was little difference in PI3K activity between mutant PIK3CA-bearing cells (mutant cells) and wild-type PIK3CA-bearing cells (wild-type cells) under optimal growth conditions. However, the mutant cells showed constitutive PI3K activity during growth factor deprivation …

Association Of The Tensin N-Terminal Protein-Tyrosine Phosphatase Domain With The Alpha Isoform Of Protein Phosphatase-1 In Focal Adhesions, Masumi Eto, Jason Kirkbride, Elizabeth Elliott, Su Hao Lo, David L. Brautigan

Department of Molecular Physiology and Biophysics Faculty Papers

Focal adhesions attach cultured cells to the extracellular matrix, and we found endogenous protein phosphatase-1alpha isoform (PP1alpha) localized in adhesions across the entire area of adherent fibroblasts. However, in fibroblasts migrating into a scrape wound or spreading after replating PP1alpha did not appear in adhesions near the leading edge but was recruited into other adhesions coincident in time and space with incorporation of tensin. Endogenous tensin and PP1alpha co-precipitated from cell lysates with isoform-specific PP1 antibodies. Chemical cross-linking of focal adhesion preparations with Lomant's reagent demonstrated molecular proximity of endogenous PP1alpha and tensin, whereas neither focal adhesion kinase nor vinculin …