Georgetown University Medical School Research Articles

Research and development in the molecular genetics of pituitary adenomas and related tumors

Interview by Rona WilliamsonConstantine A Stratakis received his MD and Doctor of Medical Sciences degrees from the University of Athens (Greece) in 1989 and 1994, respectively; he did predoctoral work at the Unit of Endocrinology, Department of Experimental Pharmacology of the same University and at Hospital Cochin (Paris, France), before joining the Developmental Endocrinology Branch of the then National Institute of Child Health & Human Development (NICHD) at the NIH (MD, USA). He continued his postgraduate medical education at Georgetown University Medical School (DC, USA), where he finished a residency in Pediatrics and two fellowships, in Pediatric Endocrinology, followed by Medical Genetics and Clinical Dysmorphology (in a joint program with the then newly founded National Center for Genomic Research, now NHGRI). Dr Stratakis is Board-certified in Pediatrics, Pediatric Endocrinology and Medical Genetics; after a brief stint as faculty at Georgetown University Department of Pediatrics and the Fairfax Children’s Hospital, he joined the Developmental Endocrinology Branch, NICHD, NIH as a Unit Chief in 1996; he continued there as a Senior Investigator and Chief of the Section on Genetics & Endocrinology. Since 2002, he is the Director of the Pediatric Endocrinology Training Fellowship and from 2007 to 2011, he served as Branch Chief and then Head of the Program on Developmental Endocrinology & Genetics (PDEGEN), the largest Department of the Intramural Clinical Research program of NICHD at the NIH Clinical Center. He is the author of more than 400 publications, and has served as a regular Reviewer in more than 100 journals, including Science, Nature Genetics, New England Journal of Medicine and others; he was Editor-in-Chief of the Journal of Endocrine Genetics (2000–2005) and is currently serving on the Editorial Boards of several journals; as of 1 January 2010, Dr Stratakis is a Deputy Editor of the Journal of Clinical Endocrinology & Metabolism, the leading journal in endocrinology. Dr Stratakis has been the recipient of the 1999 Pharmacia-Endocrine Society Award for Excellence in Published Clinical Research, three NIH Merit Awards and other honors, and has been named Visiting Professor in academic centers around the world. He was awarded the 2009 Ernst Oppenheimer Award of the Endocrine Society. Dr Stratakis has been the Scientific Director of the Eunice Kennedy Shriver National Institute of Child Health & Human Development since 2011.

Psychoeducation to Prevent PTSD: A Paucity of Evidence

Psychoeducation to Prevent PTSD: A Paucity of EvidenceJanice L. Krupnick and Bonnie L. GreenJanice L. KrupnickDepartment of Psychiatry at Georgetown University Medical School, in Washington, DC.Search for more papers by this author and Bonnie L. GreenDepartment of Psychiatry at Georgetown University Medical School, in Washington, DC.Address correspondence to Bonnie L. Green, Ph.D., Director, Georgetown Center for Trauma and the Community, Georgetown University Medical School, 310 Kober Cogan Hall, Washington, DC 20007. E-mail: [email protected]Search for more papers by this authorPublished Online:January 2009https://doi.org/10.1521/psyc.2008.71.4.329PDFPDF PLUS ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations About Previous article Next article FiguresReferencesRelatedDetails Cited byCited by1. Psychoeducation for Adults with Post-Traumatic Stress Symptomatology: A Systematic Review and Meta-AnalysisOnline publication date: 25 October 2021. Go to citation Crossref Google Scholar2. The Effectiveness of Psychoeducation and Brief Treatments in the Aftermath of Sexual AssaultOnline publication date: 19 October 2019. Go to citation Crossref Google Scholar3. Disaster Mental Health and Community-Based Psychological First Aid: Concepts and Education/TrainingOnline publication date: 13 May 2016. Go to citation Crossref Google Scholar4. The Role of Psychoeducation in Trauma Recovery: Recommendations for Content and DeliveryOnline publication date: 27 April 2016. Go to citation Crossref Google Scholar5. Trauma‐ and Stressor‐Related Disorders: Posttraumatic Stress Disorder, Acute Stress Disorder, and Adjustment DisorderOnline publication date: 20 February 2015. Go to citation Crossref Google Scholar6. Psycho-educational interventions designed to prevent deployment-related psychological ill-health in Armed Forces personnel: a reviewOnline publication date: 16 June 2010. Go to citation Crossref Google Scholar Volume 71Issue 4Dec 2008 Information© Guilford Publications Inc.PDF download

Backers Warn of Major Fallout if Industry CME Funds Banned

Backers Warn of Major Fallout if Industry CME Funds Banned

Potential Molecular Mechanism for c-Src Kinase-mediated Regulation of Intestinal Cell Migration

The ubiquitously expressed Src tyrosine kinases (c-Src, c-Yes, and c-Fyn) regulate intestinal cell growth and differentiation. Src activity is also elevated in the majority of malignant and premalignant tumors of the colon. The development of fibroblasts with the three ubiquitously expressed kinases deleted (SYF cells) has identified the role of Src proteins in the regulation of actin dynamics associated with increased cell migration and invasion. Despite this, unexpectedly nothing is known about the role of the individual Src kinases on intestinal cell cytoskeleton and/or cell migration. We have previously reported that villin, an epithelial cell-specific actin-modifying protein that regulates actin reorganization, cell morphology, cell migration, cell invasion, and apoptosis, is tyrosine-phosphorylated. In this report using the SYF cells reconstituted individually with c-Src, c-Yes, c-Fyn, and wild type or phosphorylation site mutants of villin, we demonstrate for the first time the absolute requirement for c-Src in villin-induced regulation of cell migration. The other major finding of our study is that contrary to previous reports, the nonreceptor tyrosine kinase, Jak3 (Janus kinase 3), does not regulate phosphorylation of villin or villin-induced cell migration and is, in fact, not expressed in intestinal epithelial cells. Further, we identify SHP-2 and PTP-PEST (protein-tyrosine phosphatase proline-, glutamate-, serine-, and threonine-rich sequence) as negative regulators of c-Src kinase and demonstrate a new function for these phosphatases in intestinal cell migration. Together, these data suggest that in colorectal carcinogenesis, elevation of c-Src or down-regulation of SHP-2 and/or PTP-PEST may promote cancer metastases and invasion by regulating villin-induced cell migration and cell invasion.

Hypoxia Regulates Cross-talk between Syk and Lck Leading to Breast Cancer Progression and Angiogenesis

Hypoxia is a key parameter that controls tumor angiogenesis and malignant progression by regulating the expression of several oncogenic molecules. The nonreceptor protein-tyrosine kinases Syk and Lck play crucial roles in the signaling mechanism of various cellular processes. The enhanced expression of Syk in normal breast tissue but not in malignant breast carcinoma has prompted us to investigate its potential role in mammary carcinogenesis. Accordingly, we hypothesized that hypoxia/reoxygenation (H/R) may play an important role in regulating Syk activation, and Lck may be involved in this process. In this study, we have demonstrated that H/R differentially regulates Syk phosphorylation and its subsequent interaction and cross-talk with Lck in MCF-7 cells. Moreover, Syk and Lck play differential roles in regulating Sp1 activation and expressions of melanoma cell adhesion molecule (MelCAM), urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF) in response to H/R. Overexpression of wild type Syk inhibited the H/R-induced uPA, MMP-9, and VEGF expression but up-regulated MelCAM expression. Our data also indicated that MelCAM acts as a tumor suppressor by negatively regulating H/R-induced uPA secretion and MMP-9 activation. The mice xenograft study showed the cross-talk between Syk and Lck regulated H/R-induced breast tumor progression and further correlated with the expressions of MelCAM, uPA, MMP-9, and VEGF. Human clinical specimen analysis supported the in vitro and in vivo findings. To our knowledge, this is first report that the cross-talk between Syk and Lck regulates H/R-induced breast cancer progression and further suggests that Syk may act as potential therapeutic target for the treatment of breast cancer.

Tumours of Bone. By Charles F. Geschickter, M. D., Professor of Pathology, Georgetown University Medical School, etc., and Murray M. Copeland, M.D., Professor of Oncology, Georgetown University Medical School, etc. Third edition. 67/8 × 10 in. Pp. 810 + xviii, with 642 illustrations. 1949. Philadelphia and London: J. B. Lippincott Co. 105s

Tumours of Bone. By Charles F. Geschickter, M. D., Professor of Pathology, Georgetown University Medical School, etc., and Murray M. Copeland, M.D., Professor of Oncology, Georgetown University Medical School, etc. Third edition. 67/8 × 10 in. Pp. 810 + xviii, with 642 illustrations. 1949. Philadelphia and London: J. B. Lippincott Co. 105s

Diagnosis in daily practice. By Benjamin V. White, M.D., Assistant Clinical Professor of Medicine, Yale University School of Medicine, and Charles F. Geschickter, M.D., Professor of Pathology, Georgetown University Medical School. 9¾ × 7 in. Pp. 693 + xvi with 360 illustrations. 1948. Philadelphia and London: J. B. Lippincott Co. £4 10s. net

Diagnosis in daily practice. By Benjamin V. White, M.D., Assistant Clinical Professor of Medicine, Yale University School of Medicine, and Charles F. Geschickter, M.D., Professor of Pathology, Georgetown University Medical School. 9¾ × 7 in. Pp. 693 + xvi with 360 illustrations. 1948. Philadelphia and London: J. B. Lippincott Co. £4 10s. net

The Scientific Basis of Integrative Medicine

The Scientific Basis of Integrative Medicine

Female Genital Mutilation

THE PROBLEM OF FEMALE GENITAL MUTILATION (FGM) INSPIRED NEARLY 100 medical students from 3 continents to submit their work for the 2002 John Conley Ethics Essay Contest for Medical Students. Essayists discussed ethical issues that would arise if an 18-year-old woman requested thatasurgeonintheUnitedStatesperformFGMonherbeforeshereturned home to Africa, where FGM is most commonly practiced. Also known as “female genital cutting” and “female circumcision,” FGM includes 4 types according to a classification scheme delineated by the World Health Organization in 1995. The classification is based on increasingly extensive excisions of the genitalia from types I to type III, with types I and II comprising the majority of procedures. Variations of FGM that do not meet the criteria for the first 3 types are classified as type IV. The young woman in the scenario requested that the surgeon perform type III, or infibulation, which is the most surgically extensive form of FGM. Type III includes an excision of part or all of the external genitalia and stitching of the vaginal opening, and has been associated with the most serious health complications. Ninety-five percent of FGM is performed on girls between one day to 16 years old, particularly between the ages of 4 and 10 years. However, some cultures perform FGM into adulthood, such as at the time of marriage. Thus, the patient in this scenario requested to have the procedure performed at a relatively old age. Accordingto thescenario, thewomanwantedthesurgerybeforereturning to her homeland in order to decrease her risk of complications that may occur as a result of having it done under unsterile and relatively primitive conditions. The literature on the health risks associated with FGM has mostly focused on gynecologic problems such as hemorrhage, infection, and dysmenorrhea. Other health-related parameters such as overall mortality and morbidity have yet to be documented thoroughly, and the data on which advocates have argued against FGM have been criticized for not meeting rigorous scientific standards of evidence. Nevertheless, national and international health and government organizations have taken strong stands against the practice, arguing that the currently available data sufficiently document the dangers of FGM. The winning essays in this year’s contest explore ethical, moral, and professional dilemmas raised by considering whether or not to perform FGM. Peter Moschovis argues that FGM is wrong because it violates universal moral values and harms the patient-physician relationship overall. Also arguing against FGM, Kyle Brothers challenges physicians to consider relating to their patients as covenant partners whose voices deserve to be heard. Natalie Moniaga makes the case that a physician opposed to FGM can still perform the procedure without contradicting his or her values. And finally Sara Cichowski relates a fictional dialogue between a young woman requesting FGM and the surgeon whom she asks to perform the procedure. Cichowski based the dialogue on an actual encounter she had with a young woman who requested a similar procedure. We thank this year’s judges—Jeffrey Botkin, MD, MPH, Sally Sheldon, PhD, and Sidney Wolfe, MD. ON THE COVER Aparna Mani, Georgetown University Medical School, Single Brushstroke. Oil on paper. 22.9 30.5 cm. Editors Jane van Dis University of South Dakota School of Medicine Stuart P. Weisberg Columbia University College of Physicians and Surgeons

Glass Ceiling Begins to Open, But Just a Crack

Glass Ceiling Begins to Open, But Just a Crack

Psychiatric patients and HIV.

Back to table of contents Previous article Next article ColumnFull AccessDatapoints: Psychiatric Patients and HIVJoyce Y. Chung, M.D., Ana P. Suarez, M.P.H., Deborah A. Zarin, M.D., and Harold Alan Pincus, M.D.Joyce Y. ChungSearch for more papers by this author, M.D., Ana P. SuarezSearch for more papers by this author, M.P.H., Deborah A. ZarinSearch for more papers by this author, M.D., and Harold Alan PincusSearch for more papers by this author, M.D.Published Online:1 Apr 1999https://doi.org/10.1176/ps.50.4.487AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail The death rate from AIDS has been declining since 1996, which is attributed to advances in biomedical treatments with combination antiretroviral medications (1). This good news is tempered by surveillance data showing disproportionate rates of HIV infection among ethnic minority Americans, especially women, youth, and children. Prevention of HIV infection is still the best strategy for addressing the future course of the AIDS epidemic. Survey data from the American Psychiatric Association's Practice Research Network (PRN) (2) suggest that psychiatrists can play a role in the prevention effort.In 1997 all PRN members, a total of 531 psychiatrists, were sent a mail survey on psychiatric patients and treatments that included questions about their patient caseload in their last typical work month across all work settings. Specifically, they were asked about the total number of patients treated, the number who were HIV seropositive, and the number who had any risk factor for HIV infection based on their knowledge of the patient's behavior, including unprotected sex, injection drug use, and occupational exposure. A total of 417 psychiatrists, or 79 percent, responded to the survey, and more than 96 percent of them provided data on HIV prevalence and risk among their patients. The results presented are based on unweighted data.The psychiatrists saw an average of 131 patients a month, ranging from fewer than 50 patients (seen by 19 percent of the psychiatrists) to 300 or more (seen by 6 percent); most respondents (31 percent) saw between 100 and 199 patients a month. Although less than half reported seeing at least one HIV-positive patient in a typical month (Figure 1), 84 percent reported seeing at least one patient who was at risk for HIV infection (Figure 2). Furthermore, while less than 1 percent (one patient) of the mean number of patients seen each month were HIV positive, 9.2 percent (12 patients) were considered to be at risk for HIV infection.The data suggest that psychiatrists typically have clinical encounters with a significant number of patients for whom prevention of HIV infection can be addressed through changes in risk behavior. Therefore, psychiatrists are in a position to actively educate their patients about prevention of HIV infection. APA is currently in the process of developing practice guidelines on HIV/AIDS to help psychiatrists with educational efforts.AcknowledgmentsThe authors acknowledge the support of the John D. and Catherine T. MacArthur Foundation and the Center for Mental Health Services.Dr. Chung is clinical associate professor of psychiatry at Georgetown University Medical School in Washington, D.C. Ms. Suarez, Dr. Zarin, and Dr. Pincus are on the staff of the American Psychiatric Association; Ms. Suarez is research associate in the office of research, Dr. Zarin is deputy medical director and director of APA's office of quality improvement and psychiatric services, and Dr. Pincus is deputy medical director and director of the office of research. Dr. Pincus and Terri L. Tanielian, M.A., are editors of this column.Figure 1. HIV-positive patients seen per month, by percentage of psychiatrists (N=411) responding to a 1997 Practice Research Network surveyFigure 2. Patients with any risk factor for HIV seen per month, by percentage of psychiatrists (N=402) responding to a 1997 Practice Research Network survey

Activity of anti-erbB-2 recombinant toxin OLX-209 on lung cancer cell lines in the absence of erbB-2 gene amplification: Kasprzyk PG, Sullivan TL, Hunt JD, Gubish CT, Scoppa CA, Oelkuct M et al. The Lombardi Cancer Center, Georgetown University Medical School, The Research Building, 3970 Reservoir Road, Washington, DC 20007. Clin Canc Res 1996;2:75–80

The recombinant oncotoxin OLX-209 [e23(Fv)PE38KDEL] has been developed to target cancers with erbB-2 expression and is nearing a clinical trial. Important in clinical planning is the selection of patients on the basis of tumor expression of erbB-2. ErbB-2 gene amplification occurs in cancers of the breast, stomach, and ovary. Patients with these diseases and evident overexpression are candidates for OLX-209 therapy. In lung cancer, overexpression of erbB-2 is also frequent, but in most cases, it is not caused by gene amplification. This study demonstrates that OLX-209 has activity on lung cancer cells with varying levels of erbB-2 expression in the presence and absence of gene amplification. In vitro sensitivity of cell lines to OLX-209 is related to erbB-2 expression level. Normal bronchial epithelial cells were not sensitive. Effective treatment of lung cancer cell lines growing as xenografts in nude mice was shown with Calu-3 (a lung adenocarcinoma line with high levels of p185(erbB-2) caused by gene amplification) and three other lung adenocarcinomas (A549, NCI-H1466, and 201T) with lower levels of p185(erbB-2) and no gene amplification. The 201T cell line was isolated recently from a lung tumor with erbB-2 expression in the original tumor. The results of this study indicate that patients with erbB-2-positive, non-small cell lung cancer should be included in clinical trials of OLX-209.

The complexity of defining class I alleles in African Americans: [formula omitted], ML Iandoli, AG Wagner, S Rosen-Bronson, AH Johnson and CK Hurley, Departments of Microbiology and Pediatrics, Georgetown University Medical School, Washington DC

The complexity of defining class I alleles in African Americans: [formula omitted], ML Iandoli, AG Wagner, S Rosen-Bronson, AH Johnson and CK Hurley, Departments of Microbiology and Pediatrics, Georgetown University Medical School, Washington DC

Diversity of TCR Vβ6 utilized by HLA identical siblings: [formula omitted], HA Araujo, AH Johnson and CK Hurley, Departments of Microbiology and Pediatrics, Georgetown University Medical School, Washington DC

Diversity of TCR Vβ6 utilized by HLA identical siblings: [formula omitted], HA Araujo, AH Johnson and CK Hurley, Departments of Microbiology and Pediatrics, Georgetown University Medical School, Washington DC

Method Already in Use

Method Already in Use Get access E. J. Stay, M.D., E. J. Stay, M.D. Arlington Hospital Departments of Pathology and Surgery Arlington Hospital Arlington, Virginia and Departments of Pathology and Surgery Georgetown University Medical School Washington, DC Search for other works by this author on: Oxford Academic Google Scholar F. M. Cardenas, M.D. F. M. Cardenas, M.D. Arlington Hospital Departments of Pathology and Surgery Arlington Hospital Arlington, Virginia and Departments of Pathology and Surgery Georgetown University Medical School Washington, DC Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 93, Issue 5, 1 May 1990, Page 721, https://doi.org/10.1093/ajcp/93.5.721 Published: 01 May 1990

Regional RNA metabolism in the aged and Alzheimer's disease brain : E. M. Sajdel-Sulkowska, Elizabeth S. Burnside and Herbert J. Manz. Georgetown University and Harvard Medical School, Boston, MA 02115

Regional RNA metabolism in the aged and Alzheimer's disease brain : E. M. Sajdel-Sulkowska, Elizabeth S. Burnside and Herbert J. Manz. Georgetown University and Harvard Medical School, Boston, MA 02115

The Sitting Position and Anesthetic Spread In the Epidural Space

Departments of Anesthesiology, Veterans' Administration Medical Center, and Georgetown University Medical School, Washington, DC

Estelle Ramey, PhD: her sister's keeper.

It was summer 1970, and the women's movement had begun to flower, when Edgar Berman, MD, friend and physician to Hubert told the Democratic Party's Committee on National Priorities that women were unfit for leadership because of raging hormonal imbalances. The reaction by women was swift and furious. Among the outraged letter writers demanding Berman's ouster from the committee was Estelle R. Ramey, PhD, a respected endocrinologist, former Distinguished Woman for Humphrey, and professor of physiology and biophysics at Georgetown University Medical School, Washington, DC. If Dr Berman's political advice to Hubert Humphrey was as sound as his knowledge of medicine, the whole enterprise [1968 elections] was doomed from the start, Ramey wrote in a letter to the editor of a Washington newspaper. In the hoopla that followed, Ramey, a specialist on hormones and stress, and Berman, a surgeon, appeared together on national television and debated before the press

Estelle Ramey, PhD: her sister's keeper

It was summer 1970, and the women's movement had begun to flower, when Edgar Berman, MD, friend and physician to Hubert Humphrey, told the Democratic Party's Committee on National Priorities that women were unfit for leadership because of "raging hormonal imbalances." The reaction by women was swift and furious. Among the outraged letter writers demanding Berman's ouster from the committee was Estelle R. Ramey, PhD, a respected endocrinologist, former "Distinguished Woman for Humphrey," and professor of physiology and biophysics at Georgetown University Medical School, Washington, DC. "If Dr Berman's political advice to Hubert Humphrey was as sound as his knowledge of medicine, the whole enterprise [1968 elections] was doomed from the start," Ramey wrote in a letter to the editor of a Washington newspaper. In the hoopla that followed, Ramey, a specialist on hormones and stress, and Berman, a surgeon, appeared together on national television and debated before the press

An alternative: nasal cannula oxygen therapy for infants who are oxygen dependent.

Employed as a pediatric pulmonary clinical nurse specialist, and instructor of pediatrics at Georgetown University Medical Center and School of Medicine, Washington, D.C., at the time she developed the modified nasal cannula method of oxygen administration. She is currently working on a high-risk infant follow-up project at the Perinatal Center, Sutter Memorial Hospital in Sacramento, CA