Medicine and Health Sciences Commons^™

The Kidney-Specific Wnk1 Isoform Is Induced By Aldosterone And Stimulates Epithelial Sodium Channel-Mediated Na+ Transport, Anikó Naray-Fejes-Toth, Peter M. Snyder, Géza Fejes-Toth

Dartmouth Scholarship

WNK1 belongs to a unique family of Ser/Thr kinases that have been implicated in the control of blood pressure. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. How overexpression of WNK1 leads to Na⁺ retention and hypertension is not entirely clear. Similarly, there is no information on the hormonal regulation of expression of WNK kinases. There are two main WNK1 transcripts expressed in the kidney: the originally described “long” WNK1 and a shorter transcript that is specifically expressed in the kidney (KS-WNK1). The goal …

Separate And Concomitant Use Of Lamotrigine, Lithium, And Divalproex In Bipolar Disorders., Daniel Z Lieberman, Frederick K Goodwin

Psychiatry and Behavioral Sciences Faculty Publications

Expert consensus emphasizes the need for better recognition and accurate diagnosis of bipolar disorder. Current research on lithium, divalproex, and lamotrigine provides new insight into the effective management of this illness. Advances in identifying the mechanism of action of mood stabilization has focused on signaling pathways within the cell that are associated with neurotrophic effects. Clinical research has led to confirmatory evidence of the efficacy of lithium in all phases of bipolar disorder, with the greatest effects seen in the treatment and prevention of mania. Compared to divalproex, lithium also has been found to have greater efficacy in the prevention …

Acgme Research Requirements For Residents In Psychiatry., Kathleen S. Peindl, Stephen Weinstein, Ashwin A. Patkar, Edward Silberman, Michael Vergare

Department of Psychiatry and Human Behavior Faculty Papers

No abstract provided.

Control Of Mitochondrial Motility And Distribution By The Calcium Signal: A Homeostatic Circuit., Muqing Yi, David Weaver, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria are dynamic organelles in cells. The control of mitochondrial motility by signaling mechanisms and the significance of rapid changes in motility remains elusive. In cardiac myoblasts, mitochondria were observed close to the microtubular array and displayed both short- and long-range movements along microtubules. By clamping cytoplasmic [Ca2+] ([Ca2+]c) at various levels, mitochondrial motility was found to be regulated by Ca2+ in the physiological range. Maximal movement was obtained at resting [Ca2+]c with complete arrest at 1-2 microM. Movement was fully recovered by returning to resting [Ca2+]c, and inhibition could be repeated with no apparent desensitization. The inositol 1,4,5-trisphosphate- or …

Rgs14 Is A Mitotic Spindle Protein Essential From The First Division Of The Mammalian Zygote., Luke Martin-Mccaffrey, Francis S Willard, Antonio J Oliveira-Dos-Santos, David R C Natale, Bryan E Snow, Randall J Kimple, Agnieszka Pajak, Andrew J Watson, Lina Dagnino, Josef M Penninger, David P Siderovski, Sudhir J A D'Souza

Obstetrics & Gynaecology Publications

Heterotrimeric G protein alpha subunits, RGS proteins, and GoLoco motif proteins have been recently implicated in the control of mitotic spindle dynamics in C. elegans and D. melanogaster. Here we show that "regulator of G protein signaling-14" (RGS14) is expressed by the mouse embryonic genome immediately prior to the first mitosis, where it colocalizes with the anastral mitotic apparatus of the mouse zygote. Loss of Rgs14 expression in the mouse zygote results in cytofragmentation and failure to progress to the 2-cell stage. RGS14 is found in all tissues and segregates to the nucleus in interphase and to the mitotic spindle …

Multiple Roles Of Mucins In Pancreatic Cancer, A Lethal And Challenging Malignancy., N. Moniaux, M. Andrianifahanana, R. E. Brand, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are members of an expanding family of large multifunctional glycoproteins. Pancreatic mucins have important biological functions, including the protection, lubrication, and moisturisation of the surfaces of epithelial tissues lining ductal structures within the pancreas. Several lines of evidence support the notion that deregulated mucin production is a hallmark of inflammatory and neoplastic disorders of the pancreas. Herein, we discuss the factors that contribute to the lethality of pancreatic cancer as well as the key role played by mucins, particularly MUC1 and MUC4, in the development and progression of the disease. Aspects pertaining to the aberrant expression and glycosylation of …

Improved Quantification Of Small Objects In Near-Infrared Diffuse Optical Tomography, Subhadra Srinivasan, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Xiaomei Song, Keith D. Paulsen

Dartmouth Scholarship

Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final …

Is Extended Volume External Beam Radiation Therapy Covering The Anastomotic Site Beneficial In Post-Esophagectomy High Risk Patients?, Edward Yu, Rashid Dar, George Rodrigues, Larry Stitt, Gregory Videtic, Pauline Truong, Anna Tomiak, Robert Ash, Ed Brecevic, Richard Inculet, Richard Malthaner, Mark Vincent, Ian Craig, Walter Kocha, Michael Lefcoe

Edward Yu

Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients. Patients and methods: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment …

Update On Diabetes Mellitus, Murray Korc

Dartmouth Scholarship

Diabetes mellitus is a complex multi-system disorder that may be classified as autoimmune mediated type 1 diabetes, or as insulin resistance associated type 2 diabetes. In type 1 diabetes, there is selective loss of the beta cells within the endocrine islets, as a consequence of T-cell and cytokine mediated destruction of these cells, perhaps in conjunction with destruction of the peri-islet Schwann cells. In type 2 diabetes, the etiology of the resistance ranges from post-receptor defects in the insulin signaling pathway to excessive production of adipocyte derived cytokines that antagonize insulin action to mitochondrial defects that interfere with glucose disposal. …

Felix Platter: A Sixteenth-Century Medical Student, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Differential Expression Of Toll-Like Receptors 2 And 4 In Tissues Of The Human Female Reproductive Tract, Patricia A. Pioli, Eyal Amiel, Todd M. Schaefer, John E. Connolly, Charles R. Wira, Paul M. Guyre

Dartmouth Scholarship

Toll-like receptor (TLR) signal transduction is a central component of the innate immune response to pathogenic challenge. Although recent studies have begun to elucidate differences in acquired immunity in tissues of the human female reproductive tract, there is a relative paucity of work regarding innate defense mechanisms. We investigated TLR mRNA and protein expression in tissues of the human female reproductive tract. Constitutive mRNA expression of TLRs 1 to 6 was observed in fallopian tubes, uterine endometrium, cervix, and ectocervix. Furthermore, transcripts of the signaling adapter MyD88 and the accessory molecule CD14 were also detected in all tissues assayed. Quantitative …

Relationship Of Serum Prolactin With Severity Of Drug Use And Treatment Outcome In Cocaine Dependence., Ashwin A. Patkar, Paolo Mannelli, Kenneth M. Certa, Kathleen Peindl, Heather Murray, Michael J. Vergare, Wade H. Berrettini

Department of Psychiatry and Human Behavior Faculty Papers

RATIONALE: Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence.

OBJECTIVE: We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects.

METHODS: Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed …

Evaluation Of Intra- And Inter-Fraction Motion In Breast Radiotherapy Using Electronic Portal Cine Imaging, Tomas Kron, Chrison Lee, Francisco Perera, Edward Yu

Edward Yu

Breast irradiation is one of the most challenging problems in radiotherapy due to the complex shape of the target volume, proximity of radiation sensitive normal structures and breathing motion. It was the aim of the present study to use electronic portal imaging (EPI) during treatment to determine intra- and inter-fraction motion in patients undergoing radiotherapy and to correlate the magnitude of motion with patient specific parameters. EPI cine images were acquired from the medial tangential fields of twenty radiotherapy patients on a minimum of 5 days each over the course of their treatment. The treatments were administered using 10 MV …

Multiple Mechanisms Regulate Numa Dynamics At Spindle Poles, Olga Kisurina-Evgenieva, Gary Mack, Quansheng Du, Ian Macara, Alexey Khodjakov, Duane A. Compton

Dartmouth Scholarship

The large coiled-coil protein NuMA plays an essential role in organizing microtubule minus ends at spindle poles in vertebrate cells. Here, we use both in vivo and in vitro methods to examine NuMA dynamics at mitotic spindle poles. Using fluorescence recovery after photobleaching, we show that an exogenously expressed green-fluorescent-protein/NuMA fusion undergoes continuous exchange between soluble and spindle-associated pools in living cells. These dynamics require cellular energy and display an average half-time for fluorescence recovery of approximately 3 minutes. To explore how NuMA dynamics at spindle poles is regulated, we exploited the association of NuMA with microtubule asters formed in …

Distinct Gene Expression Profiles In Different B-Cell Compartments In Human Peripheral Lymphoid Organs., Yulei Shen, Javeed Iqbal, Li Xiao, Ryan C. Lynch, Andreas Rosenwald, Louis M. Staudt, Simon Sherman, Karen Dybkaer, Guimei Zhou, James D. Eudy, Jan Delabie, Timothy W. Mckeithan, Wing C. Chan

Journal Articles: Eppley Institute

BACKGROUND: There are three major B-cell compartments in peripheral lymphoid organs: the germinal center (GC), the mantle zone (MNZ) and the marginal zone (MGZ). Unique sets of B-cells reside in these compartments, and they have specific functional roles in humoral immune response. MNZ B cells are naive cells in a quiescent state and may participate in GC reactions upon proper stimulation. The adult splenic MGZ contains mostly memory B cells and is also known to provide a rapid response to particulate antigens. The GC B-cells proliferate rapidly and undergo selection and affinity maturation. The B-cell maturational process is accompanied by …

Collecting Duct Carcinoma Of The Kidney: An Immunohistochemical Study Of 11 Cases., Andrea Vecchione, Tommaso Prayer Galetti, Marina Gardiman, Hideshi Ishii, Enrico Giarnieri, Francesco Pagano, Leonard G Gomella, Carlo M Croce, Raffaele Baffa

Department of Urology Faculty Papers

BACKGROUND: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27kip1, and BCL2). METHODS: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation …

Survival Of Patients With Metastatic Breast Cancer: Twenty-Year Data From Two Seer Registries, Patricia Tai, Edward Yu, Vincent Vinh-Hung, Gábor Cserni, Georges Vlastos

Edward Yu

Background: Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. Methods: Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 …

Nf-Kappab And Ap-1 Connection: Mechanism Of Nf-Kappab-Dependent Regulation Of Ap-1 Activity., Shuichi Fujioka, Jiangong Niu, Christian Schmidt, Guido M Sclabas, Bailu Peng, Tadashi Uwagawa, Zhongkui Li, Douglas B Evans, James L Abbruzzese, Paul J Chiao

Journal Articles

Nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors regulate many important biological and pathological processes. Activation of NF-kappaB is regulated by the inducible phosphorylation of NF-kappaB inhibitor IkappaB by IkappaB kinase. In contrast, Fos, a key component of AP-1, is primarily transcriptionally regulated by serum responsive factors (SRFs) and ternary complex factors (TCFs). Despite these different regulatory mechanisms, there is an intriguing possibility that NF-kappaB and AP-1 may modulate each other, thus expanding the scope of these two rapidly inducible transcription factors. To determine whether NF-kappaB activity is involved in the regulation of fos expression in response …

Binding Between The Niemann–Pick C1 Protein And A Photoactivatable Cholesterol Analog Requires A Functional Sterol-Sensing Domain, Nobutaka Ohgami, Dennis C. Ko, Matthew Thomas, Matthew P. Scott, Catherine C. Y. Chang, Ta-Yuan Chang

Dartmouth Scholarship

Niemann-Pick type C (NPC) 1 protein plays important roles in moving cholesterol and other lipids out of late endosomes by means of vesicular trafficking, but it is not known whether NPC1 directly interacts with cholesterol. We performed photoaffinity labeling of intact cells expressing fluorescent protein (FP)-tagged NPC1 by using [(3)H]7,7-azocholestanol ([(3)H]AC). After immunoprecipitation, (3)H-labeled NPC1-GFP appeared as a single band. Including excess unlabeled sterol to the labeling reaction significantly diminished the labeling. Altering the NPC1 sterol-sensing domain (SSD) with loss-of-function mutations (P692S and Y635C) severely reduced the extent of labeling. To further demonstrate the specificity of labeling, we show that …

Planning Evaluation Of Radiotherapy For Complex Lung Cancer Cases Using Helical Tomotherapy, Tomas Kron, Grigor Grigorov, Edward Yu, Slav Yartsev, Jeff Chen, Eugene Wong, George Rodrigues, Kris Trenka, Terry Coad, Glenn Bauman, Jake Van Dyk

Edward Yu

Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used …

Excess Stroke In Mexican Americans Compared With Non-Hispanic Whites: The Brain Attack Surveillance In Corpus Christi Project, Lewis B Morgenstern, Melinda A Smith, Lynda D Lisabeth, Jan M H Risser, Ken Uchino, Nelda Garcia, Paxton J Longwell, David A Mcfarling, Olubumi Akuwumi, Areej Al-Wabil, Fahmi Al-Senani, Devin L Brown, Lemuel A Moyé

Journal Articles

Mexican Americans are the largest subgroup of Hispanics, the largest minority population in the United States. Stroke is the leading cause of disability and third leading cause of death. The authors compared stroke incidence among Mexican Americans and non-Hispanic Whites in a population-based study. Stroke cases were ascertained in Nueces County, Texas, utilizing concomitant active and passive surveillance. Cases were validated on the basis of source documentation by board-certified neurologists masked to subjects' ethnicity. From January 2000 to December 2002, 2,350 cerebrovascular events occurred. Of the completed strokes, 53% were in Mexican Americans. The crude cumulative incidence was 168/10,000 in …

Academic Performance Of Psychiatrists Compared To Other Specialists Before, During, And After Medical School., Frederick S. Sierles, Michael Vergare, Mohammadreza Hojat, Joseph S. Gonnella

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE: This study was designed to compare psychiatrists with other physicians on measures of academic performance before, during, and after medical school.

METHOD: More than three decades of data for graduates of Jefferson Medical College (N=5,701) were analyzed. Those who pursued psychiatry were compared to physicians in seven other specialties on 18 performance measures. Analysis of covariance was used to control for gender effect.

RESULTS: Compared to other physicians, psychiatrists scored higher on measures of verbal ability and general information before medical school and on evaluations of knowledge and skills in behavioral sciences during medical school, but they scored lower …

Clinical Profiles, Occurrence, And Management Of Adolescent Patients With Hair-An Syndrome, Hatim A. Omar, Stephanie Logsdon, Jessica Richards

Pediatrics Faculty Publications

The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) is a subphenotype of the polycystic ovary syndrome. It is one of the most common causes of menstrual problems, hyperandrogenic symptoms, and insulin resistance among young women. Review of clinical data in an outpatient adolescent clinic showed that of the 1,002 young women (ages 10-21 years) attending the clinic over a 2-year period, 50 (5%) were diagnosed with HAIR-AN syndrome. Mean age of the patients was 15.5, initial mean weight at diagnosis was 94.5 kg, and the mean BMI was 33.33 kg/m2. Patients were treated with a weight-stabilization and -reduction …

Long-Term Evaluation Of The Use Of The Transdermal Contraceptive Patch In Adolescents, Stephanie Logsdon, Jessica Richards, Hatim A. Omar

Pediatrics Faculty Publications

The transdermal contraceptive patch, Ortho Evra™, was approved in December 2001 and released on the market in June 2002. In this study, we reviewed clinical data of young women who started the patch between June 2002 and December 2003 in the adolescent medicine clinic at a university-based outpatient center. A total of 62 patients started the patch in that period and two of them were lost to follow-up. Mean age of patients was 17.9 years and mean length of use was 10 cycles. Only 10 patients (16.7%) discontinued use. Reasons for discontinuation were moderate to severe skin irritation (3 patients, …

Transcriptional Activation Of The Human Prostatic Acid Phosphatase Gene By Nf-Kappab Via A Novel Hexanucleotide-Binding Site., Stanislav Zelivianski, Richard Glowacki, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. Despite the fact that the promoter of the PAcP gene has been cloned, the transcriptional factors that regulate PAcP expression remain unidentified. This article describes our analyses of the promoter of the PAcP gene. Deletion analyses of the promoter sequence up to -4893 (-4893/+87) revealed that a 577 bp fragment (-1356/-779) represents the unique positive cis-active element in human prostate cancer cells but not in HeLa cervix carcinoma cells. Interestingly, …

Predictors Of Paralysis In The Rheumatoid Cervical Spine In Patients Undergoing Total Joint Arthroplasty., Jonathan N Grauer, Edwin M Tingstad, Nahshon Rand, Michael J Christie, Alan Hilibrand

Rothman Institute Faculty Papers

BACKGROUND: Rheumatoid arthritis is sometimes associated with radiographic evidence of instability of the cervical spine, most commonly an abnormal subluxation between vertebrae. When this instability compromises the space that is available for the spinal cord, it may be predictive of paralysis. However, the prevalence of radiographic signs of instability that are predictive of paralysis among patients with nonspinal orthopaedic manifestations of rheumatoid arthritis is unknown.

METHODS: Radiographs of the cervical spine of patients with rheumatoid arthritis who had undergone total joint arthroplasty over a five-year period were retrospectively reviewed. The radiographs were evaluated for predictors of paralysis (a posterior atlantodental …

Efficacy Of Quality Criteria To Identify Potentially Harmful Information: A Cross-Sectional Survey Of Complementary And Alternative Medicine Web Sites., Muhammad Walji, Smitha Sagaram, Deepak Sagaram, Funda Meric-Bernstam, Craig Johnson, Nadeem Q Mirza, Elmer V Bernstam

Journal Articles

BACKGROUND: Many users search the Internet for answers to health questions. Complementary and alternative medicine (CAM) is a particularly common search topic. Because many CAM therapies do not require a clinician's prescription, false or misleading CAM information may be more dangerous than information about traditional therapies. Many quality criteria have been suggested to filter out potentially harmful online health information. However, assessing the accuracy of CAM information is uniquely challenging since CAM is generally not supported by conventional literature. OBJECTIVE: The purpose of this study is to determine whether domain-independent technical quality criteria can identify potentially harmful online CAM content. …

Anemia And Blood Transfusion In The Critically Ill Patient: Role Of Erythropoietin, Howard L. Corwin

Dartmouth Scholarship

Critically ill patients receive an extraordinarily large number of blood transfusions. Between 40% and 50% of all patients admitted to intensive care units receive at least 1 red blood cell (RBC) unit during their stay, and the average is close to 5 RBC units. RBC transfusion is not risk free. There is little evidence that 'routine' transfusion of stored allogeneic RBCs is beneficial to critically ill patients. The efficacy of perioperative recombinant human erythropoietin (rHuEPO) has been n demonstrated in a variety of elective surgical settings. Similarly, in critically ill patients with multiple organ failure, rHuEPO therapy will also stimulate …

Comparison Of Transcranial Electric Motor And Somatosensory Evoked Potential Monitoring During Cervical Spine Surgery., Alan S Hilibrand, Daniel M Schwartz, Venkat Sethuraman, Alexander R Vaccaro, Todd J Albert

Rothman Institute Faculty Papers

BACKGROUND: There has been little enthusiasm for somatosensory evoked potential monitoring in cervical spine surgery as a result, in part, of the increased risk of motor tract injury at this level, to which somatosensory monitoring may be insensitive. Transcranial electric motor evoked potential monitoring allows assessment of the motor tracts; therefore, we compared transcranial electric motor evoked potential and somatosensory evoked potential monitoring during cervical spine surgery to determine the temporal relationship between the changes in the potentials demonstrated by each type of monitoring and neurological sequelae and to identify patient-related and surgical factors associated with intraoperative neurophysiological changes.

METHODS: …

Test-Retest Reliability Of Temporal And Spatial Gait Characteristics Measured With An Instrumented Walkway System (Gaitrite)., Cornelis J T Van Uden, Marcus P Besser

Department of Physical Therapy Faculty Papers

BACKGROUND: The purpose of this study was to determine the test-retest reliability of temporal and spatial gait measurements over a one-week period as measured using an instrumented walkway system (GAITRite). METHODS: Subjects were tested on two occasions one week apart. Measurements were made at preferred and fast walking speeds using the GAITRite system. Measurements tested included walking speed, step length, stride length, base of support, step time, stride time, swing time, stance time, single and double support times, and toe in-toe out angle. RESULTS: Twenty-one healthy subjects participated in this study. The group consisted of 12 men and 9 women, …