Mayo Clinic College Of Medicine Research Articles

Motor Speech Disorders and the Diagnosis of Neurologic Disease

Motor Speech Disorders and the Diagnosis of Neurologic Disease

Germline duplication of chromosomes 10p15.3 and Yp11.32 in a man with learning disability and early onset cutaneous malignant melanoma

American Journal of Medical Genetics Part AVolume 146A, Issue 17 p. 2298-2300 Research Letter Germline duplication of chromosomes 10p15.3 and Yp11.32 in a man with learning disability and early onset cutaneous malignant melanoma† Ercan Mihci, Ercan Mihci Akdeniz University School of Medicine, Division of Clinical Genetics, Department of Pediatrics, Antalya, TurkeySearch for more papers by this authorNoralane M. Lindor, Corresponding Author Noralane M. Lindor nlindor@mayo.edu Department of Medical Genetics, Mayo Clinic College of Medicine, Rochester, MinnesotaDepartment of Medical Genetics, Mayo Clinic College of Medicine, 200 First Street SW, Mayo Clinic E7B, Rochester, MN 55905.Search for more papers by this author Ercan Mihci, Ercan Mihci Akdeniz University School of Medicine, Division of Clinical Genetics, Department of Pediatrics, Antalya, TurkeySearch for more papers by this authorNoralane M. Lindor, Corresponding Author Noralane M. Lindor nlindor@mayo.edu Department of Medical Genetics, Mayo Clinic College of Medicine, Rochester, MinnesotaDepartment of Medical Genetics, Mayo Clinic College of Medicine, 200 First Street SW, Mayo Clinic E7B, Rochester, MN 55905.Search for more papers by this author First published: 15 August 2008 https://doi.org/10.1002/ajmg.a.32442Citations: 1 † How to cite this article: Mihci E, Lindor NM. 2008. Germline duplication of chromosomes 10p15.3 and Yp11.32 in a man with learning disability and early onset cutaneous malignant melanoma. Am J Med Genet Part A 146A:2298–2300. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume146A, Issue171 September 2008Pages 2298-2300 RelatedInformation

Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: Proof of principle

Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcification. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium.

The Black Box Warning for Droperidol

Mayo Clinic College of Medicine, Rochester, Minnesota. nuttall.gregory@mayo.eduI thank Doctor Sosis for his thoughtful comments and the journal Anesthesiology for the opportunity to respond. As noted in our article,1the black box warning on droperidol was based solely on case reports of torsade de pointes associated with droperidol use and the known pharmacologic effect of droperidol to prolong the QT interval. Our manuscript was an attempt to determine, through a retrospective study, the true incidence of torsade de pointes associated with droperidol administration in patients who received low-dose droperidol for prophylaxis and/or treatment of nausea and vomiting associated with anesthesia and surgery. We found the incidence of torsade de pointes to be extremely low. This, combined with the fact that droperidol is one of the few very effective rescue therapies for patients who develop nausea and vomiting postoperatively, led to our conclusion that “the Food and Drug Administration black box warning for low-dose droperidol is excessive and unnecessary.”Dr. Sosis was “surprised” that according to our study, the use of droperidol completely disappeared after insertion of the black box warning. We were not, because this is consistent with what we have observed in our colleagues’ behavior throughout many institutions and expressed at many national meetings. From Dr. Sosis’ comments, I can only assume that he and his institution have continued to use droperidol for their patients despite the black box warning. However, given the last paragraph of his letter, I suspect that this is not true and that he and his institution have also stopped using droperidol. Dr. Sosis is correct that there are black box warnings on midazolam (respiratory depression and arrest), succinylcholine (acute rhabdomyolysis with hyperkalemia), and ketamine (emergence phenomena), and yet anesthesiologists still use these drugs. Most of these black box warning complications are situations that anesthesiologists are comfortable preventing or treating or avoiding via patient selection.In contrast, the black box warning on droperidol mandates that a 12-lead electrocardiogram be performed before administration of droperidol. If the QTc is greater than 440 ms for males and 450 ms for females (QTc values seen in at least 10% of all adults), droperidol is not to be administered. Further, the patient must have electrocardiographic monitoring for 2–3 h after droperidol administration. Functionally, logistically, and practically, many anesthesiologists do not want to deal with these hassles. They also fear the litigation costs should they use droperidol without following the black box–required electrocardiographic monitoring and should the patient have an adverse outcome.The withdrawal of rofecoxib (Vioxx) and other medications demonstrates the importance of postmarketing or phase IV safety studies. The goal of our study was to perform a phase IV trial of droperidol. As such, we found droperidol to be a safe, effective, and inexpensive antiemetic.Mayo Clinic College of Medicine, Rochester, Minnesota. nuttall.gregory@mayo.edu

Urologic Diseases in America Project: Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH), the most common benign neoplasm in American men, is a chronic condition that is associated with progressive lower urinary tract symptoms and affects almost 3 of 4 men during the seventh decade of life. Approximately 6.5 million of the 27 million white men who are 50 to 79 years old in the United States in 2000 were estimated to meet the criteria for discussing treatment. The analytical methods used to generate these results have been described previously. In 2000 approximately 4.5 million visits were made to physician offices to for a primary diagnosis of BPH and almost 8 million visits were made with a primary or secondary diagnosis of BPH. In the same year approximately 87,400 prostatectomies for BPH were performed in inpatients in nonfederal hospitals in the United States. While the number of outpatient visits for BPH increased consistently during the 1990s, there was a dramatic decrease in the use of transurethral prostatectomy, inpatient hospitalization and length of hospital stay for this condition. These trends reflect the changing face of medical management for BPH, ie increasing use of pharmacological agents and minimally invasive therapies. In 2000 the direct cost of BPH treatment was estimated to be $1.1 billion exclusive of outpatient pharmaceuticals. Given the impact that BPH has on quality of life and health care cost in millions of American men, additional research into risk factors, diagnostic and therapeutic resource use, and effectiveness and cost benefit of therapies are warranted.

Fear of Loss, Not Promise of Gain, Drives Practice Patterns in Barrett’s Esophagus

Rubenstein JH, Saini SD, Kuhn L, et al (Ann Arbor VA Medical Center and the University of Michigan Medical School, Ann Arbor, Michigan, and Mayo Clinic College of Medicine, Rochester, Minnesota). Influence of malpractice history on the practice of screening and surveillance for Barrett’s esophagus. Am J Gastroenterol 2007;102:1–8.

T1030 Similarities Between Constipation with and Without Irritable Bowel Syndrome in a California Medicaid (Medi-Cal) Population: Costs Trends By Category in the 12 Months After Diagnosis from 1997 to 2002

Jeonghoon Ahn, Ph.D.1; Richard A. Brook, M.S., M.B.A.2; Michael B. Nichol, Ph.D.1; Jeff McCombs, Ph.D.1; Nicholas J. Talley, M.D., Ph.D.3; G. Richard Locke, III, M.D.4; Robert W. Baran, Pharm.D.5 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California; 2Head, Retrospective Analysis, The JeSTARx Group, Newfoundland, NJ; 3Chairman of Medicine, Mayo Clinic, Jacksonville, FL; 4Professor of Medicine, Mayo Clinic College of Medicine, Rochester MN; 5Senior Manager, HEOR, Takeda Global Research and Development, Inc., Deerfield, IL

Reply

Reply

Editorial Comment

No AccessJournal of UrologyPediatric Urology1 May 2008Editorial Comment Michael Ritchey Michael RitcheyMichael Ritchey More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.01.208AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, 179(5), pp. 1959–1960 References 1 : Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer2007; 48: 493. Google Scholar 2 : Radiation therapy for favorable histology Wilms tumor: prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4. Int J Radiat Oncol Biol Phys2006; 65: 203. Google Scholar 3 : Nuclear morphometry and prognosis in favorable histology Wilms’ tumor: a prospective reevaluation. J Clin Oncol1999; 17: 2123. Google Scholar Department of Urology, Mayo Clinic College of Medicine, Scottsdale, Arizona© 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 5May 2008Page: 1959-1960 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Michael Ritchey More articles by this author Expand All Advertisement PDF downloadLoading ...

NO147: A Randomized Phase III Trial of Oxaliplatin Plus 5-Fluorouracil, and Leucovorin (Modified FOLFOX6) with or without Cetuximab after Curative Resection for Patients with Stage III Colon Cancer

"NO147: A Randomized Phase III Trial of Oxaliplatin Plus 5-Fluorouracil, and Leucovorin (Modified FOLFOX6) with or without Cetuximab after Curative Resection for Patients with Stage III Colon Cancer." Oncology Issues, 23(2), pp. 20–21 Additional informationNotes on contributorsSteven R. AlbertsSteven R. Alberts, MD, is the co-chair for the GI Committee with the North Central Cancer Treatment Group (NCCTG), Mayo Clinic College of Medicine, and the Mayo Clinic, Division of Medical Oncology in Rochester, Minn. Frank Sinicrope, MD, is the Translational Research Chair for the GI Committee with the North Central Cancer Treatment Group, Mayo Clinic College of Medicine.Frank SinicropeSteven R. Alberts, MD, is the co-chair for the GI Committee with the North Central Cancer Treatment Group (NCCTG), Mayo Clinic College of Medicine, and the Mayo Clinic, Division of Medical Oncology in Rochester, Minn. Frank Sinicrope, MD, is the Translational Research Chair for the GI Committee with the North Central Cancer Treatment Group, Mayo Clinic College of Medicine.

STIM1 regulates store operated calcium entry (SOCE) in human airway smooth muscle

Intracellular Ca2+ regulation in human airway smooth muscle (hASM) involves plasma membrane (PM) Ca2+ influx, including that triggered by sarcoplasmic reticulum (SR) Ca2+ depletion, i.e. store‐operated Ca2+ entry (SOCE). While transient receptor potential channels (e.g. TRPC3, TRPC4) are thought to mediate SOCE, the mechanisms triggering or regulating SOCE are being actively investigated. Recent studies suggest that stromal interaction molecule 1 (STIM1) acts as a signaling mediator between PM and SR, potentially regulating Ca2+entry via SOCE. In hASM, fluorescence microscopy and western blot analyses were used to verify the presence of STIM1. SR Ca2+ depletion with 10μM cyclopiazonic acid (CPA) resulted in increased STIM1 expression in the PM fraction, compared to controls. Transfection with 50nM STIM1 siRNA for 48h significantly decreased STIM1 levels. In cells where [Ca2+]i was measured using fura 2‐AM, SOCE was significantly reduced in cells transfected with STIM1 siRNA. Green‐fluorescent protein (GFP)‐tagged STIM1 transfection showed intracellular localization in non‐stimulated cells, with increased PM staining following CPA exposure. Subsequent immunostaining revealed co‐localization of STIM1 with TRPC3 and TRPC4. These results indicate that STIM1 is present in hASM and suggest a role for this protein in regulating SOCE.This work has been supported by NIH grants UL1RR024150‐01(CR to CMP, CR20 and Early Career Development Award to YSP), HL74309 (GCS), and the Department of Anesthesiology (CMP, YSP), Mayo Clinic College of Medicine, Rochester, MN

Claudia F. Lucchinetti

Claudia Lucchinetti, M.D., is the Guest Editor of this issue of Seminars in Neurology on Multiple Sclerosis and Other Demyelinating Disorders of the CNS. Dr. Lucchinetti is Professor of Neurology in the Mayo Clinic College of Medicine in Rochester, Minnesota. She did her undergraduate work at Northwestern University and went to Medical School at Rush Medical College in Chicago. She did her internship at Rush-Presbyterian-St. Luke's Medical Center and her Neurology Residency in the Mayo Graduate School of Medicine. Her Neurology Residency was followed by a Fellowship in Neuroimmunology at the Mayo Clinic, and then an adventure to the Brain Research Institute of Experimental Neurology in Vienna, Austria as a Mayo Foundation Scholar. She has received the Mayo Clinic Woltman Award for Clinical Excellence in Neurology and has been a Recipient of one of the prestigious Frontiers in Neuroscience awards by the American Academy of Neurology.

Low serum creatinine is associated with higher mortality among critically ill patients

Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Epidemiology and Translational Research in Intensive Care (M.E.T.R.I.C) Mayo Clinic College of Medicine, Rochester, MN

Index of Suspicion

Index of Suspicion

Ligand-independent androgen receptor activity is activation function-2-independent and resistant to antiandrogens in androgen refractory prostate cancer cells: Scott M. Dehm, Donald J. Tindall, Departments of Urology, Biochemistry, and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN

Androgen ablation inhibits androgen receptor (AR) activity and is an effective treatment for advanced prostate cancer (PCa). Invariably, PCa relapses in a form resistant to further hormonal manipulations. Although this stage of the disease is androgen-refractory, or androgen depletion-independent (ADI), most tumors remain AR-dependent through aberrant mechanisms of AR activation. We employed the LNCaP/C4-2 model of PCa progression to study AR activity in androgen-dependent and ADI PCa cells. In this report, we show that the AR is transcriptionally inactive in androgen-dependent LNCaP cells in the absence of androgens. However, in ADI C4-2 cells, the AR displays a high level of constitutive, androgen-independent transcriptional activity. To study the mechanisms of ligand dependent and ligand-independent AR activation in these AR-expressing cells, we generated a reporter system based on swapping the DNA binding domain of the AR with the DNA binding domain of the yeast Gal4 transcription factor. In androgen-dependent PCa cells, the well characterized C-terminal AR activation function-2 (AF-2) domain was critical for strong, ligand-dependent activity. Conversely, in ADI PCa cells, constitutive, ligand-independent AR activity was AF-2- independent but instead dependent on N-terminal AR domains. Importantly, the ligand- and AF-2-independent mode of AR activation observed in ADI PCa cells was completely resistant to the antiandrogen, bicalutamide. Our data thus demonstrate that the AR can inappropriately activate transcription in ADI PCa cells via mechanisms that are resistant to castration and AR antagonism, the 2 modes of androgen ablation used to treat advanced PCa.

Identifying Future Scientists: Predicting Persistence into Research Training

This study used semistructured interviews and grounded theory to look for characteristics among college undergraduates that predicted persistence into Ph.D. and M.D./Ph.D. training. Participants in the summer undergraduate and postbaccalaureate research programs at the Mayo Clinic College of Medicine were interviewed at the start, near the end, and 8-12 months after their research experience. Of more than 200 themes considered, five characteristics predicted those students who went on to Ph.D. and M.D./Ph.D. training or to M.D. training intending to do research: 1) Curiosity to discover the unknown, 2) Enjoyment of problem solving, 3) A high level of independence, 4) The desire to help others indirectly through research, and 5) A flexible, minimally structured approach to the future. Web-based surveys with different students confirmed the high frequency of curiosity and/or problem solving as the primary reason students planned research careers. No evidence was found for differences among men, women, and minority and nonminority students. Although these results seem logical compared with successful scientists, their constancy, predictive capabilities, and sharp contrast to students who chose clinical medicine were striking. These results provide important insights into selection and motivation of potential biomedical scientists and the early experiences that will motivate them toward research careers.

Hemorrhagic polyneuropathy in idiopathic thrombocytopenic purpura

Journal of the Peripheral Nervous SystemVolume 12, Issue 4 p. 286-289 Hemorrhagic polyneuropathy in idiopathic thrombocytopenic purpura Joon-Shik Moon, Joon-Shik Moon Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorP. James B. Dyck, P. James B. Dyck Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorJaNean K. Engelstad, JaNean K. Engelstad Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorLawrence V. Witt, Lawrence V. Witt Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorPeter J. Dyck, Corresponding Author Peter J. Dyck Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USAPeter J. Dyck, MD, Mayo Clinic, Department of Neurology, 200 First Street SW, Rochester, MN 55905, USA. Tel: (507) 284-3250; Fax: (507) 284-3133; E-mail: dyck.peter@mayo.eduSearch for more papers by this authorLouis Letendre, Louis Letendre Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this author Joon-Shik Moon, Joon-Shik Moon Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorP. James B. Dyck, P. James B. Dyck Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorJaNean K. Engelstad, JaNean K. Engelstad Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorLawrence V. Witt, Lawrence V. Witt Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this authorPeter J. Dyck, Corresponding Author Peter J. Dyck Peripheral Neuropathy Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USAPeter J. Dyck, MD, Mayo Clinic, Department of Neurology, 200 First Street SW, Rochester, MN 55905, USA. Tel: (507) 284-3250; Fax: (507) 284-3133; E-mail: dyck.peter@mayo.eduSearch for more papers by this authorLouis Letendre, Louis Letendre Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN, USASearch for more papers by this author First published: 26 November 2007 https://doi.org/10.1111/j.1529-8027.2007.00151.xCitations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume12, Issue4December 2007Pages 286-289 RelatedInformation

10 Questions About the Clinical Determination of Brain Death

From the Department of Neurology and Division of Critical Care Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota. Reprints: Eelco F. M. Wijdicks, MD, Mayo Clinic College of Medicine, Department of Neurology and Division of Critical Care Neurology, 200 First St. SW, Rochester, MN 55905. E-mail: [email protected].

HEDGEHOG PATHWAY REGULATES G1 TO S TRANSITION BY MODULATING A DEFINED CELL CYCLE TRANSCRIPTIONAL PROGRAM IN PANCREATIC CANCER CELLS

A key aspect during carcinogenesis is the deregulation of the cell cycle, a molecular process by which cells divide and participate in tumor growth. Specifically, alterations in the machinery that controls the transition from G1 into S phase (G-S) during the cell cycle are among the most common in tumor cells, including pancreatic cancer. Interestingly, altered expression of promoters of G1 phase transition such cyclins and their respective CDK partners are highly expressed in high-grade pancreatic intraepithelial neoplasms and pancreatic ductal adenocarcinoma. However, the specific molecular mechanism controlling the aberrant expression of these cell cycle activators in pancreatic cancer cells remains elusive. Hedgehog (HH) pathway plays a key role in numerous processes during embryonic development. Mutations in components as well as ectopic signaling activation of this cascade are implicated in the development of different neoplasms. Recent findings indicate that growth of pancreatic tumors require an active HH signaling. Moreover, previous studies mainly in developing organisms, have proposed that HH-mediated cell growth is due to a stimulatory effect on the cell cycle regulation. Here we demonstrate that HH signaling promotes cell cycle progression in pancreatic cancer cells by increasing the expression of the G1 phase activators, cyclin D1 and A2. Using a combination of expression, luciferase reporter, and chromatin immunoprecipiation assay (ChIP) we show that these genes are direct transcriptional targets of the HH axis, and stimulation of this oncogenic cascade upregulates their expression. Moreover, blockade of HH using either genetic tools (shRNA) or pharmacological inhibitor (cyclopamine), decreases the expression as well as the promoter activity of these regulators of the G1-S transition. Analysis of the mechanism reveals that HH requires intact GLI1 and p300 transcriptional activity to modulate the expression of these molecules. In fact, ChIP demonstrates the presence of these molecules on the promoters of cyclin D1 and A2 upon stimulation of pancreatic cancer cells using HH ligand, Sonic, or a constitutively active variant of the HH receptor Smoothened. Thus, the knowledge derived from these studies will contribute to the understanding of the events regulating cell cycle in pancreatic cancer cells and could serve as foundation for the development of new diagnostic and therapeutic approaches for this dismal disease. M.E.F.-Z. is supported by the Division of Gastroenterology (Mayo Clinic College of Medicine), Mayo Clinic Cancer Center, NCI Grant CA125127, Mayo Clinic Pancreatic SPORE CA102701 and AACR-PanCAN Career Development Award for Pancreatic Cancer in honor of Carole and Bob Daly.

Society for Obstetric Anesthesia and Perinatology 39th Annual Meeting.

Society for Obstetric Anesthesia and Perinatology 39th Annual Meeting.