tbuckley/cabot-search huggingface dataset:
Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
Authors: Kristin I. Stanford, Roeland J.W. Middelbeek, Kristy L. Townsend, Ding An, Eva B. Nygaard, Kristen M. Hitchcox, Kathleen R. Markan, Kazuhiro Nakano, Michael F. Hirshman, Yu-Hua Tseng, Laurie J. Goodyear
Journal: Journal of Clinical Investigation (2012)

Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age- and sex-matched recipient mice. By 8–12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, and a complete reversal of high-fat diet–induced insulin resistance. Increasing the quantity of BAT transplanted into recipient mice further improved the metabolic effects of transplantation. BAT transplantation increased insulin-stimulated glucose uptake in vivo into endogenous BAT, white adipose tissue (WAT), and heart muscle but, surprisingly, not skeletal muscle. The improved metabolic profile was lost when the BAT used for transplantation was obtained from Il6–knockout mice, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity. These findings reveal a previously under-appreciated role for BAT in glucose metabolism.
The bird it was that died
Authors: Hannah Povey, Duncan Cameron
Journal: Thorax (2013)

A family of four from North Wales had a miserable Christmas. Their misfortune began in early December with the sudden death of their two pet lovebirds within 24 h of each other (figure 1). Over the Christmas period they suffered further adversity as the mother developed a flu-like illness with generalised body aches, lethargy and worsening of her prolactinoma headaches. Her 4-year-old daughter developed similar symptoms, while her 2-year-old son was ‘reasonably well but not quite himself’. The father also developed mild flu-like symptoms when he returned home from working away.



Figure 1 
Bentley - the Indian ring-necked parrot. Published with permission from the family who owned Bentley.



At the turn of the New Year their favourite bird, a parrot named Bentley, dropped dead suddenly and unexpectedly. This was the last straw; the mother consulted a diagnostic website.

What is the unifying diagnosis, for bird and human? What historical resonances does the case have? Why is this diagnosis easily missed?

ANSWER See page …
Genetics, genomics, and cancer risk assessment
Authors: Jeffrey N. Weitzel, Kathleen R. Blazer, Deborah J. MacDonald, Julie O. Culver, Kenneth Offit
Journal: CA A Cancer Journal for Clinicians (2011)

Abstract Scientific and technologic advances are revolutionizing our approach to genetic cancer risk assessment, cancer screening and prevention, and targeted therapy, fulfilling the promise of personalized medicine. In this monograph, we review the evolution of scientific discovery in cancer genetics and genomics, and describe current approaches, benefits, and barriers to the translation of this information to the practice of preventive medicine. Summaries of known hereditary cancer syndromes and highly penetrant genes are provided and contrasted with recently discovered genomic variants associated with modest increases in cancer risk. We describe the scope of knowledge, tools, and expertise required for the translation of complex genetic and genomic test information into clinical practice. The challenges of genomic counseling include the need for genetics and genomics professional education and multidisciplinary team training, the need for evidence‐based information regarding the clinical utility of testing for genomic variants, the potential dangers posed by premature marketing of first‐generation genomic profiles, and the need for new clinical models to improve access to and responsible communication of complex disease risk information. We conclude that given the experiences and lessons learned in the genetics era, the multidisciplinary model of genetic cancer risk assessment and management will serve as a solid foundation to support the integration of personalized genomic information into the practice of cancer medicine. CA Cancer J Clin 2011. © 2011 American Cancer Society.
Analysis of DNA Copy Number Alterations in Ovarian Serous Tumors Identifies New Molecular Genetic Changes in Low-Grade and High-Grade Carcinomas
Authors: Kuan-Ting Kuo, Bin Guan, Yuanjian Feng, Tsui-Lien Mao, Xu Chen, Natini Jinawath, Yue Wang, Robert J. Kurman, Ie-Ming Shih, Tian-Li Wang
Journal: Cancer Research (2009)

Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, is thought to develop from two distinct molecular pathways. High-grade (HG) serous carcinomas contain frequent TP53 mutations, whereas low-grade (LG) carcinomas arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2 pathway. However, the molecular alterations involved in the progression from SBT to LG carcinoma remain unknown. In addition, the extent of deletion of tumor suppressors in ovarian serous carcinomas has not been well studied. To further address these two issues, we assessed DNA copy number changes among affinity-purified tumor cells from 37 ovarian serous neoplasms including SBT, LG, and HG tumors using high-density 250K single nucleotide polymorphism arrays. Chromosomal instability index as measured by changes in DNA copy number was significantly higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common in LG serous carcinomas but was rarely seen in SBT. This region contains several candidate tumor suppressors including miR-34a. In contrast, in HG serous carcinomas, significant numbers of amplifications and deletions, including homozygous deletions, were identified. Among homozygous deletions, loci containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in 10.6%, 6.4%, 6.4%, and 4.3%, respectively, in independent 47 affinity-purified HG serous carcinomas. Except for the CDKN2A/B region, these homozygous deletions were not present in either SBT or LG tumors. Our study provides a genome-wide homozygous deletion profile in HG serous carcinomas, which can serve as a molecular foundation to study tumor suppressors in ovarian cancer.
Poliomyelitis Associated With Type 2 Virus
Authors: Phillip D. Swanson, Robert McAlister, Donald R. Peterson
Journal: JAMA (1967)

Paralytic poliomyelitis was diagnosed clinically in a 29-year-old man three weeks after his 2-year-old son received trivalent live oral poliovirus vaccine. Type 2 poliovirus with "vaccine-like" characteristics was isolated from the patient's stool, and the serum showed a significant rise in neutralizing antibody against type 2 virus. There was no rise in complement fixation antibody titers. The patients illness was likely due to type 2 poliovirus contracted from his son. Physicians should inquire about the immunization status of parents before administering vaccine to children.
Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial
Authors: Peter Stein, Jolene K. Berg, Linda Morrow, David Polidori, Eunice Artis, Sarah Rusch, Nicole Vaccaro, Damayanthi Devineni
Journal: Metabolism (2014)

Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin.Patients (N=37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B-D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period.A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B-D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC0-2h, -7.5% for B vs A; -18.5% for C vs A; -12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC0-2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated.These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg.
New treatments for smoking cessation
Authors: J. R. Hughes
Journal: CA A Cancer Journal for Clinicians (2000)

Helping cigarette smokers to permanently stop smoking is one of the most effective ways to prevent cancer. A physician's instruction to a patient to stop smoking and to offer assistance in this endeavor is an important motivator. Current guidelines state that clinicians should encourage all smokers who want to quit to use medications and should offer psychosocial therapies, as well. It has been shown that even brief clinician advice about smoking cessation increases quit rates. Five medications—bupropion, nicotine gum, nicotine inhaler, nicotine nasal spray, and nicotine patch—and one proven psychosocial therapy (behavior therapy) appear equally effective and safe; i.e., they all double quit rates and are associated with a less than 5% dropout rate due to adverse events. In 1998, approximately one third of those who attempted to quit smoking used a medication. Attending group behavior therapy to supplement medications increases quit rates but is not essential for medications to work. As there are no proven treatment-matching protocols, patients should choose the treat-ment(s) they believe will be most effective for them. In the future, people who continue to smoke will be individuals with severe nicotine dependence or psychiatric symptoms; thus, clinicians will increasingly be called on to provide pharmacotherapy for smoking cessation.
HIGH FUROSEMIDE DOSES INCREASE MORTALITY AND MORBIDITY IN STABLE CHRONIC HEART FAILURE: A PROSPECTIVE, RANDOMIZED STUDY
Authors: John Terrovitis, Chris Kapelios, Elisabeth Kaldara, Argyrios Ntalianis, Vasilios Sousonis, Titika Sfakianaki, Zafeiria Margari, John Nanas
Journal: Journal of the American College of Cardiology (2013)
Plagues and Peoples
Authors: Lester S. King
Journal: JAMA (1976)

Many writers have discussed the impact of disease on history, but never before has there been such an overall synthesis, such a weaving together of biology with political and social history. The result is a panorama wherein many separate details fall together into an interesting pattern. To be sure, the evidence is fragmentary, yielding a hypothesis rather than a demonstration. And although only the future can tell how much of Professor McNeill's insight is true, we meanwhile have a stimulating account. McNeill makes history a part of biology, subject to the forces operative in all living creatures. Particularly relevant here are food chains with their complex ecologic interactions and resulting predation and parasitism. To the concept of micro-parasites—the sphere of microbiology wherein microorganisms prey on man (and other animals)—McNeill adds what he terms macroparasites, man preying on man. This occurs when we reach a certain density of population, with societal
Abstract IA6: Targeting PI3K in cancer, mechanistic insights from genetic mouse models
Authors: Jean J. Zhao
Journal: Clinical Cancer Research (2012)

Abstract The class 1a phosphatidylinositol 3-kinase (PI3K) signaling pathway is frequently activated in human cancer by a number of mechanisms, including amplification and/or activation of RTKs (receptor tyrosine kinases), loss of PTEN (phosphatase and tensin homologue) function and somatic mutation in the PIK3CA gene that encodes the p110α catalytic subunit of PI3K. Thus PI3K represents an attractive target for cancer therapy and tremendous efforts are being devoted to developing effective PI3K inhibitors for cancer treatment. Despite the great promise of targeted therapy, drug resistance is likely to develop, causing treatment failure. To elucidate resistance mechanisms to PI3K-targeted therapy, we constructed mouse models of breast cancer and brain tumors conditionally expressing an oncogenic allele of PIK3CA. Interestingly, we found that oncogenic PIK3CA-driven tumors in both mammary gland and brain tissues frequently recur in PI3K pathway-dependent and -independent manners. Genomic and functional analyses of recurrent tumors revealed multiple lesions, providing mechanistic insights for tumor recurrence and resistance to PI3K-targeted therapy.
Introduction to Clinical Psychiatry
Authors: Nancy P. Schell
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes20 April 1999Introduction to Clinical PsychiatryNancy P. Schell, MDNancy P. Schell, MDRush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois. (Schell)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-8-199904200-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Elkin GD; ed. 312 pages. Stamford, CT: Appleton & Lange; 1999. $29.95. ISBN 0838543332. Order phone 800-423-1359.Field of medicine: Psychiatry.Format: Softcover book.Audience: Nonpsychiatric practitioners and medical students.Purpose: To introduce nonpsychiatrists to the wide range of psychiatric disorders and their essential features in order to aid in effective assessment, diagnosis, and treatment or referral.Content: This comprehensive introductory text covers major psychiatric diagnoses; their causes, manifestations, diagnoses, and treatments; and practical discussions of psychosocial and patient–physician relationship issues. Certain chapters are dedicated solely to such issues as suicide, special populations, systems theories, cross-cultural issues, and homeless persons. ... Author, Article, and Disclosure InformationAffiliations: Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois. (Schell) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 April 1999Volume 130, Issue 8Page: 704KeywordsComputed axial tomographyDiagnostic and Statistical Manual of Mental Disorders fourth editionEmotionsEpidemiologyMedical staffPopulation statisticsSoftware toolsSuicide ePublished: 15 August 2000 Issue Published: 20 April 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
TALEN-mediated genetic tailoring as a tool to analyze the function of acquired mutations in multiple myeloma cells
Authors: X Wu, P R Blackburn, R C Tschumper, S C Ekker, D F Jelinek
Journal: Blood Cancer Journal (2014)

Multiple myeloma (MM) is a clonal plasma cell malignancy that is initiated by a number of mutations and the process of disease progression is characterized by further acquisition of mutations. The identification and functional characterization of these myelomagenic mutations is necessary to better understand the underlying pathogenic mechanisms in this disease. Recent advancements in next-generation sequencing have made the identification of most of these mutations a reality. However, the functional characterization of these mutations has been hampered by the lack of proper and efficient tools to dissect these mutations. Here we explored the possible utility of transcription activator-like effector nuclease (TALEN) genome engineering technology to tailoring the genome of MM cells. To test this possibility, we targeted the HPRT1 gene and found that TALENs are a very robust and efficient genome-editing tool in MM cells. Using cotransfected green fluorescent protein as an enrichment marker, single-cell subclones with desirable TALEN modifications in the HPRT1 gene were obtained in as little as 3–4 weeks of time. We believe that TALENs will greatly facilitate the functional study of somatic mutations in MM as well as other cancers.
Metabolic risks of completing Giro, Tour, and Vuelta in the same season
Authors: G Lippi, G Guidi
Journal: British Journal of Sports Medicine (2004)

T D Noakes. Human Kinetics Europe, 2003, £17.95, pp 944. ISBN 0873229592



What are your favourite books of all time? Which books have changed your life? Many people include Lore of running among the answers to those questions. Approaching the 20 year anniversary of the genesis of this “runner’s bible”, Tim Noakes has released the extremely comprehensive, yet very practical 4th edition.

Unlike J K Rowling, who dices her adolescent psychology and astral physiology research into seven books and four movies, T D Noakes provides his reader with the equivalent of four substantial books within the covers of this 1277 page tome. Firstly, Lore is a fascinating historical biography of runners and running. The running reader loves to know the secrets of the champion’s mind and motor, and Lore provides almost 200 pages of unique insights into the Who’s Who of running, including Deerfoot (1861), Paavo Nurmi, Arthur Newton, Emil Zatopek, Jim Peters, Kip Keino, Bruce Fordyce, Grete Waitz, Robert De Castella, Carlos Lopes, Frank …
U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease
Authors: J.J. Scarisbrick, P. Taylor, U. Holtick, Y. Makar, K. Douglas, G. Berlin, E. Juvonen, S. Marshall
Journal: British Journal of Dermatology (2008)

Extracorporeal photopheresis (ECP) has been used for over 30 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic graft-versus-host disease (cGVHD). The lack of prospective randomized trials has led to different centres having different patient selection criteria, treatment schedules, monitoring protocols and patient assessment criteria. ECP for CTCL and cGVHD is available only at six specialized centres across the U.K. In the recent Improving Outcomes Guidance the National Institute for Health and Clinical Excellence endorsed the use of ECP for CTCL and because of the complexity of treatment supported its use in specialized centres and also suggested the need for expansion of this service. In 2005 consultants and senior nurses from all U.K. sites and from Scandinavia formed a Photopheresis Expert Group. This group's first aim was to produce a consensus statement on the treatment of CTCL and cGVHD with ECP using evidence-based medicine and best medical practice, in order to standardize ECP eligibility, assessment and treatment strategies across the U.K.
The significance of spontaneous hepatitis B e antigen seroconversion in childhood: With special emphasis on the clearance of hepatitis B e antigen before 3 years of age
Authors: Mei-Hwei Chang, Hong-Yuan Hsu, Hey-Chi Hsu, Yen-Hsuan Ni, Juei-San Chen, Ding-Shinn Chen
Journal: Hepatology (1995)

To investigate the significance of spontaneous hepatitis B e antigen (HBeAg) seroconversion during childhood, 415 hepatitis B surface antigen (HBsAg) carrier children (ages 0 to 15 years) were prospectively followed for 7.1 +/- 2.9 years. Hepatitis B virus (HBV) markers and liver function profiles of each child were tested at least once every 6 months. Among them, 50 were initially anti-HBe positive and 140 seroconverted from HBeAg to anti-HBe during follow-up. Before HBeAg seroconversion, jaundice occurred in 9 and alanine transaminase (ALT) activities elevated in 99 of the 140 seroconverters. Serum ALT returned to normal in all patients within 1 to 5 years of seroconversion. Six had reelevated ALT later after seroconversion. Only 7 (9.7%) of the 72 carrier infants seroconverted before 3 years of age. The peak ALT levels in five of them exceeded 100 IU/L, and two had jaundice before HBeAg seroconversion. One of the early seroconverters developed hepatocellular carcinoma (HCC) at 11 years of age, although his liver function profiles remained normal after HBeAg seroconversion. Liver biopsy specimens from 30 children during the anti-HBe-positive stag e showed inactive cirrhosis in 2 (including one with HCC), chronic hepatitis with marked fibrosis in 1, mild activity and moderate fibrosis in 2, mild activity and mild fibrosis in 9, and minimal histologic changes in the remaining 16. Although most will achieve a normalization of ALT and inactive liver histologic changes, the seroconversion of HBsAg carrier children from HBeAg to anti-HBe is not necessarily an indicator of favorable prognosis; a small proportion of children will develop cirrhosis or even HCC.
Aspirin and Diabetes Mellitus
Authors: J. Reid, A. I. Macdougall, M. M. Andrews
Journal: BMJ (1957)

Rheumatic fever and diabetes mellitus rarely coexist (Joslin et al., 1952).An opportunity to investigate this unusual combination of disease was provided by a young male diabetic (Case 1), known to take insulin.who was receiving full salicylate treatment for acute rheumatism when admitted to hospital.At the outset we were confronted with a problem, for his urine was sugar-free and the fasting blood-sugar level was normal, though he was receiving only aspirin.The possibilities first entertained were that the previous diagnosis of diabetes was in- accurate or that spontaneous remission of the disease had occurred: neither seemed likely, and the diagnostic dilemma was resolved by the reappearance of sugar in the urine one week after discharge from hospital, when aspirin had been discontinued.On re-examination at this time he was found to have glycosuria, a high fasting blood sugar, and a diabetic glucose-tolerance curve (Fig. l).
Smoking and deep-vein thrombosis.
Authors: H Fraser, S Bishop
Journal: BMJ (1978)

provide medical care for nomadic pastoralists.They state, however, that among the Somalis iron deficiency is rarely fatal.This is not true in the North-eastern Province of Kenya, where 250 000 Somalis live.In 1974 Bontel pointed out that the North-eastern Province was unique among the provinces of Kenya in that blood diseases came top of the causes of death in hospital.Severe anaemia is the commonest single cause for hospital admission in the provincial and district hospitals.
Long-term safety and efficacy of intramuscular administration of Cl-1023 (AdGVVEGF121.10) in patients with intermittent claudication
Authors: Sanjay Rajagopalan, Jeffrey D. Trachtenberg, Jeffrey W. Olin, Emile R. Mohler, Raphael Pak, Angelo Secci, Scott McBride, Henrik Rasmussen, Ronald G. Crystal
Journal: Journal of the American College of Cardiology (2002)