tbuckley/cabot-search huggingface dataset:
Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Germline Pharmacogenetic Studies
Authors: Matthew P. Goetz, James X. Sun, Vera J. Suman, Grace O. Silva, Charles M. Perou, Yusuke Nakamura, Nancy J. Cox, Philip J. Stephens, Vincent A. Miller, Jeffrey S. Ross, David Chen, Stephanie L. Safgren, Mary J. Kuffel, Matthew M. Ames, Krishna R. Kalari, Henry L. Gomez, Ana M. Gonzalez-Angulo, Octavio Burgues, Hiltrud B. Brauch, James N. Ingle, Mark J. Ratain, Roman Yelensky
Journal: JNCI Journal of the National Cancer Institute (2014)

Background:Controversy exists regarding the impact of CYP2D6 genotype on tamoxifen responsiveness. We examined loss of heterozygosity (LOH) at the CYP2D6 locus and determined its impact on genotyping error when tumor tissue is used as a DNA source.
Intracerebral Infiltration As the Unique Cause of the Clinical Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia
Authors: Sanne H. Tonino, Astrid L. Rijssenbeek, Monique E. Oud, Steven T. Pals, Marinus H. van Oers, Arnon P. Kater
Journal: Journal of Clinical Oncology (2011)
Regression of Carotid Atherosclerosis by Control of Postprandial Hyperglycemia in Type 2 Diabetes Mellitus
Authors: Katherine Esposito, Dario Giugliano, Francesco Nappo, Raffaele Marfella
Journal: Circulation (2004)

Postprandial hyperglycemia may be a risk factor for cardiovascular disease. We compared the effects of two insulin secretagogues, repaglinide and glyburide, known to have different efficacy on postprandial hyperglycemia, on carotid intima-media thickness (CIMT) and markers of systemic vascular inflammation in type 2 diabetic patients.We performed a randomized, single-blind trial on 175 drug-naive patients with type 2 diabetes mellitus (93 men and 82 women), 35 to 70 years of age, selected from a population of 401 patients who participated in an epidemiological analysis assessing the relation of postprandial hyperglycemia to surrogate measures of atherosclerosis. Eighty-eight patients were randomly assigned to receive repaglinide and 87 patients to glyburide, with a titration period of 6 to 8 weeks for optimization of drug dosage and a subsequent 12-month treatment period. The effects of repaglinide (1.5 to 12 mg/d) and glyburide (5 to 20 mg/d) on CIMT were compared by using blinded, serial assessments of the far wall. After 12 months, postprandial glucose peak was 148+/-28 mg/dL in the repaglinide group and 180+/-32 mg/dL in the glyburide group (P<0.01). HbA(1c) showed a similar decrease in both groups (-0.9%). CIMT regression, defined as a decrease of >0.020 mm, was observed in 52% of diabetics receiving repaglinide and in 18% of those receiving glyburide (P<0.01). Interleukin-6 (P=0.04) and C-reactive protein (P=0.02) decreased more in the repaglinide group than in the glyburide group. The reduction in CIMT was associated with changes in postprandial but not fasting hyperglycemia.Reduction of postprandial hyperglycemia in type 2 diabetic patients is associated with CIMT regression.
1p36 Tumor Suppression—A Matter of Dosage?
Authors: Kai-Oliver Henrich, Manfred Schwab, Frank Westermann
Journal: Cancer Research (2012)

A broad range of human malignancies is associated with nonrandom 1p36 deletions, suggesting the existence of tumor suppressors encoded in this region. Evidence for tumor-specific inactivation of 1p36 genes in the classic "two-hit" manner is scarce; however, many tumor suppressors do not require complete inactivation but contribute to tumorigenesis by partial impairment. We discuss recent data derived from both human tumors and functional cancer models indicating that the 1p36 genes CHD5, CAMTA1, KIF1B, CASZ1, and miR-34a contribute to cancer development when reduced in dosage by genomic copy number loss or other mechanisms. We explore potential interactions among these candidates and propose a model where heterozygous 1p36 deletion impairs oncosuppressive pathways via simultaneous downregulation of several dosage-dependent tumor suppressor genes.
Para-Hyoid Ectopic Parathyroid Adenoma Localized by Tc-99m MIBI SPECT
Authors: Malolan S. Rajagopalan, Vinod V. Narla, Tanuja Kanderi, Ashok Muthukrishnan
Journal: Clinical Nuclear Medicine (2008)

A 64-year-old woman with a history of I-131 ablation for Graves hyperthyroidism and bilateral parathyroid exploration with resection of a left inferior parathyroid adenoma presented 2 years after surgery with marked fatigue, irritability, and joint pain. Laboratory testing revealed an elevated calcium and parathyroid hormone levels suspicious for hyperparathyroidism. The ultrasound indicated no evidence of a parathyroid adenoma. Tc-99m-MIBI SPECT demonstrated a focus of uptake posteroinferior to the right submandibular gland, suspicious for a parathyroid adenoma. Repeat ultrasound and CT confirmed the presence of a para-hyoid adenoma inferior to the right submandibular gland.
Comeback kids: CD8+ suppressor T cells are back in the game
Authors: Luc Van Kaer
Journal: Journal of Clinical Investigation (2010)

Suppressing unwanted immune responses without compromising host immunity against pathogens is considered the holy grail of immunology. Lack of responsiveness to self-antigens is normally maintained by multiple mechanisms, including the suppressive activities of several T cell subsets. In this issue of the JCI, Jiang and colleagues define a CD8+ suppressor T cell subset in humans that recapitulates a regulatory pathway previously described in mice. These investigators further show that patients with type 1 diabetes have defects in their CD8+ suppressor T cells, thus identifying these cells as potential therapeutic targets in human disease.
Extracellular Matrix Fibronectin Mechanically Couples Skeletal Muscle Contraction With Local Vasodilation
Authors: Denise C. Hocking, Patricia A. Titus, Ronen Sumagin, Ingrid H. Sarelius
Journal: Circulation Research (2007)

During exercise, local mechanisms in tissues cause arterioles to rapidly dilate to increase blood flow to tissues to meet the metabolic demands of contracting muscle. Despite decades of study, the mechanisms underlying this important aspect of blood flow control are still far from clear. We now report a novel mechanism wherein fibronectin fibrils in connective tissue matrices transduce signals from contracting skeletal muscle to local blood vessels to increase blood flow. Using intravital microscopy, we show that local vasodilation in response to skeletal muscle contraction is specifically inhibited by an antibody that recognizes the matricryptic site in the first type III repeat of fibronectin (FNIII-1). In the absence of skeletal muscle contraction, direct application of FNIII-1–containing fibronectin fragments to cremaster muscle arterioles in situ, triggered a rapid, specific, and reversible local dilation that was mediated by nitric oxide and required the cryptic, heparin-binding sequence of FNIII-1. Furthermore, application of function-blocking FNIII-1 peptides to cremaster muscle arterioles rapidly and specifically decreased their diameter, indicating that the matricryptic site of fibronectin also contributes to resting vascular tone. Alexa fluor 488–labeled fibronectin, administered intravenously, was rapidly assembled into elongated, branching fibrils in the extracellular matrix of intact cremaster muscle, demonstrating active polymerization of fibronectin in areas adjacent to blood vessels. Together, these data provide the first evidence that a matricryptic, heparin-binding site within fibronectin fibrils of adult connective tissue plays a dynamic role in regulating both vascular responses and vascular tone.
Standard Ph Chromosome, t(9;22)(q34;q11), as an Additional Change in a Patient With Acute Myelomonocytic Leukemia (M4Eo) Associated With inv(16)(p13q22)
Authors: I. Miura, H. Takatsu, A. Yamaguchi, K. Hashimoto, T. Nimura, T. Nishinari, H. Niitsu, A. B. Miura
Journal: American Journal of Hematology (1994)
Organic Brain Dysfunction and Child Psychiatric Disorder
Authors: P. Graham, M. Rutter
Journal: BMJ (1968)

The total population of 11,865 children of compulsory school age resident on the Isle of Wight was studied to determine the prevalence of epilepsy, cerebral palsy, and other neurological disorders. With the use of reliable methods, children selected from screening of the total population were individually studied by means of parental interviews and questionaries, neurological examination and psychiatric assessment of each child, information from school teachers, and perusal of the records of hospitals and other agencies. The association between organic brain dysfunction and psychiatric disorder was studied by comparing the findings in the children with epilepsy or with lesions above the brain stem (cerebral palsy and similar disorders) with those in (1) a random sample of the general population, (2) children with lesions below the brain stem (for example, muscular dystrophy or paralyses following poliomyelitis), and (3) children with other chronic physical handicaps not involving the nervous system (for example, asthma, heart disease, or diabetes).Psychiatric disorders in children with neuro-epileptic conditions were five times as common as in the general population and three times as common as in children with chronic physical handicaps not involving the brain. It was concluded, on the basis of a study of factors associated with psychiatric disorder, that the high rate of psychiatric disorder in the neuro-epileptic children was due to the presence of organic brain dysfunction rather than just the existence of a physical handicap (though this also played a part). However, organic brain dysfunction was not associated with any specific type of disorder. Within the neuro-epileptic group the neurological features and the type of fit, intellectual/educational factors, and socio-familial factors all interacted in the development of psychiatric disorder.
The modification of human society by natural systems: discontinuities caused by the exploitation of endemic species and the introduction of exotics.
Authors: J Cairns, J R Bidwell
Journal: Environmental Health Perspectives (1996)

Drastic reductions in Earth's biodiversity, old growth forests, top soil, clean water and air, and truly wild areas are occurring during a period when discussions of sustainable growth and sustainable production are becoming common. Using such terms as sustainable growth and sustainable production rather than the more accurate sustainable use of the planet leaves the impression that, with a little more skill, society can continue its present practices indefinitely. A number of explanations are possible for this desire to maintain two conflicting beliefs (i.e., severe environmental destruction occurs but society can continue its basic practices indefinitely): 1) the idea that a technological solution can be found for every problem; 2) an addiction to present behavioral norms, which is so strong that the consequences of continuing such behavior are irrelevant; and 3) the concept that, while human society can alter natural systems to suit its own needs, natural systems are incapable of altering human society. This last issue is the focus of this discussion: if human society eliminates all species on the planet that are incapable of tolerating human society's present practices, the only species remaining will be those that human society is unable to control successfully or eliminate; these species are called pests. Another hypothesis could be stated: a world of pests that human society cannot control effectively will inevitably reshape human society through disease and famine, technological breakdown, and interference with domesticated and wild species upon which the integrity of human societal structure depends.
Pregnancy Characteristics and Maternal Risk of Breast Cancer
Authors: Sven Cnattingius
Journal: JAMA (2005)

During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother.To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer.Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes.Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer.Incidence of invasive breast cancer.Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59).Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.
546 A SYSTEMS BIOLOGY PERSPECTIVE ON CCC DEVELOPMENT. FOCUS ON MAPK-SINGNALING AND EXTRACELLULAR ENVIRONMENT
Authors: C. Wang, T. Maass, M. Krupp, F. Thieringer, S. Strand, M.A. Wörns, A.-P. Barreiros, P.R. Galle, A. Teufel
Journal: Journal of Hepatology (2009)
ABC of 1 to 7 (revised). Services for children: primary care.
Authors: L Peter, H B Valman
Journal: BMJ (1987)

Rutter, N., Milner, A. D., and Hiller, E. J. (1975). Archives of Disease in Childhood, 50, 719. Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis. Respiratory resistance was measured using a forced oscillation technique in 16 infants and young children with bronchiolitis and wheezy bronchitis. Measurements were made before and after administration of nebulized salbutamol or isoprenaline. No significant change in resistance was found.
p19Arf Inhibits the Invasion of Hepatocellular Carcinoma Cells by Binding to C-terminal Binding Protein
Authors: Ya-Wen Chen, Seema Paliwal, Kyle Draheim, Steven R. Grossman, Brian C. Lewis
Journal: Cancer Research (2008)

Abstract The INK4A/ARF tumor suppressor locus is frequently inactivated in hepatocellular carcinoma (HCC), yet the consequences of this remain unknown. We recently described a HCC mouse model in which loss of the Ink4a/Arf locus accelerates the development of metastasis and enhances tumor cell migration and invasion in cell culture assays. We show here that knockdown of p19Arf in an HCC cell line increases invasion in cell culture assays. Furthermore, reintroduction of p19Arf into HCC cell lines lacking Ink4a/Arf inhibits tumor cell invasion, without affecting cell proliferation, or cell transformation as measured by soft agar colony formation. Inhibition of cell invasion by p19Arf was dependent on its C-terminal binding protein (CtBP) interaction domain but independent of Mdm2 binding and nucleolar localization. Indeed, RNA interference–mediated knockdown of CtBP1 or CtBP2 decreased cell invasion, and ectopic expression of CtBP2 enhanced tumor cell migration and invasion. Thus, our data indicate a novel role for the Arf tumor suppressor protein in regulating phenotypes associated with tumor progression and metastasis in HCC cells. [Cancer Res 2008;68(2):476–82]
Intestinal pseudo-obstruction
Authors: M A Kamm
Journal: Gut (2000)

Intestinal pseudo-obstruction refers to a syndrome in which the clinical picture resembles that of bowel obstruction, with failure of intestinal motility associated with pain and intestinal distension, but absence of a mechanical obstructing lesion.

The situation arises acutely in some patients admitted to hospital with non-gastrointestinal disorders (Ogilvie's syndrome), such as myocardial infarction, pneumonia, or fractured hip. Typically there is acute colonic dilatation, with pain and abdominal distension. The condition is thought to be due to an imbalance of extrinsic autonomic nerves innervating the gut, with excessive sympathetic inhibitory activity or diminished prokinetic cholinergic drive. The condition can be managed by colonic decompression, either colonoscopically …
Value of Positron Emission Tomography With [F-18]Fluorodeoxyglucose in Patients With Colorectal Liver Metastases: A Prospective Study
Authors: T.J.M. Ruers, B.S. Langenhoff, N. Neeleman, G.J. Jager, S.P. Strijk, Th. Wobbes, F.H.M. Corstens, W.J.G. Oyen
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess prospectively the value of fluor-18-deoxyglucose (FDG) positron emission tomography (PET), in addition to conventional diagnostic methods (CDM), as a staging modality in candidates for resection of colorectal liver metastases. PATIENTS AND METHODS: In 51 patients analyzed for resection of colorectal liver metastases, clinical management decisions were recorded after a complete work-up with CDM. Afterward, FDG-PET scans were performed and any change of clinical management according to FDG-PET results was carefully documented. Discordances between FDG-PET and CDM results were identified and related to the final diagnosis by histopathology, intraoperative findings, and follow-up. RESULTS: In 10 (20%) out of 51 patients, clinical management decisions based on CDM were changed after FDG-PET findings were known. FDG-PET detected unresectable pulmonary (n = 5) and hepatic metastases (n = 1) and ruled out extrahepatic (n = 2) and hepatic disease (n = 2). Due to FDG-PET, eight patients were spared unwarranted liver resection or laparotomy and two other patients were identified as candidates for liver resection. When the results of FDG-PET were regarded as decisive in a retrospective analysis, potential change of management was 29% (15 patients). FDG-PET and CDM showed discordant extrahepatic results in 11 patients (22%) and discordant hepatic results in eight patients (16%). Compared with CDM, FDG-PET resulted in true upstaging (n = 11), true downstaging (n = 5), false upstaging (n = 1), and false downstaging (n = 2). The detection rate of liver metastases on a lesion basis was generally better for computed tomography than for FDG-PET (80% v 65%); this was related to tumor size. CONCLUSION: FDG-PET as a complementary staging method improves the therapeutic management of patients with colorectal liver metastases, especially by detecting unsuspected extrahepatic disease.
Specialist nurse support for patients with stroke in the community: a randomised controlled trial
Authors: A. Forster, J. Young
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To evaluate whether specialist nurse visits enhance the social integration and perceived health of patients with stroke or alleviate stress in carers in longer term stroke care. <b>Design</b>: Stratified randomised controlled trial; both groups assessed at time of recruitment and at 3, 6, and 12 months. <b>Setting</b>: Patients with disability related to new stroke who lived in their own homes in the Bradford Metropolitan District. <b>Subjects</b>: 240 patients aged 60 years or over, randomly allocated to control group (n = 120) or intervention group (n = 120). <b>Intervention</b>: Visits by specialist outreach nurses over 12 months to provide information, advice, and support; minimum of six visits during the first six months. The control group received no visits. <b>Main outcome measures</b>: The Barthel index (functional ability), the Frenchay activities index (social activity), the Nottingham health profile (perceived health status). Stress among carers was indicated by the general health questionnaire-28 (28 items). The nurses recorded their interventions in trial diaries. <b>Results</b>: There were no significant differences in perceived health, social activities, or stress among carers between the treatment and control groups at any of the assessments points. A subgroup of mildly disabled patients with stroke (Barthel index 15-19) had an improved social outcome at six months (Frenchay activities index, median difference 3 (95% confidence interval 0 to 6; P = 0.03)) and for the full 12 months of follow up (analysis of covariance P = 0.01) compared with the control group. <b>Conclusions</b>: The specialist nurse intervention resulted in a small improvement in social activities only for the mildly disabled patients. No proved strategy yet exists that can be recommended to address the psychosocial difficulties of patients with stroke and their families. <h3>Key messages</h3> This randomised controlled trial using specialist nurses in an intervention strategy found that no significant differences were seen at one year follow up between the two groups of patients in wellbeing or social activities and no reduction in stress among carers A significant but small increase in social activities was reported by a subgroup of mildly disabled patients with stroke No proved strategy yet exists to address the psychosocial difficulties of patients with stroke and their families
A DAY WITH PROFESSOR VIRCHOW AT CHARITé HOSPITAL, BERLIN.
Authors: ROBERT REYBURN
Journal: JAMA (1893)

Among the most interesting memories that I retain of my trip to Europe last summer, was a visit that I paid to Professor Rudolph Virchow in Berlin, on July 23, 1892. Professor Virchow, to all Americans (and indeed to all men of every nation who sympathize with the cause of free speech and free thought), is the most interesting scientific man in Europe. He is not only preëminent as a scientist and pathologist, but is a man who always has aided the cause of freedom everywhere and especially in his own country. He was the man whom Bismark in his days of arbitrary power especially hated. In 1849, and for seven years thereafter, he was banished from his professional chair at Berlin, on account of his liberal opinions, but was recalled to his duties in the University in 1856. During the period of his absence he distinguished himself by the
UK spending on health doubled in past 20 years
Authors: N. Hawkes
Journal: BMJ (2015)

Spending on health has been the biggest gainer in the United Kingdom in the past 20 years, more than doubling in real terms and outstripping all other major public spending, the Office for National Statistics has reported in an article on its new Visual ONS website.1 

Defence spending was among the biggest losers, falling in real terms and as a proportion of all public spending, from 8.7% in 1993-94 to …