tbuckley/cabot-search huggingface dataset:
Tissue-Wide Expression Profiling Using cDNA Subtraction and Microarrays to Identify Tumor-Specific Genes
Authors: Stefan Amatschek, Ulrich Koenig, Herbert Auer, Peter Steinlein, Margit Pacher, Agnes Gruenfelder, Gerhard Dekan, Sonja Vogl, Ernst Kubista, Karl-Heinz Heider, Christian Stratowa, Martin Schreiber, Wolfgang Sommergruber
Journal: Cancer Research (2004)

Abstract With the objective of discovering novel putative intervention sites for anticancer therapy, we compared transcriptional profiles of breast cancer, lung squamous cell cancer (LSCC), lung adenocarcinoma (LAC), and renal cell cancer (RCC). Each of these tumor types still needs improvement in medical treatment. Our intention was to search for genes not only highly expressed in the majority of patient samples but which also exhibit very low or even absence of expression in a comprehensive panel of 16 critical (vital) normal tissues. To achieve this goal, we combined two powerful technologies, PCR-based cDNA subtraction and cDNA microarrays. Seven subtractive libraries consisting of ∼9250 clones were established and enriched for tumor-specific transcripts. These clones, together with ∼1750 additional tumor-relevant genes, were used for cDNA microarray preparation. Hybridizations were performed using a pool of 16 critical normal tissues as a reference in all experiments. In total, we analyzed 20 samples of breast cancer, 11 of LSCC, 11 of LAC, and 8 of RCC. To select for genes with low or even no expression in normal tissues, expression profiles of 22 different normal tissues were additionally analyzed. Importantly, this tissue-wide expression profiling allowed us to eliminate genes, which exhibit also high expression in normal tissues. Similarly, expression signatures of genes, which are derived from infiltrating cells of the immune system, were eliminated as well. Cluster analysis resulted in the identification of 527 expressed sequence tags specifically up-regulated in these tumors. Gene-wise hierarchical clustering of these clones clearly separated the different tumor types with RCC exhibiting the most homogenous and LAC the most diverse expression profile. In addition to already known tumor-associated genes, the majority of identified genes have not yet been brought into context with tumorigenesis such as genes involved in bone matrix mineralization (OSN, OPN, and OSF-2) in lung, breast, and kidney cancer or genes controlling Ca2+ homeostasis (RCN1,CALCA, S100 protein family). EGLN3, which recently has been shown to be involved in regulation of hypoxia-inducible factor, was found to be highly up-regulated in all RCCs and in half of the LSCCs analyzed. Furthermore, 42 genes, the expression level of which correlated with the overall survival of breast cancer patients, were identified. The gene dendogram clearly separates two groups of genes, those up-regulated such as cyclin B1, TGF-β3, B-Myb, Erg2, VCAM-1, and CD44 and those down-regulated such as MIG-6, Esp15, and CAK in patients with short survival time.
Cognition and Aging in Psychopathology: Focus on Schizophrenia and Depression
Authors: Philip D. Harvey, Abraham Reichenberg, Christopher R. Bowie
Journal: Annual Review of Clinical Psychology (2005)

Aging has effects on many features of normal functioning, particularly in the domains of cognition and adaptive life skills. Several psychiatric conditions also affect cognition and adaptive functioning; most of the research on these topics has been performed on patients early in their lives. The amount of research on older patients is smaller than in younger patients, but there is a developing research literature in several aspects of aging and psychopathology. This chapter reviews aging effects on two major psychiatric conditions: schizophrenia and depression. We examine changes in symptoms and cognitive functioning with aging and the functional implications of the development or worsening of cognitive performance. We also identify risk factors for cognitive changes within each condition and examine the implication of early- versus late-life onset. We believe that cognitive changes with aging are potentially predictable, possibly sharing a mechanism with normal aging-related changes and certainly laden with prognostic implications. We see cognitive changes as a possible commonality across persistent psychiatric disorders as well as healthy aging in late life.
Clinical Presentation and Follow-Up of 30 Patients with Congenital Nephrogenic Diabetes Insipidus
Authors: ANGENITA F. VAN LIEBURG, NINE V. A. M. KNOERS, LEO A. H. MONNENS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Congenital nephrogenic diabetes insipidus is characterized by insensitivity of the distal nephron to arginine vasopressin. Clinical knowledge of this disease is based largely on case reports. For this study, data were collected on clinical presentation and during long-term follow-up of 30 male patients with congenital nephrogenic diabetes insipidus. The majority of patients (87%) were diagnosed within the first 2.5 yr of life. Main symptoms at clinical presentation were vomiting and anorexia, failure to thrive, fever, and constipation. Three older patients were diagnosed as a result of events not directly related to the disease. Except for a possibly milder phenotype in patients with a G185C mutation, no clear relationship between clinical and genetic data could be found. Most patients were on hydrochlorothiazide-amiloride treatment without significant side effects. Two patients suffered from severe hydronephrosis with a small rupture of the urinary tract after a minor trauma, and two patients experienced episodes of acute urine retention. Height SD scores for age remained below the 50th percentile in the majority of patients, whereas weight for height SD scores showed a catch-up after several years of underweight.
Circulating Immune Complexes and Rheumatoid Factors in Patients with Farmer's Lung
Authors: E. O. TERHO, P. LINDSTRÖM, R. MÄNTYJÄRVI, H. TUKIAINEN, O. WAGER
Journal: Allergy (1983)

Circulating IgG immune complexes (CICs), IgM rheumatoid factors (RFs), complement level (C3 and C4), and IgG antibodies to Aspergillus fumigatus, Aspergillus umbrosus, Thermo‐actinomyces vulgaris , and Micropolyspora faeni were analysed in the sera of 14 patients with farmer's lung (FL), 10 in the acute and four in the subacute phase of the disease. Ten spouses of FL patients served as exposed healthy controls. C3 and C4 were measured fluoronephelometrically. C3 levels were above the normal range and C4 levels near the upper limit of the normal range in both patients and controls; no statistically significant difference between patients and controls were observed. CICs were determined by enzyme immunoassays (EIA) of conglutinin‐binding (KgB) and Clq‐binding (ClqB). CIC levels above the normal range were detected in 12 (KgB‐EIA) and nine (ClqB‐EIA) of the patients and three (KgB‐EIA) and six (ClqB‐EIA) of the controls. No statistically significant differences were found in the mean levels between patients and controls. In contrast, RF levels in the acute phase of FL were significantly higher in the patients ( P &lt; 0.01) than in the controls. CICs correlated positively with most microbial IgG antibodies, but negatively with RFs. RFs also correlated negatively with microbial IgG antibodies, as well as with both C3 and C4. In FL, the increased RF level may, in the absence of increased CIC and decreased complement levels, represent an immune response (IgM anti‐IgG autoantibodies) induced by local mechanisms of IgG immune complexes in the lungs.
Genome Scan for Determinants of Serum Uric Acid Variability
Authors: Subrata D. Nath, V. Saroja Voruganti, Nedal H. Arar, Farook Thameem, Juan C. Lopez-Alvarenga, Richard Bauer, John Blangero, Jean W. MacCluer, Anthony G. Comuzzie, Hanna E. Abboud
Journal: Journal of the American Society of Nephrology (2007)

Elevated serum uric acid level is associated with obesity, insulin resistance, diabetes, nephropathy, and hypertension. Epidemiologic studies suggest that serum uric acid levels are heritable. We sought to identify chromosomal regions harboring quantitative trait loci that influence serum uric acid in Mexican Americans using data from 644 participants in the San Antonio Family Heart Study. Serum uric acid was found to exhibit significant heritability (0.42) in this population (P = 2 x 10(-7)) after accounting for covariate effects. In addition, genetic correlations between serum uric acid and other cardiovascular risk factors, such as body mass index, waist circumference, systolic BP, and pulse pressure, were identified, suggesting that the genes associated with uric acid level are also associated with these phenotypes. Multipoint linkage analysis identified quantitative trait loci with measurable effects on serum uric acid variability. The highest multipoint logarithm of odds score of 3.3 was found at 133 cM on chromosome 6q22-23, a region that also contains genes that seem to influence familial IgA nephropathy, obesity, BP, insulin resistance, and type 2 diabetes. Given the relationship between uric acid level and these conditions, future studies should investigate potential candidate susceptibility genes found in this region.
Angiogenesis
Authors: Michael Simons
Journal: Circulation (2005)

T he concept of modulating blood vessel growth-stimu- lation or inhibition-to serve a desired clinical goal has an enormous intellectual appeal.It can be used to relieve ischemia in tissues with compromised arterial blood supply, improve edema in areas of impaired lymphatic drainage, and inhibit the growth of tumors.Other applications involve facilitating reendothelialization and inhibiting neointima formation after vascular injury, preventing the progression of atherosclerotic plaque, and promoting "vascular health" in general.The least-explored application of this concept involves modulating body and organ size by regulating the endothelial cell mass.All of these areas received a significant, albeit varied, amount of attention in past decades but only recently have we begun approaching clinical applications.Indeed, the first antiangiogenic agent has been approved by the US Food and Drug Administration for the treatment of certain types of cancer, and it is hoped that the emergence of therapeutically useful angiogenesis-promoting agents is not far behind.This article examines some of our current understanding of the regulation of blood vessel growth in mature adult tissues and the various therapeutic applications of this knowledge.Obviously, a review of this size cannot cover such a vast field in any amount of detail, and the author regrets not citing primary references for many of the facts and concepts that are mentioned.
Inactivation of fatty acid amide hydrolase exacerbates experimental fibrosis by enhanced endocannabinoid-mediated activation of CB1
Authors: Katrin Palumbo-Zerr, Angelika Horn, Alfiya Distler, Pawel Zerr, Clara Dees, Christian Beyer, Enrico Selvi, Benjamin F Cravatt, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Selective targeting of the cannabinoid receptors CB1 and CB2 by synthetic compounds has revealed opposing roles of both receptors in fibrosis. <h3>Objectives</h3> To characterise the role of endogenous cannabinoids (endocannabinoids) and their predominant receptor in fibrosis. <h3>Methods</h3> The levels of endocannabinoids in mice were modulated by pharmacological or genetic inactivation of the enzyme fatty acid amide hydrolase (FAAH). The predominant receptor for endocannabinoids was determined by selective inhibition of either CB1 or CB2. The extent of fibrosis upon challenge with bleomycin was determined by quantification of dermal thickness, hydroxyproline content and myofibroblast counts. <h3>Results</h3> The expression of FAAH is decreased in systemic sclerosis fibroblasts. FAAH-deficient mice with strongly increased levels of endocannabinoids were more sensitive to bleomycin. Consistently, pharmacological inhibition of FAAH significantly exacerbated bleomycin-induced fibrosis. Inhibition of CB1 completely abrogated the profibrotic effects of FAAH inactivation. In contrast, inhibition of CB2 only modestly enhanced fibrosis, indicating that CB1 is the predominant receptor for endocannabinoids in experimental fibrosis. <h3>Conclusions</h3> Increased levels of endocannabinoids induced by inactivation of FAAH worsen experimental fibrosis via activation of CB1. These findings highlight the profibrotic effects of endocannabinoids and suggest that CB1 maybe a more promising candidate for targeted treatments in fibrotic diseases than CB2.
Ethics in Practice: Managed Care and the Changing Health Care Environment
Authors: Gail J. Povar, Helen Blumen, John Daniel, Suzanne Daub, Lois Evans, Richard P. Holm, Natalie Levkovich, Alice O. McCarter, James Sabin, Lois Snyder, Daniel Sulmasy, Peter Vaughan, Laurence D. Wellikson, Amy Campbell
Journal: Annals of Internal Medicine (2004)

Cost pressures and changes in the health care environment pose ethical challenges and hard choices for patients, physicians, policymakers, and society. In 2000 and 2001, the American College of Physicians, with the Harvard Pilgrim Health Care Ethics Program, convened a working group of stakeholders—patients, physicians, and managed care representatives, along with medical ethicists—to develop a statement of ethics for managed care. The group explored the impact of a changing health care environment on patient–physician relationships and how to best apply the principles of professionalism in this environment. The statement that emerged offers guidance on preserving the patient–clinician relationship, patient rights and responsibilities, confidentiality and privacy, resource allocation and stewardship, the obligation of health plans to foster an ethical environment for the delivery of care, and the clinician's responsibility to individual patients, the community, and the public health, among other issues. *For members of the Medicine as a Profession Managed Care Ethics Working Group, see the Appendix.
Elevated Risk of Tobacco Dependence Among Offspring of Mothers Who Smoked During Pregnancy: A 30-Year Prospective Study
Authors: Stephen L. Buka, Edmond D. Shenassa, Raymond Niaura
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors' goal was to investigate whether maternal smoking during pregnancy is associated with an increased risk of nicotine dependence among adult offspring. METHOD: Prospective data from two samples of offspring in the National Collaborative Perinatal Project, a long-term prospective investigation from pregnancy through adulthood, were combined (N=1,248). Maternal smoking during pregnancy was assessed during each prenatal visit. Offspring smoking behavior and lifetime risk of nicotine dependence were obtained by structured interview with the Diagnostic Interview Schedule; the mean age of the offspring at the time of interview was 29 years. RESULTS: Offspring whose mothers reported smoking a pack or more of cigarettes during their pregnancy were significantly more likely to meet DSM criteria for lifetime tobacco dependence than offspring of mothers who reported that they never smoked during pregnancy. The odds of progressing from smoking to nicotine dependence were almost twice as great for offspring whose mothers smoked heavily during pregnancy. These significant differences remained after adjustments for participants' gender and age and maternal socioeconomic status and age at pregnancy. Results were comparable for men and women. The findings were specific for tobacco dependence; odds of marijuana dependence were not significantly elevated among the offspring of tobacco smokers. CONCLUSIONS: Offspring of mothers who smoked a pack or more of cigarettes during pregnancy are at elevated risk of developing nicotine dependence but not marijuana dependence as adults. Maternal smoking during pregnancy is a risk factor for subsequent nicotine dependence among offspring.
Comparison between ranitidine and ranitidine plus Caved-S in the treatment of gastric ulceration.
Authors: A G Morgan, C Pacsoo, W A McAdam
Journal: Gut (1985)

In a double blind endoscopically controlled study, 100 patients with gastric ulcers were treated with either ranitidine or ranitidine plus Caved-S. On single therapy, 58% of ulcers were healed at four weeks, 92% at eight weeks and 96% at 12 weeks. Combination therapy did not alter the healing rate, nor improve on the control of dyspeptic symptoms. No difference in healing rate was found between good and poor drug compliance patients. This suggests that ranitidine may be equally effective at lower dosages. Thirty seven patients had developed their ulcer while taking non-steroidal anti-inflammatory drugs. These patients were mainly elderly women who had a higher risk of bleeding (p = 0.006) from a large ulcer (p = 0.009).
Footballer's Migraine
Authors: W. B. Matthews
Journal: BMJ (1972)

Classical migraine, including incapacitating visual field defects, repeatedly developed in five young men immediately after blows to the head while playing football and in no other circumstances. A similar condition occurred in a professional boxer and an isolated attack in a boy footballer. Prophylactic treatment with ergotamine tartrate may not be wholly successful and it may be necessary to give up the sport. Any unitary theory of causation of attacks of migraine must account for prodromal symptoms immediately after head injury.
Going back to the future with Guthrie-powered epigenome-wide association studies
Authors: Mark N Cruickshank, James Pitt, Jeffrey M Craig
Journal: Genome Medicine (2012)

Epigenome-wide association studies (EWAS) can be used to investigate links between early life environment, epigenetics and disease. However, such studies raise the question of which came first: the mark or the malady? A recent study has demonstrated that EWAS can be performed on neonatal 'Guthrie' heel-prick blood spots. As Guthrie cards are collected from all newborn infants and stored indefinitely in many countries, they represent an important timepoint to compare with later disease-associated epigenetic marks.
Long-term culture and cloning of nontransformed human B lymphocytes.
Authors: B Sredni, D G Sieckmann, S Kumagai, S House, I Green, W E Paul
Journal: The Journal of Experimental Medicine (1981)

B lymphocyte-enriched cell populations cultured with mitogens in initial suspension cultures formed colonies in soft agar when the same mitogenic agent was present in the lower layer of a two-layer soft agar system. Colony formation depended upon the presence of T cells in the initial culture, and was optimal after an initial 72-h culture with phytohemagglutinin (PHA; 12.5 microliters/ml), pokeweed mitogen (PWM; 2.5 micrograms/ml), or protein A (10 micrograms/ml). The colonies could be picked from the agar and propagated by feeding every 3 d with medium supplemented with a growth factor-containing tissue culture supernate. The growth factor-containing supernate was prepared by stimulating pools of human peripheral blood mononuclear cells for 72 h with PHA or PWM. The lines propagated in this manner were membrane Ig+, lacked sheep erythrocyte rosette-forming ability, and did not ingest latex. They lacked the Epstein-Barr nuclear antigen (EBNA) and had 46 chromosomes. Such lines have been propagated for over 1 yr. One line (BL1) was subjected to limiting dilution cloning and a line, BL1.1, was prepared that contained 96% lambda-bearing cells and no kappa-bearing cells. This line was also EBNA negative. This procedure can thus be used to prepare and clone long-term lines of nontransformed human B lymphocytes.
Diagnosis and treatment of pyoderma gangrenosum
Authors: Trevor Brooklyn, Giles Dunnill, Chris Probert
Journal: BMJ (2006)

Pyoderma gangrenosum is a rare but serious ulcerating skin disease, the treatment of which is mostly empirical.Pyoderma can present to a variety of health professionals and several variants exist that may not be recognised immediately.This can delay the diagnosis and have serious clinical consequences. 1The mainstay of treatment is long term immunosuppression, often with high doses of corticosteroids or low doses of ciclosporin.Recently, good outcomes have been reported for treatments based on anti-tumour necrosis factor , and infliximab proved effective in a randomised controlled trial.This article reviews the presentation of pyoderma gangrenosum and the therapeutic options available. MethodsWe used the keyword "pyoderma gangrenosum" to search Medline.We also searched the Cochrane database but found no Cochrane review on this disease.
Association of lung function with declining ambient air pollution.
Authors: Christian Frye, Bernd Hoelscher, Josef Cyrys, Matthias Wjst, H-Erich Wichmann, Joachim Heinrich
Journal: Environmental Health Perspectives (2002)

Recent studies have found a declining prevalence of respiratory infections in East German children, along with a tremendous improvement of air pollution since 1990. The present study evaluates the effects of improved air quality on lung function. Three consecutive cross-sectional surveys of schoolchildren ages 11-14 years from three communities in East Germany were performed in 1992-1993, 1995-1996, and 1998-1999. Lung function tests were available from 2,493 children. The annual mean of total suspended particulates (TSP) declined from 79 to 25 micro g/m(3), whereas levels for sulfur dioxide declined from 113 to 6 micro g/m(3). Mean forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV(1)) of the children increased from 1992-1993 to 1998-1999. The adjusted percent change of the geometric mean of FVC was 4.7% for a 50 micro g/m(3) decrease of TSP (p = 0.043) and 4.9% for a decrement of 100 micro g/m(3) SO(2) (p = 0.029). Effects on FEV(1) were smaller and not statistically significant. Our study indicates that a reduction of air pollution in a short time period may improve children's lung function.
Plasma Vasopressin Response to Hypertonic Saline Infusion to Assess Posterior Pituitary Function
Authors: P H Baylis, G L Robertson
Journal: Journal of the Royal Society of Medicine (1980)

Hypertonic saline was infused into 11 volunteers to osmotically stimulate vasopressin secretion. A strong positive correlation between plasma arginine vasopressin (PAVP) and plasma osmolality (Pos) was obtained, defined by the function PAVP=0.63 (Pos-284), r=+0.80, P<0.001. The sensitivity of vasopressin secretion to osmotic stimulation was represented by the slope of the expression and the theoretical threshold of vasopressin release by the abscissal intercept. Plasma osmolality at the onset of thirst was 298.5±1.1 mmol/kg. Application of hypertonic saline infusion to 10 polyuric patients clearly separated those with normal osmoregulation of vasopressin secretion from those with cranial diabetes insipidus.