tbuckley/cabot-search huggingface dataset:
Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents
Authors: K.A. Thasni, S. Rakesh, G. Rojini, T. Ratheeshkumar, G. Srinivas, S. Priya
Journal: Annals of Oncology (2008)
Expression of L1-CAM and ADAM10 in Human Colon Cancer Cells Induces Metastasis
Authors: Nancy Gavert, Michal Sheffer, Shani Raveh, Simone Spaderna, Michael Shtutman, Thomas Brabletz, Francis Barany, Phillip Paty, Daniel Notterman, Eytan Domany, Avri Ben-Ze'ev
Journal: Cancer Research (2007)

Abstract L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of β-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of β-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy. [Cancer Res 2007;67(16):7703–12]
Central bronchiectasis in allergic bronchopulmonary aspergillosis: comparative evaluation of computed tomography of the thorax with bronchography
Authors: N Panchal, C Pant, R Bhagat, A Shah
Journal: European Respiratory Journal (1994)

Demonstration of central bronchiectasis (CB) with normal peripheral bronchi is an essential requirement for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). Although the results of bronchography remain the gold standard for demonstration of central bronchiectasis they are not always diagnostic. Moreover, it is an unpleasant invasive procedure which may be difficult to perform in a patient of allergic bronchopulmonary aspergillosis with acute severe asthma. In an attempt to find a safe and effective alternative to demonstrate central bronchiectasis computed tomography (CT) of the thorax was evaluated against bronchography. Twenty one patients with allergic bronchopulmonary aspergillosis underwent computed tomography of the thorax followed by bronchography. Of the 378 bronchopulmonary segments available for analysis, 42 had to be excluded because of consolidation or non-filling of the contrast dye, leaving 336 segments for evaluation. CB was identified on CT in all 21 patients. Detailed analysis of the visualized segments revealed that computed tomography (using 8 mm contiguous scans) identified 146 of the 212 segments showing central bronchiectasis on bronchography (sensitivity 70%) and 114 of the 124, read as normal on bronchography (specificity 92%). Supplemental 4 mm scans, used in 8 out of 21 patients improved the overall sensitivity of computed tomography to 83%, whilst the specificity remained unchanged at 92%. Thus, computed tomography of the thorax, being more acceptable to the patient, has the potential of being the investigation of choice for the demonstration of central bronchiectasis in patients with allergic bronchopulmonary aspergillosis.
Screening and Interventions for Obesity in Adults: Summary of the Evidence for the U.S. Preventive Services Task Force
Authors: Kathleen M. McTigue, Russell Harris, Brian Hemphill, Linda Lux, Sonya Sutton, Audrina J. Bunton, Kathleen N. Lohr
Journal: Annals of Internal Medicine (2003)

Background: Obesity poses a considerable and growing health burden. This review examines evidence for screening and treating obesity in adults. Data Sources: MEDLINE and Cochrane Library (January 1994 through February 2003). Study Selection: Systematic reviews; randomized, controlled trials; and observational studies of obesity's health outcomes or efficacy of obesity treatment. Data Extraction: Two reviewers independently abstracted data on study design, sample, sample size, treatment, outcomes, and quality. Data Synthesis: No trials evaluated mass screening for obesity, so the authors evaluated indirect evidence for efficacy. Pharmacotherapy or counseling interventions produced modest (generally 3 to 5 kg) weight loss over at least 6 or 12 months, respectively. Counseling was most effective when intensive and combined with behavioral therapy. Maintenance strategies helped retain weight loss. Selected surgical patients lost substantial weight (10 to 159 kg over 1 to 5 years). Weight reduction improved blood pressure, lipid levels, and glucose metabolism and decreased diabetes incidence. The internal validity of the treatment trials was fair to good, and external validity was limited by the minimal ethnic or gender diversity of volunteer participants. No data evaluated counseling harms. Primary adverse drug effects included hypertension with sibutramine (mean increase, 0 mm Hg to 3.5 mm Hg) and gastrointestinal distress with orlistat (1% to 37% of patients). Fewer than 1% (pooled samples) of surgical patients died; up to 25% needed surgery again over 5 years. Conclusions: Counseling and pharmacotherapy can promote modest sustained weight loss, improving clinical outcomes. Pharmacotherapy appears safe in the short term; long-term safety has not been as strongly established. In selected patients, surgery promotes large amounts of weight loss with rare but sometimes severe complications.
Relationship of Admission Plasma Gelsolin Levels to Clinical Outcomes in Patients after Major Trauma
Authors: KARAM C. MOUNZER, MICHAEL MONCURE, YOLANDA R. SMITH, MARK J. DiNUBILE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Actin-scavenging proteins, e.g., plasma gelsolin, counteract the pathophysiological consequences of actin leaked into the circulation from dying cells, but the capacity of this defense system can be overwhelmed by massive tissue injury. We examined the prognostic implications of plasma gelsolin levels obtained near the time of admission to our level I Trauma Unit on the subsequent clinical course in a group of patients with severe traumatic injuries. Blood samples were obtained from 13 patients shortly after major trauma and 11 healthy volunteers who served as the control group. Plasma gelsolin levels were assayed by quantitative Western blotting. Duration of mechanical ventilation, stay in the Trauma Intensive Care Unit, and development of acute respiratory distress syndrome (ARDS) were measured as clinical outcomes reflecting the complexity of the hospital course. Subsequently, we evaluated an additional 52 patients after major and minor trauma to extend our earlier observations. Plasma gelsolin concentrations were significantly lower in our 13 original patients compared with healthy controls. Levels below 250 mg/L ( > 2 standard deviations below the mean of the control group) were associated with prolonged mechanical ventilation and a stay in the intensive care unit ⩾ 13 days. Both patients whose gelsolin level was < 100 mg/L in this first series developed ARDS. Including all 65 patients, 6 of the 10 patients who developed ARDS had admission gelsolin levels less than 250 mg/L, compared with only 7 of the 55 patients without ARDS (p = 0.0028). The mean gelsolin levels were 193 and 400 mg/L in patients with and without ARDS, respectively (p < 0.0001) and 398 mg/L in survivors versus 259 mg/L for patients who expired (p < 0.0001). Ten of the 13 patients (77%) with gelsolin levels at the time of admission more than 2 SD below the control mean had "bad outcomes," defined as mechanical ventilation for ⩾ 13 days in the Trauma Intensive Unit, ARDS, and/or death. Plasma gelsolin levels appear to be an early prognostic marker in patients experiencing major trauma. Whether circulating gelsolin serves a biologically vital function or is simply depleted after massive trauma cannot be determined from our study. The potential therapeutic benefits of infusions of recombinant human plasma gelsolin for patients in whom multiorgan dysfunction commonly follows a serious but self-limited insult have not yet been investigated. Mounzer KC, Moncure M, Smith YR, DiNubile MJ. Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma.
Functional Relevance of Activated β1 Integrins in Mercury-Induced Nephritis
Authors: ESTHER ESCUDERO, ANA MARTÍN, MARTA NIETO, ELENA NIETO, ELENA NAVARRO, ALFONSO LUQUE, CARLOS CABAN[Combining Tilde]AS, FRANCISCO SÁNCHEZ-MADRID, FRANCISCO MAMPASO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Cell adhesion through different adhesion molecules is a crucial event in the inflammatory response. Integrins can only bind and mediate cellular adhesion after their activation by different specific stimuli. The state of β1 integrin activation can be assessed by a group of monoclonal antibodies (HUTS) that selectively recognize β1 integrins in their active form. A similar activated epitope in the rat was defined using the anti-human monoclonal antibody HUTS-21, which recognizes an activation-dependent epitope on the β1 chain. It was found that the divalent cations Mn 2+ and Hg 2+ were able to induce in vitro the activation of β1 integrins on rat lymphocytes. The Hg 2+ cation induces an autoimmune disease in the Brown Norway rat characterized by synthesis and glomerular deposits of anti-glomerular basement membrane antibodies, proteinuria, and interstitial nephritis. Using the mercury model of nephritis, it was found that the expression of HUTS-21 epitope is induced in vivo in rat lymphocytes, and its appearance is correlated with the other parameters at the onset of the disease. In addition, the administration of HUTS-21 monoclonal antibody to HgCl 2 -treated rats offered evidence of its protective effects ( 1 ) against infiltration of renal interstitium by leukocytes, and ( 2 ) in the reduction of anti-glomerular basement membrane synthesis and glomerular deposition. Nevertheless, urinary protein values remained unaffected. These results demonstrate a key role of β1-activated integrins in both leukocyte cell-cell interactions and leukocyte infiltration pathway mechanism, and also indicate that leukocyte migration may have less importance in the development of this disease than previously thought.
Intracerebral transplantation of mesenchymal stem cells into acid sphingomyelinase–deficient mice delays the onset of neurological abnormalities and extends their life span
Authors: Hee Kyung Jin, Janet E. Carter, George W. Huntley, Edward H. Schuchman
Journal: Journal of Clinical Investigation (2002)

Types A and B Niemann-Pick disease (NPD) are lysosomal storage disorders resulting from loss of acid sphingomyelinase (ASM) activity. We have used a knockout mouse model of NPD (ASMKO mice) to evaluate the effects of direct intracerebral transplantation of bone marrow–derived mesenchymal stem cells (MSCs) on the progression of neurological disease in this disorder. MSCs were transduced with a retroviral vector to overexpress ASM and were injected into the hippocampus and cerebellum of 3-week-old ASMKO pups. Transplanted cells migrated away from the injection sites and survived at least 6 months after transplantation. Seven of 8 treated mice, but none of the untreated controls, survived for ≥ 7 months after transplant. Survival times were greater in sex-matched than in sex-mismatched transplants. Transplantation significantly delayed the Purkinje cell loss that is characteristic of NPD, although the protective effect declined with distance from the injection site. Overall ASM activity in brain homogenates was low, but surviving Purkinje cells contained the retrovirally expressed human enzyme, and transplanted animals showed a reduction in cerebral sphingomyelin. These results reveal the potential of treating neurodegenerative lysosomal storage disorders by intracerebral transplantation of bone marrow–derived MSCs.
Ursodeoxycholic acid prevents hepatic cytochrome P450 isozyme reduction in rats with deoxycholic acid-induced liver injury
Authors: Masami Tanaka, Hironori Nakura, Tomonori Tateishi, Minoru Watanabe, Sachiko Nakaya, Toshio Kumai, Shinichi Kobayashi
Journal: Journal of Hepatology (1999)
Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array
Authors: P. J Mazzone, J. Hammel, R. Dweik, J. Na, C. Czich, D. Laskowski, T. Mekhail
Journal: Thorax (2007)

<b>Background:</b> The pattern of volatile organic compounds (VOCs) in the exhaled breath of patients with lung cancer may be unique. New sensor systems that detect patterns of VOCs have been developed. One of these sensor systems, a colorimetric sensor array, has 36 spots composed of different chemically sensitive compounds impregnated on a disposable cartridge. The colours of these spots change based on the chemicals with which they come into contact. In this proof of principle study, the ability of this sensor system to detect a pattern of VOCs unique to lung cancer is assessed. <b>Methods:</b> Individuals with lung cancer, those with other lung diseases and healthy controls performed tidal breathing of room air for 12 min while exhaling into a device designed to draw their breath across a colorimetric sensor array. The colour changes that occurred for each individual were converted into a numerical vector. The vectors were analysed statistically, using a random forests technique, to determine whether lung cancer could be predicted from the responses of the sensor. <b>Results:</b> 143 individuals participated in the study: 49 with non-small cell lung cancer, 18 with chronic obstructive pulmonary disease 15 with idiopathic pulmonary fibrosis 20 with pulmonary arterial hypertension 20 with sarcoidosis and 21 controls. A prediction model was developed using observations from 70% of the subjects. This model was able to predict the presence of lung cancer in the remaining 30% of subjects with a sensitivity of 73.3% and a specificity of 72.4% (p = 0.01). <b>Conclusions:</b> The unique chemical signature of the breath of patients with lung cancer can be detected with moderate accuracy by a colorimetric sensor array.
Monoclonal Immunoglobulin Production Is a Frequent Event in Patients with Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Stefan Wöhrer, Berthold Streubel, Rupert Bartsch, Andreas Chott, Markus Raderer
Journal: Clinical Cancer Research (2004)

Mucosa-associated lymphoid tissue (MALT) lymphoma comprises 7% of all newly diagnosed non-Hodgkin's lymphomas and is therefore among the most common lymphoma entities. Monoclonal gammopathy due to production of a monoclonal immunoglobulin by lymphoma cells is a well-known phenomenon associated with various types of B-cell non-Hodgkin's lymphomas. The objective of the present study was to evaluate the incidence and clinical relevance of paraprotein (PP) production in patients with MALT lymphoma.Fifty two patients were prospectively evaluated with regard to differentiation of the MALT lymphoma cells, t(11;18) translocation, monoclonal immunoglobulin production, Helicobacter pylori (HP) status, stage, treatment, and clinical outcome.Nineteen of 52 MALT lymphoma patients (36%) had PP (8 IgMkappa, 6 IgGkappa, 4 IgMlambda, and 1 IgAkappa). The histologic feature of plasmacytic differentiation correlated significantly with the production of PP (P = 0.001). No correlation was found between PP and clinical stage, HP status, and t(11;18) status. PP was, however, negatively associated with response to eradication of HP in gastric MALT lymphoma, and PP levels declined significantly in patients responding to chemotherapy or radiation. Importantly, both immunofixation and serum electrophoresis have to be performed to detect low PP levels.In conclusion, PP levels may probably be used as a potential prognostic tool for response to HP eradication, and serial measurements may also allow for noninvasive assessment of response to radiation or chemotherapy in patients with MALT lymphoma.
Connective tissue naevus with pseudo-Hurler polydystrophy
Authors: H. SHINKAI, K. KATAGIRI, Y. ISHII, S. TAKAYASU
Journal: British Journal of Dermatology (1994)

We report a 39‐year‐old patient with a huge connective tissue naevus on his back, in association with pseudo‐Hurler polydystrophy (mucolipidosis III). As far as we are aware, this is the first report of the coexistence of these two rare conditions. The lesional skin was composed of densely packed, coarse collagen fibres, which were immunohistochemically found to consist of type I, type III and type VI collagens. The amount of elastic fibres was moderately reduced. The glycosaminoglycan content of lesional skin was similar to that in a normal control. Activities of several glycosidases were markedly decreased in cultured fibroblasts.
Fundamental Difference in the Reactivity of the Blood Vessels in Skin Compared with those in Muscle
Authors: JOHN T. LANIER, HAROLD D. GREEN, JOHN HARDAWAY, HOOPER D. JOHNSON, WILLIAM B. DONALD
Journal: Circulation Research (1953)

Blood flow was measured with the electromagnetic flowmeter in the saphenous artery bed (cutaneous) and in the distal femoral and popliteal beds (muscle). The effects of ischemia and of intra-arterial injection with methacholine, l-epinephrine and l-norepinephrine were studied before and again after each injection of progressively increased doses of antiadrenergic drugs. These studies indicate a fundamental difference between the reactivity of cutaneous and muscular vascular beds.
Comparison of methods to identify aberrant expression patterns in individual patients: augmenting our toolkit for precision medicine
Authors: Daniel Bottomly, Peter A Ryabinin, Jeffrey W Tyner, Bill H Chang, Marc M Loriaux, Brian J Druker, Shannon K McWeeney, Beth Wilmot
Journal: Genome Medicine (2013)

Patient-specific aberrant expression patterns in conjunction with functional screening assays can guide elucidation of the cancer genome architecture and identification of therapeutic targets. Since most statistical methods for expression analysis are focused on differences between experimental groups, the performance of approaches for patient-specific expression analyses are currently less well characterized. A comparison of methods for the identification of genes that are dysregulated relative to a single sample in a given set of experimental samples, to our knowledge, has not been performed. We systematically evaluated several methods including variations on the nearest neighbor based outlying degree method, as well as the Zscore and a robust variant for their suitability to detect patient-specific events. The methods were assessed using both simulations and expression data from a cohort of pediatric acute B lymphoblastic leukemia patients. We first assessed power and false discovery rates using simulations and found that even under optimal conditions, high effect sizes (>4 unit differences) were necessary to have acceptable power for any method (>0.9) though high false discovery rates (>0.1) were pervasive across simulation conditions. Next we introduced a technical factor into the simulation and found that performance was reduced for all methods and that using weights with the outlying degree could provide performance gains depending on the number of samples and genes affected by the technical factor. In our use case that highlights the integration of functional assays and aberrant expression in a patient cohort (the identification of gene dysregulation events associated with the targets from a siRNA screen), we demonstrated that both the outlying degree and the Zscore can successfully identify genes dysregulated in one patient sample. However, only the outlying degree can identify genes dysregulated across several patient samples. Our results show that outlying degree methods may be a useful alternative to the Zscore or Rscore in a personalized medicine context especially in small to medium sized (between 10 and 50 samples) expression datasets with moderate to high sample-to-sample variability. From these results we provide guidelines for detection of aberrant expression in a precision medicine context.
Patterns of alcohol consumption after liver transplantation
Authors: H Tang, R Boulton, B Gunson, S Hubscher, J Neuberger
Journal: Gut (1998)

Background —Uncertainty exists about the extent and consequences of a return to alcohol consumption after liver transplantation for alcoholic liver disease (ALD). Aims —To determine the prevalence and consequences of alcohol consumption in patients transplanted for ALD. Methods —A retrospective case controlled study of all patients transplanted for ALD at the Queen Elizabeth Hospital, Birmingham, between 1987 and 1996. Results —Seventy patients with ALD were transplanted, of which 59 survived more than three months; 56 were interviewed. Twenty eight had consumed some alcohol after transplantation; for the nine “heavy drinkers” (HD), the median time to resumption of alcohol intake was six months and for the 19 “moderate drinkers” (MD) it was eight months. There was no significant difference in episodes of acute rejection or compliance with medication between those who were abstinent, MD, or HD. Histological evidence of liver injury was common in ALD patients who had returned to drink. Mild fatty change was found in 1/11 biopsy specimens from abstinent patients but moderate to severe fatty change and ballooned hepatocytes were seen in 3/5 MD and 2/5 HD specimens. Two HD patients had early fibrosis. One HD patient has died of alcohol related complications. Conclusions —Moderate to heavy alcohol consumption occurs in patients transplanted for ALD. Patient recall of abstinence advice is unreliable, and patients return to alcohol mainly within the first year after liver transplantation. Return to alcohol consumption after liver transplantation is associated with rapid development of histological liver injury including fibrosis.