tbuckley/cabot-search huggingface dataset:
Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques.
Authors: W S Selby, G Janossy, M Bofill, D P Jewell
Journal: Gut (1984)

Lymphocyte subpopulations in the intestinal mucosa of patients with ulcerative colitis or Crohn9s disease have been studied using a double marker immunofluorescence technique. Analysis of tissue sections revealed that the majority of intraepithelial lymphocytes (IEL) were T cells (Hle-1+ HuTLA+ UCHT1+). Of these, over 80% were of suppressor-cytotoxic phenotype (OKT8+:83 +/- 10.2%) with a small population of helper type IEL (OKT4+). Only one third of OKT8+ IEL reacted with the T cell antibody, anti-Leu-1. IEL were also Tac-, C3b-receptor- (C3RT05-), and Ig-. Within the lamina propria, OKT4+ T cells predominated (ulcerative colitis 64 +/- 6.0%; Crohn9s disease 63 +/- 6.0%). Less than half of the smaller OKT8+ population in the lamina propria was Leu-1+. These finding did not differ from those seen in histologically normal tissues from controls, and are similar to those reported in the small intestine. Mononuclear cells were also isolated from the intestinal lamina propria using an enzymatic technique. The majority of lymphocytes obtained were T cells (OKT3+), with populations of OKT4+ and OKT8+ cells. Comparison of the ratio of OKT4+ to OKT8+ lymphocytes determined by immunohistological analysis with that obtained in mucosal isolates, however, suggested that the isolation procedure may deplete OKT8+ cells. These findings indicate that an imbalance of mucosal immunoregulatory T cells, as defined by monoclonal antibodies, does not occur in inflammatory bowel disease. They also emphasize that functional studies of isolated intestinal mucosal cells should be combined with morphological studies of cell populations in situ.
Periannular extension of infective endocarditis
Authors: Catherine Graupner, Isidre Vilacosta, JoséAlberto SanRomán, Ricardo Ronderos, Cristina Sarriá, Cristina Fernández, Ricardo Mújica, Olga Sanz, Juan Victor Sanmartín, Angel González Pinto
Journal: Journal of the American College of Cardiology (2002)
Precipitation of Autoimmune Diabetes With Anti-PD-1 Immunotherapy
Authors: Jing Hughes, Nalini Vudattu, Mario Sznol, Scott Gettinger, Harriet Kluger, Beatrice Lupsa, Kevan C. Herold
Journal: Diabetes Care (2015)

Immunotherapy targeting T-cell regulatory molecules is highly effective in multiple cancers refractory to standard chemotherapies. However, blocking inhibitory molecules on activated T cells not only increases tumor cell destruction but also can breach tolerance, enabling pathological T cells to react with self-antigens. Indeed, autoimmune endocrinopathies, including hypophysitis, hypopituitarism, and thyroiditis, have been reported in trials involving anti-CTLA-4 and anti-PD-1 monoclonal antibodies (1–3). But autoimmune diabetes has not been definitively linked to these agents.

We describe the development of new-onset insulin-dependent diabetes in five patients after receiving anti-PD-1 antibodies, either as single agent or in combination with other cancer drugs. Clinical history and key laboratory findings are summarized in Table 1. Notably, while the patients presented with diverse cancer types, and some had been treated with other immunological agents, their …
Endoscopic ultrasonography for differential diagnosis of polypoid gall bladder lesions: analysis in surgical and follow up series
Authors: M Sugiyama
Journal: Gut (2000)

Differential diagnosis is often difficult for small (</=20 mm) polypoid lesions of the gall bladder.To assess the diagnostic accuracy of endoscopic ultrasonography (EUS) for polypoid lesions in a surgical and follow up series.A total of 194 patients with small polypoid lesions underwent both ultrasonography and EUS. A tiny echogenic spot or an aggregation of echogenic spots and multiple microcysts or a comet tail artefact indicated cholesterol polyp and adenomyomatosis respectively. Other lesions were diagnosed as neoplastic (adenoma or adenocarcinoma). In the 58 patients who underwent surgery, the histological diagnoses were cholesterol polyp (n = 36), adenomyomatosis (n = 7), adenoma (n = 4), and adenocarcinoma (n = 11). Of the remaining 136 patients with an EUS diagnosis of non-neoplastic lesions, 125 were followed up with ultrasonography alone or with EUS for 1-8.7 years (mean 2.6 years).In the surgical series, EUS (97%) differentiated polypoid lesions more precisely than ultrasonography (76%). During follow up, the lesions remained unchanged in size in 109 (87%) of the 125 patients with non-neoplastic lesions diagnosed by EUS. No neoplastic lesions developed in these patients. Ultrasonography had shown lesions to be neoplastic in 13% of the follow up series.EUS is highly accurate for differentially diagnosing polypoid gall bladder lesions. It is recommended when ultrasonography cannot rule out neoplastic lesions. Non-neoplastic lesions diagnosed by EUS may be followed and observed with ultrasonography.
Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data
Authors: Marina Sirota, Joel T. Dudley, Jeewon Kim, Annie P. Chiang, Alex A. Morgan, Alejandro Sweet-Cordero, Julien Sage, Atul J. Butte
Journal: Science Translational Medicine (2011)

A systematic computational method predicts new uses for existing drugs by integrating public gene expression signatures of drugs and diseases.
Cost-effectiveness of Screening for Colorectal Cancer in the General Population
Authors: A. Lindsay Frazier, Graham A. Colditz, Charles S. Fuchs, Karen M. Kuntz
Journal: JAMA (2000)

A recent expert panel recommended that persons at average risk of colorectal cancer (CRC) begin screening for CRC at age 50 years using 1 of several strategies. However, many aspects of different CRC screening strategies remain uncertain.To assess the consequences, costs, and cost-effectiveness of CRC screening in average-risk individuals.Cost-effectiveness analysis from a societal perspective using a Markov model.Hypothetical subjects representative of the 50-year-old US population at average risk for CRC.Simulated clinical practice in the United States.Discounted lifetime costs, life expectancy, and incremental cost-effectiveness (CE) ratio, compared used 22 different CRC screening strategies, including those recommended by the expert panel.In 1 base-case analysis, compliance was assumed to be 60% with the initial screen and 80% with follow-up or surveillance colonoscopy. The most effective strategy for white men was annual rehydrated fecal occult blood testing (FOBT) plus sigmoidoscopy (followed by colonoscopy if either a low- or high-risk polyp was found) every 5 years from age 50 to 85 years, which resulted in a 60% reduction in cancer incidence and an 80% reduction in CRC mortality compared with no screening, and an incremental CE ratio of $92,900 per year of life gained compared with annual unrehydrated FOBT plus sigmoidoscopy every 5 years. In a base-case analysis in which compliance with screening and follow-up is assumed to be 100%, screening more often than every 10 years was prohibitively expensive; annual rehydrated FOBT plus sigmoidoscopy every 5 years had an incremental CE ratio of $489,900 per life-year gained compared with the same strategy every 10 years. Other strategies recommended by the expert panel were either less effective or cost more per year of life gained than the alternatives. Colonoscopy every 10 years was less effective than the combination of annual FOBT plus sigmoidoscopy every 5 years. However, a single colonoscopy at age 55 years achieves nearly half of the reduction in CRC mortality obtainable with colonoscopy every 10 years. Because of increased life expectancy among white women and increased cancer mortality among blacks, CRC screening was even more cost-effective in these groups than in white men.Screening for CRC, even in the setting of imperfect compliance, significantly reduces CRC mortality at costs comparable to other cancer screening procedures. However, compliance rates significantly affect the incremental CE ratios. In this model of CRC, 60% compliance with an every 5-year schedule of screening was roughly equivalent to 100% compliance with an every 10-year schedule. Mathematical modeling used to inform clinical guidelines needs to take into account expected compliance rates. JAMA. 2000;284:1954-1961.
Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial
Authors: Michele D Tameris, Mark Hatherill, Bernard S Landry, Thomas J Scriba, Margaret Ann Snowden, Stephen Lockhart, Jacqueline E Shea, J Bruce McClain, Gregory D Hussey, Willem A Hanekom, Hassan Mahomed, Helen McShane
Journal: The Lancet (2013)
Might we adopt the learning-related account instead of the talent account?
Authors: Giyoo Hatano
Journal: Behavioral and Brain Sciences (1998)

Although Howe et al.'s survey shows little evidence for the talent account, it is premature to conclude that individual differences in achievement can be attributed largely to training and early experience. Moreover, such an empiricist account has problematic social implications, especially in cultures in which effort is emphasized. The aptitude account is thus proposed as a third alternative.
<i>In vivo</i>Effects of Vaccination with Six-Transmembrane Epithelial Antigen of the Prostate: A Candidate Antigen for Treating Prostate Cancer
Authors: Maria de la Luz Garcia-Hernandez, Andrew Gray, Bolyn Hubby, W. Martin Kast
Journal: Cancer Research (2007)

Abstract Immunotherapy may provide an alternative treatment for cancer patients, especially when tumors overexpress antigens that can be recognized by immune cells. The identification of markers and therapeutic targets that are up-regulated in prostate cancer has been important to design new potential treatments for prostate cancer. Among them, the recently identified six-transmembrane epithelial antigen of the prostate (STEAP) is considered attractive due to its overexpression in human prostate cancer tissues. Our study constitutes the first assessment of the in vivo effectiveness of STEAP-based vaccination in prophylactic and therapeutic mouse models. Two delivery systems, cDNA delivered by gene gun and Venezuelan equine encephalitis virus-like replicon particles (VRP), both encoding mouse STEAP (mSTEAP) and three vaccination strategies were used. Our results show that mSTEAP-based vaccination was able to induce a specific CD8 T-cell response against a newly defined mSTEAP epitope that prolonged the overall survival rate in tumor-challenged mice very significantly. This was achieved without any development of autoimmunity. Surprisingly, CD4 T cells that produced IFNγ, tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2) played the main role in tumor rejection in our model as shown by using CD4- and CD8-deficient mice. In addition, the presence of high IL-12 levels in the tumor environment was associated with a favorable antitumor response. Finally, the therapeutic effect of STEAP vaccination was also assessed and induced a modest but significant delay in growth of established, 31 day old tumors. Taken together, our data suggest that vaccination against mSTEAP is a viable option to delay tumor growth. [Cancer Res 2007;67(3):1344–51]
Denosumab: Second Chapter in Controlling Bone Metastases or a New Book?
Authors: Monica N. Fornier
Journal: Journal of Clinical Oncology (2010)

Boney involvement develops in approximately 73% of patients with metastatic breast carcinoma, 68% of patients with prostate can- cer, and in nearly all patients with multiple myeloma. 1 Before the introduction of bisphosphonates, patients with carcinoma that had metastasized to bones were often hospitalized for skeletal-related events (SREs) such as pain, hypercalcemia, spinal cord compromise, andpathologicfractures,whichledtosignificantmorbidityandmor- tality, reduced quality of life, and high cost of care. Randomized trials show that bisphosphonates, including pamidronate and zoledronic acid,significantlydecreasetheincidenceofSREsinpatientswithbone metastases. 2-4 TheUSFoodandDrugAdministrationapprovedthese compoundsforthetreatmentofmetastaticbonediseaseintheUnited States, and both agents were quickly adopted in clinical practice. Two other bisphosphonates, clodronate and ibandronate, have been ap- provedoutsideoftheUnitedStatesfortreatmentofpatientswithbone metastases (Table 1). Metastatic bone lesions can be osteolytic (bone destruction that results from increased bone resorption), osteoblastic (increased bone formation), or both. Metastatic bone disease associated with breast cancer is often predominantly osteolytic, whereas lesions from pros- tatecancerarepredominantlyosteoblastic.However,bonemetastases
Prognosis in Patients With Sentinel Node–Positive Melanoma Is Accurately Defined by the Combined Rotterdam Tumor Load and Dewar Topography Criteria
Authors: Augustinus P.T. van der Ploeg, Alexander C.J. van Akkooi, Piotr Rutkowski, Zbigniew I. Nowecki, Wanda Michej, Angana Mitra, Julia A. Newton-Bishop, Martin Cook, Iris M.C. van der Ploeg, Omgo E. Nieweg, Mari F.C.M. van den Hout, Paul A.M. van Leeuwen, Christiane A. Voit, Francesco Cataldo, Alessandro Testori, Caroline Robert, Harald J. Hoekstra, Cornelis Verhoef, Alain Spatz, Alexander M.M. Eggermont
Journal: Journal of Clinical Oncology (2011)

Purpose Prognosis in patients with sentinel node (SN) –positive melanoma correlates with several characteristics of the metastases in the SN such as size and site. These factors reflect biologic behavior and may separate out patients who may or may not need additional locoregional and/or systemic therapy. Patients and Methods Between 1993 and 2008, 1,080 patients (509 women and 571 men) were diagnosed with tumor burden in the SN in nine European Organisation for Research and Treatment of Cancer (EORTC) melanoma group centers. In total, 1,009 patients (93%) underwent completion lymph node dissection (CLND). Median Breslow thickness was 3.00 mm. The median follow-up time was 37 months. Tumor load and tumor site were reclassified in all nodes by the Rotterdam criteria for size and in 88% by the Dewar criteria for topography. Results Patients with submicrometastases (&lt; 0.1 mm in diameter) were shown to have an estimated 5-year overall survival rate of 91% and a low nonsentinel node (NSN) positivity rate of 9%. This is comparable to the rate in SN-negative patients. The strongest predictive parameter for NSN positivity and prognostic parameter for survival was the Rotterdam-Dewar Combined (RDC) criteria. Patients with submicrometastases that were present in the subcapsular area only, had an NSN positivity rate of 2% and an estimated 5- and 10-year melanoma-specific survival (MSS) of 95%. Conclusion Patients with metastases &lt; 0.1 mm, especially when present in the subcapsular area only, may be overtreated by a routine CLND and have an MSS that is indistinguishable from that of SN-negative patients. Thus the RDC criteria provide a rational basis for decision making in the absence of conclusions provided by randomized controlled trials.
Depth of Insertion At Flexible Sigmoidoscopy: Implications for Colorectal Cancer Screening and Instrument Design
Authors: J. Painter, D. B. Saunders, G. D. Bell, C. B. Williams, R. Pitt, J. Bladen
Journal: Endoscopy (1999)

The depth of insertion at flexible sigmoidoscopy is variable, depending upon bowel preparation, patient tolerance and distal colonic anatomy. Many endoscopists routinely aim to insert the 60 cm flexible sigmoidoscope to the splenic flexure; however internal endoscopic markers are unreliable, making the true anatomical extent of the examination difficult to assess. The aim of this study was to assess the depth of insertion at flexible sigmoidoscopy.Two separate studies were done. In the first (study 1), magnetic endoscopic imaging was used to determine the final depth of insertion at non-sedated, screening flexible sigmoidoscopy. In the second (study 2), "real-time" imaging was utilized to determine sigmoid looping and the anatomical location of the endoscope tip after 60 cm of instrument had been inserted during total or limited colonoscopy. A total of 117 consecutive average-risk patients, aged 55-65 years participated in study 1, and 136 patients underwent either limited, (33) or attempted total colonoscopy (103) in study 2.In study 1 the median insertion distance was 52 cm, range 20-58. In 61 % of patients the imaging system showed that the descending colon had not been visualized by the end of the procedure. Failure to reach the sigmoid/descending junction occurred in 29 (24%) patients. Reasons for failure included poor tolerance of the procedure due to pain (23 patients) inadequate preparation (3 patients) and, excessive looping (3 patients). In study 2, after 60 cm of instrument had been inserted, the splenic flexure or beyond was reached in 29% and the descending colon in 9%, whilst in 62 % the endoscope tip had not passed beyond the sigmoid/descending colon junction. A sigmoid loop formed in 70% of patients, and unusual loops such as the alpha, reverse alpha and reverse sigmoid spiral loop occurred more frequently in women compared to men (P = 0.0249). In those 104 patients where the splenic flexure was reached the mean maximum length of instrument inserted prior to reaching the flexure was 75.4 cm, (SD = 21.9).Examination of the entire sigmoid was not achieved in approximately one-quarter of patients undergoing screening flexible sigmoidoscopy, mainly because of discomfort. The descending colon is intubated in a minority of cases (using standard instruments), even after 60 cm has been inserted. Alternative instruments with different shaft characteristics (floppy, narrow calibre, 80-100 cm in length) may be necessary to ensure deeper routine intubation in nonsedated patients.
An oral selective M3 cholinergic receptor antagonist in COPD
Authors: S. Lu, D. D. Parekh, O. Kuznetsova, S. A. Green, C. A. Tozzi, T. F. Reiss
Journal: European Respiratory Journal (2006)

Cholinergic antagonists have been used since the early 1900s as bronchodilators for chronic obstructive pulmonary disease (COPD). The present study investigated whether an oral muscarinic M3-selective anticholinergic agent (OrM3) would provide an improved therapeutic advantage compared with an inhaled anticholinergic agent in patients with COPD. A 6-week, multicentre, randomised, placebo- and active-controlled, parallel-group study was performed at 56 sites in the USA. In total, 412 male and female patients (aged 35–86 yrs) with a clinical history consistent with COPD were randomised to receive OrM3 0.5, 2, 3 or 4 mg orally once daily, ipratropium bromide 36 μg by inhalation four times daily or placebo. OrM3 demonstrated a significant dose-related improvement in serial forced expiratory volume in one second and a trend for dose-related improvement in patient-reported symptoms compared with placebo. However, at a dose that provided efficacy less than that of ipratropium, the incidence of dose-related, mechanism-based side-effects for OrM3 exceeded those observed for ipratropium. In patients with chronic obstructive pulmonary disease, the oral M3-selective agent did not offer a therapeutic advantage over inhaled ipratropium. These results do not support the hypothesis that high selectivity for muscarinic M3 receptors over airway neuronal M2 receptors will represent a more effective therapy than current inhaled anticholinergics in obstructive airway disease.
Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical Management
Authors: Brian Shuch, Srinivas Vourganti, Christopher J. Ricketts, Lindsay Middleton, James Peterson, Maria J. Merino, Adam R. Metwalli, Ramaprasad Srinivasan, W. Marston Linehan
Journal: Journal of Clinical Oncology (2013)

Purpose Approximately 5% to 8% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC germline mutation testing. We evaluate how age of onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer. Patients and Methods We analyzed the age distribution of RCC cases in the SEER-17 program and in our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary cancer syndrome. Models were established to evaluate the specific age thresholds for genetic testing. Results The median age of patients with RCC in SEER-17 was 64 years, with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (P &lt; .05). The bottom decile cutoff was ≤ 46 years of age and slightly differed by sex, race, and histology. The mean and median ages at presentation of 608 patients with hereditary kidney cancer were 39.3 years and 37 years, respectively. Although age varied by specific syndrome, 70% of these cases were found to lie at or below the bottom age decile. Modeling age-based genetic testing thresholds demonstrated that the 10th percentile maximized sensitivity and specificity. Conclusion Early age of onset might be a sign of hereditary RCC. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines.
Glucose Control in the ICU — How Tight Is Too Tight?
Authors: Silvio E. Inzucchi, Mark D. Siegel
Journal: New England Journal of Medicine (2009)

For the past decade, hospitals have focused on the inpatient management of hyperglycemia, particularly in the intensive care unit (ICU). Extensive observational data have shown a consistent, almost linear relationship between blood glucose levels in hospitalized patients and adverse clinical outcomes, even in patients without established diabetes.1 It has never been entirely clear, however, whether glycemia serves as a mediator of these outcomes or merely as a marker of the sickest patients, who present with the well-known counterregulatory stress response to illness. Several early studies suggested a clinical benefit from strict glucose control during critical care but were weakened by . . .
Arylamine<i>N</i>-Acetyltransferase 1: A Novel Drug Target in Cancer Development
Authors: Neville J. Butcher, Rodney F. Minchin
Journal: Pharmacological Reviews (2011)

The human arylamine N-acetyltransferases first attracted attention because of their role in drug metabolism. However, much of the current literature has focused on their role in the activation and detoxification of environmental carcinogens and how genetic polymorphisms in the genes create predispositions to increased or decreased cancer risk. There are two closely related genes on chromosome 8 that encode the two human arylamine N-acetyltransferases--NAT1 and NAT2. Although NAT2 has restricted tissue expression, NAT1 is found in almost all tissues of the body. There are several single-nucleotide polymorphisms in the protein coding and 3'-untranslated regions of the gene that affect enzyme activity. However, NAT1 is also regulated by post-translational and environmental factors, which may be of greater importance than genotype in determining tissue NAT1 activities. Recent studies have suggested a novel role for this enzyme in cancer cell growth. NAT1 is up-regulated in several cancer types, and overexpression can lead to increased survival and resistance to chemotherapy. Although a link to folate homeostasis has been suggested, many of the effects attributed to NAT1 and cancer cell growth remain to be explained. Nevertheless, the enzyme has emerged as a viable candidate for drug development, which should lead to small molecule inhibitors for preclinical and clinical evaluation.
UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes
Authors: Robert Turner, Irene Stratton, Virginia Horton, Sue Manley, Paul Zimmet, Ian R Mackay, Marion Shattock, Gian Franco Bottazzo, Rury Holman
Journal: The Lancet (1997)