tbuckley/cabot-search huggingface dataset:
Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG)
Authors: Ingeborg A. Hauser, Sandra Spiegler, Eva Kiss, Stefan Gauer, Olaf Sichler, Ernst H. Scheuermann, Hanns Ackermann, Josef M. Pfeilschifter, Helmut Geiger, Hermann-Josef Gröne, Heinfried H. Radeke
Journal: Journal of the American Society of Nephrology (2005)

Early diagnosis of acute allograft rejection (AR) is still decisive for long-term renal allograft survival. The aim of this study was to define the role of the chemokine monokine induced by IFN-gamma (MIG) (CXCL9) and IFN-gamma-inducible protein 10 (IP-10) (CXCL10) as early markers of AR in renal transplantation (NTX). In a prospective study, 69 de novo renal transplant recipients were monitored and urine samples were collected after NTX for a median of 29 d. In pH-adjusted urine, MIG and IP-10 were determined by modified ELISA. AR was clinically diagnosed in 15 of 69 recipients and confirmed by biopsy in 14 of 15 AR patients (Banff classification). Corresponding to CXCR3-positive infiltrates in renal tissue, urinary MIG was elevated in 14 of 15 AR patients with a median of 2809 pg/ml (quartile 25% and 75% = 870 and 13,000; n = 15), being significantly (P < 0.0001) different from both nonrejecting allograft patients (NO-AR) (median, 25%, and 75%: 96, 1.0, and 161, n = 54) and healthy controls (median, 25%, and 75%: 144, 19, and 208, n = 13). Urinary MIG predicted AR with a sensitivity of 93% and a specificity of 89%. In AR and NO-AR groups, MIG values correlated well with IP-10 (P < 0.001). MIG values indicated both imminent rejection and response to successful antirejection therapy. MIG was not related to intercurrent infections or other causes for impairment of renal function. In a multivariate analysis, MIG correlated best (P < 0.001) with AR from all AR-associated parameters. In conclusion, urinary MIG serves as a very sensitive and specific predictor for AR, mirrors response to antirejection therapy, and thus may contribute to improved long-term renal allograft survival.
Identification of MCAM/CD146 as the Target Antigen of a Human Monoclonal Antibody that Recognizes Both Epithelioid and Sarcomatoid Types of Mesothelioma
Authors: Scott Bidlingmaier, Jiang He, Yong Wang, Feng An, Jinjin Feng, Dario Barbone, Dongwei Gao, Ben Franc, V. Courtney Broaddus, Bin Liu
Journal: Cancer Research (2009)

Abstract The prognosis for patients diagnosed with mesothelioma is generally poor, and currently available treatments are usually ineffective. Therapies that specifically target tumor cells hold much promise for the treatment of cancers that are resistant to current approaches. We have previously selected phage antibody display libraries on mesothelioma cell lines to identify a panel of internalizing human single chain (scFv) antibodies that target mesothelioma-associated, clinically represented cell surface antigens and further exploited the internalizing function of these scFvs to specifically deliver lethal doses of liposome-encapsulated small molecule drugs to both epithelioid and sarcomatous subtypes of mesothelioma cells. Here, we report the identification of MCAM/MUC18/CD146 as the surface antigen bound by one of the mesothelioma-targeting scFvs using a novel cloning strategy based on yeast surface human proteome display. Immunohistochemical analysis of mesothelioma tissue microarrays confirmed that MCAM is widely expressed by both epithelioid and sarcomatous types of mesothelioma tumor cells in situ but not by normal mesothelial cells. In addition, quantum dot-labeled anti-MCAM scFv targets primary meosthelioma cells in tumor fragment spheroids cultured ex vivo. As the first step in evaluating the therapeutic potential of MCAM-targeting antibodies, we performed single-photon emission computed tomography studies using the anti-MCAM scFv and found that it recognizes mesothelioma organotypic xenografts in vivo. The combination of phage antibody library selection on tumor cells and rapid target antigen identification by screening the yeast surface-displayed human proteome could be a powerful method for mapping the targetable tumor cell surface epitope space. [Cancer Res 2009;69(4):1570–7]
Secular Trends in Mortality From Common Cancers in the United States by Educational Attainment, 1993–2001
Authors: Tracy Kinsey, Ahmedin Jemal, Jonathan Liff, Elizabeth Ward, Michael Thun
Journal: JNCI Journal of the National Cancer Institute (2008)

Death rates for the four major cancer sites (lung, breast, prostate, and colon and rectum) have declined steadily in the United States among persons aged 25-64 years since the early 1990s. We used national data to examine these trends in relation to educational attainment.We calculated age-standardized death rates for each of the four cancers by level of education among 25- to 64-year-old non-Hispanic white and non-Hispanic black men and women for 1993 through 2001 using data on approximately 86% of US deaths from the National Center for Health Statistics, education level as recorded on the death certificate, and population data from the US Bureau of Census Current Population Survey. Annual percent changes in age-adjusted death rates were estimated using weighted log-linear regression models. All statistical tests were two-sided.Death rates for each cancer decreased statistically significantly from 1993 to 2001 in people with at least 16 years of education in every sex and race stratum except lung cancer in black women, for whom death rates were stable. For example, colorectal cancer death rates among white men, black men, white women, and black women with at least 16 years of education decreased by 2.4% (P < .001), 4.8% (P = .011), 3.0% (P < .001), and 2.6% (P = .030) annually, respectively. By contrast, among people with less than 12 years of education, a statistically significant decrease in death rates from 1993 through 2001 was seen only for breast cancer in white women (1.4% per year; P = .029). Death rates among persons with less than 12 years of education over the same time interval increased for lung cancer in white women (2.4% per year; P < .001) and for colon cancer in black men (2.7% per year; P < .001) and were stable for the remaining race/sex/site strata. Temporal trends generally followed an educational gradient in which the slopes of the decreases in death rate became steeper with higher educational attainment.The recent declines in death rates from major cancers in the United States mainly reflect declines in more highly educated individuals.
Acute interstitial pneumonitis induced by carbamazepine
Authors: N Takahashi, H Aizawa, S Takata, K Matsumoto, H Koto, H Inoue, N Hara
Journal: European Respiratory Journal (1993)

A 62 year old man treated with carbamazepine for 3 months developed eczema and acute interstitial pneumonitis. A lymphocyte-stimulation test was reactive to carbamazepine. Withdrawal of the drug resulted in prompt improvement. Only 10 cases of this type of drug-induced lung disease have previously been reported.
Endpiece: A doctor's reputation
Authors: S. G. B. Shaw
Journal: BMJ (1999)

community, good management, newish buildings, and comparatively generous funding.But it's becoming increasingly difficult to satisfy the expectations of patients and politicians.Neither Stranraer nor Dumfries can offer the access to the specialist services that can be expected in the centre of Glasgow, and the citizens and the local politicians have to accept that.There are huge compensations: the level of care for the more ordinary conditions that make up the vast majority of medical practice is probably better and certainly much more personal than in central Glasgow, and the place is so beautiful.I look forward to returning in 10 years, assuming that the NHS still exists and that I'm still alive, sane, and employable-all doubtful assumptions.
Understanding and Promoting Smoking Cessation: Overview and Guidelines for Physician Intervention
Authors: C. Tracy Orleans
Journal: Annual Review of Medicine (1985)

This chapter outlines requirements for quitting smoking successfully, and for effective treatments. It presents practical guidelines for physicians and allied health care providers with specific recommendations for how to motivate and help patients quit “on their own” and how to select more intensive backup treatment if needed. Useful guides, references, and resources are suggested, with recommendations concerning optimal use of nicotine chewing gum.
Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis
Authors: Takashi Wada, Hitoshi Yokoyama, Shao-bo Su, Naofumi Mukaida, Masayuki Iwano, Kazuhiro Dohi, Yuichi Takahashi, Takeshi Sasaki, Kengo Furuichi, Chikako Segawa, Yukimasa Hisada, Satoshi Ohta, Kazuya Takasawa, Ken-ichi Kobayashi, Kouji Matsushima
Journal: Kidney International (1996)
Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation
Authors: Annemiek B. van Spriel, Jeanette H. W. Leusen, Marjolein van Egmond, Henry B. P. M. Dijkman, Karel J. M. Assmann, Tanya N. Mayadas, Jan G. J. van de Winkel
Journal: Blood (2001)

Abstract Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1 (complement receptor type 3, CD11b/CD18) has previously been implicated in receptor cooperation with Fc receptors (FcRs). The role of Mac-1 in FcR-mediated lysis of tumor cells was characterized by studying normal human PMNs, Mac-1–deficient mouse PMNs, and mouse PMNs transgenic for human FcR. All PMNs efficiently phagocytosed Ab-coated particles. However, antibody-dependent cellular cytotoxicity (ADCC) was abrogated in Mac-1−/− PMNs and in human PMNs blocked with anti–Mac-1 monoclonal Ab (mAb). Mac-1−/− PMNs were unable to spread on Ab-opsonized target cells and other Ab-coated surfaces. Confocal laser scanning and electron microscopy revealed a striking difference in immunologic synapse formation between Mac-1−/− and wild-type PMNs. Also, respiratory burst activity could be measured outside membrane-enclosed compartments by using Mac-1−/− PMNs bound to Ab-coated tumor cells, in contrast to wild-type PMNs. In summary, these data document an absolute requirement of Mac-1 for FcR-mediated PMN cytotoxicity toward tumor targets. Mac-1−/− PMNs exhibit defective spreading on Ab-coated targets, impaired formation of immunologic synapses, and absent tumor cytolysis.
Why is our Population of Uninsured and Underinsured Persons Growing? The Consequences of the "Deindustrialization" of America
Authors: C Renner, V Navarro
Journal: Annual Review of Public Health (1989)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of ...Read More
Coroners' verdicts and suicide statistics in England and Wales
Authors: D. Gunnell, K. Hawton, N. Kapur
Journal: BMJ (2011)

Increasing use of narrative verdicts raises serious concerns

Suicide is the most tragic consequence of mental illness, and it accounted for 4648 deaths in England and Wales in 2009.1 Reliable suicide statistics are essential to inform and evaluate suicide prevention strategies,2 highlight changes in rates (perhaps as a result of changing socioeconomic conditions), and detect emergence of new methods of suicide.3

Suicide statistics in England and Wales are derived from death certificates issued after coroners’ inquests into unnatural or unexpected deaths. Around 30 000 such inquests are held each year, and coroners usually give a “short form” verdict for the cause of death—the most commonly recorded verdicts are accident, natural causes, suicide, industrial disease, and “open.”4 Most deaths given open verdicts are likely to be suicides.5 However, the legal requirements for identifying suicide (beyond reasonable doubt) differ from the less stringent criteria used by health professionals.6 Furthermore, some coroners may give open or accidental verdicts in the belief that this avoids adding to a family’s distress.7 For these reasons official suicide statistics produced by the Office for National Statistics (ONS) combine suicide and open verdict deaths.8

Suicide statistics have long been recognised as imperfect.9 Suicides may be especially difficult to identify when methods such as drowning and overdose are used and intent is unclear.10 Suicide rates are therefore likely to be underestimated, but recent research by the ONS signals a new and growing problem with the accuracy of national data.11

Since 2001 a growing number of coroners have summarised their inquest findings with a “narrative verdict”—which records, in several sentences, how, and in what circumstances, the death occurred—rather than giving a short form verdict. The numbers of narrative verdicts …
Analysis of the Relationship Between the Pro12Ala Variant in the PPAR-γ2 Gene and the Response Rate to Therapy With Pioglitazone in Patients With Type 2 Diabetes
Authors: Matthias Blüher, Georg Lübben, Ralf Paschke
Journal: Diabetes Care (2003)

OBJECTIVE—To investigate the influence of peroxisome proliferator-activated receptor-γ (PPAR-γ) gene variants on the response rate to therapy with the thiazolidinedione (TZD) pioglitazone, because in vitro studies have suggested that genetic variants of the PPAR-γ gene may influence the drug efficacy of TZD. RESEARCH DESIGN AND METHODS—A total of 131 patients were treated in an open-label, randomized, multicenter study with pioglitazone (45 mg o.d.) during a course of ≥26 weeks. Response to the pioglitazone therapy was defined by either a &amp;gt;20% decrease in fasting plasma glucose or a &amp;gt;15% decrease in HbA1c values after 26 weeks of pioglitazone treatment. We evaluated the association between the PPAR-γ genotype and the response rate to pioglitazone treatment. RESULTS—The Pro12Ala and the Pro12Pro variants in the PPAR-γ gene are not associated with the response rate to pioglitazone treatment in patients with type 2 diabetes. However, we identified initial fasting plasma glucose level &amp;gt;11.0 mmol/l, HbA1c value &amp;gt;9.0%, BMI &amp;gt;32 kg/m2, and fasting C-peptide concentrations at baseline &amp;gt;2.5 pmol/l as predominant confounding factors for the responder frequency to pioglitazone treatment. CONCLUSIONS—The Pro12Ala variant in the PPAR-γ gene does not affect the therapy efficacy of pioglitazone, suggesting that the drug-treatment response is independent from pharmacogenetic effects between PPAR-γ and its ligand pioglitazone. Whether the Ala12Ala genotype plays a role in the response rate to TZD therapy remains to be determined.
Real time polyp diagnosis: where do we go from here?
Authors: Heiko Pohl
Journal: Gut (2013)

Gastroenterology is in many ways a technology-driven field. One might expect rapid gains and advancements; however, incorporation of new technology is not easy for many reasons. Most importantly this is medicine. It is not about the best gadget that will boost the bottom line. We need to do right by our patients and their health. We need proof that a new technology works and that it can be implemented effectively and safely.

The approach to small polyps is a good example of how difficult it is to advance the field through technology. We have developed better imaging techniques—narrow band imaging (NBI), Fujinon intelligence chromoendoscopy, iScan and others—with the promise to predict polyp histology real time.1 ,2 Especially for diminutive polyps, real time diagnosis may improve efficiency, lower cost and improve patient safety.3–5

But what is really needed to bring real time polyp diagnosis into clinical practice? The American Society of Gastrointestinal Endoscopy led Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) initiative has provided a roadmap and suggested thresholds that need to be met before incorporating two changes to our clinical practice of polyp resection:2 

1.  Confidently diagnosed diminutive polyps can be resected and discarded if the recommended surveillance interval that is based on real time diagnosis agrees with the surveillance interval based on the pathology in at least 90% of patients.

2.  Confidently diagnosed diminutive hyperplastic …
Erythrophagocytosis in vivo in sickle cell anemia
Authors: Dilip L. Solanki
Journal: American Journal of Hematology (1985)

Recent observations that the sickle RBC are excessively susceptible to phagocytosis by macrophages in vitro prompted me to look for evidence of in vivo erythrophagocytosis (Ep) in patients with sickle cell anemia (SS). Freshly prepared smears of unmanipulated blood of 27 patients with SS in steady state were examined for Ep by a 500-cell differential white blood cell (WBC) count performed in duplicate. Ten of 27 (37%) SS patients showed Ep (1-6/1,000 WBC or 1-10/100 monocytes). By contrast, no Ep was found in similarly prepared blood smears of 25 normal adult controls and nine splenectomized subjects. The mean hemotocrit value of the Ep(+) SS patients was significantly lower than that of the Ep(-) patients (21.0 +/- 1.7% vs 24.0 +/- 2.7% p less than 0.01). Considering the rarity of spontaneous Ep in unmanipulated blood from normal subjects and the relative insensitivity of the method used, the finding of Ep in over one third of SS patients indicates a significant membrane injury of the sickle RBC and serves to validate the in vitro observations. The possible role of the "senescence" mechanism in the induction of Ep is discussed.
WHITE CELL MORPHOLOGY IN RABBITS WITH INDUCED PERITONEAL EXUDATES
Authors: Eric Ponder, John MacLeod
Journal: The Journal of Experimental Medicine (1938)

1. When peritoneal exudates are produced in the rabbit by the injection of a large volume of isotonic saline, nearly all the cells in the exudate are polymorphonuclear leucocytes, and the number contained in a single exudate may exceed the entire number originally present in the circulation. 2. The migration of polymorphonuclear leucocytes from the blood stream into the exudate is followed by a stimulation of the marrow, so that the blood stream is filled with young cells, many of which also pass into the exudate. This marrow stimulation, with the resultant shift of the polynuclear count to the left, is probably produced by the absorption of breakdown products of the cells which first appear in the exudate. 3. If exudates are produced repeatedly at intervals of from 4 to 10 days, the marrow responds by throwing younger and younger cells into the circulation, so that the blood stream becomes full of very young polymorphonuclear leucocytes of class I, or even metamyelocytes. If 4 or 5 exudates are produced in rapid succession, the polymorphonuclear leucocytes in the circulation are all replaced by metamyelocytes and myelocytes.
Interacting Effects of Sulfonylureas and Glucose on Cyclic AMP Metabolism and Insulin Release in Pancreatic Islets of the Rat
Authors: V. Grill, E. Cerasi
Journal: Journal of Clinical Investigation (1978)

The effects of tolbutamide and glibenclamide on the metabolism of cyclic AMP were investigated in pancreatic islets of the rat. Changes in cyclic AMP were assessed by measuring [(3)H]cyclic AMP after labeling of the islets with [2-(3)H]adenine. In the presence of a nonstimulatory concentration of glucose (3.3 mM), both sulfonylureas caused a rapid increase in islet [(3)H]cyclic AMP, which declined within 5 (tolbutamide) or 10 min (glibenclamide). In the absence of glucose, the glibenclamide effect was shortened, but the initial (1 min) response of [(3)H]-cyclic AMP was unaffected. Glucose could be substituted with d-glyceraldehyde but not pyruvate for prolongation of the glibenclamide response. The effect of glucose withdrawal on the glibenclamide response was reproduced by the addition of d-mannoheptulose to glucose containing media. The [(3)H]cyclic AMP response to glibenclamide was influenced by prior exposure of the islets to glucose, a 30-min preincubation with 27.7 mM glucose, enhancing the response to the sulfonylurea over a subsequent 5-min stimulation period. Sulfonylureas exerted their effects at low but not at high glucose concentrations, i.e., shifted the glucose dose-response curve to the left both for [(3)H]cyclic AMP accumulation and insulin release. On the other hand, increasing concentrations of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, progressively augmented the effects of the drugs. Omission of Ca(++) from the incubation media inhibited both the glucose and the sulfonylurea [(3)H]-cyclic AMP and insulin responses. Epinephrine (1 muM) partially inhibited the [(3)H]cyclic AMP response to both glucose and sulfonylurea, whereas insulin release was completely abolished. It is concluded that the sulfonylurea effects on islet cyclic AMP are intimately related to those of glucose. It is suggested that sulfonylureas exert a major part of their action by facilitating the effect of glucose on the beta-cell adenylate cyclase; the increased cyclic AMP level, in its turn, enhances the secretion rate of insulin.
Tumor Suppressor Function of the Plasma Glutathione Peroxidase Gpx3 in Colitis-Associated Carcinoma
Authors: Caitlyn W. Barrett, Wei Ning, Xi Chen, Jesse Joshua Smith, Mary K. Washington, Kristina E. Hill, Lori A. Coburn, Richard M. Peek, Rupesh Chaturvedi, Keith T. Wilson, Raymond F. Burk, Christopher S. Williams
Journal: Cancer Research (2012)

Abstract The glutathione peroxidases, a family of selenocysteine-containing redox enzymes, play pivotal roles in balancing the signaling, immunomodulatory, and deleterious effects of reactive oxygen species (ROS). The glutathione peroxidase GPX3 is the only extracellular member of this family, suggesting it may defend cells against ROS in the extracellular environment. Notably, GPX3 hypermethylation and underexpression occur commonly in prostate, gastric, cervical, thyroid, and colon cancers. We took a reverse genetics approach to investigate whether GPX3 would augment inflammatory colonic tumorigenesis, a process characterized by oxidative stress and inflammation, comparing Gpx3−/− mice in an established two-stage model of inflammatory colon carcinogenesis. Gpx3-deficient mice exhibited an increased tumor number, though not size, along with a higher degree of dysplasia. In addition, they exhibited increased inflammation with redistribution toward protumorigenic M2 macrophage subsets, increased proliferation, hyperactive WNT signaling, and increased DNA damage. To determine the impact of acute gene loss in an established colon cancer line, we silenced GPX3 in human Caco2 cells, resulting in increased ROS production, DNA damage and apoptosis in response to oxidative stress, combined with decreased contact-independent growth. Taken together, our results suggested an immunomodulatory role for GPX3 that limits the development of colitis-associated carcinoma. Cancer Res; 73(3); 1245–55. ©2012 AACR.
Gastrointestinal disturbances in marathon runners.
Authors: F A Halvorsen, J Lyng, T Glomsaker, S Ritland
Journal: British Journal of Sports Medicine (1990)

To determine the prevalence of various gastrointestinal disturbances related to long-distance running and its effect on weight, diet and everyday digestive problems, we gave a questionnaire to 279 leisure-time marathon runners, comprising 10% of the participants in a local marathon race. Their answers disclosed a prevalence of dietary changes, weight reduction and altered bowel habits (mainly looser stools and/or more frequent defaecation) of 37, 38 and 48% respectively. A quarter reported earlier long lasting gastrointestinal problems, which improved in 41% of the runners after they started regular training. Thirty-four percent experienced gastrointestinal disturbances during or after running, 20% to such an extent that it seriously affected their performance.