tbuckley/cabot-search huggingface dataset:
Expression of p16, CD95, CD95L and Helix pomatia agglutinin in relapsing and nonrelapsing very thin melanoma
Authors: L.A. Fearfield, J.M.G. Larkin, A. Rowe, R. A'Hern, C. Fisher, N. Francis, R. MacKie, B. McCann, M.E. Gore, C.B. Bunker
Journal: British Journal of Dermatology (2006)

The incidence of malignant melanoma is increasing worldwide and patients are being diagnosed earlier with thinner primary lesions. Most patients with very thin melanoma (Breslow thickness < 0.76 mm) are cured by surgery but 2-18% relapse locally or with distant metastases.The objective of this study was to establish potential new prognostic markers in very thin melanoma.We identified a group of subjects with relapsing very thin primary cutaneous melanoma and a matched control group who had not relapsed. We investigated the expression of p16, Helix pomatia agglutinin (HPA), CD95 and CD95 ligand (CD95L) by immunohistochemistry on paraffin-embedded tissue sections from the subject group, their subsequent metastases and the control group.Reduced p16 expression was significantly associated with relapse in very thin melanoma (P = 0.0129). Loss of p16 expression was also found in 76% of metastases. There was no significant association between HPA, CD95 or CD95L expression and subsequent relapse.This work is the first to show a significant loss of p16 in relapsing very thin melanoma.
Why do house jobs always start on the same day?
Authors: R C King
Journal: BMJ (1989)

three patients who required vitrectomy in the past 12 months were from this district (which has a population of 400 000).Sufficient treatment is hard to define but includes assessment of location, size, and number of effective burns; the counter on the laser photocoagulator is not a good guide.Never- theless, patients often need more than the 2000 burns that Dr Richardson and his colleagues regard as being indisputably adequate, and even as many as 13000 burns have been necessary and effective on occasion.2Although it is gratifying to have the technology to salvage some vision in patients with late complications of diabetic retinopathy, how much better it would be to prevent these complications in the first place.Screening for sight threatening diabetic retinopathy followed by timely, adequate photo- coagulation is effective in minimising blindness; vitrectomy should become a rare sign of failure of this service.Diabetes is the commonest cause of registrable blindness in people of working age.Provision of screening and photocoagulation services for diabetic retinopathy must merit a high priority in every district.
National Health Service Corps and Primary Care Training
Authors: Philip Pollner
Journal: JAMA (1974)

The National Health Service Corps (NHSC), established by passage of the Emergency Health Personnel Act of 1970, was set up to provide for the redistribution of medical personnel to communities with critical health manpower shortages. Three years later, only 4% of the 5,000 "underserved" areas have received physicians; dentists and allied personnel are still missing. Further inadequacies of the Corps are demonstrated by the substantial decline in physical applicants paralleling the end of the doctor draft and Vietnam War. To reawaken physician interest, the NHSC seeks new financial benefits to replace the defunct military fulfillment incentive. Such artificial benefits have previously proven inadequate as incentives for effecting enlistment in underserved areas. Furthermore, most physicians will no longer be available for service commitments during training because of the continuity established by the combined internship-residency. Instead we propose that establishment of a working relationship between primary care training programs and NHSC has substantive value in solving problems plaguing both groups, as well as helping to improve physician distribution nationally. (<i>JAMA</i>228:1405-1407, 1974).
396 EPIDEMIOLOGY OF HCV AND HBV IN THE GENERAL POPULATION: A SURVEY IN A SOUTHERN ITALIAN TOWN
Authors: R. Cozzolongo, A.R. Osella, S. Elba, J. Petruzzi, G. Buongiorno, V. Giannuzzi, G. Leone, C. Bonfiglio, E. Lanzilotta, O.G. Manghisi, G. Leandro
Journal: Journal of Hepatology (2009)
Abstract 3460: Liver-type Fatty Acid-binding Protein Is A Promising Predictive Marker Of Contrast-induced Nephropathy
Authors: Kenichi Manabe, Hiroshi Kamihata, Takeshi Senoo, Susumu Yoshida, Takao Sakuma, Tsuyoshi Isono, Satoshi Yamamoto, Yoshiji Iharada, Masayuki Motohiro, Takeshi Sugaya, Toshiji Iwasaka
Journal: Circulation (2007)

Contrast-induced nephropathy (CIN), a well-known complication of contrast media exposure for the patients with chronic kidney disease (CKD), may results from acute tubular necrosis. Although 4 to 11 percent with mild to moderate renal insufficiency develop CIN, there were no biological markers to more accurately predict the occurrence of CIN than the existing makers such as serum creatinine (sCr). Liver-type fatty acid-binding protein (L-FABP) as a novel maker, is an intracellular carrier protein of free fatty acids that marked upregulated and expressed abundantly in proximal tubules after renal ischemia.We prospectively investigated whether urinary L-FABP is an alternative maker of predicting CIN. Methods: We enrolled sixty-five patients (46 male, 71.8 ± 8.2years) undergoing scheduled coronary angiography who had mild kidney disease with CKD stage3 (glomelurar filtration ratio (GFR) &lt;60 ml/1.73 m 2 or albuminuria (u-Alb)≥ 300 mg/gCRE), treated with one-half isotonic (0.45 percent) saline between 12 hours before and after the procedure. We measured urinary L-FABP, u-Alb,β 2 -microglobulin, α 1 -microglobulin, sCr and NAG( N -acetyl-β-d-glucosaminidase). CIN was defined as an increase of sCr of &gt;25% or 0.5 mg/dl (44.2micromol/l) within 2 days of contrast. The cohort was divided into two groups according to occurrence of CIN; CIN-G and nonCIN-G. Results: CIN occurred in 4 of 65 patients (6%). Demographics, the pre-procedural level of makers (β 2 -microglobulin, α 1 -microglobulin, sCr, NAG) and used contrast volume are no significant differences between the two groups. Pre-procedural urinary L-FABP levels were significantly greater in CIN-G than in nonCIN-G(112.5 ± 81.4μg/g Cr;19.7 ± 43μg/g Cr; P&lt; 0.01) as well as u-Alb (CIN-G;1711.3 31386.6 mg/gCRE nonCIN-G; 192.3 3482.3 mg/gCRE Cr; P &lt; 0.01). On the basis of ROC curve of urinary parameters , u-Alb and urinary L-FABP had the significantly high predictive value than other markers(p&lt;0.05). Conclusion: Urinary L-FABP combined with u-Alb can be more accurate markers to predict the risk of CIN than other existing urinary parameters.
Superiority of Nitrate-Enhanced <sup>201</sup> Tl Over Conventional Redistribution <sup>201</sup> Tl Imaging for Prognostic Evaluation After Myocardial Infarction and Thrombolysis
Authors: Sumit Basu, Roxy Senior, Usha Raval, Avijit Lahiri
Journal: Circulation (1997)

Background 201 Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201 Tl imaging, such as reinjection and nitrate-enhanced rest 201 Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. Methods and Results We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201 Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P =NS). Nitrate-enhanced rest 201 Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P &lt;.001). Conclusions Thus, after myocardial infarction and thrombolysis, even “stable” patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.
Distribution of myocardial blood flow before and after coronary artery ligation in the baboon. Relation to early ventricular fibrillation
Authors: W. F. LUBBE, M. PEISACH, R. PRETORIUS, K. J. J. BRUYNEEL, L. H. OPIE
Journal: Cardiovascular Research (1974)

Journal Article Distribution of myocardial blood flow before and after coronary artery ligation in the baboon. Relation to early ventricular fibrillation Get access W. F. LUBBE, W. F. LUBBE 2 2Ischaemic Heart Disease Laboratory, Department of Medicine, Groote Schuur Hospital and the University of Cape Town, Cape Town, Republic of South Africa. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. PEISACH, M. PEISACH Search for other works by this author on: Oxford Academic PubMed Google Scholar R. PRETORIUS, R. PRETORIUS Search for other works by this author on: Oxford Academic PubMed Google Scholar K. J. J. BRUYNEEL, K. J. J. BRUYNEEL 2 2Ischaemic Heart Disease Laboratory, Department of Medicine, Groote Schuur Hospital and the University of Cape Town, Cape Town, Republic of South Africa. Search for other works by this author on: Oxford Academic PubMed Google Scholar L. H. OPIE L. H. OPIE 2 2Ischaemic Heart Disease Laboratory, Department of Medicine, Groote Schuur Hospital and the University of Cape Town, Cape Town, Republic of South Africa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 4, July 1974, Pages 478–487, https://doi.org/10.1093/cvr/8.4.478 Published: 01 July 1974
CD4 antibody treatment in patients with active Crohn's disease: a phase 1 dose finding study.
Authors: A Stronkhorst, S Radema, S L Yong, H Bijl, I J ten Berge, G N Tytgat, S J van Deventer
Journal: Gut (1997)

T cells play an important part in Crohn's disease. Immunomodulating therapies that target T cell activation may have clinical effects in Crohn's disease.To investigate the toxicity and potential efficacy of anti-CD4 monoclonal antibody therapy in patients with Crohn's disease.A dose escalating pilot study was conducted in three groups of four patients with intractable Crohn's disease, refractory to steroids. They received 70, 210, or 700 mg of cM-T412, a depleting anti-CD4 monoclonal antibody (mAb).The mean reduction in Crohn's disease activity index (CDAI) was respectively 25%, 24%, and 36% at four weeks, and 24% and 52% at 10 weeks in the 210 mg and 700 mg groups. There was only a minor effect on endoscopically evaluated disease activity. Side effects were mild to moderate fever with chills and headache. No signs of opportunistic infection were seen. There was a sustained decrease in CD4 count which lasted at least four weeks in the 70 mg group (76.3 (SD 40.6)% of the baseline value), and 10 weeks in both the 210 mg group (80.8 (SD 60.9)%) and the 700 mg group (24.8 (SD 15.4)%). The primary and secondary humoral immune response was not influenced by anti-CD4 mAb treatment.This study shows the moderate potential efficacy of treatment of patients with Crohn's disease using a depleting chimeric monoclonal anti-CD4 antibody.
Metformin in chronic hepatitis C virus hepatitis: Caution needed with sex-based subgroup analysis
Authors: Diego Geroldi, Enzo Emanuele
Journal: Hepatology (2009)

We read with great interest the study by Romero-Gómez et al.1 demonstrating that the combination of metformin, peginterferon alfa-2, and ribavirin improved insulin resistance in >50% of patients and increased sustained virological response (SVR) rate in 10% of patients with hepatitis C genotype 1 and homeostasis model assessment (HOMA) >2. Intriguingly, in female participants, the addition of metformin to the standard of care for chronic HCV infection doubled the SVR rate.1 Since 1994, the U.S. National Institutes of Health requires that at least half of all clinical trial participants enrolled are females,2 and increasing interest in women's health and sex-specific outcomes have led to the increase in subgroup analyses stratified by sex. However, improperly conducted sex-based subgroup analysis in clinical trials can yield incorrect conclusions that may result in adverse effects on women's health. It has been therefore suggested that: (1) sex-based subgroup analysis should be planned a priori to the study commencement; (2) hypothesis or rationale for the analysis should be provided; (3) a statistical tests for interaction with sex should be performed when analyzing the outcomes; and (4) the overall treatment results should be emphasized more than the findings of the sex-based subgroup analysis.3 The study by Romero-Gómez et al.1 clearly had not planned the sex-based subgroup analysis a priori because the authors did not mention any adjustment by sex in the Methods section of the article. In addition, there is no clear hypothesis or rationale for a sex-based subgroup analysis in the Introduction or Methods section. The Methods and Results sections were searched for information regarding a statistical test for interaction between sex and the SVR, but no mention was found. In contrast, the authors properly placed equal emphasis on sex-based subgroup results as they did with the overall trial results. Given the frequency with which subgroup analyses by sex are now being performed, it is paramount that investigators should caution the scientific community in their interpretation. Discussion of the sex-specific effects of metformin in chronic HCV infection should be considered proper only when sex-specific analysis are viewed as hypothesis-generating, and further research to confirm these observations is recommended. Diego Geroldi*, Enzo Emanuele , * Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy, Department of Health Sciences, University of Pavia, Pavia, Italy.
Privatisation of water is high on Kyoto summit agenda
Authors: P. Brown
Journal: BMJ (2003)

Arguments over who should govern and finance water services are expected to top the agenda at the third meeting of the world water forum, which was held in Kyoto, Japan, this week.

The United Nations has warned that political inertia over water management is deepening a crisis caused by dwindling supplies, while demand is soaring at an “unsustainable” rate. The impact of water shortages will be greatest for the poorest nations, whose food supplies and health are directly threatened.

According to a UN report released before the conference, one billion people currently lack access to …
New perspective on targeting the tumor suppressor p53 pathway in the tumor microenvironment to enhance the efficacy of immunotherapy
Authors: Gang Guo, Yan Cui
Journal: Journal for ImmunoTherapy of Cancer (2015)

About 50% of human cancers harbor somatic mutations of the tumor suppressor p53 (p53 or Trp53) gene. Many of those mutations result in the inactivation of the p53 pathway and are often associated with the stabilization and accumulation of mutant p53 proteins. Therefore, increased p53 expression in tumors is frequently used as a surrogate marker for p53 mutation and inactivation. Moreover, this elevated p53 expression also makes it an ideal tumor associated antigen (TAA) for cancer vaccines. Recent advances in our understanding of p53 as a crucial transcription factor reveal that p53 is an important sensor of cellular stress under genotoxic, chemotoxic, pathological, and even normal physiological conditions. Experimental and clinical observations by our laboratory and others have demonstrated that p53 also participates in immune regulation as p53 dysfunction skews host immune responses towards pro-inflammation, which further promotes tumor progression. Furthermore, recent studies using a genetic approach revealed that p53-restoration or re-activation led to tumor regression and clearance, which were at least partially caused by the activation of innate antitumor immunity. Since many of the currently used cancer therapeutics, including radiotherapy and chemotherapy, disrupt tumor growth by inducing DNA damage via genotoxic or chemotoxic stress, which activates the p53 pathway in the tumor microenvironment, we postulate that some of those observed therapeutic benefits might also be partially mediated through their immune stimulatory effects. Here, we briefly review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and, subsequently, extend our discussion to the immunostimulatory potential of existing and new approaches of targeting the p53-pathway to alter the immunological landscape of tumors for maximizing immunotherapy outcome.
On linezolid efficacy and tolerability
Authors: S. De Lorenzo, R. Centis, L. D'Ambrosio, G. Sotgiu, G. B. Migliori
Journal: European Respiratory Journal (2012)

assays of PBMCs and CSF-MCs are useful adjuncts to current tests for diagnosing TBM.The PBMC ELISPOT assay combined with CSF ADA is a useful rapid rule-out test and the CSF-MC/PBMC ELISPOT ratio is an accurate rule-in test.
Herpes Zoster and Multiple Sclerosis
Authors: J. A. R. Lenman, T. J. Peters
Journal: BMJ (1969)

No significant difference was found between 50 consecutive patients with multiple sclerosis and matched controls in respect of previous infection with rubella or measles and chicken-pox, or of previous vaccination and immunizing injections. Significantly more patients had a past history of herpes zoster compared with the controls.
Qa-1b Binds Conserved Class I Leader Peptides Derived from Several Mammalian Species
Authors: Zoran Kurepa, Charles A. Hasemann, James Forman
Journal: The Journal of Experimental Medicine (1998)

Qa-1b binds a peptide (AMAPRTLLL), referred to as Qdm (for Qa-1 determinant modifier), derived from the signal sequence of murine class Ia molecules. This peptide binds with high affinity and accounts for almost all of the peptides associated with this molecule. Human histocompatibility leukocyte antigen (HLA)-E, a homologue of Qa-1b, binds similar peptides derived from human class Ia molecules and interacts with CD94/NKG2 receptors on natural killer cells. We used surface plasmon resonance to determine the ability of Qa-1b to bind related ligands representing peptides derived from the leaders of class I molecules from several mammalian species. All of the peptides reported to bind HLA-E bound readily to Qa-1b. In addition, peptides derived from leader segments of different mammals also bound to Qa-1b, indicating a conservation of this “Qdm-like” epitope throughout mammalian evolution. We have attempted to define a minimal peptide on a polyglycine backbone that binds Qa-1b. Our previous findings showed that P2 and P9 are important but not sufficient for binding to Qa-1b. Although a minimum peptide (GMGGGGLLL) bound Qa-1b, its interaction was relatively weak, as were peptides sharing five or six residues with Qdm, indicating that multiple native residues are required for a strong interaction. This finding is consistent with the observation that this molecule preferentially binds this single ligand.
Prognostic Utility of HOXB13:IL17BR and Molecular Grade Index for Node-Negative Breast Cancer Patients.
Authors: L. Habel, M. Erlander, N. Achacoso, X. Ma, D. Sgroi, L. Fehrenbacher, D. Greenberg, C. Quesenberry
Journal: Cancer Research (2009)

Abstract Background: Four studies have reported that a two-gene ratio (HOXB13:IL17BR) may be prognostic and/or predictive of tamoxifen benefit among early stage breast cancer patients. More recently, a 5-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) was reported to predict clinical outcome. We evaluated the performance of these two gene signatures among an independent population of lymph node-negative breast cancer patients from a community hospital setting.Methods: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985-94 and not treated with adjuvant chemotherapy (Habel, 2006). Archived tumor tissues were available on 169 cases (breast cancer deaths) and 335 matched controls and, using RT-PCR, were analyzed for expression levels of the above 7 cancer-related genes and 4 reference genes. Logistic regression methods were used to estimate the 10-year risk and the relative risk (RR) of breast cancer death associated with pre-specified risk categories based on cross-classification of HOXB13:IL17BR and MGI scores.Results: Approximately 50% of patients were classified as low risk by the HOXB13:IL17BR+MGI risk classifier. At 10 years, the risks of breast cancer death for ER+, tamoxifen-treated patients were 3.9% (95% confidence interval (CI) 2.2% - 5.5%), 5.6% (95% CI 2.6% - 8.5%), and 15.6% (95% CI 8.7% - 21.9%) for those in the low, intermediate and high risk groups, respectively. They were 5.9% (95% CI 4.2% - 7.5%), 15.2% (95% CI 8.3% - 21.5%), and 16.5% (95% CI 10.4% - 22.2%) for ER+ patients not treated with tamoxifen. After adjusting for tumor size and grade, the RRs of breast cancer death associated with high vs. low HOXB13:IL17BR+MGI risk categories were attenuated but remained elevated in both treatment groups; the RR continued to be statistically significant in tamoxifen treated patients only.Conclusion: In this population of lymph-node negative patients not treated with adjuvant chemotherapy, the HOXB13:IL17BR+MGI risk classifier was predictive of risk of breast cancer death and appeared to provide risk information beyond standard prognostic factors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4034.
Antiphospholipid Antibodies From Antiphospholipid Syndrome Patients Activate Endothelial Cells In Vitro and In Vivo
Authors: Silvia S. Pierangeli, Margaret Colden-Stanfield, Xiaowei Liu, John H. Barker, Gary L. Anderson, E. Nigel Harris
Journal: Circulation (1999)

Background —Antiphospholipid (aPL) antibodies are associated with thrombosis in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. Although aPL antibodies have been shown to inhibit protein C activation and activate endothelial cells (ECs) in vitro, no study has examined whether these antibodies activate ECs in vivo. Therefore, human affinity-purified aPL (ap aPL) antibodies from APS patients were tested in a mouse model of microcirculation using the cremaster muscle that allows direct microscopic examination of thrombus formation and adhesion of white blood cells (WBCs) to ECs as an indication of EC activation in vivo. Adhesion molecule expression on human umbilical vein endothelial cells (HUVECs) after aPL exposure was performed to confirm EC activation in vitro. Methods and Results —All 6 ap aPL antibodies significantly increased the expression of VCAM-1 (2.3- to 4.4-fold), with one of the antibodies also increasing the expression of E-selectin (1.6-fold) on HUVECs in vitro. In the in vivo experiments, each ap aPL antibody except for 1 preparation increased WBC sticking (mean number of WBCs ranged from 22.7 to 50.6) compared with control (14.4), which correlated with enhanced thrombus formation (mean thrombus size ranged from 1098 to 6476 versus 594 μm 2 for control). Conclusions —Activation of ECs by aPL antibodies in vivo may create a prothrombotic state on ECs, which may be the first pathophysiological event of thrombosis in APS.