tbuckley/cabot-search huggingface dataset:
Two loci affecting B cell responses to B cell maturation factors.
Authors: C L Sidman, J D Marshall, W G Beamer, J H Nadeau, E R Unanue
Journal: The Journal of Experimental Medicine (1986)

B lymphocytes from DBA/2Ha mice have a genetic defect characterized by a failure to differentiate into antibody-secreting cells in response to a family of lymphokines termed B cell maturation factors (BMFs). By contrast, B cells from DBA/2Ha mice respond normally in PFC assays to the B cell mitogen LPS, and macrophages from these mice are activated by one of the three BMFs. Two loci are responsible for the B cell defect in DBA/2Ha mice. One locus (Bmfr-1) is constitutively expressed throughout life, and maps approximately 13 cM distal to the brown locus on chromosome 4. A second locus (Bmfr-2) becomes active only after sexual maturity and is closely linked to the dilute locus on chromosome 9. At both loci, alleles determining responsiveness to BMFs are dominant over nonresponder alleles. The effect of Bmfr-2 on B cell responsiveness may be related to levels of the steroid sex hormones. DBA/2Ha mice offer a tool for studying the genetic and hormonal regulation of the immune system.
Randomized Phase II Trial of Erlotinib With and Without Entinostat in Patients With Advanced Non–Small-Cell Lung Cancer Who Progressed on Prior Chemotherapy
Authors: Samir E. Witta, Robert M. Jotte, Katrik Konduri, Marcus A. Neubauer, Alexander I. Spira, Robert L. Ruxer, Marileila Varella-Garcia, Paul A. Bunn, Fred R. Hirsch
Journal: Journal of Clinical Oncology (2012)

Histone deacetylase inhibitors (HDACis) have been shown to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) linked to epigenetic changes and epithelial-mesenchymal transition (EMT) state. This randomized phase II study evaluated the outcome of erlotinib with and without the isoform selective HDACi, entinostat.Previously treated patients with stage IIIB/IV non-small-cell lung cancer, no prior EGFR-TKIs, and performance status ≤ 2 were randomly administered erlotinib 150 mg on days 1 through 28 plus entinostat 10 mg orally on days 1 and 15 every 28 days (EE) or erlotinib plus placebo (EP). The primary end point was 4-month progression-free survival (PFS) rate with additional end points including 6-month PFS rate, PFS, and overall survival (OS). Exploratory analyses included EMT- and EGFR-related biomarker analysis on archival tissue.One hundred thirty-two patients were enrolled (EE, 67; EP, 65). The 4-month PFS rate was comparable for both groups (EE, 18% v EP, 20%; P = .7). In the subset of patients with high E-cadherin levels, OS was longer in the EE group compared with the EP group (9.4 v 5.4 months; hazard ratio, 0.35; 95% CI, 0.13 to 0.92; P = .03) with a corresponding trend toward increased PFS. The adverse event (AE) profile was acceptable, with rash, fatigue, diarrhea, and nausea the most common AEs in both groups.Erlotinib combined with entinostat did not improve the outcomes of patients in the overall study population when compared with erlotinib monotherapy. High E-cadherin expression levels at time of diagnosis indicate an increased sensitivity to HDACi/EGFR-TKI inhibition providing the basis for a biomarker-driven validation study.
Results of transvenous occlusion of secundum atrial septal defects with the fourth generation buttoned device: comparison with first, second and third generation devices
Authors: P.Syamasundar Rao, Felix Berger, Christian Rey, Jorge Haddad, Bernhard Meier, Kevin P Walsh, Jay S Chandar, Thomas R Lloyd, Jose Suarez de Lezo, Rolando Zamora, Eleftherios B Sideris
Journal: Journal of the American College of Cardiology (2000)
Core values: doctor or everyman?
Authors: J. Macnaughtou
Journal: BMJ (1996)

Doctors have recently been grappling with their changing role in society. To this end the first summit meeting of the profession since 1961 was held in November 1994 and a consultation document, Core Values for the Medical Profession in the 21st Century, was produced. This was intended to stimulate debate about the future of medicine but seems to have provoked little comment. Why?

The problem stems from the question that the conference set itself: “What are the core values for the medical profession in the 21st century?” This has encouraged the production of a list of good activities and attributes which might be associated with the practice of medicine but are not inherent to it or defining of it. A better question might have been “What is the good doctor good at?” An example of the vagueness attached to the document's broad central question is the list of basic and ancient virtues, which are given as “commitment, caring, compassion, integrity, competence, spirit of inquiry, confidentiality, responsibility, and advocacy.” These read like a list of good things which, we might hope, would be associated with any upright citizen, not just a member of the medical profession.

Why does the profession so readily adopt the moral high ground, and why, indeed, is it encouraged …
IgA class reticulin antibodies in relatives of patients with coeliac disease.
Authors: E G Mallas, N Williamson, B T Cooper, W T Cooke
Journal: Gut (1977)

IgA class reticulin antibodies were not found in patients with Crohn9s disease, ulcerative colitis, and hiatus hernia despite a significant incidence of IgG class reticulin antibodies. None of 56 normal healthy subjects was positive. In contrast, 13 (76%) of the sera from 17 patients with coeliac disease on normal diet were positive for IgA class antibodies as were 19 (20%) of 93 first degree relatives. Seventy-three relatives underwent jejunal biopsy. Grade III (flat) histology was found in 13 and, of these patients, 10 (77%) showed IgA class reticulin antibody in their serum. It is suggested that determination of IgA class reticulin antibodies was a useful test to determine which relative must be biopsied.
The role of circadian rhythmicity in reproduction
Authors: David J. Kennaway
Journal: Human Reproduction Update (2004)

Circadian rhythmicity is evident in a wide range of physiological systems including the reproductive axis. The recent discoveries of rhythmic clock gene expression in peripheral tissues, including reproductive tissue, suggests that they may play an important role in optimizing fertility. The evidence for rhythmic control of reproduction from studies in laboratory animals is reviewed and where possible this includes evidence from human studies. Clock genes are highly conserved across species including humans and there is no reason to suggest that they are functionless in humans. The challenge issued here is for researchers to probe their function and the consequences of their disruption in both animal and human reproduction.
Improved survival after orthotopic liver grafting.
Authors: R Y Calne, R Williams, M Lindop, J V Farman, M E Tolley, K Rolles, B MacDougall, J Neuberger, R J Wyke, A T Raftery, T J Duffy, D G Wight, D J White
Journal: BMJ (1981)

A total of 108 orthotopic liver transplants have been carried out in the Cambridge/King9s College Hospital series. Over 13 years, changes in patient selection, immunosuppression, and surgical and anaesthetic techniques have led to a steady improvement in results. Results obtained in the last 22 patients indicated that over half survive for one year. Although at considerable risk during the operation, patients with non-malignant cirrhotic diseases who survive one year have a good long-term chance of survival
Nailfold capillaroscopy for day-to-day clinical use: construction of a simple scoring modality as a clinical prognostic index for digital trophic lesions
Authors: V. Smith, F. De Keyser, C. Pizzorni, J. T. Van Praet, S. Decuman, A. Sulli, E. Deschepper, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> Construction of a simple nailfold videocapillaroscopic (NVC) scoring modality as a prognostic index for digital trophic lesions for day-to-day clinical use. <h3>Methods</h3> An association with a single simple (semi)-quantitatively scored NVC parameter, mean score of capillary loss, was explored in 71 consecutive patients with systemic sclerosis (SSc), and reliable reduction in the number of investigated fields (F32–F16–F8–F4). The cut-off value of the prognostic index (mean score of capillary loss calculated over a reduced number of fields) for present/future digital trophic lesions was selected by receiver operating curve (ROC) analysis. <h3>Results</h3> Reduction in the number of fields for mean score of capillary loss was reliable from F32 to F8 (intraclass correlation coefficient of F16/F32: 0.97; F8/F32: 0.90). Based on ROC analysis, a prognostic index (mean score of capillary loss as calculated over F8) with a cut-off value of 1.67 is proposed. This value has a sensitivity of 72.22/70.00, specificity of 70.59/69.77, positive likelihood ratio of 2.46/2.32 and a negative likelihood ratio of 0.39/0.43 for present/future digital trophic lesions. <h3>Conclusions</h3> A simple prognostic index for digital trophic lesions for daily use in SSc clinics is proposed, limited to the mean score of capillary loss as calculated over eight fields (8 fingers, 1 field per finger).
Recombinant human erythropoietin in the treatment of chemotherapy-induced anemia and prevention of transfusion requirement associated with solid tumors: A randomized, controlled study
Authors: C. Oberhoff, B. Neri, D. Amadori, K.U. Petry, T. Gamucci, U. Rebmann, M.R. Nowrousian, R. Voigtmann, S. Monfardini, J.P. Armand, R. Herrmann, J. Netter-Pinon, N. Tubiana-Mathieu, H. Zwierzina
Journal: Annals of Oncology (1998)
Biomarkers in hidradenitis suppurativa
Authors: G.B.E. Jemec
Journal: British Journal of Dermatology (2013)

ORIGINAL ARTICLE, p 1252 Only the study of monocausal lethal diseases does not require quantitative outcomes. In the complex multicausal continuous world of nonlethal disease, quantification is key to accelerated development as has been shown in rheumatology. Within a short time span, rheumatology has transformed itself into a modern speciality more akin to applied immunology, by developing clear measures of disease severity. In spite of the immediate visibility and easy access to skin compared with joints, dermatology appears to be lagging behind rheumatology in this aspect. For nonlethal diseases, disease quantification is a prerequisite for evidence‐based medicine, for studies of pathogenesis and risk factors. Because the skin represents our interface with the ever‐changing environment, this holds particularly true for dermatology. Hidradenitis suppurativa (HS) is attracting increasing attention in the academic community. It causes significant morbidity, it is a common disease, it is difficult to treat and many important discoveries remain to be made. Accurate disease quantification would be a significant help in the process. It is therefore highly welcome that Wieland and co‐workers have studied the possible role of myeloid marker S100A8/A9 and lymphocyte marker soluble interleukin (IL)‐2 receptor as possible biomarkers in HS.1
E2F1 in Melanoma Progression and Metastasis
Authors: Vijay Alla, David Engelmann, Annett Niemetz, Jens Pahnke, Anke Schmidt, Manfred Kunz, Stephan Emmrich, Marc Steder, Dirk Koczan, Brigitte M. Pützer
Journal: JNCI Journal of the National Cancer Institute (2009)

Metastases are responsible for cancer deaths, but the molecular alterations leading to tumor progression are unclear. Overexpression of the E2F1 transcription factor is common in high-grade tumors that are associated with poor patient survival. To investigate the association of enhanced E2F1 activity with aggressive phenotype, we performed a gene-specific silencing approach in a metastatic melanoma model. Knockdown of endogenous E2F1 via E2F1 small hairpin RNA (shRNA) expression increased E-cadherin expression of metastatic SK-Mel-147 melanoma cells and reduced their invasive potential but not their proliferative activity. Although growth rates of SK-Mel-147 and SK-Mel-103 xenograft tumors expressing E2F1 shRNA or control shRNA were similar, mice implanted with cells expressing E2F1 shRNA had a smaller area of metastases per lung than control mice (n = 3 mice per group; 5% vs 46%, difference = 41%, 95% confidence interval = 15% to 67%; P = .01; one-way analysis of variance). We identified epidermal growth factor receptor as a direct target of E2F1 and demonstrated that inhibition of receptor signaling abrogates E2F1-induced invasiveness, emphasizing the importance of the E2F1-epidermal growth factor receptor interaction as a driving force in melanoma progression that may serve as a paradigm for E2F1-induced metastasis in other human cancers.
Meiotic Recombination Strongly Influences GC-Content Evolution in Short Regions in the Mouse Genome
Authors: Yves Clément, Peter F. Arndt
Journal: Molecular Biology and Evolution (2013)

Meiotic recombination is known to influence GC-content evolution in large regions of mammalian genomes by favoring the fixation of G and C alleles and increasing the rate of A/T to G/C substitutions. This process is known as GC-biased gene conversion (gBGC). Until recently, genome-wide measures of fine-scale recombination activity were unavailable in mice. Additionally, comparative studies focusing on mouse were limited as the closest organism with its genome fully sequenced was rat. Here, we make use of the recent mapping of double strand breaks (DSBs), the first step of meiotic recombination, in the mouse genome and of the sequencing of mouse closely related subspecies to analyze the fine-scale evolutionary signature of meiotic recombination on GC-content evolution in recombination hotspots, short regions that undergo extreme rates of recombination. We measure substitution rates around DSB hotspots and observe that gBGC is affecting a very short region (∼1 kbp) in length around these hotspots. Furthermore, we can infer that the locations of hotspots evolved rapidly during mouse evolution.
Time to Shift the Focus of the War: It Is Not All About the Enemy
Authors: John L. Marshall
Journal: Journal of Clinical Oncology (2008)

Since the war on cancer was declared in 1971 by Richard Nixon, we have made significant strides in the treatment of cancer. As in traditional wars, our primary strategy has been to understand and control the behavior of the tumor—or the enemy—itself. We began by using simple histopathology as a means to distinguish one cancer type from another. In this way, we have distinguished tumors on the basis of differentiation, invasiveness, signet rings, large cells, small cells, clear cytoplasm, no cytoplasm, necrosis, mitosis, lymph nodes positive, and lymph nodes negative. Histopathology has proved extremely useful in determining prognosis, but rarely has it taught us anything about treatment choices. More recently, we have shifted our focus to the molecular analysis of tumors at both protein and genetic levels. The molecular profile of tumors has provided us with an improved prognostic ability, but more importantly, it has provided us with more refined, targeted therapies. As the best example, no physician would attempt to fight a battle against breast cancer without knowing the hormone receptor and human epidermal growth factor receptor2statusoftheenemy:thepatient’stumor.Asweuncovernew
The Etiology of Gastric Cancer&lt;subtitle&gt;Intragastric Nitrosamide Formation and Other Theories&lt;/subtitle&gt;
Authors: Sidney S. Mirvish
Journal: JNCI Journal of the National Cancer Institute (1983)

Possible etiologic agents for human gastric cancer (GC) are reviewed, especially nitrosamides that might be produced intragastrically from nitrite. The metabolism of nitrite and nitrate is surveyed, including the correlation between nitrate intake and GC mortality in 12 countries. The negative correlation between GC incidence and fresh fruit and vegetable intake is examined; this correlation may be due to inhibition of nitrosamide formation by ascorbate and polyphenols. GC-associated foods are listed, including dried, salted fish and meat products and fava beans, treatment of which with nitrite yields mutagens and nitroso-methylurea. Also discussed is whether cimetidine treatment produces GC; the association of GC with high-starch diets and highly salted foods; the question of whether nitrosamides are produced and act in the normal or achlorhydric stomach; the falling GC rate in the United States; and the association of GC with soft water, peaty soils, and certain industries and occupations. Practical measures are suggested for reducing GC incidence.
A Case of Fatal Pernicious Anaemia in a Girl Aged 20
Authors: J. B. Ridley
Journal: BMJ (1896)

LMNDICAL JOURAL II 43 ,occurred externally.Therefore in this case, if in any, one would expect to find the placental tissue as vital and un- altered as it could be five months after its function and fcetal circulation ceased.The drawing shows a villus from this
Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity
Authors: Rik H.G. Olde Engberink, Nienke M.G. Rorije, Jaap J. Homan van der Heide, Bert-Jan H. van den Born, Liffert Vogt
Journal: Journal of the American Society of Nephrology (2014)

Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume.
Combinatorial Screenings in Patients
Authors: Amado J. Zurita, Patricia Troncoso, Marina Cardó-Vila, Christopher J. Logothetis, Renata Pasqualini, Wadih Arap
Journal: Cancer Research (2004)

Abstract Direct screening of combinatorial peptide libraries in patients may allow the identification of ligands that target biochemical differences in the endothelium of blood vessels. In a screening performed in a patient, we selected and isolated a mimic motif of interleukin 11 (IL-11) from prostate biopsies after an i.v. administration of a phage display peptide library. We also demonstrated that the IL-11 phage mimic (displaying the cyclic nonapeptide CGRRAGGSC) bound specifically to a corresponding IL-11 receptor (IL-11Rα). Here we show that IL-11Rα is a potential target for intervention in human prostate cancer through morphological and functional analyses. First, a comprehensive serial immunohistochemical analysis of primary and metastatic prostate cancer samples showed increased stage-specific expression of IL-11Rα during disease progression. Second, a proapoptotic peptide was specifically targeted and internalized through this functional IL-11Rα-based ligand-receptor pair: treatment of prostate cancer cells in vitro with a proapoptotic peptide guided by the CGRRAGGSC peptide to the IL-11Rα resulted in dose-dependent apoptosis. Together, these data indicate that the IL-11Rα is a candidate target for translational clinical trials against advanced and metastatic prostate cancer. Moreover, our results illustrate the ability of direct combinatorial screening systems in cancer patients for identification of relevant targets in the context of human disease.
Improving donor lung evaluation: a new approach to increase organ supply for lung transplantation
Authors: A J FISHER, J H DARK, P A CORRIS
Journal: Thorax (1998)

12 Unfortunately up to 50% of patients identified as suitable candidates to undergo lung transplantation will die from their underlying lung disease before an organ becomes available. 34 The severe shortage of donor lungs is now the major limitation to the use of the procedure as a widely available therapeutic option. The current method of donor lung evaluation excludes the vast majority of potential lung donors. New objective indices of donor lung injury may help to rationalise the selection process. This would enable many of the previously excluded organs to be accepted, addressing the current problem of organ shortage. Donor lungs originate from ventilated brain dead patients whose relatives have given consent for organ donation. Multiple strategies have been adopted by the transplant community to increase the number of donor organs for all types of solid organ transplantation. Attempts at raising awareness in medical staV to identify potential brain dead donors and in the general public to encourage consent when approached have failed to dramatically increase the number of organs available for transplantation. Despite 25% of the public carrying a donor card, both emotional and cultural reasons within families have prevented this leading to a significant increase in donors. In other countries legislation requiring medical staV to approach all potential donor families and the introduction of opt-out rather than opt-in systems of donation have not resulted in a major increase in the donor pool. 5 To date the attempts at increasing numbers of potential donors have been disappointing and transplant teams have turned to other possible ways of addressing the shortage of donor lungs. Lung transplantation using lobes from living family members has proved a useful procedure in selected cases, especially in teenagers, 6
What Is the Psychological Impact of Mammographic Screening on Younger Women With a Family History of Breast Cancer? Findings From a Prospective Cohort Study by the PIMMS Management Group
Authors: Sally Tyndel, Joan Austoker, Bethan J. Henderson, Kate Brain, Clare Bankhead, Alison Clements, Eila K. Watson
Journal: Journal of Clinical Oncology (2007)

Studies are underway to establish the clinical effectiveness of annual mammographic screening in women younger than 50 years with a family history of breast cancer. This study investigated both the positive and negative psychological effects of screening on these women.Women who received an immediate all-clear result after mammography (n = 1,174) and women who were recalled for additional tests before receiving an all-clear result (false positive; n = 112) completed questionnaires: 1 month before mammography, and 1 and 6 months after receiving final results. The questionnaires included measures of cancer worry, psychological consequences, and perceived benefits of breast screening.Women who received an immediate all-clear result experienced a decrease in cancer worry and negative psychological consequences immediately after the result, whereas women who were recalled for additional tests did not. By 6 months this cancer-specific distress had reduced significantly in both groups. Changes in levels of distress were significantly different between the two groups, but in absolute terms the differences were not large. Recalled women reported significantly greater positive psychological consequences of screening immediately after the result, and were also more positive about the benefits of screening compared with women who received an immediate all-clear result.For women receiving an immediate all-clear result, participating in annual mammographic screening is psychologically beneficial. Furthermore, women who are recalled for additional tests do not appear to be harmed by screening: these women's positive views about mammography suggest that they view any distress caused by recall as an acceptable part of screening.