tbuckley/cabot-search huggingface dataset:
Defective Expression of Transforming Growth Factor β Receptor Type II Is Associated with CpG Methylated Promoter in Primary Non-Small Cell Lung Cancer
Authors: Hong-Tao Zhang, Xiao-Feng Chen, Ming-Hua Wang, Jiu-Cun Wang, Qing-Yuan Qi, Rong-Mei Zhang, Wei-Qing Xu, Qing-Yan Fei, Fei Wang, Qi-Qun Cheng, Feng Chen, Cheng-Song Zhu, Shi-Heng Tao, Zewei Luo
Journal: Clinical Cancer Research (2004)

Reduced expression of the transforming growth factor beta receptor type II (TGF beta RII), a key inhibitor of epithelial cell growth and tumor suppressor gene, was reported frequently in many types of tumors including non-small cell lung cancer (NSCLC). This study explored the significance of the TGF beta RII gene in NSCLC carcinogenesis.With 43 independent pairs of tumor and paracarcinoma tissue samples from patients with primary NSCLC, we carried out PCR-denaturing gradient gel electrophoresis screening for DNA variants over the coding sequence of the TGF beta RII gene, immunohistochemical assay of TGF beta RII expression, methylation-specific PCR analysis, and semiquantitative reverse transcription-PCR.The PCR-denaturing gradient gel electrophoresis did not detect variation in the whole coding sequence of the TGF beta RII gene, but the immunohistochemistry experiment revealed reduced or lost expression of the gene in 44% (19 of 43) of the tumor samples. The methylation analysis on the 19 pairs detected the frequent occurrence of methylated TGF beta RII promoter in tumor tissues, whereas most of the paracarcinoma tissues were free of methylation. The reduced TGF beta RII expression was highly significantly associated with the methylation event (P < 10(-4)). The reverse transcription-PCR analysis demonstrated a clear agreement between reduced TGF beta RII expression and decreased mRNA level of the gene in the tumor tissue samples.TGF beta RII plays an important role as a tumor suppressor in NSCLC carcinogenesis. The defective expression may serve as one of most important molecular mechanisms in explaining progression of the disease. In particular, aberrant 5' CpG methylation of the gene has explained the down-regulation of the gene at a transcriptional level.
Oxford Textbook of Oncology, Second Edition
Authors: M. Ghielmini
Journal: Annals of Oncology (2002)

When I came home with this huge 3000 page book, saying that I was due to review it, my son commented that by the time I had finished reading it, the next edition would probably have been published. Is it possible to express a sound judgement on such a complex text, written by so many authors, on so many subjects? Waiting to be inspired, I left the ‘Oxford’ on my desk, where it stayed for at least a month. During this time I opened it a number of times to look for help with uncommon cases in my general oncology practice.•A close relative with early stage prostate cancer was advised not to have an operation; he asked me for data in support of a ‘wait and see’ policy, I found them in the ‘Oxford’.•For a lesson to junior doctors on the cytogenetics of hematologic malignancies, I found all the data, tables and explanations needed.•I was asked what to do in a locally advanced squamous cell carcinoma of the thymus. I found some hints, but for a definitive decision on neoadjuvant treatment I had to search elsewere.•A patient underwent a radical operation for a pilomatrixoma, and I was asked whether this required adjuvant radiotherapy. I did not find this disease in the book, as this epithelioma is a benign entity.•I had to give a lesson to gynecologists on in situ carcinoma of the breast. I found useful material, but it was insufficient and not up-to-date, the most recent reference being from 1998, with all the recent and essential NSABP (National Surgical Adjuvant Breast and Bowel Project) data missing.•For a patient with severely compromised lung function and a peripheral lung carcinoma, I was asked to choose the best treatment option between lobectomy, wedge resection or observation. I found that “segmentectomy is a valid compromise for patients with limited pulmonary reserve”, and references which I could provide to the surgeon were available.•For a second opinion on a probably chemotherapy-induced pulmonary failure, I searched the text fruitlessly, as I did for a case of isolated eosinophylic granuloma of the rib, despite the presence of a quite complex chapter on histiocyte disorders. In other words, as is often the case for these ‘bible type’ textbooks, some answers I found, others I didn’t. As is also common for textbooks needing a long and complex preparation, many chapters are not completely up-to-date, the most recent references being from 1998, although in some cases an effort was made to insert at least the most relevant new discoveries, such as Glivec in the chronic myelogenous leukemia (CML) chapter. Overall, the three new editors of this second edition have managed a tremendous job. The introductory chapters on the biology of cancer and the basics of treatment, as well as the general discussion of each disease, give an excellent perspective of cancer biology and treatment. Being exhaustive and completely up-to-date is probably no longer a priority in these internet times, so having a copy of the ‘Oxford’ on the bookshelf will still be useful for many clinical and teaching situations.
Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis
Authors: Philip O. Scumpia, Matthew J. Delano, Kindra M. Kelly-Scumpia, Jason S. Weinstein, James L. Wynn, Robert D. Winfield, Changqing Xia, Chun Shiang Chung, Alfred Ayala, Mark A. Atkinson, Westley H. Reeves, Michael J. Clare-Salzler, Lyle L. Moldawer
Journal: Blood (2007)
Hemostatic Effectiveness of Liquid-Preserved and Previously Frozen Human Platelets
Authors: C. R. Valeri
Journal: New England Journal of Medicine (1974)

To determine the effectiveness of various platelet preparations, a single unit of fresh or preserved platelet concentrate was transfused into 42 healthy male volunteers who had been given 650 mg of aspirin 24 hours before, and platelet survival and ability to reduce bleeding time was studied. The bleeding time was reduced by 1 U of platelets stored at 4°C for 24 hours, but they had a short survival. The bleeding time was not reduced by fresh platelets, platelets stored at 22°C for 24 hours, or platelets stored with 5 per cent dimethyl sulfoxide at -150°C for 24 hours, but these platelets had normal life-span. Platelets stored with 6 per cent dimethyl sulfoxide at -80°C for 24 hours had normal life-span and hemostatic effectiveness. Thus, the in vivo effect of aspirin on bleeding time may be corrected by short-lived platelets but may not be corrected by platelets with normal life-span, depending upon their preservation. (N Engl J Med 290:353–358, 1974)
HLA antigens in psoriatic arthritis subtypes of a Spanish population.
Authors: C López-Larrea, J.C Torre Alonso, A Rodriguez Perez, E Coto
Journal: Annals of the Rheumatic Diseases (1990)

HLA-A, B, and C antigens were studied in 104 Spanish patients with psoriatic arthritis. Different clinical features were evaluated and the patients divided into disease subsets. HLA-B17, B27, B16, and Cw6 were the most common haplotypes in the total group. The HLA-B17/Cw6 haplotype was increased in patients with oligoarthritis. The increase of antigen B17 correlated with oligoarthritis and spondarthritis, whereas Cw6 was more significant in oligoarthritis. The prevalence of the B27/Cw1 haplotype was greater in association with spondarthritis and was probably related to the B27.5 subtype linked to Cw1. A significant negative association between the B44/Cw5 haplotype and psoriatic arthritis was found. The existence of several haplotypic factors in the different subsets is discussed. Lack of one or more HLA factors is thought to be responsible for the different clinical forms of psoriatic arthritis.
Visceral sensory and cognitive-affective neuroscience: towards integration?
Authors: L. Van Oudenhove
Journal: Gut (2010)

Despite rapidly growing evidence supporting a link between psychological processes—both cognitive and affective—and visceral sensation in health as well as functional gastrointestinal disorders (FGIDs), the neural mechanisms underlying these interactions remain infrequently studied within the field of ‘neurogastroenterology’ and therefore rather poorly understood.1 The somatic pain field, in contrast, has already made considerable progress in unravelling these complex brain mechanisms by which emotion (eg, anxiety) and cognition (eg, attention) influence the processing and perception of bodily signals.2 More specifically, the amygdala, insula, and cingulate and prefrontal subregions have been shown to be involved in pain–emotion interactions. This knowledge is the result of a fruitful integration between different branches of science within the somatic pain field over the past decades, including psychology, psychiatry, anaesthesiology and the affective, cognitive and sensory branches of neuroscience. Such a degree of integration has not been achieved yet within ‘visceral sensory neuroscience’ but is, in my opinion, much needed if we really want to move the field forward. This may be especially critical if we want to make progress in the understanding of the multifactorial pathophysiology of complex, symptom-based disorders including FGIDs. Although rather sparse, recent attempts towards such integration have been made, and I will try to situate these against a long tradition of studying the interactions between mind, brain and body underlying visceral sensation.

In the present issue of Gut , Elsenbruch and colleagues ( see page 489 ) report on a functional MRI study showing that, in irritable bowel syndrome (IBS), anxiety and …
Recurrence After Recovery From Major Depressive Disorder During 15 Years of Observational Follow-Up
Authors: Timothy I. Mueller, Andrew C. Leon, Martin B. Keller, David A. Solomon, Jean Endicott, William Coryell, Meredith Warshaw, Jack D. Maser
Journal: American Journal of Psychiatry (1999)

The recurrence of an affective disorder in people who initially recover from major depressive disorder was characterized by using the unique longitudinal prospective follow-up data from the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies.Up to 15 years of prospective follow-up data on the course of major depressive disorder were available for 380 subjects who recovered from an index episode of major depressive disorder and for 105 subjects who subsequently remained well for at least 5 years after recovery. Baseline demographic and clinical characteristics were examined as predictors of recurrence of an affective disorder. The authors also examined naturalistically applied antidepressant therapy.A cumulative proportion of 85% (Kaplan-Meier estimate) of the 380 recovered subjects experienced a recurrence, as did 58% (Kaplan-Meier estimate) of those who remained well for at least 5 years. Female sex, a longer depressive episode before intake, more prior episodes, and never marrying were significant predictors of a recurrence. None of these or any other characteristic persisted as a predictor of recurrence in subjects who recovered and were subsequently well for at least 5 years. Subjects reported receiving low levels of antidepressant treatment during the index episode, which further decreased in amount and extent during the well interval.Few baseline demographic or clinical characteristics predict who will or will not experience a recurrence of an affective disorder after recovery from an index episode of major depressive disorder, even in persons with lengthy well intervals. Naturalistically applied levels of antidepressant treatment are well below those shown effective in maintenance pharmacotherapy studies.
Interspecies comparisons of tissue DNA damage, repair, fixation, and replication.
Authors: T J Slaga
Journal: Environmental Health Perspectives (1988)

The many anatomical, physiological, and biochemical differences among various mammalian species make it difficult to extrapolate carcinogenic potency data from animals to humans. The process is further complicated by the multistep origin of most malignant tumors in animals and humans due to the interaction of target cells with both endogenous and exogenous factors. Species differences in these aspects of carcinogenesis must also be considered when attempting to evaluate the carcinogenic risks of chemicals to humans. Cancer development in animals involves at least three distinct stages: initiation, promotion, and progression. Intra- and interspecies differences in susceptibility to carcinogenesis may be related to any one or a combination of these stages. Variation in species susceptibility to tumor initiation may result from differences in the abilities of various species to metabolize a potential carcinogen to an ultimate carcinogenic form and/or to detoxify the carcinogen. Most comparative studies among species have only revealed subtle differences in metabolism. DNA adducts from several activated carcinogens have been found to be the same in a number of tissues from various species, including humans. Capacity for DNA repair is apparently a critical factor in the initiation of carcinogenesis in target cells of different species but is less critical among mice that differ in susceptibility to two-stage carcinogenesis of the skin and liver. Susceptibility variations among stocks and strains to such carcinogenesis appear to be related to alterations in tumor promotion. Additional comparative studies are critically needed on all aspects of carcinogenesis to permit effective extrapolation of carcinogenic potency data from animals to humans.
Pancreatico-duodenectomy for Relapsing Pancreatitis
Authors: T. E. Wilson
Journal: BMJ (1954)

uncommon in rural areas.Consanguinity was not admitted in any case.However, the tendency of farming or village populations to marry locally may be of importance.This apparently high incidence in a rural population, if confirmed by a larger survey, would be additional evidence of a recessive genetic factor in the transmission of persistent ductus, and perhaps of congenital heart disease in general. Summary and ConclusionsDetails of four siblings with congenital heart disease are presented.They include three cases with persistent ductus and one with cyanotic heart disease.The aetiology of congenital heart disease is discussed and evidence indicating the importance of a genetic factor is presented.Addendum.-Since this paper was sent for publication the diagnosis of persistent ductus in the boy aged 11 has been confirmed at operation.
Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation
Authors: Serge A van de Pavert, Brenda J Olivier, Gera Goverse, Mark F Vondenhoff, Mascha Greuter, Patrick Beke, Kim Kusser, Uta E Höpken, Martin Lipp, Karen Niederreither, Rune Blomhoff, Kasia Sitnik, William W Agace, Troy D Randall, Wouter J de Jonge, Reina E Mebius
Journal: Nature Immunology (2009)
Impact of professionalism on injuries in rugby
Authors: N J Henderson
Journal: British Journal of Sports Medicine (2000)

Editor,—Garraway and colleagues have recently written an important follow up study1 to their 1995 survey on rugby injuries in senior rugby clubs in the Scottish Borders.2 This comprehensive review of rugby injuries and their implications set standards in injury definition and information gathering. They have now studied the same model and population to assess the changes over the last four years and to define increased injury rates, which …
Some technical modifications in oesophageal resection for carcinoma
Authors: S. J. Stephen, C. G. Uragoda
Journal: Thorax (1972)

The frequency of oesophageal carcinoma in Ceylon provides an opportunity for elaborating certain modifications in the technique of oesophageal resection. Initial subadventitial ligation of oesophageal branches of the aorta renders the operative field relatively bloodless, thus facilitating the removal en bloc of the tumour together with the lymphatic and loose cellular tissue, as well as the adventitia of the aorta when it is involved. The division of the oesophagus above the growth in an oblique plane, leaving a posterior flap, helps to minimize the incidence of fibrous strictures and anastomotic leaks. In fashioning the stomach tube, the stomach is divided just proximal to the beginning of the left gastro-epiploic arch. This procedure ensures that the blood supply to the gastric component of the oesophagogastric anastomosis is least disturbed. In cases where the transverse colon and hepatic flexure are used as an interposition, a dual blood supply derived from the middle colic as well as the ascending branch of the left colic artery is retained. This procedure increases the margin of safety in case one artery obstructs.
TβRI Independently Activates Smad- and CD2AP-Dependent Pathways in Podocytes
Authors: Sandhya Xavier, Thiruvur Niranjan, Stefanie Krick, Taoran Zhang, Wenjun Ju, Andrey S. Shaw, Mario Schiffer, Erwin P. Böttinger
Journal: Journal of the American Society of Nephrology (2009)

TGF-beta regulates differentiation, growth, and apoptosis of podocytes and mediates podocyte depletion in glomerulosclerosis. TGF-beta promotes proapoptotic signaling mediated by Smad3 but also activates prosurvival pathways such as phosphoinositide-3 kinase (PI3K)/AKT; the latter requires the CD2-associated adaptor protein (CD2AP) in podocytes. Whether the opposing activities mediated by Smad proteins and CD2AP involve molecular cross-talk is unknown. Here, we report that CD2AP-dependent early activation of the antiapoptotic PI3K/AKT pathway does not require TGF-beta receptor-regulated Smad2 and Smad3. We found that the C-terminal region of CD2AP interacts directly with the cytoplasmic tail of the TGF-beta receptor type I (TbetaRI) in a kinase-dependent manner and that the interaction between the TbetaRI and the p85 subunit of PI3K requires CD2AP. Consistent with the proapoptotic function of Smad signaling, Smad2/3-deficient podocytes were hyperproliferative and resistant to TGF-beta-induced growth inhibition and apoptosis. In contrast, CD2AP-deficient cells were hypoproliferative and hypersensitive to TGF-beta-induced apoptosis. In vivo, to determine the effects of reduced Smad3 or CD2AP gene dosage on podocyte apoptosis and proteinuria characteristic of TGF-beta1 transgenic mice, we generated TGF-beta1 transgenic mice deficient for Smad3 or heterozygous for CD2AP. Smad3 deficiency ameliorated podocyte apoptosis, and CD2AP heterozygosity increased both podocyte apoptosis and proteinuria. These data define distinct canonical (Smad) and noncanonical (CD2AP/PI3K/AKT) pathways that arise from direct, independent interactions with the TbetaRI and that mediate opposing signals for podocyte death or survival.
CONTROLLED CLINICAL TRIAL OF ANTILYMPHOCYTE GLOBULIN IN PATIENTS WITH RENAL ALLOGRAFTS FROM CADAVER DONORS
Authors: A.G.R Sheil, G.E Kelly, B.G Storey, J May, S Kalowski, D Mears, J.H Rogers, J.R Johnson, J Charlesworth, J.H Stewart
Journal: The Lancet (1971)
Chronic Myelocytic Leukemia
Authors: Philip J. Fialkow, A. Michael Denman, Robert J. Jacobson, Mark N. Lowenthal
Journal: Journal of Clinical Investigation (1978)

In three patients with chronic myelocytic leukemia who were heterozygous at the X-linked glucose-6-phospháte dehydrogenase locus, lymphocytes were studied to determine if they had the same stem cell origin as the leukemic myeloid cells. Normal tissues such as skin had both B and A glucose-6-phosphate dehydrogenase isoenzymes, but the leukemic myelogenous cells displayed only one isoenzyme type, consistent with their clonal origin. A population of cells with undoubted thymus-derived (T)-lymphocyte characteristics had both isoenzymes. Presumably, then, these T cells did not arise from the leukemic stem cell, either because they antedated the development of leukemia in that stem cell or, more likely, because they arose from progenitors not involved by the disease. In contrast, another population of lymphocytes showed only one isoenzyme type, suggesting that it arose from the chronic myelocytic leukemia stem cell. However, although this population contained many cells with the characteristics of bone marrow-derived (B) lymphocytes, it is not certain that the single enzyme produced by the cells over all can be attributed to B lymphocytes rather than to contaminating non-B-lymphoid cells.
Subclinical alveolitis in immunological systemic disorders. Transition between health and disease?
Authors: B Wallaert, M Dugas, E Dansin, T Perez, CH Marquette, P Ramon, AB Tonnel, C Voisin
Journal: European Respiratory Journal (1990)

A subclinical inflammatory alveolitis as assessed by BAL cell analysis may be present in a high proportion of symptomless patients with immunological systemic disorders and with normal chest roentgenogram. Subclinical alveolitis can be characterized by the relative proportions of the different cell populations comprising the alveolitis and by the activated state of the cells. Thus, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. Lymphocyte alveolitis is frequently found in patients with extrathoracic granulomatosis (Crohn's disease, primary biliary cirrhosis, extrathoracic sarcoidosis) or with some collagen vascular diseases (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus). Neutrophil alveolitis is a main finding in collagen vascular diseases, especially progressive systemic sclerosis, dermatopolymyositis and mixed connective tissue disease. In addition, alveolar macrophages may be spontaneously activated and release various mediators that could be relevant to the pathogenesis of interstitial lung disease. On the other hand, some other alveolar macrophage functions (antibacterial activity may be severely impaired in some diseases, for example systemic lupus erythematosus). Alveolar inflammation is associated with an increase in the permeability of the alveolar membrane responsible for an increased influx of blood proteins in the alveolar spaces. Although subclinical inflammation may also be detected by high resolution computed tomography (HRCT) scan and/or lung permeability scintigraphic studies, the significance and prognostic value remains unclear and clearly differs according to both the disease and the pattern of alveolitis.