tbuckley/cabot-search huggingface dataset:
Induction of cell cycle regulatory proteins in anti-immunoglobulin-stimulated mature B lymphocytes.
Authors: N Solvason, W W Wu, N Kabra, X Wu, E Lees, M C Howard
Journal: The Journal of Experimental Medicine (1996)

Progression through the cell cycle is a tightly controlled process that integrates signals generated at the plasma membrane with the proteins that form the cell cycle machinery. The current study chronicles the induction of cyclins, cyclin-dependent kinases (cdk), and cdk inhibitors in low density primary mouse B lymphocytes after anti-immunoglobulin plus interleukin 4 (IgM + IL-4) stimulation. In this system, &amp;gt; 85% of cells remain in the G0/G1 phase of cell cycle for an initial 24-h period, followed by entry of up to 50% of the cells into S phase, commencing around 30 h and peaking at 48 h. Extensive time course analyses of these anti-IgM + IL-4-stimulated B cells revealed that the G1-associated D-type cyclins D2 and D3 were induced by 3 h after stimulation, and that cyclins E, A, and B were subsequently induced sequentially, beginning at mid-G1, G1/S transition, and S phase, respectively. The G1-associated cyclin D1 was not expressed at any stage of the anti-Ig + IL-4-induced B cell cycle. cdk2, cdk4, and cdk6 were induced during G1, whereas cell division cycle-2 (cdc2) was induced concomitantly with S phase. Irrespective of their expression, the kinases cdk2 and cdc2 were only active from S phase onwards, suggesting that productive cyclin/kinase complex formation did not occur until that time. Cell cycle inhibitors p21 and p19 were induced by anti-Ig + IL-4, peaking in expression at mid-G1 and S phase, respectively. Stimulation of low density B cells with anti-Ig + IL-4 caused rapid down regulation of the p27 inhibitor, however this protein was reexpressed at 54-96 h after stimulation. In contrast, B cells stimulated with anti-CD40, a stimulus which induces long-term B cell proliferation, permanently down regulated p27. These findings are consistent with the concept that p27 reexpression contributes to the G1 arrest that follows antigen receptor crosslinking. Low density B cells cultured in the viability-enhancing cytokine IL-4 alone also showed induction of D2 and D3 cyclin expression. However, the D2 expression was transient, and the D3 expression was substantially lower than that observed in B cells induced to proliferate by anti-Ig + IL-4. This partial induction of D2 and D3 expression may explain IL-4's ability to promote B cell entry into G1 but not S phase of cell cycle, and furthermore, its ability to truncate G1 progression when B cells are subsequently stimulated with anti-Ig.
Cholinergic nicotinic receptors: Competitive ligands, allosteric modulators, and their potential applications
Authors: M. Novella Romanelli, Fulvio Gualtieri
Journal: Medicinal Research Reviews (2003)

Abstract Discovery of the important role played by nicotinic acetylcholine receptors (nAChRs) in several CNS disorders has called attention to these membrane proteins and to ligands able to modulate their functions. The existence of different subtypes at multiple levels has complicated the understanding of this receptor's physiological role, but at the same time has increased the efforts to discover selective compounds in order to improve the pharmacological characterization of this kind of receptor and to make the possible therapeutical use of its modulators safer. This review focuses on the structure of new ligands for nAChRs, agonists, antagonists and allosteric modulators, and on their possible applications. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 4, 393–426, 2003
Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia
Authors: Deepa Bhojwani, Noah D. Sabin, Deqing Pei, Jun J. Yang, Raja B. Khan, John C. Panetta, Kevin R. Krull, Hiroto Inaba, Jeffrey E. Rubnitz, Monika L. Metzger, Scott C. Howard, Raul C. Ribeiro, Cheng Cheng, Wilburn E. Reddick, Sima Jeha, John T. Sandlund, William E. Evans, Ching-Hon Pui, Mary V. Relling
Journal: Journal of Clinical Oncology (2014)

Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity.Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities.Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity.MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity.
Tainted eponyms in medicine: the “Clara” cell joins the list
Authors: A. Woywodt, S. Lefrak, E. Matteson
Journal: European Respiratory Journal (2010)

Eponyms are a time-honoured tradition in medicine as well as the sciences. Some fields of medicine, such as rheumatology and neurology, are particularly fond of them and the term “eponymophilia” has been coined to describe their affinity 1. Those who like their eponyms argue that their use adds flavour to our daily practice and that they are universally understood. They also claim that, as they are everywhere anyway, change would be impractical 2.

During the last decade or so, the use of eponyms has become the subject of intense controversy. In 2003, Panush et al. 3 reported on the biography of Hans Reiter, after whom a form of reactive arthritis was named despite the fact that others had described the condition well before him. Apart from being an outspoken lecturer in favour of “racial hygiene”, Reiter served on the advisory board to Hitler's physician, Karl Brandt, who headed the infamous “euthanasia” programme. This systematic killing of patients with mental and other illnesses developed the killing mechanism utilised in the genocide of the Jews, and the Roma and Sinti people. Brandt was executed for this and other crimes in 1948. Moreover, Reiter, as Chief of the Reich Health Service, approved not only the sterilisation programmes but also the deliberate infection of concentration camp inmates with rickettsia. The report by Panush et al. 3 led many physicians, particularly in the USA and Germany, to abandon the use of the eponym in favour of a more descriptive name 4. Panush's work also led to the formal retraction, in 2007, of the initial publication that coined this particular eponym 5. It is probably fair to say that there is no coherent approach to these issues within the rheumatology community. Some have disdained its use, whereas others continue the use of …
A European Organisation for Research and Treatment of Cancer Phase III Trial of Adjuvant Whole-Brain Radiotherapy Versus Observation in Patients With One to Three Brain Metastases From Solid Tumors After Surgical Resection or Radiosurgery: Quality-of-Life Results
Authors: Riccardo Soffietti, Martin Kocher, Ufuk M. Abacioglu, Salvador Villa, François Fauchon, Brigitta G. Baumert, Laura Fariselli, Tzahala Tzuk-Shina, Rolf-Dieter Kortmann, Christian Carrie, Mohamed Ben Hassel, Mauri Kouri, Egils Valeinis, Dirk van den Berge, Rolf-Peter Mueller, Gloria Tridello, Laurence Collette, Andrew Bottomley
Journal: Journal of Clinical Oncology (2012)

This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results.HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference.Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who received WBRT. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months, and fatigue at 8 weeks). Exploratory analysis of all other HRQOL scales suggested worse scores for the WBRT group, but none was clinically relevant.This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.
Use of antisecretory agents as a trial of therapy
Authors: M B Fennerty
Journal: Gut (2002)

Dyspepsia is a common clinical condition, and its diagnostic evaluation and treatment result in the expenditure of enormous healthcare resources each year. Studies indicate that the omeprazole test is the most sensitive and cost effective test for diagnosing gastro-oesophageal reflux disease (GORD) in patients with extra-oesophageal or more "classic" symptoms suggestive of GORD. Studies also indicate that a therapeutic trial of omeprazole in patients with dyspepsia results in greater symptom improvement and lower costs than treatment with less potent acid suppression.
Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases
Authors: K. GrønbAEk, P.H. MØller, T. Nedergaard, K. Thomsen, O. Baadsgaard, K. Hou-Jensen, J. Zeuthen, P. Guldberg, E. RalfkiAEr
Journal: British Journal of Dermatology (2000)

The clinical, histological, phenotypic and genotypic features of 21 primary cutaneous B-cell lymphomas (CBCLs) have been investigated. The patients were 13 men and eight women aged 34–91 years (median 67) at diagnosis. Eighteen patients had localized disease, and three had multiple skin lesions at diagnosis. Twelve patients developed cutaneous or extracutaneous recurrences, and five died from malignant lymphoma 7–84 months (median 36) after diagnosis. Histological examination showed features of marginal zone/mucosa-associated lymphoid tissue (MALT)-type lymphoma in 12 cases. Three of these had transformed to diffuse large B-cell lymphoma (DLBCL) in relapse biopsies. The remaining cases were seven primary DLBCLs and two cases tentatively classified as follicle centre cell (FCC) lymphoma. The neoplastic B cells showed similar phenotypes and genotypes in most cases (CD20+, CD79+, CD5–, CD10–, cyclin D1–, bcl-2+, bcl-x–, bax–, t(14;18)-negative). p53 protein was expressed in five cases, and four harboured mis-sense or loss-of-function mutations in the p53 gene. Deletion or promoter region hypermethylation of the p16INK4a gene was detected in two patients with DLBCL. The level of retinoblastoma protein expression and the proliferative fraction were significantly higher in DLBCL (> 50%) than in MALT- or FCC-type lymphomas (< 10%). Features associated with an unfavourable prognosis were the presence of multiple skin lesions at diagnosis, transformation from MALT-type lymphoma to DLBCL, and possibly p16INK4a aberrations. It is concluded that most CBCLs are dissimilar from FCC lymphomas and seem to be more closely related to marginal zone/MALT-type lymphomas. It is also suggested that there are fundamental differences between DLBCL and other histological categories of CBCL, indicating that cutaneous DLBCL is a separate entity with an increased growth potential and genetic features similar to DLBCL originating in other anatomical sites.
HLA-G Proteins in Cancer: Do They Provide Tumor Cells with an Escape Mechanism?
Authors: Nathalie Rouas-Freiss, Philippe Moreau, Soldano Ferrone, Edgardo D. Carosella
Journal: Cancer Research (2005)

Abstract Convincing clinical evidence indicates that the limited success of T-cell–based immunotherapy of malignant diseases is caused, at least in part, by the ability of malignant cells to escape from immune recognition and destruction. Among the multiple escape mechanisms identified, a major role is played by changes in the expression and/or function of HLA antigens expressed by tumor cells, because they may markedly affect tumor cell-host's immune system interactions. In this article, we review the data about the aberrant expression of the nonclassical HLA class I antigen HLA-G by tumor cells. Furthermore, we discuss the possible reasons for the conflicting information in the literature about HLA-G antigen expression by malignant cells. Lastly, in light of the well-documented immunotolerant function of HLA-G, we discuss the potential role of these antigens in the escape of tumor cells from immune recognition and destruction and in the clinical course of malignant diseases.
Paint-Remover Hazard
Authors: Richard D. Stewart
Journal: JAMA (1976)

The in-home use of paint removers containing methylene chloride results in the absorption of this solvent, which is metabolized to carbon monoxide. Exposure for two to three hours can result in the elevation of carboxyhemoglobin (COHb) to levels that stress the cardiovascular system. The metabolic formation of COHb continues following the paint-remover exposure, doubling the duration of the cardiovascular stress produced by a comparable COHb level after exposure to CO. Patients with diseased cardiovascular systems may not be able to tolerate this unexpected stress.
Metabolism and the electrical activity of human atrial myocardium
Authors: J. SENGES, J. BRACHMANN, I. RIZOS, R. JAUERNIG, B. HASPER, L. BECK, W. BRAUN, W. KUBLER
Journal: Cardiovascular Research (1981)

The electrophysiological effects of hypoxia, glucose and iodoacetic acid (IAA) were studied in 16 preparations of human right atrial tissue obtained during corrective open heart surgery. During atrial pacing, transmembrane action potentials were recorded with intracellular micro-electrodes. Hypoxia caused predominant alterations in the repolarisation phase of the action potential including depression of the plateau and a decrease in duration associated with a shortening of the effective refractory period and an increase in the maximum atrial rate at which 1:1 conduction was still maintained. The maximum rate of rise was moderately reduced but the resting potential, action potential amplitude and conduction time were not significantly altered. The critical range of stimulus intervals at which inhomogeneity of conduction first occurred was shifted to shorter values. An increase in the extracellular glucose concentration from 5 to 50 mmol·litre−1 in the presence of persisting hypoxia reversed the anoxic effects. The action of IAA (7.5 × 10−5 mol·litre−1) alone on repolarisation resembled qualitatively that obtained with hypoxia but with a slower time course. The maximum rate of rise was not significantly altered. Combination of IAA with hypoxia rapidly abolished all atrial electrical activity. The results support the hypothesis that: (1) human atrial fibres can utilise both aerobic and glycolytic energy for maintenance of electrical activity; (2) under physiological extracellular glucose concentrations, either aerobic or glycolytic processes alone can provide sufficient energy to maintain the action potential amplitude but not the action potential plateau; and (3) stimulation of glycolysis by high extracellular glucose during hypoxia allows additional energy production that effectively contributes to the maintenance of the electrical activity of the human heart.
Chlamydia Pneumoniae, Strain Twar Pneumonia
Authors: J T Grayston
Journal: Annual Review of Medicine (1992)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Inflammation: Hunter's Views and Modern Conceptions
Authors: G. L. Cheatle
Journal: BMJ (1936)

U CABJs* Conclusions 1. Medical and surgical treatment of peptic ulcers give approximately the same late results, judged by the fre- quency of failures and relapses and subsequent working capacity.2. The operative mortality is considerable and is higher than has been generally believed, especially in the case of gastric ulcers, in which it may be between 10 and 20 per cent.under favourable circumstances.3. The immediate results of gastro-enterostomy for duodenal ulcer are-appreciably better than those of medical treatment.4. The incidence of gastro-jejunal ulcer after gastro- enterostomy for duodenal ulcer is not less than 10 per cent.5. Evidence is lacking to support the view that cases which are medical failures will in general do better permanently after operation, or will do sufficiently better to couilterbalance the operative mortality and the risk of gastro-jejunal ulcer.6. Cases which relapse after a first course of medical treatment may be successfully treated by a second.7. Grave cases of haemorrhage from peptic ulcer have so high a mortality that operation is indicated to check the bleeding point.There is no indication for operating when haemorrhage has ceased.8. The medical treatmnent of haemorrhage should not involve prolonged starvation.9.The medical treatment of active peptic ulcer should be based on the principle that the stomach is not left for more than two hours without treatment.
Differences of skin irritation between Japanese and European women
Authors: J. Aramaki, S. Kawana, I. Effendy, R. Happle, H. LOffler
Journal: British Journal of Dermatology (2002)

After using cosmetics, Japanese women frequently complain about sensitive, stinging skin. We wondered whether Japanese women's skin is more sensitive than that of Caucasians.To examine possible racial differences of skin irritation and subjective sensations.We performed patch testing on the forearm with sodium lauryl sulphate (SLS) at different concentrations (0.25%, 0.5%) and 24-h exposure time. Skin reaction was evaluated by measurement of transepidermal water loss (TEWL), stratum corneum hydration, sebum secretion, laser Doppler flowmetry (LD), content of melanin and erythema. During a stinging test with 10% lactic acid (applied to one side of the cheeks) the subjects were asked to describe the present intensity of any sensation. We used a Chromameter to measure skin colour before and after application of lactic acid. This study was performed in Marburg, Germany, with healthy Japanese and German women living in Marburg.After SLS testing, we found no significant differences of the barrier function in the stratum corneum, but we found significant subjective sensory differences between Japanese and German women.Japanese women may complain about stronger sensations reflecting a different cultural behaviour rather than measurable differences in skin physiology; however, a faster penetration of SLS in Japanese cannot be excluded.
Topical tacrolimus treatment in a patient with dermatomyositis
Authors: C E Lampropoulos
Journal: Annals of the Rheumatic Diseases (2005)

This case illustrates the usefulness of a therapeutic trial of colchicine monitored objectively by frequent acute phase protein measurements in patients with undiagnosed periodic fever syndromes.It also raises the possibility that a low threshold for analysing the FMF gene might disclose a wider spectrum of associated disease.
Superior Quality of Life and Improved Surgical Margins Are Achievable with Robotic Radical Prostatectomy After a Long Learning Curve: A Prospective Single-surgeon Study of 1552 Consecutive Cases
Authors: James E. Thompson, Sam Egger, Maret Böhm, Anne-Maree Haynes, Jayne Matthews, Krishan Rasiah, Phillip D. Stricker
Journal: European Urology (2013)
Retinol-Binding Protein 4 Is Associated With Prediabetes in Adults From the General Population
Authors: Christa Meisinger, Ina M. Rückert, Wolfgang Rathmann, Angela Döring, Barbara Thorand, Cornelia Huth, Bernd Kowall, Wolfgang Koenig
Journal: Diabetes Care (2011)

We examined the association between retinol-binding protein 4 (RBP4), a novel adipokine, and prediabetes (isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT], and combined IFG and IGT) in men and women aged 32-81 years.The analysis was based on 2,614 participants without previously diagnosed diabetes and those with newly diagnosed diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study, conducted from 2006 to 2008 in southern Germany. Plasma RBP4 was analyzed by immunonephelometry.In logistic regression analysis, RBP4 levels in the fourth quartile versus the first quartile were significantly associated with prediabetes (i-IGT, i-IFG, and IFG/IGT; reference normal glucose tolerance) independent of known metabolic risk factors and lifestyle variables (odds ratio 1.63 [95% CI 1.17-2.27] after multivariable adjustment). Stratification by sex showed generally similar results.RBP4 levels were associated with prediabetes in individuals from the general population. Prospective studies investigating the impact of RBP4 on the development of glucose intolerance are needed.
A method to test blood flow limitation of peritoneal-blood solute transport.
Authors: M Kim, J Lofthouse, M F Flessner
Journal: Journal of the American Society of Nephrology (1997)

Current transperitoneal transport models assume that effective blood flow to the microcirculation does not limit solute exchange with dialysate in the cavity. Despite evidence that gas transfer across the peritoneum (assumed to equal the effective blood flow) occurs at rates that exceed maximum urea transfer rates by a factor of two to three, the assumption has been strongly challenged. To address this problem at the tissue level, a technique to determine the effect of local blood flow on small-solute transport was developed in this study. Diffusion chambers were affixed to the serosal side of the anterior abdominal wall of rats, and solutions containing radiolabeled urea or mannitol were placed in the chambers. During each experiment, the local blood flow beneath the chamber was monitored with laser Doppler flowmetry and the disappearance of the tracer versus time was simultaneously measured under three conditions of blood flow: control, 30% of control, and zero blood flow. The results demonstrated no significant differences for either solute between control and the condition in which blood flow was reduced by 70%. However, there was a significant reduction in the rate of mass transfer with no blood flow. It was concluded that blood flow at > or = 30% of control values does not limit solute transfer across the abdominal wall peritoneum during dialysis.