tbuckley/cabot-search huggingface dataset:
The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited
Authors: Jan J. Weening, Vivette D. D’Agati, Melvin M. Schwartz, Surya V. Seshan, Charles E. Alpers, Gerald B. Appel, James E. Balow, Jan A. Bruijn, Terence Cook, Franco Ferrario, Agnes B. Fogo, Ellen M. Ginzler, Lee Hebert, Gary Hill, Prue Hill, J. Charles Jennette, Norella C. Kong, Philippe Lesavre, Michael Lockshin, Lai-Meng Looi, Hirofumi Makino, Luiz A. Moura, Michio Nagata
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving &lt;50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving ≥50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
Nomograms to Predict Serious Adverse Events in Phase II Clinical Trials of Molecularly Targeted Agents
Authors: Gregory R. Pond, Lillian L. Siu, Malcolm Moore, Amit Oza, Hal W. Hirte, Eric Winquist, Glenwood Goss, Gary Hudes, Carol A. Townsley
Journal: Journal of Clinical Oncology (2008)

A tool that quantifies the risk of treatment-related toxicity based on individual patient characteristics can augment the informed consent process and safety monitoring in the setting of phase II cancer treatment trials of molecularly targeted agents (MTAs).A regression model was constructed to predict the risk of a serious adverse event (SAE) with an MTA and presented as a nomogram. Estimation of risk can be performed by integrating risk estimates from the nomogram and from a reference or average patient. Internal validation was performed using bootstrapping techniques.A total of 578 patients were treated with one of 14 MTAs given alone or in combination on one of 27 clinical trials performed by the Princess Margaret Hospital Drug Development Program between 2001 and 2006. Approximately 50% and 24% of patients experienced an SAE and an attributable SAE (SAEatt) during cycle 1, respectively. Albumin, lactate dehydrogenase (LDH), number of target lesions, prior radiotherapy, Charlson score, age, and performance status were included in the optimal model as predictors of a cycle 1 SAE, whereas the number of prior chemotherapy regimens, baseline creatinine, LDH, prior radiotherapy, Charlson score, body-surface area, and performance status were included as predictors of an SAEatt. Moderate-good internal validity was demonstrated, with area under the curve estimates ranging from 56.7% to 86.1% for all SAEs and 63.0% to 89.7% for SAEatts.A regression model was constructed that predicts the SAE and SAEatt risk for an individual patient during cycle 1 of phase II trial treatment with moderate to good internal validity. External validation is still required.
Comparison of anti-inflammatory and clinical effects of beclomethasone dipropionate and salmeterol in moderate asthma
Authors: E. Bacci, A. Di Franco, M.L. Bartoli, S. Carnevali, S. Cianchetti, F.L. Dente, D. Giannini, B. Vagaggini, L. Ruocco, P.L. Paggiaro
Journal: European Respiratory Journal (2002)

Inhaled corticosteroids and long-acting β 2 ‐agonists effectively control asthma symptoms and improve airway function. The effects of beclomethasone were compared with those of salmeterol on markers of eosinophilic inflammation in induced sputum in steroid-naïve asthmatic subjects with moderate asthma. Fifteen moderate asthmatics were treated with either beclomethasone dipropionate (500 µg b.i.d ) or salmeterol (50 µg b.i.d ) for 4 weeks, according to a randomised, double-blind, parallel-group study design. All patients underwent spirometry, methacholine test, sputum induction, and blood sampling before and after 2 and 4 weeks of treatment. They also recorded daily symptoms and peak expiratory flow (PEF). Sputum eosinophils, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and blood eosinophils, as well as the forced expiratory volume in one second (FEV 1 ) and morning PEF, significantly improved after beclomethasone but not after salmeterol. PEF variability, the symptom score and rescue β 2 ‐agonist use significantly improved after both treatments, although the improvement in the symptom score tended to be greater after beclomethasone. After 2 and 4 weeks of beclomethasone treatment, both serum ECP and EPX decreased. With salmeterol, only serum EPX decreased, after 4 weeks. Bronchial hyperresponsiveness to methacholine did not change after either treatment. The authors conclude that beclomethasone, but not salmeterol, substantially improves airway inflammation in asthma. Beclomethasone also had an overall greater clinical effect, although the improvement in symptoms and peak expiratory flow variability was similar after both treatments.
Serum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma
Authors: Ming Liu, Leilei Chen, Tim Hon Man Chan, Jian Wang, Yan Li, Ting-Ting Zeng, Yun-Fei Yuan, Xin-Yuan Guan
Journal: Hepatology (2012)

Amplification of broad regions of 8q is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC), suggesting the existence of oncogenes in addition to MYC at 8q24.21. In this report we examine the potential role of the candidate amplified oncogene serum and glucocorticoid kinase 3 ( SGK3 ) at 8q13.1 in HCC pathogenesis. We found amplification and overexpression of SGK3 was frequently detected in clinical HCC specimens and that SGK3 genomic activation was significantly associated with poor outcome of patients ( P = 0.028). Functionally, we found that overexpression of SGK3 in HCC cells increased cell cycle progression through G1, cell survival, clonogenicity, anchorage-independent growth, and tumor formation in nude mice. In contrast, RNA interference (RNAi) silencing of SGK3 inhibited its oncogenic effects. We provide evidence that SGK3 promotes HCC growth and survival through inactivating glycogen synthase kinase 3 beta and Bcl-2-associated death promoter, respectively. We also found that expression of SGK3, which like AKT is activated by PI3K/PDK1 signaling, has more significance than overexpression of AKT in predicting poor outcome in HCC patients. Taken together, our findings in the present study suggests that the SGK3 pathway may function in parallel with the AKT pathway and undergoes an AKT-independent signaling pathway in the pathogenesis of HCC. Further characterization of SGK3 may provide a prognostic biomarker for HCC outcome prediction and a novel therapeutic target in HCC treatment.
Macrophages genetically resistant to mouse hepatitis virus converted in vitro to susceptible macrophages.
Authors: W Weiser, F B Bang
Journal: The Journal of Experimental Medicine (1976)

Genetic resistance to mouse hepatitis, which resides largely in the macrophages of resistant C3H mice, may be altered by exposing the cells in vitro to fluid from allogeneic mixed lymphocytes. A 1,000-fold increase in susceptibility was produced in these genetically resistant cells by exposure to this fluid. This presumed lymphokine was effective without producing any change in host adaption of the virus.
Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma
Authors: Jiankun Tong, Hozefa S. Bandulwala, Bryan S. Clay, Robert A. Anders, Rebecca A. Shilling, Diwakar D. Balachandran, Bohao Chen, Joel V. Weinstock, Julian Solway, Kimm J. Hamann, Anne I. Sperling
Journal: The Journal of Experimental Medicine (2006)

Persistent airway inflammation, mucus production, and airway hyperreactivity are the major contributors to the frequency and severity of asthma. Why lung inflammation persists in asthmatics remains unclear. It has been proposed that Fas-mediated apoptosis of inflammatory cells is a fundamental mechanism involved in the resolution of eosinophilic airway inflammation. Because infiltrating eosinophils are highly sensitive to Fas-mediated apoptosis, it has been presumed that direct ligation of Fas on eosinophils is involved. Here, we utilize adoptive transfers of T cells to demonstrate that the delayed resolution of eosinophilia in Fas-deficient mice is a downstream effect of Fas deficiency on T cells, not eosinophils. Interestingly, the mice that received Fas-deficient T cells, but not the controls, developed a persistent phase of inflammation that failed to resolve even 6 wk after the last challenge. This persistent phase correlated with decreased interferon (IFN)γ production by Fas-deficient T cells and could be reproduced with adoptive transfer of IFNγ-deficient T cells. These data demonstrate that Fas deficiency on T cells is sufficient for the development of long-term allergic airway disease in mice and implies that deregulation of death receptors such as Fas on human T cells could be an important factor in the development and/or chronic nature of asthma.
Management of<i>Helicobacter pylori</i>infection—the Maastricht IV/ Florence Consensus Report
Authors: Peter Malfertheiner, Francis Megraud, Colm A O'Morain, John Atherton, Anthony T R Axon, Franco Bazzoli, Gian Franco Gensini, Javier P Gisbert, David Y Graham, Theodore Rokkas, Emad M El-Omar, Ernst J Kuipers
Journal: Gut (2012)

Management of Helicobacter pylori infection is evolving and in this 4th edition of the Maastricht consensus report aspects related to the clinical role of H pylori were looked at again in 2010. In the 4th Maastricht/Florence Consensus Conference 44 experts from 24 countries took active part and examined key clinical aspects in three subdivided workshops: (1) Indications and contraindications for diagnosis and treatment, focusing on dyspepsia, non-steroidal anti-inflammatory drugs or aspirin use, gastro-oesophageal reflux disease and extraintestinal manifestations of the infection. (2) Diagnostic tests and treatment of infection. (3) Prevention of gastric cancer and other complications. The results of the individual workshops were submitted to a final consensus voting to all participants. Recommendations are provided on the basis of the best current evidence and plausibility to guide doctors involved in the management of this infection associated with various clinical conditions.
The Terri Schiavo Case: Legal, Ethical, and Medical Perspectives
Authors: Joshua E. Perry, Larry R. Churchill, Howard S. Kirshner
Journal: Annals of Internal Medicine (2005)

Although tragic, the plight of Terri Schiavo provides a valuable case study. The conflicts and misunderstandings surrounding her situation offer important lessons in medicine, law, and ethics. Despite media saturation and intense public interest, widespread confusion lingers regarding the diagnosis of persistent vegetative state, the judicial processes involved, and the appropriateness of the ethical framework used by those entrusted with Terri Schiavo's care. First, the authors review the current medical understanding of persistent vegetative state, including the requirements for patient examination, the differential diagnosis, and the practice guidelines of the American Academy of Neurology regarding artificial nutrition and hydration for patients with this diagnosis. Second, they examine the legal history, including the 2000 trial, the 2002 evidentiary hearing, and the subsequent appeals. The authors argue that the law did not fail Terri Schiavo, but produced the highest-quality evidence and provided the most judicial review of any end-of-life guardianship case in U.S. history. Third, they review alternative ethical frameworks for understanding the Terri Schiavo case and contend that the principle of respect for autonomy is paramount in this case and in similar cases. Far from being unusual, the manner in which Terri Schiavo's case was reviewed and the basis for the decision reflect a broad medical, legal, and ethical consensus. Greater clarity regarding the persistent vegetative state, less apprehension of the presumed mysteries of legal proceedings, and greater appreciation of the ethical principles at work are the chief benefits obtained from studying this provocative case.
Paracentesis Thoracis as a Therapeutic Agent
Authors: W. H. White
Journal: BMJ (1884)

Assistanit-rhysician to the Royal Hospital for Diseases or the Chest.FItom the earliest period, no subject has excited moro discussion, or has evoked greater divergence of opinion, than the treatment of effusion into the thorax.This divergence, however, whilst of late years much lessened, yet continues; and the profession is still far from unanimous as to the best methods of dealing with such cases of thoracic effusion as are found to resist routine treatment. Ever sinceHippocrates advocated tapping the chest, a constant ebb and flow of opinion, for or against its use, has been observed.This is well shown by the oblivion into which this therapeutic agent had fallen at the tinme when Trousseau, Hamilton Roe, and others, directed their attention to the subject, and reinstated the operation.We owe much to Trousseau in this matter, for his vigorous advocacy drew attention to the successful treatment of pleurisy by operation; and his influence still dominates our efforts.The rules drawn up by him for our guidance as to when, how, and where it may be necessary to interfere were invaluable, and the stress laid by him relative to the exclusion of air froin the pleura, was shown by his use of Reybard's cannula, with a valve of goldbeater's skin, which, whilst permitting free exit of fluid, prevented the entrance of air.His reintroduction of this operation heralded a distinct advance in the treatment of thoracic effusion, and his results demonstrate its success as a means of saving life.By the introduction of his aspirator, with its admirably adapted appliances amid readily induced vacuum, Dr. Dieulafoy has furnished us with an instrument which has considerably diminished the difficulties of the operation, not only in respect of those connected with the operation itself, but those which arise from the objections of the patient.Many other aspirators have since been invented, but those which caine into use almost simultaneously, or soon after, Dr. Dieulafoy's, were Potain's and Rasmussen's. Pleumritic Eo. -Before proceeding to consider effusion into the pleura and its treatment, it is important to bear in mind the normal relations and condition of the parts involved.The pleura, which is a serous membrane, not only lines the lung, but also the parietes of the chest on each side.
Acute renal failure: definitions, diagnosis, pathogenesis, and therapy
Authors: Robert W. Schrier, Wei Wang, Brian Poole, Amit Mitra
Journal: Journal of Clinical Investigation (2004)

Acute renal failure (ARF), characterized by sudden loss of the ability of the kidneys to excrete wastes, concentrate urine, conserve electrolytes, and maintain fluid balance, is a frequent clinical problem, particularly in the intensive care unit, where it is associated with a mortality of between 50% and 80%. In this review, the epidemiology and pathophysiology of ARF are discussed, including the vascular, tubular, and inflammatory perturbations. The clinical evaluation of ARF and implications for potential future therapies to decrease the high mortality are described.
The Effect of Hemodialysis on Isoniazid, Rifampin, Pyrazinamide, and Ethambutol
Authors: REBECCA S. MALONE, DOUGLAS N. FISH, DAVID M. SPIEGEL, JAMES M. CHILDS, CHARLES A. PELOQUIN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

This study examines hemodialysis clearances of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Seven chronic hemodialysis patients were studied. Six were given single oral doses (INH 300 mg, RIF 600 mg, PZA 1000 mg, and EMB 25 mg/kg) 2 h before hemodialysis (Cobe Centrysystem 3 hemodialysis machine; Fresenius F80B dialyzer; median blood flow rate 400 ml/min; dialysate flow rate 600 ml/min; median hemodialysis time 3.5 h). The seventh subject, being treated for tuberculosis (TB), was studied with his usual regimen. Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using high-performance liquid chromatography (HPLC) (INH, RIF) and gas chromatography/mass spectrometry (GC/MS) (PZA, EMB) methods. Median recoveries of drug in dialysate were 9% (INH), 4% (RIF), 45% (PZA), and 2% (EMB) of the doses administered. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during hemodialysis were 124 (INH), 40 (RIF), 270 (PZA), and 46 (EMB) ml/min. INH, RIF, and EMB were not significantly removed by hemodialysis. PZA is significantly dialyzed and should be dosed after hemodialysis.
Differential expression and functional behaviour of the alpha v and beta 3 integrin subunits in cytokine stimulated fibroblast-like cells derived from synovial tissue of rheumatoid arthritis and osteoarthritis in vitro
Authors: N. Rinaldi, D Weis, B Brado, M Schwarz-Eywill, M Lukoschek, A Pezzutto, U Keilholz, T F E Barth
Journal: Annals of the Rheumatic Diseases (1997)

The aim of this study was to investigate in situ the expression of the classic vitronectin (VN) receptor consisting of the alpha v and beta 3 subunits in synovial lining cells (SLC) of chronic synovitis occurring in osteoarthritis (OA) and in rheumatoid arthritis (RA). The expression and function of alpha v and beta 3 as VN receptor in cultured fibroblast-like synoviocytes (FBS) derived from patients with OA and RA was also compared.Expression of alpha v and beta 3 was examined immunohistochemically in normal synovial tissue and in synovial tissue from patients with OA and RA. The effect of proinflammatory cytokines and of a synovial fluid of a patient with RA on the expression of the alpha v and beta 3 subunits of cultured FBS was determined by flow cytometry. Binding of OA and RA-FBS to VN was quantified using adhesion assays and the effect of interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) on adhesion was measured. The specificity of the adhesion was tested by inhibition studies using monoclonal antibodies to integrin subunits.In in situ studies normal SLC showed a parallel distribution of alpha v and beta 3 subunits. OA-SLC strongly and uniformly expressed alpha v whereas RA-SLC showed heterogeneous expression of alpha v. In situ both OA-SLC and RA-SLC lacked the expression of the integrin subunit beta 3. In in vitro studies, OA-FBS and RA-FBS did not differ as regards expression of alpha v and beta 3, and VN attachment. Binding of RA-FBS to VN was partially blocked by antibodies against alpha v, beta 1, and beta 3 subunits, whereas only antibodies against alpha v and beta 3 inhibited the binding of OA-FBS to VN. The proinflammatory cytokines TNF alpha and IL1 beta increased the expression of alpha v and beta 3, and the VN binding of OA-FBS, whereas alpha v and beta 3 expression, and VN binding were downregulated in RA-FBS. Similar effects were found when the synovial fluid of an RA patient was used.The integrin subunit beta 3 seems to be one partner but not the major one with which the subunit alpha v forms functional vitronectin receptors in OA-FBS and RA-FBS. The interaction between synovial cells and inflammatory cytokines seems to be different for OA and RA; the basis for this difference, however, remains to be established.
Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer
Authors: I. Treilleux, M. Arnedos, C. Cropet, Q. Wang, J.-M. Ferrero, S. Abadie-Lacourtoisie, C. Levy, E. Legouffe, A. Lortholary, E. Pujade-Lauraine, A.-V. Bourcier, J.-C. Eymard, D. Spaeth, T. Bachelot
Journal: Annals of Oncology (2014)
Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans
Authors: Daniel G MacArthur, Jane T Seto, Joanna M Raftery, Kate G Quinlan, Gavin A Huttley, Jeff W Hook, Frances A Lemckert, Anthony J Kee, Michael R Edwards, Yemima Berman, Edna C Hardeman, Peter W Gunning, Simon Easteal, Nan Yang, Kathryn N North
Journal: Nature Genetics (2007)
Effect of recombinant human erythropoietin on anaemia and disease activity in patients with rheumatoid arthritis and anaemia of chronic disease: a randomised placebo controlled double blind 52 weeks clinical trial.
Authors: H.R Peeters, M Jongen-Lavrencic, G Vreugdenhil, A.J Swaak
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To study whether recombinant human erythropoietin (r-hu-Epo) improves anaemia and reduces disease activity in patients with rheumatoid arthritis and anaemia of chronic disease (ACD). METHODS: A 52 week placebo controlled randomised double blind trial with r-hu-Epo was performed in 70 patients with active rheumatoid arthritis and ACD. Thirty four patients were treated with 240 U kg-1 r-hu-Epo subcutaneously, initially three doses weekly, while 36 patients received placebo. RESULTS: A significant increase of haemoglobin from a median of 112 to 135 g litre-1 occurred in the Epo group within six weeks and could be sustained with reduced doses (median 240 U kg-1 once weekly). Sustained benefit compared to placebo was also apparent by six weeks for disease activity, as indicated by the Paulus 20% response rate. Of patients in the Epo group, 32% eventually showed a Paulus 20% response, compared to 8% of the placebo group (P = 0.016). Significant differences in favour of the Epo group were also observed in the secondary disease activity measures Ritchie index, number of swollen joints, pain score, ESR, and patients9 global assessment of disease activity. C reactive protein concentrations did not change significantly. CONCLUSIONS: Treatment of ACD in rheumatoid arthritis with r-hu-Epo is effective in restoring normal haemoglobin levels and also exerts a beneficial effect on disease activity.