tbuckley/cabot-search huggingface dataset:
WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update
Authors: D. Falzon, E. Jaramillo, H.J. Schünemann, M. Arentz, M. Bauer, J. Bayona, L. Blanc, J.A. Caminero, C.L. Daley, C. Duncombe, C. Fitzpatrick, A. Gebhard, H. Getahun, M. Henkens, T.H. Holtz, J. Keravec, S. Keshavjee, A.J. Khan, R. Kulier, V. Leimane, C. Lienhardt, C. Lu, A. Mariandyshev, G.B. Migliori, F. Mirzayev, C.D. Mitnick, P. Nunn, G. Nwagboniwe, O. Oxlade, D. Palmero, P. Pavlinac, M.I. Quelapio, M.C. Raviglione, M.L. Rich, S. Royce, S. Rüsch-Gerdes, A. Salakaia, R. Sarin, D. Sculier, F. Varaine, M. Vitoria, J.L. Walson, F. Wares, K. Weyer, R.A. White, M. Zignol
Journal: European Respiratory Journal (2011)

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.
Telerehabilitation Research: Emerging Opportunities
Authors: Jack M. Winters
Journal: Annual Review of Biomedical Engineering (2002)

The field of clinical rehabilitation is rooted in the premise that carefully planned and delivered therapeutic intervention enhances patient outcomes. Underlying this statement is a deeper scientific reality: The field exists because biosystems (e.g., tissues, cells, organs, persons) are inherently adaptive and can dynamically change as a function of a sequence of inputs (e.g., exercise, pharmaceuticals). The tools of telerehabilitation help minimize the barrier of distance, both of patients to rehabilitative services and of researchers to subject populations. This enhanced access opens up new possibilities for discovering and implementing optimized intervention strategies across the continuum of care. Telecommunications technologies are reviewed from the perspective of systems models of the telerehabilitation process, with a focus on human-technology interface design and a special emphasis on emerging home and mobile technologies. Approaches for providing clinical rehabilitation services through telerehabilitation are addressed, including innovative consumer-centered approaches. Finally, telerehabilitation is proposed as a tool for reinvigorating the rehabilitative bioengineering research enterprise.
Reduction in Disease Progression by Inhibition of Transforming Growth Factor α–CCL2 Signaling in Experimental Posttraumatic Osteoarthritis
Authors: C. Thomas G. Appleton, Shirine E. Usmani, Michael A. Pest, Vasek Pitelka, John S. Mort, Frank Beier
Journal: Arthritis & Rheumatology (2015)

Objective Transforming growth factor α (TGFα) is increased in osteoarthritic (OA) cartilage in rats and humans and modifies chondrocyte phenotype. CCL2 is increased in OA cartilage and stimulates proteoglycan loss. This study was undertaken to test whether TGFα and CCL2 cooperate to promote cartilage degradation and whether inhibiting either reduces disease progression in a rat model of posttraumatic OA. Methods Microarray analysis was used to profile expression of messenger RNA (mRNA) for Tgfa , Ccl2 , and related genes in a rat model of posttraumatic OA. Rat primary chondrocytes and articular cartilage explants were treated with TGFα in the presence or absence of MEK‐1/2, p38, phosphatidylinositol 3‐kinase, Rho‐associated protein kinase, or CCR2 inhibitors and immunostained for markers of cartilage degradation. The rat model was used to administer pharmacologic inhibitors of TGFα (AG1478) and CCL2 (RS504393) signaling for up to 10 weeks and assess histopathology and serum biomarkers of cartilage synthesis (C‐propeptide of type II collagen [CPII]) and breakdown (C2C). Results Tgfa and Ccl2 mRNA were simultaneously up‐regulated in articular cartilage in the rat model of posttraumatic OA. TGFα induced expression of CCL2 , Mmp3 , and Tnf in primary chondrocytes. Cleavage of type II collagen and aggrecan (by matrix metalloproteinases and ADAMTS‐4/5, respectively) induced by TGFα was blocked by pharmacologic inhibition of CCL2 in cartilage explants. In vivo pharmacologic inhibition of TGFα or CCL2 signaling reduced Osteoarthritis Research Society International cartilage histopathology scores and increased serum CPII levels, but only TGFα inhibition reduced C2C levels intreated versus untreated rat OA cartilage. Conclusion TGFα signaling stimulates cartilage degradation via a CCL2‐dependent mechanism, but pharmacologic inhibition of the TGFα–CCL2 axis reduces experimental posttraumatic OA progression in vivo.
Pioglitazone Reduces Neointima Volume After Coronary Stent Implantation
Authors: Nikolaus Marx, Jochen Wöhrle, Thorsten Nusser, Daniel Walcher, Angelika Rinker, Vinzenz Hombach, Wolfgang Koenig, Martin Höher
Journal: Circulation (2005)

Background— Restenosis requiring reintervention limits the long-term success after coronary stent implantation. Thiazolidinediones, like pioglitazone or rosiglitazone, are oral antidiabetic drugs with additional antirestenotic properties. In a randomized, placebo-controlled, double-blind trial, we examined the effect of 6-month pioglitazone therapy on neointima volume after coronary stenting in nondiabetic coronary artery disease patients. Methods and Results— Fifty nondiabetic patients after coronary stent implantation were randomly assigned to pioglitazone (30 mg daily; pio) or placebo (control) treatment in addition to standard therapy, and neointima volume was assessed by intravascular ultrasound at the 6-month follow-up. Both groups were comparable with regard to baseline characteristics, angiographic lesion morphology, target vessel, and length of the stented segment. In addition, there were no statistical differences in minimal lumen diameter before and after intervention, as well as reference diameter after stent implantation. In this study population of nondiabetic patients, pio treatment did not significantly change fasting blood glucose, fasting insulin, or glycosylated hemoglobin levels, as well as lipid parameters. In contrast, pio treatment significantly reduced neointima volume within the stented segment, with 2.3±1.1 mm 3 /mm in the pio group versus 3.1±1.6 mm 3 /mm in controls ( P =0.04). Total plaque volume (adventitia-lumen area) was significantly lower at follow-up in the pio group (11.2±3.2 mm 3 /mm) compared with controls (13.2±4.2 mm 3 /mm; P =0.04). Moreover, the binary restenosis rate was 3.4% in the pio group versus 32.3% in controls ( P &lt;0.01). Conclusions— Thus, 6-month treatment with pio significantly reduced neointima volume after coronary stent implantation in nondiabetic patients. These data bolster the hypothesis that antidiabetic thiazolidinediones, in addition to their metabolic effects, exhibit direct antirestenotic effects in the vasculature.
LIVER FUNCTION TESTS IN CHRONIC RELAPSING VIVAX MALARIA 1
Authors: Stuart W. Lippincott, Lester D. Ellerbrook, Wm. B. Hesselbrock, Harry H. Gordon, Leo Gottlieb, Alexander Marble
Journal: Journal of Clinical Investigation (1945)

Hepatic function in chronic relapsing malaria caused by Plasmodium vivax and treated princi- pally by atabrine has been investigated at Harmon General Hospital in 317 soldiers.This study seemed advisable because of previous reports that impairment of liver function may occur in both naturally-acquired (1 to 3) and induced malaria (4).Several types of tests were performed on our patients both during recurrent attacks and at various intervals afterwards.Most of these same tests were also performed on healthy individuals to determine whether in our laboratory the meth- ods gave normal ranges of values corresponding to those found in the literature.This made it pos- sible to compare the findings in our patients with those of our healthy control series, as well as with the results of other investigators.The liver function tests used may be grouped roughly into 3 categories: (a) those in which hepatic dysfunction is suspected when abnormal values are found-bromsulfalein, cephalin floccu- lation, galactose tolerance and hippuric acid tests; (b) those in which an abnormal value may be as- sociated with increased red blood cell destruction and/or hepatic dysfunction-icterus index, serum bilirubin concentration, and urine urobilinogen concentration; and (c) quantitative determina- tions of some constituents of blood serum occa- sionally found to yield abnormal results in persons with hepatic disease-albumin, globulin, total pro- tein, cholesterol and phosphatase.METHODS 1. Bromsulfalein (5): The amount of dye injected in- travenously was 5 mgm.per kgm. of body weight.The permanent standards used were supplied by Hynson, Westcott and Dunning.Since the standards were pre- pared for the 2 mgm.test, the calculations were made by dividing the readings obtained by 2.5.
The Association Between Genes in the Major Histocompatibility Complex and Disease Susceptibility
Authors: T Sasazuki, H O McDevitt, F C Grumet
Journal: Annual Review of Medicine (1977)

During the past four years, there has been an extraordinarily rapid accumulation of evidence showing that genes of the human major histocompatibility system have a marked effect on susceptibility to a wide variety of diseases. The human major histocompatibility system is a'cluster of genes on the VIth human chromosome that determine the structure of cell-surface glycoproteins found on all the cells of the body. These glycoproteins differ from individual to individual and form a complex set of antigenic determinants that constitute the strongest (major) antigenic barrier to tissue transplantation between genetically nonidentical individuals. In addition, by analogy to the major histocompatibility system in several animal species, other genes in the same chromosomal region have marked regulatory effects on immune responsiveness to a wide variety of antigens. Indeed, it appears that almost all of the genes that have been identified in this chromosomal region have some effect upon, or relation to, the immune system, as is shown below. Perhaps the first demonstration of an association between the major histocompati­ bility system and susceptibility or resistance to disease was reported by Lilly (I), who showed that genes linked to the mouse major histocompatibility system, the H-2 system, determined resistance to Gross virus-induced leukemia. The mecha­ nism of action of this genetic factor for resistance to viral leukemogenesis was not
Origins and Functions of B-1 Cells with Notes on the Role of CD5
Authors: Robert Berland, Henry H. Wortis
Journal: Annual Review of Immunology (2002)

Whether B-1a (CD5+) cells are a distinct lineage derived from committed fetal/neonatal precursors or arise from follicular B-2 cells in response to BCR ligation and other, unknown signals remains controversial. Recent evidence indicates that B-1a cells can derive from adult precursors expressing an appropriate specificity when the (self-) antigen is present. Antibody specificity determines whether a B cell expressing immunoglobulin transgenes has a B-2, B-1a or marginal zone (MZ) phenotype. MZ cells share many phenotypic characteristics of B-1 cells and, like them, appear to develop in response to T independent type 2 antigens. Because fetal-derived B cell progenitors fail to express terminal deoxynucleotidyl transferase (TdT) and for other reasons, they are likely to express a repertoire that allows selection into the B-1a population. As it is selected by self-antigen, the B-1 repertoire tends to be autoreactive. This potentially dangerous repertoire is also useful, as B-1 cells are essential for resistance to several pathogens and they play an important role in mucosal immunity. The CD5 molecule can function as a negative regulator of BCR signaling that may help prevent inappropriate activation of autoreactive B-1a cells.
Increased Expression of Secreted Frizzled-Related Protein 4 in Polycystic Kidneys
Authors: Daniel Romaker, Michael Puetz, Sven Teschner, Johannes Donauer, Marcel Geyer, Peter Gerke, Brigitta Rumberger, Bernd Dworniczak, Petra Pennekamp, Bjo[Combining Diaeresis] Buchholz, H.P.H. Neumann, Rajiv Kumar, Joachim Gloy, Kai-Uwe Eckardt, Gerd Walz
Journal: Journal of the American Society of Nephrology (2008)

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease associated with progressive renal failure. Although cyst growth and compression of surrounding tissue may account for some loss of renal tissue, the other factors contributing to the progressive renal failure in patients with ADPKD are incompletely understood. Here, we report that secreted frizzled-related protein 4 (sFRP4) is upregulated in human ADPKD and in four different animal models of PKD, suggesting that sFRP4 expression is triggered by a common mechanism that underlies cyst formation. Cyst fluid from ADPKD kidneys activated the sFRP4 promoter and induced production of sFRP4 protein in renal tubular epithelial cell lines. Antagonism of the vasopressin 2 receptor blocked both promoter activity and tubular sFRP4 expression. In addition, sFRP4 selectively influenced members of the canonical Wnt signaling cascade and promoted cystogenesis of the zebrafish pronephros. sFRP4 was detected in the urine of both patients and animals with PKD, suggesting that sFRP4 may be a potential biomarker for monitoring the progression of ADPKD. Taken together, these observations suggest a potential role for SFRP4 in the pathogenesis of ADPKD.
Loss of Nuclear Factor-κB Is Tumor Promoting but Does Not Substitute for Loss of p53
Authors: Kevin M. Ryan, Jim O’Prey, Karen H. Vousden
Journal: Cancer Research (2004)

Abstract Inactivation of apoptotic pathways is a common event in cancer. Two transcription factors that regulate apoptosis during tumorigenesis are p53 and nuclear factor (NF)-κB. Although NF-κB is generally considered a suppressor of cell death, we showed previously that NF-κB can contribute to p53-induced death. Here, we show that loss of p65, a critical subunit of NF-κB, can cause resistance to different agents that signal death through p53. Loss of p65 also enhances tumorigenesis induced by E1a and Ras. Unlike loss of p53, however, loss of p65 does not cause anchorage-independent growth or enable tumor development following expression of a single oncogene. These findings reaffirm the role of NF-κB in p53-induced death but show that its loss does not substitute for loss of p53 in tumor development. Moreover, this indicates that, although perhaps central to p53 function, loss of the ability to induce programmed cell death does not completely inactivate p53’s tumor-suppressive effects.
Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement
Authors: O. Vandenplas, H. Suojalehto, T. B. Aasen, X. Baur, P. S. Burge, F. de Blay, D. Fishwick, J. Hoyle, P. Maestrelli, X. Munoz, G. Moscato, J. Sastre, T. Sigsgaard, K. Suuronen, J. Walusiak-Skorupa, P. Cullinan
Journal: European Respiratory Journal (2014)

This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed. Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare. A positive response is defined by a fall in forced expiratory volume in 1 s ≥ 15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma.
The disappearing gallstone and the National Cooperative Gallstone Study
Authors: L. J. Schoenfeld
Journal: JAMA (1978)

Thistle, Hofmann, and colleagues, in two articles in JAMA (239:1041-1046, 1978, and in this issue, p 1138), have summarized the total pioneering Mayo Clinic experience with chenodeoxycholic acid (CDC) for dissolution of gallstones, clearly attesting to the efficacy of CDC capsules. They found that the dose of CDC, the size and type of stones, and roentgenographic visualization of the gallbladder were important, though incomplete, determinants of response. In addition, an uncontrolled observation by the Mayo group warranting further study was the disappearance of stones in the common bile duct of five of ten patients treated with CDC orally.  The investigators concluded that this agent continues to appear promising as medical therapy for radiolucent gallstones in the gallbladder. With appropriate caution, however, they indicated the need for more information on specific determinants of efficacy, the long-term safety of CDC, and on the medical management of gallstone recurrence after dissolution.  Although CDC
Genetic Predisposition for Chemotherapy-Induced Neuropathy in Multiple Myeloma
Authors: Pamela S. Becker
Journal: Journal of Clinical Oncology (2011)

INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 363(12):1117-1127, 2010 4. Pardanani A, Gotlib JR, Jamieson C, et al: Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 29:789796, 2011 5. Santos FP, Kantarjian HM, Jain N, et al: Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/ essential thrombocythemia myelofibrosis. Blood 115:1131-1136, 2010 6. Verstovsek S: Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis. Clin Cancer Res 16:1988-1996, 2010 7. Barosi G, Bergamaschi G, Marchetti M, et al: JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood 110:4030-4036, 2007 8. Guglielmelli P, Barosi G, Specchia G, et al: Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood 114:1477-1483, 2009 9. Tefferi A, Lasho TL, Huang J, et al: Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 22:756-761, 2008 10. Mesa RA: How I treat symptomatic splenomegaly in patients with myelofibrosis. Blood 113:5394-5400, 2009 11. Steensma DP, Mesa RA, Li CY, et al: Etanercept, a soluble tumor necrosis factor receptor, palliates constitutional symptoms in patients with myelofibrosis with myeloid metaplasia: Results of a pilot study. Blood 99: 2252-2254, 2002 12. Jedidi A, Marty C, Oligo C, et al: Selective reduction of JAK2V617Fdependent cell growth by siRNA/shRNA and its reversal by cytokines. Blood 114:1842-1851, 2009 13. Mesa RA, Kantarjian H, Tefferi A, et al: Functional assessment of performance status in patients with myelofibrosis (MF): Utility and feasibility of the 6-minute walk test (6MWT). J Clin Oncol 27:376s, 2009 (suppl; abstr 7083)
Proteomic and Genetic Approaches Identify Syk as an AML Target
Authors: Cynthia K. Hahn, Jacob E. Berchuck, Kenneth N. Ross, Rose M. Kakoza, Karl Clauser, Anna C. Schinzel, Linda Ross, Ilene Galinsky, Tina N. Davis, Serena J. Silver, David E. Root, Richard M. Stone, Daniel J. DeAngelo, Martin Carroll, William C. Hahn, Steven A. Carr, Todd R. Golub, Andrew L. Kung, Kimberly Stegmaier
Journal: Cancer Cell (2009)
Potentiation of Lonidamine and Diazepam, Two Agents Acting on Mitochondria, in Human Glioblastoma Treatment
Authors: Laurent Miccoli, Florence Poirson-Bichat, Franck Sureau, Rui Bras Gonçalves, Yveline Bourgeois, Bernard Dutrillaux, Marie-France Poupon, Stéphane Oudard
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Cellular metabolism in glioblastoma multiforme, the most common primary brain tumor in humans, is characterized by a high rate of aerobic glycolysis that is dependent on mitochondria-bound hexokinase. Moreover, high levels of glucose utilization and tumor aggressiveness in glioblastoma are associated with a high density of mitochondrial benzodiazepine receptors. We sought to inhibit glioblastoma metabolism by simultaneously inhibiting hexokinase with lonidamine and binding benzodiazepine receptors with diazepam. Methods: Cellular glioblastoma metabolism in five glioblastoma cell lines was assessed in vitro by measuring cell proliferation (by use of a tetrazolium-based colorimetric assay, measurement of DNA synthesis, and assessment of cell cycle distribution), by measuring membrane fluidity (by fluorescence polarization measurement of cells stained with a fluorescent probe), and by measuring changes in intracellular pH. Immunodeficient nude mice bearing subcutaneous xenografts of human glioblastoma cells were used to assess the antitumor activities of lonidamine and diazepam; the mice were treated twice daily with lonidamine (total daily dose of 160 mg/kg body weight) and/or diazepam (total daily dose of 1 mg/kg body weight) for 10 consecutive days. Results: When used in combination, the two drugs had a stronger effect on glioblastoma cell proliferation and metabolism in vitro than did either agent used alone. in vivo, the combination of lonidamine and diazepam was significantly more effective in reducing glioblastoma tumor growth than either drug alone (two-sided P<.01, Mann-Whitney U test, comparing growth of treated tumors with that of untreated tumors); this tumor growth retardation was maintained as long as treatment was given. Conclusion: The combination of lonidamine and diazepam—drugs that target two distinct mitochondrial sites involved in cellular energy metabolism— potentiates the effects of the individual drugs and may prove useful in the treatment of human glioblastomas. [J Natl Cancer Inst 1998;90:1400-6]