tbuckley/cabot-search huggingface dataset:
Screening for Skin Cancer: An Update of the Evidence for the U.S. Preventive Services Task Force
Authors: Tracy Wolff
Journal: Annals of Internal Medicine (2009)

Background: Skin cancer is the most commonly diagnosed cancer in the United States. The majority of skin cancer is nonmelanoma cancer, either basal cell cancer or squamous cell cancer. The incidence of both melanoma and nonmelanoma skin cancer has been increasing over the past 3 decades. In 2001, the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against routine screening for skin cancer by using whole-body skin examination for early detection of skin cancer. Purpose: To update the evidence of benefits and harms of screening for skin cancer in the general population. Data Sources: MEDLINE and Cochrane Library searches from 1 June 1999 to 9 August 2005 for English-language articles; recent systematic reviews; reference lists of retrieved articles; and expert suggestions. Study Selection: English-language studies were selected to answer the following key question: Does screening in asymptomatic persons with whole-body examination by a primary care clinician or by self-examination reduce morbidity and mortality from skin cancer? Randomized, controlled trials and case–control studies of screening for skin cancer were selected. One author selected English-language studies to answer the following contextual questions: Can screening with whole-body examination by primary care clinicians or by self-examination accurately detect skin cancer? Does screening with whole-body examination or by self-examination detect melanomas at an earlier stage (thinner lesions)? Data Extraction: All studies for the key question were reviewed, abstracted, and rated for quality by using predefined USPSTF criteria. Data Synthesis: No new evidence from controlled studies was found that addressed the benefit of screening for skin cancer with a whole-body examination by a physician. One article of fair quality, which reanalyzed data from a 1996 study identified for the 2001 report for the USPSTF, provides limited but insufficient evidence on the benefit of skin self-examination in the reduction of morbidity and mortality from melanoma. Limitations: Direct evidence linking skin cancer screening to improved health outcomes is lacking. Information is limited on the accuracy of screening by physicians or patients using real patients and lesions. Conclusion: The limited evidence prevents accurate estimation of the benefits of screening for skin cancer in the general primary care population.
Update on osteoarthritis part 1: current concepts and the relation to exercise
Authors: P G Conaghan
Journal: British Journal of Sports Medicine (2002)

There appears to be an increased risk of lower limb osteoarthritis in participants of repetitive, high impact sports, and this is strongly associated with joint injury. There seems to be little risk associated with recreational running. Assessment of risk for osteoarthritis should take into account the nature of the sport, intensity of training, presence of previous injury, body mass index, and occupation.
Resistance training in musculoskeletal rehabilitation: a systematic review
Authors: Jakob Kristensen, Andy Franklyn-Miller
Journal: British Journal of Sports Medicine (2011)

Objective To review the efficacy of resistance training (RT) as a therapeutic modality in various musculoskeletal conditions. Design Systematic review. Subjects Data from 1545 rehabilitation patients who had participated in structured RT programmes were included into the review. The total number of patients was composed of separate musculoskeletal conditions—chronic low back pain (CLBP) (549), tendinopathy (299), knee osteoarthritis (433), anterior cruciate ligament reconstruction (189) and hip replacement surgery (75). Results Evidence suggests that RT can increase muscle strength, reduce pain and improve functional ability in patients suffering from CLBP, knee osteoarthritis, and chronic tendinopathy and those under recovery after hip replacement surgery. Conclusion RT can be used successfully as a therapeutic modality in several musculoskeletal conditions, especially those of a chronic variety. Although the exact application of training intensity and volume for maximal therapeutic effects is still unclear, it appears that RT guidelines, which have proven effective in a healthy population, can also be successfully applied in a rehabilitation context.
The nuclear receptor PPARγ selectively inhibits Th17 differentiation in a T cell–intrinsic fashion and suppresses CNS autoimmunity
Authors: Luisa Klotz, Sven Burgdorf, Indra Dani, Kaoru Saijo, Juliane Flossdorf, Stephanie Hucke, Judith Alferink, Natalija Novak, Marc Beyer, Gunter Mayer, Birgit Langhans, Thomas Klockgether, Ari Waisman, Gerard Eberl, Joachim Schultze, Michael Famulok, Waldemar Kolanus, Christopher Glass, Christian Kurts, Percy A. Knolle
Journal: The Journal of Experimental Medicine (2009)

T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-β/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor–related orphan receptor γt (RORγt). We identify the nuclear receptor peroxisome proliferator–activated receptor γ (PPARγ) as a key negative regulator of human and mouse Th17 differentiation. PPARγ activation in CD4+ T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentiation by PPARγ involved inhibition of TGF-β/IL-6–induced expression of RORγt in T cells. Pharmacologic activation of PPARγ prevented removal of the silencing mediator for retinoid and thyroid hormone receptors corepressor from the RORγt promoter in T cells, thus interfering with RORγt transcription. Both T cell–specific PPARγ knockout and endogenous ligand activation revealed the physiological role of PPARγ for continuous T cell–intrinsic control of Th17 differentiation and development of autoimmunity. Importantly, human CD4+ T cells from healthy controls and MS patients were strongly susceptible to PPARγ-mediated suppression of Th17 differentiation. In summary, we report a PPARγ-mediated T cell–intrinsic molecular mechanism that selectively controls Th17 differentiation in mice and in humans and that is amenable to pharmacologic modulation. We therefore propose that PPARγ represents a promising molecular target for specific immunointervention in Th17-mediated autoimmune diseases such as MS.
The Radioisotope Contributes Significantly to the Activity of Radioimmunotherapy
Authors: Thomas A. Davis, Mark S. Kaminski, John P. Leonard, Frank J. Hsu, Mary Wilkinson, Andrew Zelenetz, Richard L. Wahl, Stewart Kroll, Morton Coleman, Michael Goris, Ronald Levy, Susan J. Knox
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A multicenter, randomized study was undertaken to estimate the single agent activity of Tositumomab and to determine the contribution of radioisotope-labeling with 131I to activity and toxicity by comparing treatment outcomes for Tositumomab and Iodine I 131 Tositumomab (BEXXAR) to an equivalent total dose of unlabeled Tositumomab. Experimental Design: Seventy-eight patients with refractory/relapsed non-Hodgkin’s lymphoma were randomized to either unlabeled Tositumomab or Iodine I 131 Tositumomab. Patients progressing after unlabeled Tositumomab could cross over to receive Iodine I 131 Tositumomab. The median follow-up at analysis was 42.6 months (range 1.9 to 71.5 months). Results: Responses in the Iodine I 131 Tositumomab versus unlabeled Tositumomab groups: overall response 55% versus 19% (P = 0.002); complete response 33% versus 8% (P = 0.012); median duration of overall response not reached versus 28.1 months (95% confidence interval: 7.6, not reached); median duration of complete response not reached in either arm; and median TTP 6.3 versus 5.5 months (P = 0.031), respectively. Of the patients who had a complete response after initial Iodine I 131 Tositumomab therapy, 71% (10 of 14) continued in complete response at 29.8 to 71.1 months. Two patients who achieved a complete response after unlabeled Tositumomab had ongoing responses at 48.1 to 56.9 months. Nineteen patients received Iodine I 131 Tositumomab crossover therapy. Responses after crossover versus prior response to unlabeled Tositumomab were as follows: complete response rates of 42% versus 0% (P = 0.008); overall response 68% versus 16% (P = 0.002); median durations of overall response 12.6 versus 7.6 months (P = 0.001); and median TTP 12.4 versus 5.5 months (P = 0.01), respectively. Hematologic toxicity was more severe and nonhematologic adverse events were more frequent after Iodine I 131 Tositumomab than after Tositumomab alone. Elevated thyrotropin occurred in 5% of patients. Seroconversion to human antimurine antibody after Iodine I 131 Tositumomab, unlabeled Tositumomab, and Iodine I 131 Tositumomab-crossover was 27%, 19%, and 0%, respectively. Conclusions: Unlabeled Tositumomab showed single agent activity, but in this direct comparison, all of the therapeutic outcome measures were significantly enhanced by the conjugation of 131I to Tositumomab.
1098-101 Risk stratification in unstable angina/non-ST elevation myocardial infarction using plasma N-terminal pro-atrial natriuretic peptide, troponin I and high-sensitive C-reactive protein levels
Authors: Rudolf Jarai, Nelly Jordanova, Robert Jarai, Wolfgang Woloszczuk, Johann Wojta, Kurt Huber
Journal: Journal of the American College of Cardiology (2004)
Hormonal and Physiological Background in the Production of B Particles by the Mouse Mammary Epithelium in Organ Cultures
Authors: Etienne Y. Lasfargues, Dorothy Gelber Feldman
Journal: Cancer Research (1963)

The production of B particles in organ cultures of RIII mammary glands can be influenced by hormonal stimulation. The results depend on the physiological status of the explants and the type of hormone used.

Two peaks of higher production of B particles have been observed through the pregnancy-lactation cycle of the glands: the first one, in early pregnancy, is induced by an ovarian-hypophyseal combination. It corresponds to an active alveolar differentiation and growth of the epithelium. The second, in lactation, is originated by the combined effects of two secretory inducing hormones: mammotropin and cortisol. This corresponds to a period of functional activity. In either case the formation of the B particles occurs in a phase of high protein synthesis and depends on the complete physiological integrity of the cell. The absence of hormonal stimulation or the effects of an improper combination results in the inhibition of B particles production.

Duplicate cultures of agent-free C57 mammary tissues react morphologically to the various hormone combinations in the same fashion as the RIII's; however, no B particle is formed. This is considered as further evidence that the viral particles produced in agent-positive RIII cultures might represent the milk factor.
High failure rate in spinal ependymomas with long-term follow-up
Authors: D. R. Gomez, B. T. Missett, W. M. Wara, D. A. Larson, P. K. Sneed, M. D. Prados, S. M. Chang, M. S. Berger, N. Gupta, D. A. Haas-Kogan
Journal: Journal of Clinical Oncology (2004)

1528 Background: Data on spinal ependymomas are sparse, and the prognostic value of many clinical variables remains controversial. The purpose of this study is to review a historical cohort of patients with spinal cord ependymomas treated with post-operative radiotherapy and assess the impact of extent of resection and radiation dose on progression-free survival (PFS) and overall survival (OS). We hoped the large patient number and long follow-up would lead to significant and relevant conclusions about a relatively rare and indolent disease. Methods: Thirty-seven patients with primary spinal cord ependymomas received postoperative radiation therapy from 1955–2001. The influence of radiation dose (range 45–59.4 Gy), extent of resection, KPS, tumor location, multifocality, and tumor grade was analyzed using the Cox proportional hazards model. Results: With a median follow-up of 157 months (range 8–492), 5-, 10-, and 15-year PFS rates are 75% ± 7.4%, 50% ± 9.1%, and 46% ± 9.3%, respectively, while OS rates are 83% ± 6.2, 74% ± 7.5%, and 61% ± 8.5%, respectively. The median time to recurrence is 68 months, with 57% of failures occurring after 5 years. Of the prognostic factors examined, only greater extent of resection significantly correlated with longer PFS (P=0.001). High-grade histology was associated with worse PFS in multivariate analysis (P=0.027). Conclusions: Large patient numbers and long follow-up demonstrate that local relapse rates for spinal ependymomas are higher than previously cited, with a large proportion of failures occurring more than 5 years after diagnosis. Aggressive surgical resection correlates with improved outcome and we thus recommend excision aimed at maximal resection while avoiding surgical morbidity. Regardless of the extent of resection, we recommend postoperative radiation to doses of 50–54 Gy and extended, close follow-up. No significant financial relationships to disclose.
Prevalence and risk factors of hepatitis C virus infection in haemodialysis patients: a multicentre study in 2796 patients
Authors: H Hinrichsen
Journal: Gut (2002)

<b>Background:</b> Hepatitis C virus (HCV) infection is a significant problem in the management of haemodialysis patients. A high prevalence of HCV infection in haemodialysis patients has been reported. Risk factors such as the number of blood transfusions or duration on haemodialysis have been identified. <b>Aim:</b> To determine the prevalence of HCV by antibody testing and HCV-RNA determination by polymerase chain reaction (PCR) in haemodialysis patients. Furthermore, liver function tests were performed and epidemiological data were obtained to determine risk factors for HCV in this cohort of patients. <b>Results:</b> A total of 2796 patients from 43 dialysis centres were enrolled. The overall prevalence of HCV (HCV antibody and/or HCV-RNA positivity) was 7.0% (195 patients). Antibody positivity occurred in 171 patients (6.1%). Viraemia was detectable in 111 patients (4.0%). Twenty four of 111 HCV RNA positive patients (21.6%) were negative for HCV antibodies. Thus 0.8% of the entire study population was HCV positive but could not be diagnosed by routine HCV antibody testing. Major risk factors identified by a standard questionnaire in 1717 of 2796 patients were the number of blood transfusions individuals had received and duration of dialysis, the latter including patients who received no blood transfusions. Sequencing of the 5`untranslated region of the genome showed a dominant genotype 1 (77.6%) within the cohort. Further reverse transcription-PCR of the NS5b and core region were performed to document phylogenetic analysis. Comparing nucleic acid sequences detected by PCR, no homogeneity was found and thus nosocomial transmission was excluded. <b>Conclusions:</b> HCV is common in German haemodialysis patients but screening for HCV antibodies alone does not exclude infection with HCV.
Deficient interleukin 2 dependent proliferation pathway in T lymphocytes from active and inactive ulcerative colitis patients.
Authors: L Manzano, M Alvarez-Mon, J A Vargas, J A Giron, L Abreu, A Fernandez-Corugedo, L I Roman, F Albarran, A Durantez
Journal: Gut (1994)

There is increasing evidence that ulcerative colitis is associated with an abnormality of the immune system. Although the aetiology remains unknown, it has been suggested that the immune system of these patients is implicated in the pathogenesis of their disease. T cell function was investigated in ulcerative colitis patients and defective phytohaemagglutinin induced T cell mitogenesis was found. The DNA synthesis induced by stimulation with phorbol esters plus ionophore (ionomycin), however, was normal. These changes cannot be ascribed to either decreased interleukin 2 synthesis or to a defective interleukin 2 receptor expression after cellular activation. Moreover, this defective proliferative response of the T lymphocytes was observed even in the presence of saturated concentrations of exogenous interleukin 2. These results emphasise that the interleukin 2 dependent proliferation pathway is deficient in T lymphocytes from ulcerative colitis patients.
Evidence for the involvement of interleukin 6 in experimental cancer cachexia.
Authors: G Strassmann, M Fong, J S Kenney, C O Jacob
Journal: Journal of Clinical Investigation (1992)

In this report we describe an experimental model of cachexia that fulfills the criteria of an early effect with a small tumor mass not related to the growth rate of the tumor, and progressive wasting of muscle and fat without a detectable loss of appetite. C-26.IVX is a cell line derived from murine colon-26 adenocarcinoma which retains the transplantability of the original tumor and induces true cachexia in syngeneic hosts. Evidence is presented to support a role for interleukin (IL-6) as a cachectic factor in the development of cancer cachexia in this model system. Thus, increasing levels of IL-6 in C-26.IVX-bearing mice correlate with the development of cachexia. If the primary tumors were resected, mice gained weight and the levels of IL-6 in the serum were reduced significantly. Moreover, monoclonal antibody to murine IL-6 (but not anti-tumor necrosis factor antibody) was able to significantly suppress the development of key parameters of cachexia in tumor bearing mice.
Cancer stem cells in basic science and in translational oncology: can we translate into clinical application?
Authors: Axel Schulenburg, Katharina Blatt, Sabine Cerny-Reiterer, Irina Sadovnik, Harald Herrmann, Brigitte Marian, Thomas W Grunt, Christoph C Zielinski, Peter Valent
Journal: Journal of Hematology & Oncology (2015)

Since their description and identification in leukemias and solid tumors, cancer stem cells (CSC) have been the subject of intensive research in translational oncology. Indeed, recent advances have led to the identification of CSC markers, CSC targets, and the preclinical and clinical evaluation of the CSC-eradicating (curative) potential of various drugs. However, although diverse CSC markers and targets have been identified, several questions remain, such as the origin and evolution of CSC, mechanisms underlying resistance of CSC against various targeted drugs, and the biochemical basis and function of stroma cell-CSC interactions in the so-called 'stem cell niche.' Additional aspects that have to be taken into account when considering CSC elimination as primary treatment-goal are the genomic plasticity and extensive subclone formation of CSC. Notably, various cell fractions with different combinations of molecular aberrations and varying proliferative potential may display CSC function in a given neoplasm, and the related molecular complexity of the genome in CSC subsets is considered to contribute essentially to disease evolution and acquired drug resistance. In the current article, we discuss new developments in the field of CSC research and whether these new concepts can be exploited in clinical practice in the future.
Does nitric oxide modulate cardiac ryanodine receptor function? Implications for excitation-contraction coupling
Authors: G. Lim, L. Venetucci, D. A. Eisner, B. Casadei
Journal: Cardiovascular Research (2007)

Nitric oxide (NO) is a highly reactive, free radical signalling molecule that is constitutively released in cardiomyocytes by both the endothelial and neuronal isoforms of nitric oxide synthase (eNOS and nNOS, respectively). There are increasing data indicating that NO modulates various proteins involved in excitation–contraction coupling (ECC), and here we discuss the evidence that NO may modulate the function of the ryanodine receptor Ca2+ release channel (RyR2) on the cardiac sarcoplasmic reticulum (SR). Both constitutive isoforms of NOS have been shown to co-immunoprecipitate with RyR2, suggesting that the channel may be a target protein for NO. eNOS gene deletion has been shown to abolish the increase in spontaneous Ca2+ spark frequency in cardiomyocytes exposed to sustained stretch, whereas the effect of nNOS-derived NO on RyR2 function remains to be investigated. Single channel studies have been performed with RyR2 reconstituted in planar lipid bilayers and exposed to various NO donors and, under these conditions, NO appears to have a dose-dependent, stimulatory effect on channel open probability (Popen). We discuss whether NO has a direct effect on RyR2 via covalent S-nitrosylation of reactive thiol residues within the protein, or whether there are downstream effects via cyclic nucleotides, phosphodiesterases, and protein kinases. Finally, we consider whether the proposed migration of nNOS from the SR to the sarcolemma in the failing heart may have consequences for the nitrosative vs. oxidative balance at the level of the RyR2, and whether this may contribute to an increased diastolic Ca2+ leak, depleted SR Ca2+ store, and reduced contractility in heart failure.
Anti–Endothelin Receptor Type A Autoantibodies in Systemic Lupus Erythematosus–Associated Pulmonary Arterial Hypertension
Authors: Li Guo, Mengtao Li, Yi Chen, Qian Wang, Zhuang Tian, Shuming Pan, Xiaofeng Zeng, Shuang Ye
Journal: Arthritis & Rheumatology (2015)

Objective To investigate the role of autoantibodies against endothelin 1 receptor type A (ETRA) in patients with systemic lupus erythematosus (SLE)–associated pulmonary arterial hypertension (PAH) and to examine the possibility that the pathogenesis of this disease is mediated by these autoantibodies. Methods ETRA autoantibodies in serum from patients with SLE‐associated PAH and serum from controls (SLE patients without PAH) were detected via a human ETRA epitope peptide–based enzyme‐linked immunosorbent assay. An exploratory cohort of patients with SLE‐associated PAH (n = 76) and an independent validation cohort of patients with SLE‐associated PAH confirmed by right‐sided heart catheterization (RHC) (n = 82) were enrolled. The clinical relevance of ETRA autoantibodies in SLE‐associated PAH was analyzed. The proliferation of vascular smooth muscle cells (SMCs) and the permeability of endothelial cells (ECs) were assessed in vitro in cells stimulated with polyclonal ETRA IgG autoantibodies. Expression of PAH‐related markers, i.e., serotonin transporter, platelet‐derived growth factor receptor β, vascular endothelial growth factor A, and platelet‐derived growth factor B was measured by quantitative polymerase chain reaction. In addition, a suboptimal dose of monocrotaline was used to induce PAH in rats, and the effect of ETRA autoantibodies in vivo was determined using a right ventricular hypertrophy index, pulmonary angiography, and laboratory parameters. Results ETRA autoantibodies occurred more frequently in SLE‐associated PAH (41.5%) than in controls (17.1%). There was a significant correlation between ETRA autoantibody titers and pulmonary artery systolic pressure measured by echocardiography (r = 0.2978, P = 0.0038) or pulmonary artery systolic pressure measured by RHC (r = 0.2159, P = 0.0257) in SLE‐associated PAH. ETRA autoantibodies could promote SMC proliferation, disrupt the endothelial barrier, and up‐regulate expression of PAH‐related markers, which could be blocked in the presence of an endothelin receptor antagonist. ETRA autoantibodies aggravated right ventricular hypertrophy and vascular remodeling in vivo. Conclusion We identified ETRA autoantibodies as a biomarker of mechanistic relevance in SLE. These autoantibodies may mediate PAH development in SLE.