tbuckley/cabot-search huggingface dataset:
Calprotectin serum level is an independent marker for radiographic spinal progression in axial spondyloarthritis
Authors: Maureen C Turina, Joachim Sieper, Nataliya Yeremenko, Kristina Conrad, Hildrun Haibel, Martin Rudwaleit, Dominique Baeten, Denis Poddubnyy
Journal: Annals of the Rheumatic Diseases (2014)

In previous works, we demonstrated that markers of systemic inflammation (elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) are independently associated with radiographic spinal progression over 2 years in axial spondyloarthritis (axSpA) in the German spondyloarthritis inception cohort (GESPIC).1 We also found previously that calprotectin, which is secreted during monocyte infiltration into inflamed tissues, and thus, directly reflects a potentially important pathophysiological mechanism in SpA,2 ,3 and which was found to be associated with structural joint damage in psoriatic arthritis4 and in rheumatoid arthritis,5 is clearly elevated in SpA as compared to healthy controls, and decreases rapidly and consistently upon effective treatment,2 although in another work, no differences in serum calprotectin between ankylosing spondylitis patients and healthy controls could be found.6 We aimed here to assess whether serum calprotectin levels are predictive for progression of structural damage in the spine in axSpA.

Seventy-six patients (mean age 38.0±11.5 years, mean symptom duration 4.6±2.8 years, 66% males, 82% HLA-B27-positives) with definite axSpA (n=63 fulfilling the modified New York criteria for ankylosing spondylitis and n=13 patients with axSpA not fulfilling the radiographic part …
The Role of Active Surveillance in the Management of Prostate Cancer
Authors: Simon D. Fung-Kee-Fung, Sima P. Porten, Maxwell V. Meng, Michael Kuettel
Journal: Journal of the National Comprehensive Cancer Network (2013)

In 2010, NCCN incorporated active surveillance (AS) into the NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer, and the 2012 update serves as an excellent resource with the most current evidence regarding treatment options for men with all stages of disease. However, the lack of clinical trials that directly compare various treatment modalities or identify the best management, especially for men with low-risk prostate cancer, makes the decision-making process difficult for both patients and physicians. Although general agreement exists on definitions of candidates for AS—men with low-volume and low-grade disease thought to be at low risk for rapid progression—several key issues remain in establishing and supporting the role of AS in the management of prostate cancer, such as optimal timing and appropriate triggers for active treatment. The decision to initially pursue AS rather than active treatment after prostate cancer diagnosis is complex and involves myriad factors, including estimation of life expectancy, consideration of quality of life, and assessment of ultimate oncologic outcome.
Development of erythroleukaemia after myelodysplastic syndrome in a patient with Wegener's granulomatosis
Authors: T TAKAOKA, Y MATSUKAWA, Y TOMITA, N KITAMURA, T YAMAZAKI, J TAKEUCHI, S NISHINARITA, U SAWADA, T HORIE
Journal: Annals of the Rheumatic Diseases (2001)

Clinical use of cyclophosphamide (CYC) improves the prognosis of Wegener's granulomatosis (WG),1 2 though treatment related malignancies have been recorded.3-5 Among treatment related malignancies, the development of erythroleukaemia has been rarely reported.6 In addition, there have been no reports of erythroleukaemia arising in patients with WG.

A 59 year old woman presented with nasal bleeding, nasal obstruction, and fever in December 1994. A biopsy specimen from nasal mucosa was compatible with WG, and cytoplasmic antineutrophil cytoplasmic antibodies (cANCA) were 13 EU (normally undetectable). A chest x ray examination on admission showed the presence of a cavity in the right lung field. She received 30 mg/day of prednisolone, with limited improvements. CYC (100 mg/day) was therefore given orally from 19 December. As …
Smooth Muscle Cells Give Rise to Osteochondrogenic Precursors and Chondrocytes in Calcifying Arteries
Authors: Mei Y. Speer, Hsueh-Ying Yang, Thea Brabb, Elizabeth Leaf, Amy Look, Wei-Ling Lin, Andrew Frutkin, David Dichek, Cecilia M. Giachelli
Journal: Circulation Research (2009)

Vascular calcification is a major risk factor for cardiovascular morbidity and mortality. To develop appropriate prevention and/or therapeutic strategies for vascular calcification, it is important to understand the origins of the cells that participate in this process. In this report, we used the SM22-Cre recombinase and Rosa26-LacZ alleles to genetically trace cells derived from smooth muscle. We found that smooth muscle cells (SMCs) gave rise to osteochondrogenic precursor- and chondrocyte-like cells in calcified blood vessels of matrix Gla protein deficient (MGP(-/-)) mice. This lineage reprogramming of SMCs occurred before calcium deposition and was associated with an early onset of Runx2/Cbfa1 expression and the downregulation of myocardin and Msx2. There was no change in the constitutive expression of Sox9 or bone morphogenetic protein 2. Osterix, Wnt3a, and Wnt7a mRNAs were not detected in either calcified MGP(-/-) or noncalcified wild-type (MGP(+/+)) vessels. Finally, mechanistic studies in vitro suggest that Erk signaling might be required for SMC transdifferentiation under calcifying conditions. These results provide strong support for the hypothesis that adult SMCs can transdifferentiate and that SMC transdifferentiation is an important process driving vascular calcification and the appearance of skeletal elements in calcified vascular lesions.
Zonal heterogeneity of peroxisomal enzymes in rat liver: Differential induction by three divergent hypolipidemic drugs
Authors: Markus Lindauer, Konstantin Beier, Alfred Völkl, H. Dariush Fahimi
Journal: Hepatology (1994)

The hepatic zonation of peroxisomes and four of their matrical enzyme proteins (catalase, acyl coenzyme A oxidase, multifunctional protein, thiolase) has been investigated in normal male rats and after treatment with three divergent hypolipidemic drugs by means of automatic image analysis and quantitative immunoelectron microscopy. The induction of peroxisomal enzymes was confirmed by Western blotting and enzyme activity determinations in liver homogenates and in highly purified peroxisome fractions. In control animals the volume density of peroxisomes and the concentrations of all four enzymes were comparable across the liver acinus. The treatment with all three compounds induced stronger proliferation of peroxisomes in zone 3 than in zone 1 hepatocytes, and significant differences between the different compounds were detectable only in pericentral hepatocytes. The immunolabeling density reflecting the enzyme protein concentration in the peroxisomal matrix was unchanged or reduced for catalase but showed significant elevations for β-oxidation enzymes in treated animals. It did not increase, however, in parallel with the augmentation of the volume density but showed a different pattern for each enzyme, depending on the acinar location and the type of compound used, suggesting a complex fine regulation for each protein. The total labeling index, reflecting the total amount of each protein, was for almost all enzymes higher in perivenous hepatocytes, indicating that they respond more intensely to hypolipidemic drugs than periportal cells. The elevations of the peroxisomal enzymes in zone 3 of the acinus may contribute to the perturbation of the sterol and bile acid metabolism associated with hypolipidemic therapy. (Hepatology 1994;20:475–486.)
Preservation of mesangium and immunohistochemically defined antigens in glomerular basement membrane isolated by detergent extraction.
Authors: M T Houser, J I Scheinman, J Basgen, M W Steffes, A F Michael
Journal: Journal of Clinical Investigation (1982)

To define the characteristics of isolated glomerular basement membrane (GBM), immunohistochemical and morphometric analyses have been carried out on rat and human tissues. Site-specific arrays of antigens were identified in detergent-isolated GBM in a distribution similar to that observed in intact kidney. In the human, fibronectin, procollagen IV, and collagen V were observed along the internal aspect of GBM continuous with antigenic sites in the mesangium. Another array of antigens was identified in the GBM but not within the mesangium--Goodpasture's antigen, bovine lens capsule type IV collagen, and amyloid P component. In addition, sites reactive with rabbit antiserum to laminin were present on both sides of the lamina densa as well as within the mesangial region. Actomyosin, a presumed mesangial cell antigen persisted in the mesangium of isolated GBM. Mesangial matrix was identified in detergent-isolated GBM in an amount equivalent to that present in intact glomeruli. Sonicated GBM contained the same antigens but it was not possible to quantitate the amount of mesangial material by immunofluorescence or morphometric analysis. The thickness of the lamina densa was greater in sonicated and detergent-treated rat GBM preparations than in native rat kidney. These studies demonstrated that isolated GBM is heterogeneous with respect to its antigenic constituents and in addition contains mesangial matrix, which is morphologically and immunohistochemically distinct from peripheral GBM.
Effect of pirfenidone (PFD) on cytokine/chemokine release from alveolar macrophages (AMs) in interstitial lung diseases (ILD): Preliminary results
Authors: Xuan He, Dirk Theegarten, Josune Guzman, Ulrich Costabel, Francesco Bonella
Journal: European Respiratory Journal (2013)

Rationale: PFD, the first approved treatment for idiopathic pulmonary fibrosis (IPF), exhibits antifibrotic and antiinflammatory activity. The aim of this study is to evaluate the effect of PFD on cytokine/chemokine production by AMs in ILD.

Methods: AMs from BAL of 4 ILD patients (2 IPF and 2 nonspecific interstitial pneumonias (NSIP)) were cultured with and without lipopolysaccharide (LPS). The effect of PFD at different concentrations (0.01, 0.03, 0.1, 0.3 mg·ml-1) on the production of TNF-α, TGF-β1, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17, GM-CSF, IFN-γ, IP-10, MIP-1α, MIP-1β and PDGF-BB was tested by Luminex bead based assay (Bioplex, Bio-Rad GmbH, Germany).

Results: LPS stimulated the production of TNF-α, IL-1β, IL-8, IL-10, IL-17, GM-CSF, IP-10, MIP-1β and PDGF-BB. PFD suppressed each of these in a dose-dependent manner except for IL-8, IL-17 and PDGF-BB (Table). TGF-β was not induced by LPS and pirfenidone did not affect modest basal expression.IFN-γ, IL-4, IL-13 and IL-12p70 were not detected in either the presence or absence of LPS. Analysis of the effect of pirfenidone on IL-6 and MIP-1α is ongoing.

Conclusions: PFD seems to reduce the release of TNF-α, IL-1β, IL-10, GM-CSF, MIP-1β and IP-10 from AMs in patients with IPF and NSIP.

View this table:

Effect of PFD on cytokine/chemokine release from AMs
Human Immunodeficiency Virus Type 1 Vpr Is a Positive Regulator of Viral Transcription and Infectivity in Primary Human Macrophages
Authors: Ramu A. Subbramanian, Allegria Kessous-Elbaz, Robert Lodge, Janique Forget, Xiao-Jian Yao, Dominique Bergeron, Eric A. Cohen
Journal: The Journal of Experimental Medicine (1998)

It is currently well established that HIV-1 Vpr augments viral replication in primary human macrophages. In its virion-associated form, Vpr has been suggested to aid efficient translocation of the proviral DNA into the cell nucleus. Although Vpr growth-arrests dividing T cells, the relevance of this biological activity in nondividing macrophages is unclear. Here we use Vpr-mutants to demonstrate that the molecular determinants involved in G2-arresting T cells are also involved in increasing viral transcription in macrophages, even though these cells are refractive to the diploid DNA status typical of G2 phase. Our results suggest that the two phenotypes, namely the nuclear localization and the G2-arrest activity of the protein, segregate functionally among the late and early functions of Vpr. The nuclear localization property of Vpr correlates with its ability to effectively target the proviral DNA to the cell nucleus early in the infection, whereas the G2-arrest phenotype correlates with its ability to activate viral transcription after establishment of an infection. These two functions may render Vpr's role essential and not accessory under infection conditions that closely mimic the in vivo situation, that is, primary cells being infected at low viral inputs.
Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes.
Authors: D Emilie, M Peuchmaur, M C Maillot, M C Crevon, N Brousse, J F Delfraissy, J Dormont, P Galanaud
Journal: Journal of Clinical Investigation (1990)

To document the in vivo interactions occurring between the immune system and HIV replicating cells, we analyzed using in situ hybridization the production of IL-1 beta, IL-6, IL-2, and INF-gamma in eight hyperplastic lymph nodes from HIV-1 infected patients. Numerous IL-1 beta- and IL-6-producing cells associated in clusters were detected in sinuses. Few individual IL-1 beta- and IL-6-producing cells were present in interfollicular and follicular areas. IL-2- and INF-gamma-producing cells were observed in all lymph node compartments, with a selective enrichment in germinal centers. The amount and distribution of IL-1 beta, IL-6-, and IL-2-producing cells in HIV lymph nodes were not different from those found in six HIV unrelated hyperplastic lymph nodes. In contrast, a higher level of INF-gamma production was observed in HIV-1 lymph nodes. The CD8+ cells that accumulate in germinal centers of HIV lymph nodes (and not in non-HIV germinal centers) were actively involved in this INF-gamma production. INF-gamma synthesizing cells were in direct contact with cells containing HIV core antigens and HIV RNA. Thus a high INF-gamma production may characterize anti-HIV T cell immune response, potentially contributing to control of viral spreading as well as to the development of follicle lysis.
Treating head lice
Authors: B. Nash
Journal: BMJ (2003)

<h3>Objectives</h3> To explore community pharmacists and key stakeholders' perspectives and reflections on the community pharmacy workforce's preparedness for, and response to, COVID-19, including lessons for future public health crises. <h3>Design, setting and participants</h3> Qualitative study using semistructured interviews (via telephone or online videoconferencing platform), with community pharmacists and a range of key stakeholders (representing other health professions, professional/governing organisations concerned with community pharmacy and patient advocacy groups) from across Northern Ireland. Data were analysed using thematic analysis and constant comparison. <h3>Results</h3> Thirty interviews were conducted with community pharmacists (n=15) and key stakeholders (n=15). Four themes were identified: (1) adaptation and adjustment (reflecting how community responded quickly to the need to maintain services and adjusted and adapted services accordingly); (2) the primary point of contact (the continuing accessibility of community pharmacy when other services were not available and role as a communication hub, particularly in relation to information for patients and maintaining contact with other healthcare professionals); (3) lessons learnt (the flexibility of community pharmacy, the lack of infrastructure, especially in relation to information technology, and the need to build on the pandemic experience to develop practice); and (4) planning for the future (better infrastructure which reinforced concerns about poor technology, coordination of primary care services and preparing for the next public health crisis). There was a general view that community pharmacy needed to build on what had been learnt to advance the role of the profession. <h3>Conclusions</h3> The strengths of community pharmacy and its contribution to healthcare services in the COVID-19 pandemic were noted by community pharmacists and acknowledged by key stakeholders. The findings from this study should inform the policy debate on community pharmacy and its contribution to the public health agenda.
No Evidence for Effects of Family Environment on Asthma
Authors: JENNIFER R. HARRIS, PER MAGNUS, SVEN O. SAMUELSEN, KRISTIAN TAMBS
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The risk of developing asthma contingent upon the co-twins' history of asthma was analyzed in a population-based study of 5,864 Norwegian twins. A primary aim was to assess the significance of shared environment for the development of asthma from infancy through age 25. Retrospective reports were collected when the twins were 18 to 25 yr of age. The risk of developing asthma, contingent upon the co-twin's history of asthma, was estimated using survival analyses, and genetic and environmental sources of variation in liability for asthma were analyzed with structural equation models. The cumulative incidence of asthma was 6% for males and 5.4% for females. The relative risk of developing asthma among twins whose co-twin had a positive history of asthma compared with those whose co-twin had no history of asthma was 17.9 (95% CI, 10.3 to 31.0) for identical, and 2.3 (95% CI, 1.2 to 4.4) for fraternal twins. Although shared environment encompasses many of the exposures that are putative risk factors for asthma in this age range, there is no evidence of shared environmental influences for asthma. Rather, 75% of the variation in liability for asthma was explained by genetic effects and the remaining variation was due to nonshared environmental influences. These results suggest that the familial risk for asthma is primarily, genetic.
Brachial-Ankle Pulse Wave Velocity Predicts All-Cause Mortality and Cardiovascular Events in Patients With Diabetes: The Kyushu Prevention Study of Atherosclerosis
Authors: Yasutaka Maeda, Toyoshi Inoguchi, Erina Etoh, Yoshimi Kodama, Shuji Sasaki, Noriyuki Sonoda, Hajime Nawata, Michio Shimabukuro, Ryoichi Takayanagi
Journal: Diabetes Care (2014)

Whether brachial-ankle pulse wave velocity (baPWV), a noninvasive marker for arterial stiffness, is a useful predictive maker for cardiovascular events in subjects with diabetes is not established. In the present cohort study, we evaluated the benefit of baPWV for the prediction of cardiovascular morbidity and mortality in subjects with diabetes.A total of 4,272 outpatients with diabetes were enrolled in the Kyushu Prevention Study of Atherosclerosis. Of these, 3,628 subjects, excluding those with an ankle-brachial index of <0.9, were prospectively followed for 3.2 ± 2.2 years. The baPWV at baseline was classified by recursive partitioning (RP) for each end point. We plotted the Kaplan-Meier curves for high- and low-baPWV groups, which were designated based on the cutoff points, and calculated Cox proportional hazards models.The elevation of baPWV quartiles was significantly correlated to the incidence of coronary artery events, cerebrovascular events, and all-cause mortality. RP revealed baPWVs of 14 and 24 m/s as statistically adequate cutoff points for cardiovascular events and mortality, respectively. High-baPWV classes showed significantly low event-free ratios in Kaplan-Meier curves for all end points and remained independent risks for all-cause mortality and cerebrovascular events, but not for coronary artery events after adjustments for age, sex, BMI, hypertension, hyperlipidemia, smoking, and hemoglobin A1c by Cox proportional hazards models.This large-scale cohort study provided evidence that high baPWV is a useful independent predictor of mortality and cardiovascular morbidity in subjects with diabetes.
A Pharmacokinetic/Pharmacodynamic Model of Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia Patients Treated with Flavopiridol
Authors: Jia Ji, Diane R. Mould, Kristie A. Blum, Amy S. Ruppert, Ming Poi, Yuan Zhao, Amy J. Johnson, John C. Byrd, Michael R. Grever, Mitch A. Phelps
Journal: Clinical Cancer Research (2013)

Flavopiridol, the first clinically evaluated cyclin-dependent kinase inhibitor, shows activity in patients with refractory chronic lymphocytic leukemia, but prevalent and unpredictable tumor lysis syndrome (TLS) presents a major barrier to its broad clinical use. The purpose of this study was to investigate the relationships between pretreatment risk factors, drug pharmacokinetics, and TLS.A population pharmacokinetic/pharmacodynamic model linking drug exposure and TLS was developed. Plasma data of flavopiridol and its glucuronide metabolite (flavo-G) were obtained from 111 patients treated in early-phase trials with frequent sampling following initial and/or escalated doses. TLS grading was modeled with logistic regression as a pharmacodynamic endpoint. Demographics, baseline disease status, and blood chemistry variables were evaluated as covariates.Gender was the most significant pharmacokinetic covariate, with females displaying higher flavo-G exposure than males. Glucuronide metabolite exposure was predictive of TLS occurrence, and bulky lymphadenopathy was identified as a significant covariate on TLS probability. The estimated probability of TLS occurrence in patients with baseline bulky lymphadenopathy less than 10 cm or 10 cm or more during the first 2 treatments was 0.111 (SE% 13.0%) and 0.265 (SE% 17.9%), respectively, when flavo-G area under the plasma concentration versus time curve was at its median value in whole-patient group.This is the first population pharmacokinetic/pharmacodynamic model of TLS. Further work is needed to explore potential mechanisms and to determine whether the associations between TLS, gender, and glucuronide metabolites are relevant in patients with chronic lymphocytic leukemia treated with other cyclin-dependent kinase inhibitors.