tbuckley/cabot-search huggingface dataset:
Synovial fluid chondroitin sulphate epitopes 3B3 and 7D4, and glycosaminoglycan in human knee osteoarthritis after exercise
Authors: J. C Bautch
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> Walking exercise alleviates some symptoms, such as pain, in patients with mild to moderate knee osteoarthritis (OA). However, a major concern is that weightbearing exercise on osteoarthritic joints may exacerbate articular cartilage degradation. Loading of proteoglycan depleted articular cartilage in vitro increased expression of the chondroitin sulphate epitope 3B3, suggesting that loading may influence metabolism of osteoarthritic cartilage. This study aimed at evaluating the effects of walking exercise on articular cartilage metabolism in patients with knee OA, as reflected by changes in concentrations of synovial fluid markers. <h3>METHODS</h3> Thirty elderly patients with knee OA (Kellgren-Lawrence grades II to IV) were randomly allocated to control (n = 15) and 12 week exercise (n = 15) groups. Synovial fluid obtained from 21 of the patients at time zero and after 12 weeks was examined by enzyme linked immunosorbent assay (ELISA) for the chondroitin sulphate epitopes 3B3 and 7D4, and by a dye binding assay with 1,9-dimethylmethylene blue for total sulphated glycosaminoglycan (GAG) concentrations. The 3B3/GAG and 7D4/GAG ratios were calculated. <h3>RESULTS</h3> No significant changes in concentrations of 3B3, 7D4, GAG, 3B3/GAG, or 7D4/GAG between time zero and 12 weeks were found in either group. However, there were significant declines in 3B3 (p=0.001), GAG (p=0.007), and the 3B3/GAG ratio (p=0.049) with aging. <h3>CONCLUSION</h3> Twelve weeks of walking exercise had no demonstrable adverse effects on articular cartilage metabolism, as reflected by the concentrations of synovial fluid GAG or the chondroitin sulphate epitopes 3B3 and 7D4.
Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis
Authors: Jérôme Avouac, Christophe Meune, Barbara Ruiz, Pierre Olivier Couraud, Georges Uzan, Catherine Boileau, André Kahan, Gilles Chiocchia, Yannick Allanore
Journal: Annals of the Rheumatic Diseases (2011)

Objective To evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc). Methods Circulating endothelial progenitor cells (EPC), circulating endothelial cells and serum levels of placental growth factor (PlGF), soluble vascular adhesion molecule and vascular endothelial growth factor were measured in a prospective cohort of 100 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. Results After the follow-up period, 17 patients developed new digital ulcers. By multivariate analysis focused on biomarkers, high PlGF serum levels and low EPC counts were identified as predictors of the occurrence of at least one new digital ulcer. In a secondary model including biomarkers together with clinical SSc characteristics all predictors of digital ulcers defined by p≤0.1 in univariate analysis, high PlGF serum levels (HR 7.26, 95% CI 1.92 to 27.41) and a history of digital ulcers (HR 9.32, 95% CI 1.51 to 59.83) were identified as independent predictors of a new digital ulcer. In an alternative model excluding patients with a history of digital ulcers at baseline, high PlGF serum levels (HR 13.46, 95% CI 1.58 to 114.73) and low EPC counts (HR 7.95, 95% CI 2.09 to 30.09) remained predictive of new digital ulcer occurrence during follow-up. Conclusion This study identified high PlGF serum levels and low circulating EPC counts as predictors of new digital ulcers in SSc. It highlights the critical role of angiogenesis in this vascular outcome. These markers may improve digital ulcer risk stratification and therefore allow earlier therapeutic intervention.
Expression of CD44 variants and prognosis in oesophageal squamous cell carcinoma
Authors: T Gotoda
Journal: Gut (2000)

<h3>BACKGROUND</h3> The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas. <h3>AIMS</h3> To investigate whether CD44v, especially the CD44v2 (v2) isoform, may be a useful prognostic factor for patients with oesophageal squamous cell carcinoma, using a recently developed monoclonal antibody against a v2 epitope. <h3>PATIENTS</h3> 233 patients (211 men and 22 women; mean age 61.9 years), with oesophageal squamous cell carcinomas curatively removed without additional treatment between 1987 and 1996 at the National Cancer Center Hospital, were analysed for CD44v expression. <h3>METHODS</h3> The expression of CD44v was evaluated immunohistochemically using monoclonal antibodies against epitopes of the standard and variant protein, in paraffin embedded oesophageal squamous cell carcinoma tissue from 233 patients who had undergone cervical, mediastinal, and abdominal lymphadenectomy (three field dissection) for oesophagectomy. The data were evaluated for any correlation with clinicopathological indices or prognosis. <h3>RESULTS</h3> Although total CD44 and CD44v6 (v6) were respectively observed in 99% and 97% of the cancer specimens, the expression of v2 was only 30%. Patients whose tumours were v2 positive had a significantly better prognosis than those whose tumours were v2 negative (p = 0.031). Furthermore, in patients without lymph node metastasis, v2 positivity alone was a significant independent factor of prognosis (relative risk of death associated with v2 negativity, 4.7; p = 0.037) in multivariate analysis. <h3>CONCLUSIONS</h3> These results indicate that v2 is a useful marker for clinical prognosis in patients with oesophageal squamous cell carcinoma. Particularly in patients without lymph node metastasis, v2 status may thus have implications for the use of adjuvant chemotherapy and/or radiotherapy in patients with oesophageal cancer at an early stage.
Hepatitis C virus RNA and antibodies among blood donors in Beijing
Authors: Yu Wang, Qi-Min Tao, Hai-Yan Zhao, Fumio Tsuda, Ryozo Nagayama, Kayoko Yamamoto, Takeshi Tanaka, Hajime Tokita, Hiroaki Okamoto, Yuzo Miyakawa, Makoto Mayumi
Journal: Journal of Hepatology (1994)
Management of stage one and two-E gastric large B-cell lymphoma: chemotherapy alone or surgery followed by chemotherapy?
Authors: Yassir Sbitti, Nabil Ismaili, Youssef Bensouda, Habiba Kadiri, Mohammed Ichou, Hassan Errihani
Journal: Journal of Hematology & Oncology (2010)

Management of localized primary gastric B lymphoma (PGL) remains controversial. The aim of this study is to compare two treatments: chemotherapy alone and surgery plus chemotherapy. Records of all patients with a diagnosis of gastric lymphoma and which were treated in the National Institute of Oncology, between 1999 and 2006, were reviewed and patients fulfilling the following criteria were included in this study: histologically proven large-cell B lymphoma of the stomach; complete clinical information stage I/II disease according to the Musshoff staging; patients who received surgery followed by chemotherapy (group I) or chemotherapy alone (group II). This study included 82 patients who were treated for cancer in our Institute. All clinical and pathological features were similar between the two groups, except that patients of group-I had significantly more stage II disease (P = 0.023) than that of group II. Among the 52 patients who could be evaluated for response to chemotherapy, there were 45 who had complete response to treatment, 3 had partial response to the treatment and 4 had progressive disease. The projected 5-year relapse-free survival (RFS) and overall survival (OS) of group I were 86.69% (95% CI, 57.9 - 97.7%) and 90.0% (95% CI, 58.0 - 97.8%), respectively. And the projected 5-year relapse-free survival RFS and OS of group II were 86.67% (95% CI, 57.0 - 88.2%) and 93.33% (95% CI, 73.3 - 98.7%) respectively. There were no statistically significant differences in RFS (P = 0.485) and OS (P = 0.551) between the two groups. Our data suggest that chemotherapy alone may be a reasonable alternative treatment for stage I/II gastric large-cell lymphoma but this result must be confirmed by prospective randomized clinical trials.
Cooperation of activating Ras/rtk signal transduction pathway mutations and inactivating myeloid differentiation gene mutations in M0 AML: a study of 45 patients
Authors: C Roumier, S Lejeune-Dumoulin, A Renneville, A S Goethgeluck, N Philippe, P Fenaux, C Preudhomme
Journal: Leukemia (2006)
Accelerating Evidence Reviews and Broadening Evidence Standards to Identify Effective, Promising, and Emerging Policy and Environmental Strategies for Prevention of Childhood Obesity
Authors: Laura Brennan, Sarah Castro, Ross C. Brownson, Julie Claus, C. Tracy Orleans
Journal: Annual Review of Public Health (2011)

The childhood obesity epidemic has stimulated the emergence of many policy and environmental strategies to increase healthy eating and active living, with relatively few research recommendations identifying the most effective and generalizable strategies. Yet, local, state, and national decision makers have an urgent need to take action, particularly with respect to lower-income and racial and ethnic populations at greatest risk. With the surge of promising and emerging policy and environmental strategies, this review provides a framework, criteria, and process modeled from existing expert classification systems to assess the strength of evidence for these strategies. Likewise, this review highlights evidence gaps and ways to increase the types and amount of evidence available to inform policy and environmental strategies. These priorities include documenting independent and interdependent effects, determining applicability to different populations and settings, assessing implementation fidelity and feasibility, identifying cumulative benefits and costs, ascertaining impacts on health equity, and tracking sustainability.
Cost-effectiveness of using continuous positive airway pressure in the treatment of severe obstructive sleep apnoea/hypopnoea syndrome in the UK
Authors: J F Guest, M T Helter, A Morga, J R Stradling
Journal: Thorax (2008)

A study was undertaken to estimate the cost-effectiveness of using continuous positive airway pressure (CPAP) in the management of patients with severe obstructive sleep apnoea/hypopnoea syndrome (OSAHS) compared with no treatment from the perspective of the UK's National Health Service (NHS).A Markov model was constructed to assess the cost-effectiveness of CPAP compared with no treatment. The model depicted the management of a 55-year-old patient with severe OSAHS as defined by an apnoea-hypopnoea index (AHI) >30 and daytime sleepiness (Epworth Sleepiness Scale score >or=12). The model spans a period of 14 years.According to the model, 57% of untreated patients are expected to be alive at the end of 14 years compared with 72% of patients treated with CPAP. Untreated patients are expected to cost the NHS pound10 645 (95% CI pound7988 to pound14,098) per patient over 14 years compared with pound9672 (95% CI pound8057 to pound12,860) per CPAP-treated patient. Treatment with CPAP for a period of 1 year was found not to be a cost-effective option since the cost per quality-adjusted life year (QALY) gained is expected to be > pound20,000, but after 2 years of treatment the cost per QALY gained is expected to be pound10,000 or less and, after 13 years of treatment, CPAP becomes a dominant treatment (ie, more effective than no treatment for less cost).Within the limitations of the model, CPAP was found to be clinically more effective than no treatment and, from the perspective of the UK's NHS, a cost-effective strategy after a minimum of 2 years of treatment.
A pulmonary hypertension-producing plant from Tanzania.
Authors: D Heath, J Shaba, A Williams, P Smith, A Kombe
Journal: Thorax (1975)

An African youth who had died from primary pulmonary hypertension was suspected of having ingested a herbal remedy containing the seeds of the local plant Crotalaria laburnoides. Consequently powdered seeds of this plant were fed to 20 Wistar albino rats for 60 dyas to see if this would induce ventricular hypertrophy and associated hypertensive pulmonary vascular disease. At the end of the experimental period right ventricular hypertrophy, medial hypertrophy of the pulmonary trunk and 9muscular pulmonary arteries9, and muscularization of the pulmonary arterioles had developed in a proportion of the test animals. These are the morbid anatomical features pathognomonic of a raised pulmonary arterial pressure and show that the seeds of Crotalaria laburnoides contain an agent capable of inducing pulmonary hypertension in rats. This study suggests the value of seeking a history of ingestion of herbal remedies and drugs in cases of unexplained pulmonary hypertension in man.
On the design of clone-based haplotyping
Authors: Christine Lo, Rui Liu, Jehyuk Lee, Kimberly Robasky, Susan Byrne, Carolina Lucchesi, John Aach, George Church, Vineet Bafna, Kun Zhang
Journal: Genome biology (2013)

Haplotypes are important for assessing genealogy and disease susceptibility of individual genomes,but are difficult to obtain with routine sequencing approaches. Experimental haplotype reconstruction based on assembling fragments of individual chromosomes is promising, but with variable yields due to incompletely understood parameter choices.We parameterize the clone-based haplotyping problem in order to provide theoretical and empirical assessments of the impact of different parameters on haplotype assembly. We confirm the intuition that long clones help link together heterozygous variants and thus improve haplotype length. Furthermore, given the length of the clones, we address how to choose the other parameters, including number of pools, clone coverage and sequencing coverage, so as to maximize haplotype length. We model the problem theoretically and show empirically the benefits of using larger clones with moderate number of pools and sequencing coverage. In particular, using 140 kb BAC clones, we construct haplotypes for a personal genome and assemble haplotypes with N50 values greater than 2.6 Mb. These assembled haplotypes are longer and at least as accurate as haplotypes of existing clone-based strategies, whether in vivo or in vitro.Our results provide practical guidelines for the development and design of clone-based methods to achieve long range, high-resolution and accurate haplotypes.
Asymmetric Dimethylarginine Plasma Concentrations Differ in Patients with End-Stage Renal Disease
Authors: JAN T. KIELSTEIN, RAINER H. BÖGER, STEFANINE M. BODE-BÖGER, JÜRGEN SCHÄFFER, MARK BARBEY, KARL M. KOCH, JÜRGEN C. FRÖLICH
Journal: Journal of the American Society of Nephrology (1999)

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In this study, the plasma concentrations of ADMA, symmetric dimethylarginine, and L-arginine were determined in relation to plasma nitrate levels (as an index of NO formation) for a group of 80 patients with ESRD. The effects of two treatment methods, i.e., hemodialysis (HD) and peritoneal dialysis (PD), and the role of the presence of atherosclerotic disease were evaluated. Forty-three patients receiving HD and 37 patients receiving PD were compared with healthy control subjects. Plasma L-arginine and dimethylarginine levels were determined by HPLC, using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels were determined by gas chromatography-mass spectrometry. Predialysis ADMA concentrations in HD-treated patients were approximately sixfold higher than those in the control group (6.0+/-0.5 versus 1.0+/-0.1 micromol/L; P < 0.05). Plasma nitrate concentrations were significantly lower in HD-treated patients, which suggests that ADMA may inhibit NO synthase. In contrast, plasma ADMA levels and nitrate concentrations in PD-treated patients were similar to those in control subjects. Plasma L-arginine concentrations were not significantly decreased in patients with ESRD. ADMA concentrations were significantly decreased 5 h after HD, compared with baseline values. ADMA levels were significantly higher in HD-treated patients with manifest atherosclerotic disease than in HD-treated patients without atherosclerotic disease (7.31+/-0.70 versus 3.95+/-0.52 micromol/L; P < 0.05). This study confirms that ADMA is accumulated in ESRD. PD-treated patients exhibit significantly lower ADMA levels than do HD-treated patients. Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patients with ESRD.
Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia: Results of the CA180-018 Phase I Dose-Escalation Study of the Innovative Therapies for Children With Cancer Consortium
Authors: C. Michel Zwaan, Carmelo Rizzari, Francoise Mechinaud, Donna L. Lancaster, Thomas Lehrnbecher, Vincent H.J. van der Velden, B. Berna Beverloo, Monique L. den Boer, Rob Pieters, Dirk Reinhardt, Michael Dworzak, Julie Rosenberg, George Manos, Shruti Agrawal, Lewis Strauss, André Baruchel, Pamela R. Kearns
Journal: Journal of Clinical Oncology (2013)

Purpose Dasatinib is a potent BCR-ABL inhibitor with proven efficacy in adults with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) and in imatinib-resistant/intolerant disease. This phase I study of the Innovative Therapies for Children with Cancer Consortium assessed dasatinib safety and efficacy in pediatric patients. Patients and Methods Escalating once-daily dasatinib doses (60 to 120 mg/m 2 ) were administered to children (n = 58) with (i) imatinib-pretreated CML or Philadelphia chromosome (Ph)–positive acute lymhoblastic leukemia (ALL) and (ii) treatment-refractory Ph-negative ALL or acute myeloid leukemia (AML). Results Dasatinib safety and efficacy profiles compared favorably with those in adults. The most common drug-related nonhematologic adverse events were nausea (31%, all grades; 2%, grade 3 to 4), headache (22%, 3%), diarrhea (21%, 0%), and vomiting (17%, 2%). Of 17 patients with CML-CP, 14 (82%) achieved complete cytogenetic response (CCyR) and eight (47%) achieved major molecular response. After ≥ 24 months of follow-up, median complete hematologic response (CHR) and major cytogenetic response (MCyR) durations were not reached. Of 17 patients with advanced-phase CML or Ph-positive ALL, six (35%) achieved confirmed CHR and 11 (65%) achieved CCyR. Median MCyR duration was 4.6 months (95% CI, 2.1 to 17.4 months). No patient with Ph-negative ALL or AML responded. Dasatinib pediatric pharmacokinetic parameters were comparable with those in adult studies, showing rapid absorption (time to reach maximum concentration, 0.5 to 6.0 hours) and elimination (mean half-life, 3.0 to 4.4 hours). Conclusion Dasatinib 60 mg/m 2 and 80 mg/m 2 once-daily dosing were selected for phase II studies in children with Ph-positive leukemias.
The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies.
Authors: J P Metlay, M D Witmer-Pack, R Agger, M T Crowley, D Lawless, R M Steinman
Journal: The Journal of Experimental Medicine (1990)

Hybridoma fusions with hamster hosts were undertaken to generate mAbs to mouse spleen dendritic cells. Two mAb were obtained and used to uncover the distinct integrins of these APC. One, 2E6, bound a determinant common to all members of the CD11/CD18 family, most likely the shared 90 kD CD18 beta chain. 2E6 immunoprecipitated the characteristic beta 2 integrin heterodimers from lymphocytes (p180, 90; CD11a) and macrophages (p170,90; CD11b), but from dendritic cells, a p150,90 (presumably CD11c) integrin was the predominant species. 2E6 inhibited the binding function of the CD11a and CD11b integrins on B cells and macrophages in appropriate assays, but 2E6 exerted little or no inhibition on the clustering of dendritic cells to T cells early in primary MLR, suggesting a CD11/CD18-independent mechanism for this binding. The second mAb, N418, precipitated a 150, 90 kD heterodimer that shared the 2E6 CD18 epitope. This N418 epitope may be the murine homologue of the previously characterized human CD11c molecule, but the epitope was only detected on dendritic cells. N418 did not react with peritoneal macrophages, anti-Ig-induced spleen B blasts, or bulk lymph node cells. When used to stain sections of spleen, N418 stained dendritic cells in the T-dependent areas, much like anti-class II mAbs that were also generated in these fusions. In addition, N418 revealed nests of dendritic cells that punctuated the rim of marginal zone macrophages between red and white pulp. This localization positioned most dendritic cells at regions where arterial vessels and T cells enter the white pulp. We conclude that the p150, 90 heterodimer is the major beta 2 integrin of spleen dendritic cells, and we speculate that it may function to localize these APC at sites that permit access to the recirculating pool of resting T cells.
Leukotrienes C4 and D4 are potent endothelium-dependent relaxing agents in canine splanchnic venous capacitance vessels.
Authors: J R Pawloski, B M Chapnick
Journal: Circulation Research (1993)

In the present study, the vasomotor effects of the peptide leukotrienes (LTs) LTC4 and LTD4 on isolated canine venous capacitance vessels were evaluated. Both LTs evoked marked concentration-dependent relaxation of norepinephrine-contracted rings of mesenteric and splenic veins and inferior vena cava but had minimal activity in the femoral vein. Relaxation induced by either LT was abolished after physical removal of the vascular endothelium, whereas marked relaxation responses were evoked by glyceryl trinitrate in the same endothelium-denuded rings. The nitric oxide synthase antagonist NG-nitro-L-arginine methyl ester (L-NAME) completely abolished LT-induced mesenteric vein relaxation and unmasked a contractile effect of LTC4. Only partial attenuation of LT-induced relaxation of the inferior vena cava in the presence of L-NAME was observed. In the splenic vein, responses solely to LTC4 were very slightly reduced in the presence of L-NAME. Reduced hemoglobin (10(-6) and 10(-5) M) inhibited LTC4-evoked splenic vein relaxation and, in a concentration of 10(-5) M, inhibited LTD4-evoked relaxation of the splenic vein. On the other hand, methylene blue (10(-6) and 10(-5) M) attenuated splenic vein relaxation produced by both LTs but solely reduced LTC4-evoked inferior vena cava relaxation. Thus, the peptide LTs, the major components of the slow-reacting substance of anaphylaxis, exert a profound endothelium-dependent relaxant effect on venous capacitance vessels, which is only partially dependent on L-arginine and nitric oxide. A role for LT-evoked capacitance venodilation as a mechanism contributing to the reduced venous return and cardiac output associated with systemic anaphylaxis is postulated.