tbuckley/cabot-search huggingface dataset:
Periodontitis and <i>Porphyromonas gingivalis</i> in Patients With Rheumatoid Arthritis
Authors: Ted R. Mikuls, Jeffrey B. Payne, Fang Yu, Geoffrey M. Thiele, Richard J. Reynolds, Grant W. Cannon, Jeffrey Markt, David McGowan, Gail S. Kerr, Robert S. Redman, Andreas Reimold, Garth Griffiths, Mark Beatty, Shawneen M. Gonzalez, Debra A. Bergman, Bartlett C. Hamilton, Alan R. Erickson, Jeremy Sokolove, William H. Robinson, Clay Walker, Fatiha Chandad, James R. O'Dell
Journal: Arthritis & Rheumatology (2014)

To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression.Presence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection.Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.
Association between lung function and subclinical atherosclerosis in overweight subjects
Authors: W. Thijs, K.B. Gast, R. Mutsert, F.H. Krouwels, C.F. Melissant, P.S. Hiemstra, F.R. Rosendaal, S. Middeldorp, K.F. Rabe
Journal: European Respiratory Journal (2011)

An association between COPD and subclinical atherosclerosis that persisted after adjusting for cardiovascular risk factors has been reported. This may explain the excess cardiovascular mortality seen in patients with COPD.   Objective:  To investigate the association between lung function and subclinical atherosclerosis in a population of obese adults with a normal lung function.   Methods:  This is a cross-sectional analysis of the NEO (Netherlands Epidemiology of Obesity) study, a cohort of adults aged 45 to 65 years with a Body Mass Index (BMI) 27≥ kg/m 2 . The association between FEV1 and subclinical atherosclerosis (mean maximal common carotid intima- media thickness [cIMT] measured by ultrasound) was assessed using linear regression.   Results:  1115 adults were included with a mean (25th-75th percentiles) age of 56 (51-61) y, BMI of 31 (28-32) kg/m 2 , FEV1 of 104% (94-113) and 48,7% men. One percent FEV1% increase was associated with 0.001 mm (95% CI -0.001, -0.002) decrease in mean maximal cIMT.  After adjustment for age, sex, pack years and BMI the β was 0.001 (95%CI -0.001, 0.000).   Conclusion:  The association between lung function and subclinical atherosclerosis in obese subjects with a normal lung function is weak and a great part of the initial association is explained by confounders. The small association is probably due to residual confounding.
Bronchial hyperresponsiveness to methacholine in relation to asthma control - Results from the MIDAS study
Authors: Andrei Malinovschi, Christer Janson, Lennart Nordvall, Hans Hedenström, Kjell Alving
Journal: European Respiratory Journal (2013)

Bronchial hyperresponsiveness (BHR) is a hallmark of asthma. BHR to methacholine is used for diagnosis, but the role in monitoring treated asthma is not established. In the present study we assessed the relation between BHR to methacholine, airways inflammation, asthma control and symptoms.  Methacholine challenge and FeNO measurements were done in 371 asthmatics (aged 10-35 years) with inhaled corticosteroids prescribed. PD 20   1.0 mg normal response (Schulze et al. Resp Med 2009). Well-controlled asthma (≥20 in Asthma Control Test) was found in 68% of children (  Moderate-severe BHR was found in 61% of children and 44% of adults. FeNO increased with more severe BHR in both children and adults, with a higher explanatory value in children (R 2 =0.15 vs 0.06). Well-controlled asthma was less prevalent in the moderate-severe BHR group than the other two BHR groups in adults (66% vs 83% and 82%, p  In conclusion, bronchial hyperresponsiveness to methacholine was common in this treated asthma population and related both to airways inflammation and clinical aspects of asthma. BHR appears to be stronger related to poorer asthma control and exercise-induced dyspnea in adults than children.
Change in Editorial Command
Authors: Bruce F. Scharschmidt
Journal: Journal of Clinical Investigation (1992)

of the University of Cali- fornia, San Diego, and his colleagues will assume editorial re- sponsibility for The Journal ofClinical Investigation (JCI).The Journal is presently in a strong position, both scientifically and fiscally, but faces new challenges if it is to continue to thrive.The current editors, at the time of our first meeting in March of 1987, discussed key objectives which we hoped to achieve during our tenure.
Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis
Authors: Na Xie, Zheng Tan, Sami Banerjee, Huachun Cui, Jing Ge, Rui-Ming Liu, Karen Bernard, Victor J. Thannickal, Gang Liu
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Dysregulation of cellular metabolism has been shown to participate in several pathologic processes. However, the role of metabolic reprogramming is not well appreciated in the pathogenesis of organ fibrosis.
Krüppel-like Factor 4 Blocks Hepatocellular Carcinoma Dedifferentiation and Progression through Activation of Hepatocyte Nuclear Factor-6
Authors: Hongcheng Sun, Huamei Tang, Dacheng Xie, Zhiliang Jia, Zhenyu Ma, Daoyan Wei, Lopa Mishra, Yong Gao, Shaojiang Zheng, Keping Xie, Zhihai Peng
Journal: Clinical Cancer Research (2015)

Tumor differentiation is a behavioral index for hepatocellular carcinoma (HCC) and a prognostic factor for patients with HCC who undergo orthotopic liver transplantation (OLT). However, the molecular basis for HCC differentiation and prognostic value of the underlying molecules that regulate HCC differentiation are unclear. In this study, we defined a potential driver pathway for HCC differentiation and prognostication.The regulation and function of Krüppel-like factor 4 (KLF4) and hepatocyte nuclear factor-6 (HNF-6) in HCC differentiation was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival.There was a direct relationship between the expression levels of KLF4 and HNF6 in HCC. Reduced KLF4 or HNF6 expression correlated with high HCC grade. Poorly differentiated HCC cells had lower expression of KLF4 or HNF6 and differentiation-associated markers than did well-differentiated cells. Elevated KLF4 of HNF6 expression induced differentiation of poorly differentiated hepatoma cells. Mechanistically, KLF4 trans-activated HNF-6 expression. Restored HNF-6 expression upregulated expression of differentiation-associated markers and inhibited HCC cell migration and invasion, whereas HNF-6 knockdown did the opposite. Loss of KLF4 expression in primary HCC correlated with reduced overall survival and shortened relapse-free survival durations after OLT. Combination of KLF4 expression and the Milan criteria improved prognostication for HCC after OLT.The dysregulated KLF4/HNF-6 pathway drives dedifferentition and progression of HCC, and KLF4 is a biomarker for accurate prognostication of patients with HCC treated by OLT when integrated with the Milan Criteria.
A new prognostic score for patients with lower-risk myelodysplastic syndrome (MDS) allows the identification of a subset of patients with poor prognosis
Authors: J. Shan, H. Kantarjian, S. Pierce, E. Estey, G. Garcia-Manero
Journal: Journal of Clinical Oncology (2007)

7076 Background: Current prognostic models of MDS do not allow the identification of patients (pts) with lower risk disease and poor prognosis. Methods: We evaluated the characteristics of 898 pts with low or intermediate-1 disease by IPSS referred at MDACC from 1976 to 2005. Distributions of OS and progression-free-survival (PFS) were estimated by the method of Kaplan and Meier and compared between subgroups using the log rank test. Cox proportional hazards regression model was used to assess the ability of patient characteristics to predict OS and PFS, with goodness-of-fit assessed by Martingale residual plots, the Grambsch-Therneau test, Schoenfeld residual plots, and the likelihood ratio (LR) test. Multiple patient characteristics were evaluated including ferritin and β2- microglobulin, but these last two were not included in the multivariate model because their values were only known for a subset of patients.None of the patients had received chemotherapy prior to referral. Results: Median age was 66 years (range 16–94), and 65% had diploid cytogenetics. Only 88 pts (10%) transformed to AML and 388 (43%) had died. By multivariate analysis, characteristics associated with a worse OS were low platelets, anemia, older age, higher percent of marrow blasts and poor risk cytogenetics. Although not included in the model, higher ferritin (p=0.03) and β2-microglobulin (p=0.001) levels were associated with worse prognosis.These allowed the development of a scoring system in which patients could be grouped in 3 categories. Patients in category 1 (score less than 0.7) (n=22%) had a median survival of 69 months (95% CI 55-NA) and a 4-year OS of 67%, in category 2 (score 0.7–1.2) (n=40%) of 25 months (95% CI 18–31) and a 4-year survival of 28%, and in category 3 (score more than 1.2) (n=38%) of 17 months (95% CI 15–20), and a 4 -year survival of 12%. The model could segregate patients in each IPSS category (low and int-1). A subset of patients with intermediate-1 risk treated with decitabine could also be stratified by the model. Conclusions: This data indicates that it is possible to identify patients with lower-risk MDS and poor prognosis that may benefit from early therapeutic intervention. No significant financial relationships to disclose.
The membrane attack mechanism of complement. Isolation and subunit composition of the C5b-9 complex.
Authors: W P Kolb, H J Muller-Eberhard
Journal: The Journal of Experimental Medicine (1975)

Isolation of the C5b-9 complex from inulin-activated whole human serum was effected by molecular sieve column chromatography employing Biogel A-15 M, preparative Pevikon block electrophoresis, and removal of low density beta-lipoproteins by flotation in CsCl. The final product was homogeneous upon cellulose acetate strip electrophoresis and analytical ultracentrifugation. Ouchterlony analyses indicated that the complex reacted with antisera to C5, C6, C7, C8, and C9 to form a continuous, circular precipitin line without spurs. The C5b-9 complex was dissociated by sodium dodecyl sulfate (SDS) in the absence of reducing agents, and analytical SDS-polyacrylamide gel electrophoresis revealed seven protein bands after straining with Coomassie Blue. Bands 1, 2, 3, and 6 were identified as C5b, C7, C6, and C9, respectively. Bands 4 and 7 were identified as two noncovalently bound subunits of C8. Molar ratios among C5b, C6, C7, C8, and C9 dissociated from the complex by SDS were estimated to be 1:1:1:1:3. Band 5 protein, which had an estimated mol wt of 88,000 and was found to occur with a molar ratio of 3, has not yet been identified. Its nature and possible biological functions are discussed.
Cytologic Changes in the Mouse Intestine under Daily Exposure to Gamma Rays2
Authors: S. Lesher
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Cytologic Changes in the Mouse Intestine under Daily Exposure to Gamma Rays Get access S. Lesher S. Lesher Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 3, September 1957, Pages 419–449, https://doi.org/10.1093/jnci/19.3.419 Published: 01 September 1957 Article history Received: 03 May 1957 Published: 01 September 1957
Prevalence of obstructive sleep apnea syndrome in patients with risk factors for cardiovascular diseases in a large population in Zaragoza (Spain)
Authors: Javier Lázaro, Cristina Gómez, Paloma Claveria, Antonio Castanera, Carmen Sanchez, Antonio Caballero
Journal: European Respiratory Journal (2014)

Background   Obesity, hypertension, dyslipemia, smoking and hyperglycemia are prevalent in sleep apnea syndrome (OSAS). We investigated how these components affect the prevalente of obstructive sleep apnea syndrome in our population at the Hospital Royo Villanova (Zaragoza, Spain).   Objectives   The purpose of this study was to investigate whether some risks factors as hypertension, dyslipemia, smoking, obesity and hyperglycemia were present in patients with obstructive sleep apnea syndrome.   Methods   A total of 525 patients were included, 371 patients were men and 154 patients were women. We studied the occurrence of hypertension, dyslipemia, smoking, obesity and hyperglycemia in 408 patients with OSAS and 117 patients without OSAS.  Multiple logistic and regression analyses were conducted to evaluate the factors influencing the risk of OSAS.   Results   There is a strong association of OSAS with hypertension, dyslipemia, smoking, obesity and hyperglycemia. The presence of three or more risk factors were significantly higher in the group of OSAS (29.9% vs 17.9%) than in the group without OSAS. In addition, the prevalence of risks factors in men were high in patients with OSAS (29,1% vs 18,3%)than without OSAS. In women, the prevalence of risk factors were high in patients with OSAS (31.9% vs 17.1%) than without OSAS.   Conclusions   In our patients with sleep related disorders the prevalence of cardiovascular risk factors is clearly increased in comparison to the general population in Zaragoza (Spain).
Regulation of pancreatic β-cell growth and survival by the serine/threonine protein kinase Akt1/PKBα
Authors: Robyn L. Tuttle, Navdeep S. Gill, William Pugh, Jean-Pyo Lee, Brigitte Koeberlein, Emma E. Furth, Kenneth S. Polonsky, Ali Naji, Morris J. Birnbaum
Journal: Nature Medicine (2001)
Image-guided core-needle biopsy in malignant lymphoma: experience with 100 patients that suggests the technique is reliable.
Authors: D Ben-Yehuda, A Polliack, E Okon, Y Sherman, S Fields, P Lebenshart, H Lotan, E Libson
Journal: Journal of Clinical Oncology (1996)

PURPOSE In an initial evaluation of 1,500 computed tomography (CT)-guided core-needle biopsies performed at our institute during the period from 1989 to 1994, we encountered 100 patients with the diagnosis of lymphoma. Here, we review the clinical impact of 109 image-guided needle biopsies in these 100 patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). PATIENTS AND METHODS NHL was diagnosed in 71 patients, and 29 had HD. Among the NHL patients, 17 (24%) had proven lymphoma diagnosed before the biopsy was performed; in 54 (76%) core-needle biopsy was performed as the first diagnostic procedure. Of 29 HD patients, nine (31%) were already established cases of HD, and in 20 (69%) core-needle biopsy was the first diagnostic procedure attempted. Most of the biopsies were performed under CT control using a 20- or 18-gauge Turner biopsy needle. RESULTS Eighty-six patients received therapy based on the results of the needle biopsy alone. Fourteen patients received therapy after undergoing surgical biopsy for a suspected diagnosis of lymphoma, which could not be established with certainty on the basis of an earlier core-needle biopsy alone. In 78% of the patients, the needle biopsy saved a further surgical procedure that may have been difficult to perform because of the primary location of the tumor. CONCLUSION From our experience in this study, image-guided core-needle biopsies provide sufficient information for the diagnosis of and subsequent therapeutic decision to treat most cases of lymphoma.
Drug points: Bronchospasm induced by isotretinoin
Authors: R A Sabroe, R C D Staughton, C B Bunker
Journal: BMJ (1996)

We report a case of bronchospasm occurring during treatment with isotretinoin.

A 16 year old boy with resistant acne and a long history of atopic eczema and mild asthma (requiring only intermittent salbutamol) was treated with isotretinoin (Roaccutane). Within one month of the start of treatment his asthma had deteriorated, with symptoms of exercise induced bronchospasm and nocturnal wakening. He required high dose inhaled corticosteroids (beclomethasone 500 µg …
Management of Lichen Sclerosus and Intraepithelial Neoplasia of the Vulva in the UK
Authors: J A Tidy, W P Soutter, D M Luesley, A B MacLean, C H Buckley, C M Ridley
Journal: Journal of the Royal Society of Medicine (1996)

Women with vulval intraepithelial neoplasia (VIN), lichen sclerosus (LS) and Paget's disease are referred either to gynaecologists or to dermatologists. We have ascertained the caseloads, referral patterns and treatment modalities used in the two specialties. A postal questionnaire was sent to 540 consultant gynaecologists and 225 consultant and senior registrar members of the British Association of Dermatologists. 350 gynaecologists and 161 dermatologists returned completed questionnaires. The workload of LS and Paget's disease was evenly distributed, with 54% of dermatologists and 58% of gynaecologists seeing more than six cases of LS per annum and less than 1% seeing more than five cases of Paget's disease. 92% of responding gynaecologists saw at least one case of VIN per year whereas 43% of dermatologists saw no cases. Patients with VIN and Paget's were referred to gynaecologists for treatment by 66% of dermatologists. Both groups are equally prepared to treat LS. Indications for treatment of VIN and LS were suspicion of invasion and symptoms. Local excision of VIN is the treatment of choice by both gynaecologists and dermatologists. LS is predominantly treated with topical steroids but gynaecologists also use topical oestrogen and testosterone. The great majority of responders favoured establishing a national register to study the outcome of vulval lesions.
Predictors of lung function improvement following smoking cessation
Authors: Daiana Stolz, Rebecca Finger, Bruno Seiffert, Martin Kuster, Anja Meyer, Michael Tamm
Journal: European Respiratory Journal (2011)

Smoking cessation is associated with substantial health benefits. Nevertheless outcome of smoking cessation was often investigated on strongly selected populations. We aimed to assess the influence of our smoking cessation programme on lung function under real life conditions.  703 smoking employees from University Hospital Basel, Switzerland, and two local health industry companies (Novartis Pharma AG, F.Hoffmann- La Roche AG) participated on a structured smoking cessation programm. The programm consisted of 10 visits with counselling and motivational support within 2 years of follow-up. Various modalities of both nicotine replacement therapy and/or bupropion could be offered. The impact of several factors on FEV1 was analyzed by a linear mixed effect model (fixed effects with 95% confidence intervalls are shown in parentheses)   Results:  Successful smoking cessation at 24 months was associated with an increase of FEV1 of 2.75% (95% CI [0.64;0.76] p= 0.045). Improvement in lung func-tion was observed independently from age (-0.01 95% CI [-0.20;0.01] p=0.067) and gender (1.84 95% CI [-0.22; 3.91] p= 0.08). Changes in FEV1 varied between study centres (6.55 95% CI [3.22; 9.88] p  The outcome of a smoking cessation attempt as well as baseline lung function and medication significantly influenced FEV1 within 2 years of a quit attempt. These observations could be important in encouraging smokers to stop smoking.
Gene therapy trial for cystic fibrosis shows modest benefits:
Authors: Nigel Hawkes
Journal: BMJ (2015)

A gene therapy trial has shown a small but notable health benefit in people with cystic fibrosis—proof of principle that, after a long wait, hopes of effective treatments for inherited diseases may one day be realised.

In a trial involving 136 cystic fibrosis patients aged over 12 who used nebulisers to inhale the correct gene wrapped in an envelope of fat, modest benefits were observed over a range of measurements when compared with patients inhaling a placebo. The main aim was to show that the treatment, given monthly for a year, would improve lung function measured by the volume of air the patients could expel in one second.

The improvement was just 3.7%—insufficient to justify the treatment’s use in clinical practice but hugely encouraging to the UK Cystic Fibrosis Gene Therapy Consortium, which ran the trial in 18 …
Role of image-guided core-needle biopsy in the management of patients with lymphoma.
Authors: V I Pappa, H K Hussain, R H Reznek, J Whelan, A J Norton, A M Wilson, S Love, T A Lister, A Z Rohatiner
Journal: Journal of Clinical Oncology (1996)

The results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success.Biopsies were performed in 51 patients with low-grade non-Hodgkin's lymphoma (NHL), 24 with high-grade NHL, 16 with previously diagnosed Hodgkin's disease (HD), and 15 with no previous history of lymphoma. Disease was infradiaphragmatic in 92 patients and supradiaphragmatic in 14. Computed tomography (CT) guidance was used in 98 biopsies and ultrasonography (US) in eight.The biopsy was diagnostic and yielded information on the basis of which treatment was started in 88 of 106 patients. The procedure was well tolerated and there were no major complications. Small size of the sample or inappropriate tissue sampled were the main causes of failure. The technique was equally successful in the diagnosis of HD and both high-grade and low-grade NHL as in nonlymphoproliferative disorders. The procedure was equally successful at diagnosis as at suspected recurrence or progression. In 33 of 80 cases in which the biopsy was performed at the time of recurrence or progression, the histology had changed; in 31 of 33, this influenced treatment. The technique was efficient at diagnosing transformation of follicular NHL in 16 of 18 patients, which allowed early adjustment of treatment at recurrence.At St Bartholomew's Hospital (SBH), image-guided core-needle biopsy has proven to be a quick, safe, and efficient alternative to excisional biopsy in the evaluation of lymphoproliferative disorders at presentation, recurrence, or progression. It should become the procedure of choice for histologic sampling in the absence of peripheral lymphadenopathy.