tbuckley/cabot-search huggingface dataset:
Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity
Authors: M E Doorenspleet, P L Klarenbeek, M J H de Hair, B D C van Schaik, R E E Esveldt, A H C van Kampen, D M Gerlag, A Musters, F Baas, P P Tak, N de Vries
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To identify potential autoreactive B-cell and plasma-cell clones by quantitatively analysing the complete human B-cell receptor (BCR) repertoire in synovium and peripheral blood in early and established rheumatoid arthritis (RA). <h3>Methods</h3> The BCR repertoire was screened in synovium and blood of six patients with early RA (ERA) (&lt;6 months) and six with established RA (ESRA) (&gt;20 months). In two patients, the repertoires in different joints were compared. Repertoires were analysed by next-generation sequencing from mRNA, generating &gt;10 000 BCR heavy-chain sequence reads per sample. For each clone, the degree of expansion was calculated as the percentage of the total number of reads encoding the specific clonal sequence. Clones with a frequency ≥0.5% were considered dominant. <h3>Results</h3> Multiple dominant clones were found in inflamed synovium but hardly any in blood. Within an individual patient, the same dominant clones were detected in different joints. The majority of the synovial clones were class-switched; however, the fraction of clones that expressed IgM was higher in ESRA than ERA patients. Dominant synovial clones showed autoreactive features: in ERA in particular the clones were enriched for immunoglobulin heavy chain gene segment V4–34 (IGHV4–34) and showed longer CDR3 lengths. Dominant synovial clones that did not encode IGHV4–34 also had longer CDR3s than peripheral blood. <h3>Conclusions</h3> In RA, the synovium forms a niche where expanded—potentially autoreactive—B cells and plasma cells reside. The inflamed target tissue, especially in the earliest phase of disease, seems to be the most promising compartment for studying autoreactive cells.
Histological evidence for recurrence of primary biliary cirrhosis after liver transplantation
Authors: Vijayan Balan, Kennetii P. Batts, Michael K. Porayko, Ruud A. F. Krom, Jurgen Ludwig, Russell H. Wiesner
Journal: Hepatology (1993)

Whether primary biliary cirrhosis recurs after orthotopic liver transplantation remains a controversial issue. Sixty consecutive patients with primary biliary cirrhosis with at least 1 yr of follow-up after liver transplantation were studied. All patients were treated with triple-drug immunosuppression (cyclosporine, prednisone, azathioprine). Hepatic biochemical parameters and protocol liver biopsy specimens were evaluated 1 wk, 3 wk, 4 mo and yearly after orthotopic liver transplantation and at times of liver dysfunction. Antimitochondrial antibody titers and IgM levels were determined at 4 mo and yearly. At the time of last follow-up, all patients had marked symptomatic improvement compared with their pretransplant condition, and 91% of the patients had normal hepatic biochemical parameters, including serum levels of alkaline phosphatase, bilirubin, ALT and IgM. In addition, all patients had significant decreases in antimitochondrial antibody titer (p = 0.0001) and significant decreases in serum levels of IgM (p = 0.0001). Forty-one of the 60 patients had near-normal liver histological appearance. Of those with abnormal histological appearance, five patients, 2 to 6 yr after orthotopic liver transplantation, had histological features typical of a florid duct lesion, suggesting recurrent primary biliary cirrhosis. All five patients with portal granulomas had normal hepatic biochemical values and were clinically asymptomatic. Two of the five patients had persistent antimitochondrial antibody titers. We consider the documented histological changes highly suggestive of recurrence of primary biliary cirrhosis after liver transplantation but, so far, have no evidence that the condition in these patients is progressive.
Blood Mercury Levels and Neurobehavioral Function
Authors: Megan Weil, Joseph Bressler, Patrick Parsons, Karen Bolla, Thomas Glass, Brian Schwartz
Journal: JAMA (2005)

Context Due to its cardiovascular benefits, fish consumption is widely encouraged among older Americans.However, this fast-growing population is at increased risk of cognitive impairment and may be particularly sensitive to methylmercury, a neurotoxicant found in fish.Objective To describe associations of blood mercury levels with neurobehavioral test scores in an urban adult population.Design, Setting, and Participants Cross-sectional analysis to determine the effect of mercury levels on neurobehavior in 474 randomly selected participants in the Baltimore Memory Study, a longitudinal study of cognitive decline involving 1140 Baltimore residents aged 50 to 70 years.We measured total mercury in whole blood samples and used multiple linear regression to examine its associations with neurobehavioral test scores.First-visit data were obtained in 2001-2002.Main Outcome Measures Twenty scores from 12 neurobehavioral tests. ResultsThe median blood mercury level was 2.1 µg/L (range, 0-16 µg/L).After adjustment for covariates, increasing blood mercury was associated with worse performance on Rey complex figure delayed recall, a test of visual memory (␤, -0.224; 95% confidence interval, -0.402 to -0.047).However, increasing blood mercury levels were associated with better performance on finger tapping, a test of manual dexterity (␤ for dominant hand, 0.351; 95% confidence interval, 0.017-0.686). ConclusionOverall, the data do not provide strong evidence that blood mercury levels are associated with worse neurobehavioral performance in this population of older urban adults.
Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting 2 agonist: observational matched cohort study (PATHOS)
Authors: C. Janson, K. Larsson, K. H. Lisspers, B. Stallberg, G. Stratelis, H. Goike, L. Jorgensen, G. Johansson
Journal: BMJ (2013)

Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist. Design Observational retrospective pairwise cohort study matched (1:1) for propensity score. Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009. Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol. Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality. Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each. In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up. Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively. The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6). The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003). All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59). Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD. Trial registration Clinical Trials.gov [NCT01146392][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01146392&atom=%2Fbmj%2F346%2Fbmj.f3306.atom
A phase I trial of intraperitoneal recombinant gamma-interferon in advanced ovarian carcinoma.
Authors: R D'Acquisto, M Markman, T Hakes, S Rubin, W Hoskins, J L Lewis
Journal: Journal of Clinical Oncology (1988)

The interferons are a class of biological agents that have demonstrated antineoplastic activity in a variety of tumors both in vitro and in vivo. Previous reports have suggested that interferons can be safely administered by the intraperitoneal (IP) route with a pharmacokinetic advantage for peritoneal cavity exposure compared with the systemic circulation and with objective antitumor activity being demonstrated. On the basis of these reports and laboratory data suggesting activity for recombinant gamma-interferon (r-GIFN) against several malignant cell lines, we treated 27 refractory ovarian carcinoma patients, including six with very-small-volume residual disease, with this agent delivered by the IP route. While r-GIFN was found to be remarkably well tolerated, with a 150- to 200-fold pharmacokinetic advantage for peak levels achieved in the peritoneal cavity compared with the plasma, no objective responses were observed. Despite the lack of demonstrated activity for single-agent IP-administered r-GIFN in this clinical setting, there remains considerable interest in this agent when delivered by the IP route because of in vitro data suggesting concentration-dependent synergy between r-GIFN and other biological agents.
Mutations in the ABC 1 gene in familial HDL deficiency with defective cholesterol efflux
Authors: Michel Marcil, Angela Brooks-Wilson, Susanne M Clee, Kirsten Roomp, Lin-Hua Zhang, Lu Yu, Jennifer A Collins, Marjel van Dam, Henri OF Molhuizen, Odell Loubster, BF Francis Ouellette, Christoph W Sensen, Keith Fichter, Stephanie Mott, Maxime Denis, Betsie Boucher, Simon Pimstone, Jacques Genest, John JP Kastelein, Michael R Hayden
Journal: The Lancet (1999)
Podocyte-specific deletion of NDST1, a key enzyme in the sulfation of heparan sulfate glycosaminoglycans, leads to abnormalities in podocyte organization in vivo
Authors: Terrel Sugar, Deborah J. Wassenhove-McCarthy, Jeffrey D. Esko, Toin H. van Kuppevelt, Lawrence Holzman, Kevin J. McCarthy
Journal: Kidney International (2013)

Heparan sulfate proteoglycans have been shown to modulate podocyte adhesion to--and pedicel organization on--the glomerular basement membrane. Recent studies showed that foot process effacement developed in a mutant mouse model whose podocytes were unable to assemble heparan sulfate glycosaminoglycan chains. This study, a further refinement, explored the role of heparan N-sulfation on podocyte behavior. A novel mutant mouse (Ndst1(-/-)) was developed, having podocyte-specific deletion of Ndst1, the enzyme responsible for N-sulfation of heparan sulfate chains. Podocytes having this mutation had foot process effacement and abnormal adhesion to Bowman's capsule. Although glomerular hypertrophy did develop in the kidneys of mutant animals, mesangial expansion was not seen. The lack of heparan N-sulfation did not affect the expression of agrin or perlecan proteoglycan core proteins. Loss of N-sulfation did not result in significant proteinuria, but the increase in the albumin/creatinine ratio was coincident with the development of the enlarged lysosomes in the proximal tubules. Thus, although the renal phenotype of the Ndst1(-/-) mouse is mild, the data show that heparan chain N-sulfation plays a key role in podocyte organization.
Inflammatory bowel disease and laterality: is left handedness a risk?
Authors: D L Morris, S M Montgomery, M L Galloway, R E Pounder, A J Wakefield
Journal: Gut (2001)

BACKGROUND Left handedness has been associated with inflammatory bowel disease (IBD) and autoimmune diseases. AIMS To determine whether left handedness is associated with IBD in two prospective national birth cohorts. METHODS Subjects with Crohn's disease (CD) and ulcerative colitis (UC) were identified from two national longitudinal birth cohorts at age 26 years (1970 British Cohort Study (BCS70), born in 1970) and age 33 years (National Child Development Study (NCDS), born in 1958). Laterality was determined at age 10 (BCS70) or seven (NCDS) years, based on hand preference for writing and foot preference for kicking a ball (BCS70 only). Multiple logistic regression was used to assess the relationship of handedness with CD, UC, and IBD in the cohorts combined and adjusted for sex. RESULTS Both cohorts combined showed increased adjusted relative odds of 2.13 (95% confidence interval (CI) 0.97–4.65; p=0.059), 2.13 (95% CI 0.92–4.91; p=0. 077), and 2.13 (95% CI 1.20–3.78; p=0.010) for CD, UC, and IBD, respectively in left handers. CONCLUSIONS The study suggests a link between IBD and left handedness which may be genetic and/or environmental in origin.
A randomized phase II study comparing induction or consolidation chemotherapy with cisplatin–docetaxel, plus radical concurrent chemoradiotherapy with cisplatin–docetaxel, in patients with unresectable locally advanced non-small-cell lung cancer
Authors: S. Senan, F. Cardenal, J. Vansteenkiste, J. Stigt, F. Akyol, W. De Neve, J. Bakker, J.-M. Dupont, G.V. Scagliotti, U. Ricardi, J.P. van Meerbeeck
Journal: Annals of Oncology (2010)
Health Care Provider Satisfaction With a New Electronic Progress Note Format: SOAP vs APSO Format
Authors: Chen-Tan Lin, Marlene McKenzie, Jonathan Pell, Liron Caplan
Journal: JAMA Internal Medicine (2012)

with 1992, this represented a 65% decrease in ischemic stroke in the Medicare population.In contrast, the hemorrhagic stroke rate remained constant at nearly 2 per 1000 patient-years throughout the study period.Coincident with decreasing ischemic stroke rates was a trend toward greater use of anticoagulation among patients with prevalent AF; warfarin use among patients with prevalent AF increased from 26. 7% in 1992 to 63.1% in 2007 (Figure).Comment.The continued, steady decline in ischemic stroke rates between 1992 and 2007 in patients with prevalent AF is extremely encouraging.This decrease was associated with increasing warfarin use (26.7% in 1992; 63.1% in 2007), which is noteworthy.These data indicate continued dissemination of evidence-based medicine from clinical trials into routine practice.While causality cannot be established on the basis of these observational data, one can hypothesize that diffusion of warfarin into clinical practice likely contributed substantially to reduction in ischemic stroke rates in this time frame, in combination with better control of modifiable atherosclerotic cardiovascular risk factors.Mercaldi et al 7 reported that 41.5% of Medicare patients with nonvalvular AF do not receive anticoagulation; this is concordant with our data showing that 37% of Medicare beneficiaries with AF did not receive warfarin for anticoagulation therapy in 2007.In this patient subset, substantial numbers likely had a personal preference to forego anticoagulation or logistical constraints, making warfarin therapy not feasible.This group of patients might benefit from the advent of newer anticoagulants that do not require frequent monitoring and have a lower reported risk of significant bleeding.This study is limited owing to the observational design; the declining rates of ischemic stroke with increasing warfarin use reflect temporal associations and not necessarily the effect of anticoagulation.We used a surrogate method to ascertain warfarin use, which could result in underestimating numbers of individuals undergoing testing in alternative settings.In conclusion, ischemic stroke rates continue to decrease in the Medicare population, parallel to increases in warfarin use, although these rates appear to have leveled off.On the basis of these data, the 37% of Medicare beneficiaries not currently receiving warfarin for anticoagulation may offer a window of opportunity for further reduction in ischemic stroke rates and should be targeted in future studies.
Dendriform pulmonary ossification: unusual cause of spontaneous pneumothorax
Authors: Jiro Abe, Hiroyuki Oura, Hiromichi Niikawa, Hiroshi Yaegashi, Takashi Kondo
Journal: Thorax (2013)

A 53-year-old man was admitted to our hospital with a recurrence of spontaneous pneumothorax. He had no history of other diseases including chronic lung diseases. A month prior to this admission, he had a first pneumothorax and was treated with 4 days of intercostal drainage. CT scan showed no bulla, but revealed multiple small polygonal lesions consistent with fibrotic lesions mainly in the right lower lobe (figure 1). We performed right thoracotomy and found that air leakage arose from torn visceral pleura which had been pierced by a drumstick-shaped bony structure (figure 2A). Some other solid flat lesions were palpable in the …
Letter: A human right.
Authors: K J Dennis
Journal: BMJ (1974)

than 40 Mg/ 100 ml one begins to have somne awareness of the gravity of the situation.7In view of these results we think it regrettable that the authorities in Britain have not seen fit to institute a similar screening programin,e on children in British cities.No doubt too much time would be spent in d-eciding which laboratory could be trusted to provide the right blood lead levels.The appearance of the "chicken-or-the- egg" hypothesis was predictable but un- necessary in view of a nunber of ellegant s:udies from America which ihave demon- stra:.edthat hyperactivity can be induced in rats suckled by mothers fed lead in their diets,8-"1 whereas those suckled by mothers on nornal diets are unaffected.This hyperactive behaviour shows a paradoxical pattern of response to drug treatment identical with that of "pure" hyperactivity in children1l
Immunopathology of psoriasis and psoriatic arthritis
Authors: D J Veale
Journal: Annals of the Rheumatic Diseases (2005)

Psoriatic arthritis (PsA) is characterised by several unique clinical features that differentiate it from rheumatoid arthritis (RA). Attempts to identify immunopathological mechanisms, some shared with psoriasis, that underlie these differences from RA have been most challenging. Recent research studies, however, highlight novel findings in PsA at the molecular, cellular, and tissue levels that form the basis for a new understanding of this relatively common form of inflammatory arthritis. In particular, the availability of new, biological antitumour necrosis factor α therapies have allowed further insight into the immunopathology of psoriasis and PsA. This brief review focuses on immunohistological studies in psoriatic skin, PsA synovium, and bone to demonstrate how these data advance our knowledge of disease pathogenesis.
Antiangiogenic Effect of Angiotensin II Type 2 Receptor in Ischemia-Induced Angiogenesis in Mice Hindlimb
Authors: Jean-Sébastien Silvestre, Radia Tamarat, Takaaki Senbonmatsu, Toshihiro Icchiki, Teni Ebrahimian, Marc Iglarz, Sandrine Besnard, Micheline Duriez, Tadashi Inagami, Bernard I. Lévy
Journal: Circulation Research (2002)

Abstract — This study examined the potential role of angiotensin type 2 (AT 2 ) receptor on angiogenesis in a model of surgically induced hindlimb ischemia. Ischemia was produced by femoral artery ligature in both wild-type and AT 2 gene–deleted mice ( Agtr2 − /Y). After 28 days, angiogenesis was quantitated by microangiography, capillary density measurement, and laser Doppler perfusion imaging. Protein levels of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), Bax, and Bcl-2 were determined by Western blot analysis in hindlimbs. The AT 2 mRNA level (assessed by semiquantitative RT-PCR) was increased in the ischemic hindlimb of wild-type mice. Angiographic vessel density and laser Doppler perfusion data showed significant improvement in ischemic/nonischemic leg ratio, 1.9- and 1.7-fold, respectively, in Agtr2 − /Y mice compared with controls. In ischemic leg of Agtr2 − /Y mice, revascularization was associated with an increase in the antiapoptotic protein content, Bcl-2 (211% of basal), and a decrease (60% of basal) in the number of cell death, determined by TUNEL method. Angiotensin II treatment (0.3 mg/kg per day) raised angiogenic score, blood perfusion, and both VEGF and eNOS protein content in ischemic leg of wild-type control but did not modulate the enhanced angiogenic response observed in untreated Agtr2 − /Y mice. Finally, immunohistochemistry analysis revealed that VEGF was mainly localized to myocyte, whereas eNOS-positive staining was mainly observed in the capillary of ischemic leg of both wild-type and AT 2 -deficient mice. This study demonstrates for the first time that the AT 2 receptor subtype may negatively modulate ischemia-induced angiogenesis through an activation of the apoptotic process.
Effects of the Mammalian Target of Rapamycin Inhibitor CCI-779 Used Alone or with Chemotherapy on Human Prostate Cancer Cells and Xenografts
Authors: Licun Wu, Diana C. Birle, Ian F. Tannock
Journal: Cancer Research (2005)

Abstract Selective inhibition of repopulation of surviving tumor cells between courses of chemotherapy might improve the outcome of treatment. A potential target for inhibiting repopulation is the mammalian target of rapamycin pathway; PTEN-negative tumor cells are particularly sensitive to inhibition of this pathway. Here we study the rapamycin analogue CCI-779, alone or with chemotherapy, as an inhibitor of proliferation of the human prostate cancer cell lines PC-3 and DU145. The PTEN and phospho-Akt/PKB status and the effect of CCI-779 on phosphorylation of ribosomal protein S6 were evaluated by immunostaining and/or Western blotting. Expression of phospho-Akt/PKB in PTEN mutant PC-3 cells and xenografts was higher than in PTEN wild-type DU145 cells. Phosphorylation of S6 was inhibited by CCI-779 in both cell lines. Cultured cells were treated weekly with mitoxantrone or docetaxel for two cycles, and CCI-779 or vehicle was given between courses. Growth and clonogenic survival of both cell lines were inhibited in a dose-dependent manner by CCI-779, but there were minimal effects when CCI-779 was given between courses of chemotherapy. CCI-779 inhibited the growth of xenografts derived from both cell lines with greater effects against PC-3 than DU145 tumors. CCI-779 caused mild myelosuppression. The activity of mitoxantrone or docetaxel was limited, but CCI-779 given between courses of chemotherapy increased growth delay of PC-3 xenografts. Our results suggest that repopulation of PTEN-negative cancer cells between courses of chemotherapy might be inhibited by CCI-779.
Infection rate and use of antibiotics in patients with rheumatoid arthritis treated with methotrexate.
Authors: M J van der Veen, A van der Heide, A A Kruize, J W Bijlsma
Journal: Annals of the Rheumatic Diseases (1994)

To investigate prospectively the frequency and type of infections and the use of antibiotics among patients with rheumatoid arthritis (RA) on methotrexate (MTX) and patients with RA without MTX.Every three months for one year 77 patients on MTX and 151 patients without MTX were asked about infections and the use of antibiotics by means of a standardised questionnaire. Medication was checked with the pharmacist.In the MTX group there were significantly more infections and more antibiotic therapy. The relative risks for patients on MTX of infection or antibiotics use were 1.52 (95% Confidence Interval (CI) 1.04-2.22) and 1.49 (95% CI 1.04-2.13), respectively. The relative risk of MTX for respiratory tract infections was 1.43 (95% CI 0.96-2.14) and for skin infections 2.19 (95% CI 1.45-3.31). The increased risks could only partly be explained by differences in disease severity and were not related to either duration of MTX therapy or use of prednisone. Three patients in the MTX group had herpes zoster versus one in the control group.Treatment with MTX increases the rate of infection and thus the use of antibiotics but does not lead to serious complications necessitating discontinuation of the drug.