tbuckley/cabot-search huggingface dataset:
Vitamin D–dependent induction of cathelicidin in human macrophages results in cytotoxicity against high-grade B cell lymphoma
Authors: Heiko Bruns, Maike Büttner, Mario Fabri, Dimitrios Mougiakakos, Jörg T. Bittenbring, Markus H. Hoffmann, Fabian Beier, Shirin Pasemann, Regina Jitschin, Andreas D. Hofmann, Frank Neumann, Christoph Daniel, Anna Maurberger, Bettina Kempkes, Kerstin Amann, Andreas Mackensen, Armin Gerbitz
Journal: Science Translational Medicine (2015)

Infiltration by macrophages represents a characteristic morphological hallmark in high-grade lymphatic malignancies such as Burkitt's lymphoma (BL). Although macrophages can, in principle, target neoplastic cells and mediate antibody-dependent cellular cytotoxicity (ADCC), tumor-associated macrophages (TAMs) regularly fail to exert direct cytotoxic functions. The underlying mechanisms responsible for this observation remain unclear. We demonstrate that inflammatory M1 macrophages kill proliferating high-grade B cell lymphoma cells by releasing the antimicrobial peptide cathelicidin in a vitamin D-dependent fashion. We show that cathelicidin directly induces cell death by targeting mitochondria of BL cells. In contrast, anti-inflammatory M2 macrophages and M2-like TAMs in BL exhibit an altered vitamin D metabolism, resulting in a reduced production of cathelicidin and consequently in inability to lyse BL cells. However, treatment of M2 macrophages with the bioactive form of vitamin D, 1,25D3, or a vitamin D receptor agonist effectively induces cathelicidin production and triggers tumoricidal activity against BL cells. Furthermore, rituximab-mediated cytotoxicity of vitamin D-treated M2 macrophages is cathelicidin-dependent. Finally, vitamin D treatment of 25-hydroxyvitamin D (25D)-deficient volunteers in vivo or primary TAMs in vitro improves rituximab-mediated ADCC against B cell lymphoma cells. These data indicate that activation of the vitamin D signaling pathway activates antitumor activity of TAMs and improves the efficacy of ADCC.
A first or dominant immunization. I. Suppression of simultaneous cytolytic T cell responses to unrelated alloantigens.
Authors: D A Rowley, R M Stach
Journal: The Journal of Experimental Medicine (1993)

A first or dominant immunization with one antigen markedly inhibited specific cytolytic T lymphocyte (CTL) responses to a second unrelated alloantigen without suppressing antibody responses to other antigens. Suppression was induced rapidly, became systemic, and could be transferred passively with only serum. Suppression did not result from elimination of cells capable of responding to the second antigen. The mechanisms responsible for this "priority of the first response" may be the same that help protect the fetus during pregnancy, promote renal allograft survival after multiple blood transfusions, and prevent effective CTL-mediated immunity to variants of tumor cells or infectious agents that arise during tumor progression or chronic infections.
Investigation of a<i>PON1</i>gene polymorphism (rs662 polymorphism) as predictor of subclinical atherosclerosis in patients with rheumatoid arthritis: Table 1
Authors: Raquel López-Mejías, Fernanda Genre, Alfonso Corrales, Carlos González-Juanatey, Begoña Ubilla, Javier Llorca, José A Miranda-Filloy, Trinitario Pina, Ricardo Blanco, Santos Castañeda, Javier Martín, Miguel A González-Gay
Journal: Annals of the Rheumatic Diseases (2014)

Several pieces of evidence indicate that rheumatoid arthritis (RA) is a proatherogenic disease associated with increased cardiovascular (CV) death rate.1 The mechanisms leading to that are complex, including traditional CV risk factors and also the presence of a chronic inflammatory state.1 Dyslipidemia with reduction in total cholesterol and its fractions and qualitative impairment in the high density lipoprotein (HDL)-cholesterol has been observed in RA patients with active disease.2 Chronic inflammation promotes oxidative changes that alter HDL structure and reduce apolipoprotein-A-I in patients with active RA. Decreased levels of the antioxidant HDL-associated enzyme paraoxonase (PON1) have been observed in these patients.3 Improvement of inflammation, as shown in patients undergoing biologic therapy, is associated with increases of PON1 activities.4 

RA is a polygenic disease. Previous studies have emphasised the implication of a genetic component in the risk of CV disease in RA.5 ,6 A functional, genetic T/C amino acid variant found within the PON1 gene (rs662) confers an amino acid change (Q192R) influential in determining PON1 activity values. …
Effects of recombinant human growth hormone in adults receiving maintenance hemodialysis.
Authors: T R Ziegler, J M Lazarus, L S Young, R Hakim, D W Wilmore
Journal: Journal of the American Society of Nephrology (1991)

Administration of recombinant human growth hormone stimulates protein synthesis, decreases urea generation, and improves nitrogen balance in individuals with normal renal function. However, little information is available concerning the effects of growth hormone in patients with renal disease. This pilot study evaluated urea kinetics and clinical/metabolic responses to short-term growth hormone administration in five clinically stable adult patients requiring maintenance hemodialysis for end-stage renal failure. The dialysis prescription, medications, and oral calorie and protein intake of each patient remained constant during an initial control week and a subsequent 2-wk growth hormone treatment period. During treatment, growth hormone (5 or 10 mg) was administered s.c. immediately after each dialysis session. Protein and calorie intake, vital signs, body weight, and other clinical parameters remained stable throughout the 3-wk study. BUN values fell significantly (approximately 20 to 25%) during growth hormone administration compared with control week values. Similarly, urea kinetic modeling demonstrated a significant reduction in urea generation and the protein catabolic rate during each week of growth hormone treatment. Plasma insulin-like growth factor I levels rose significantly, and serum phosphorus and intact parathyroid hormone levels fell significantly during growth hormone administration. Serum glucose and other blood values remained stable. This preliminary study suggests that growth hormone administration reduces urea generation and improves the efficiency of dietary protein utilization in stable adult hemodialysis patients. Growth hormone may be a useful adjunctive therapy to diminish body protein catabolism in this patient population.
Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum
Authors: T Uraoka, Y Saito, T Matsuda, H Ikehara, T Gotoda, D Saito, T Fujii
Journal: Gut (2006)

Laterally spreading tumours (LSTs) in the colorectum are usually removed by endoscopic mucosal resection (EMR) even when large in size. LSTs with deeper submucosal (sm) invasion, however, should not be treated by EMR because of the higher risk of lymph node metastasis.To determine which endoscopic criteria, including high magnification pit pattern analysis, are associated with sm invasion in LSTs and clarify indications for EMR.Eight endoscopic criteria from 511 colorectal LSTs (granular type (LST-G type); non-granular type (LST-NG type)) were evaluated retrospectively for association with sm invasion, and compared with histopathological findings.LST-NG type had a significantly higher frequency of sm invasion than LST-G type (14% v 7%; p<0.01). Presence of a large nodule in LST-G type was associated with higher sm invasion while pit pattern (invasive pattern), sclerous wall change, and larger tumour size were significantly associated with higher sm invasion in LST-NG type. In 19 LST-G type with sm invasion, sm penetration determined histopathologically occurred under the largest nodules (84%; 16/19) and depressed areas (16%; 3/19). Deepest sm penetration in 32 LST-NG type was either under depressed areas (72%; 23/32) or lymph follicular or multifocal sm invasion (28%; 1/32 and 8/32, respectively).When considering the most suitable therapeutic strategy for LST-G type, we recommend endoscopic piecemeal resection with the area including the large nodule resected first. In contrast, LST-NG type should be removed en bloc because of the higher potential for malignancy and greater difficulty in diagnosing sm depth and extent of invasion compared with LST-G type.
Effects of large-volume paracentesis on pulmonary function in patients with tense cirrhotic ascites
Authors: Carlos E. Angueira, Shailesh C. Kadakia
Journal: Hepatology (1994)

Large–volume paracentesis is an accepted therapeutic modality for the treatment of tense ascites in patients with cirrhosis. Whereas the effects of large–volume paracentesis on the cardiovascular system have been studied in great detail, the effects of tense ascites and large–volume paracentesis on the respiratory system have undergone only limited evaluation. Most patients report symptomatic improvement in breathing after large–volume paracentesis. The aim of our study was to prospectively evaluate the effects of large–volume paracentesis on the pulmonary function of patients with tense ascites. Nine patients with alcoholic cirrhosis and tense ascites underwent large–volume paracentesis (mean, 3,500 ml of ascites removed) followed by intravenous albumin infusion (10 gm/L ascites removed). Pulmonary function tests were performed just before and 2 hr after large–volume paracentesis. The functional residual capacity increased from 2.46 ± 0.92 to 2.99 ± 0.97 L (p = 0.01) and total lung capacity from 5.08 ± 1.18 to 5.72 ± 1.32 L (p = 0.03). The forced vital capacity, expiratory reserve volume and residual volume also increased but were not statistically significant (p = 0.07 for all). We noted no significant improvement in forced expiratory volume in 1 sec, forced expiratory effort 25% to 75%, vital capacity or diffusion capacity. There was marked symptomatic improvement in all patients. We conclude that large–volume paracentesis improves measured lung volumes within hours in patients with tense ascites. (Hepatology 1994;20:825-828).
Predictors of Lower-Extremity Amputation in Patients With an Infected Diabetic Foot Ulcer
Authors: Kristy Pickwell, Volkert Siersma, Marleen Kars, Jan Apelqvist, Karel Bakker, Michael Edmonds, Per Holstein, Alexandra Jirkovská, Edward Jude, Didac Mauricio, Alberto Piaggesi, Gunnel Ragnarson Tennvall, Heinrich Reike, Maximilian Spraul, Luigi Uccioli, Vilma Urbancic, Kristien van Acker, Jeff van Baal, Nicolaas Schaper
Journal: Diabetes Care (2015)

Infection commonly complicates diabetic foot ulcers and is associated with a poor outcome. In a cohort of individuals with an infected diabetic foot ulcer, we aimed to determine independent predictors of lower-extremity amputation and the predictive value for amputation of the International Working Group on the Diabetic Foot (IWGDF) classification system and to develop a risk score for predicting amputation.We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries.Among these patients, 159 (28%) underwent an amputation. Independent risk factors for amputation were as follows: periwound edema, foul smell, (non)purulent exudate, deep ulcer, positive probe-to-bone test, pretibial edema, fever, and elevated C-reactive protein. Increasing IWGDF severity of infection also independently predicted amputation. We developed a risk score for any amputation and for amputations excluding the lesser toes (including the variables sex, pain on palpation, periwound edema, ulcer size, ulcer depth, and peripheral arterial disease) that predicted amputation better than the IWGDF system (area under the ROC curves 0.80, 0.78, and 0.67, respectively).For individuals with an infected diabetic foot ulcer, we identified independent predictors of amputation, validated the prognostic value of the IWGDF classification system, and developed a new risk score for amputation that can be readily used in daily clinical practice. Our risk score may have better prognostic accuracy than the IWGDF system, the only currently available system, but our findings need to be validated in other cohorts.
Catheter-Based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure
Authors: Pieter C Smits, Robert-Jan M van Geuns, Don Poldermans, Manolis Bountioukos, Emile E.M Onderwater, Chi Hang Lee, Alex P.W.M Maat, Patrick W Serruys
Journal: Journal of the American College of Cardiology (2003)
Phase I Study of the Combination of Sorafenib and Temsirolimus in Patients with Metastatic Melanoma
Authors: Michael A. Davies, Patricia S. Fox, Nicholas E. Papadopoulos, Agop Y. Bedikian, Wen-Jen Hwu, Alexander J. Lazar, Victor G. Prieto, Kirk S. Culotta, Timothy L. Madden, Quanyun Xu, Sha Huang, Wanleng Deng, Chaan S. Ng, Sanjay Gupta, Wenbin Liu, Janet E. Dancey, John J. Wright, Roland L. Bassett, Patrick Hwu, Kevin B. Kim
Journal: Clinical Cancer Research (2012)

This phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma.Patients with stage IV or unresectable or recurrent stage III melanoma and Eastern Cooperative Oncology Group performance status of 0 to 1 were eligible. Sorafenib was given orally once or twice daily and temsirolimus was given i.v. weekly, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per Response Evaluation Criteria in Solid Tumors criteria. Consenting patients with accessible tumors underwent optional tumor biopsies before treatment and after the second infusion of temsirolimus. Tumor biopsies were analyzed for activating mutations in BRAF and NRAS, and for expression of P-extracellular signal-regulated kinase (P-ERK) and P-S6 proteins.A total of 25 patients were accrued to the study. The maximum tolerated doses were sorafenib 400 mg every morning and 200 mg every evening and temsirolimus 25 mg i.v. weekly. Dose-limiting toxicities included thrombocytopenia, hand-foot syndrome, serum transaminase elevation, and hypertriglyceridemia. There were no complete or partial responses with the combination; 10 patients achieved stabilization of disease as their best response. The median progression-free survival was 2.1 months. Matching pretreatment and day 15 tumor biopsies showed marked inhibition of P-S6 with treatment in 3 of 4 evaluable patients, but minimal inhibition of P-ERK.Combination therapy with sorafenib and temsirolimus resulted in significant toxicity at higher dose levels, failed to achieve any clinical responses in genetically unselected patient population, and did not inhibit P-ERK.
Comment on: ‘Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry’ by Sørensen<i>et al</i>
Authors: Mark Sykes, Helen Doll, Karl Gaffney
Journal: Annals of the Rheumatic Diseases (2014)

Diagnostic delay is one of the key clinical challenges in ankylosing spondylitis (AS). Recent publications have continued to show an average delay of 8–10 years.1 ,2 We read with interest that the diagnostic delay in the DANBIO cohort had apparently reduced from 66 months in 2000 to 4 months in 2011.3

In our opinion, however, there is a potential methodological problem with this paper. The authors have implied that they have a prospective study following …
Is multidisciplinary teamwork the key? A qualitative study of the development of respiratory services in the UK
Authors: Hilary Pinnock, Guro Huby, Alison Tierney, Sonya Hamilton, Alison Powell, Tara Kielmann, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2009)

Summary Objectives Using frameworks, such as the long-term conditions pyramid of healthcare, primary care organizations (PCOs) in England and Wales are exploring ways of developing services for people with long-term respiratory disease. We aimed to explore the current and planned respiratory services and the roles of people responsible for change. Setting A purposive sample of 30 PCOs in England and Wales. Design Semi-structured telephone interviews with the person responsible for driving the reconfiguration of respiratory services. Recorded interviews were transcribed and coded, and themes identified. The association of the composition of the team driving change with the breadth of services provided was explored using a matrix. Results All but two of the PCOs described clinical services developed to address the needs of people with respiratory conditions, usually with a focus on preventing admissions for chronic obstructive pulmonary disease (COPD). Although the majority identified the need to develop a strategic approach to service development and to meet educational needs of primary care professionals, relatively few described clearly developed plans for addressing these issues. Involvement of clinicians from both primary and secondary care was associated with a broad multifaceted approach to service development. Teamwork was often challenging, but could prove rewarding for participants and could result in a fruitful alignment of objectives. The imminent merger of PCOs and overriding financial constraints resulted in a ‘fluid’ context which challenged successful implementation of plans. Conclusions While the majority of PCOs are developing clinical services for people with complex needs (principally in order to reduce admissions), relatively few are addressing the broader strategic issues and providing for local educational needs. The presence of multidisciplinary teams, which integrated primary and secondary care clinicians with PCO management, was associated with more comprehensive service provision addressing the needs of all respiratory patients. Future research needs to provide insight into the structures, processes and inter-professional relationships that facilitate development of clinical, educational and policy initiatives which aim to enhance local delivery of respiratory care.
The age invariance of working memory measures and noninvariance of producing complex syntax
Authors: Susan Kemper, Karen A. Kemtes
Journal: Behavioral and Brain Sciences (1999)

In challenging current conceptions of the role of working memory in sentence processing, Caplan & Waters consider studies comparing young and older adults on sentence processing. This commentary raises two challenges to Caplan & Waters's conclusions: first, working memory tasks appear to be age invariant. Second, the production of complex syntactic constructions appears not to be age invariant.
Hospital jobs on the Internet
Authors: T. Delamothe
Journal: BMJ (1995)

Older readers of the journal turn first to the obituary pages to check whether they are still alive; younger readers turn to the classified supplements to find their next job. While the obituary pages have been discussed at the highest levels (two editorials,1 2 a “how to do it,”3 and 10 letters to the editor having been published on the topic already this year4), the classified supplements have been quietly minding their own business, which has been expanding apace. …
Vascular Calcification Mechanisms
Authors: Cecilia M. Giachelli
Journal: Journal of the American Society of Nephrology (2004)

Vascular calcification is highly correlated with cardiovascular disease mortality, especially in patients with ESRD or diabetes. In addition to the devastating effects of inappropriate biomineralization seen in cardiac valvulopathies, calciphylaxis, and idiopathic arterial calcification, vascular calcification is now recognized as a marker of atherosclerotic plaque burden as well as a major contributor to loss of arterial compliance and increased pulse pressure seen with age, diabetes, and renal insufficiency. In recent years, several mechanisms to explain vascular calcification have been identified including (1) loss of inhibition, (2) induction of bone formation, (3) circulating nucleational complexes, and (4) cell death. Alterations in calcium (Ca) and phosphorus (P) balance as seen in patients with ESRD promotes vascular calcification via multiple mechanisms and may explain the alarmingly high levels of cardiovascular disease deaths in these patients. Strategies to control Ca and P levels in patients with ESRD have met with early success in preventing progression of vascular calcification. Whether or not vascular calcification can be reversed is not yet known, but exciting new studies suggest that this may be possible in the future.
Salerno-Something Old, Something New...
Authors: M. Therese Southgate
Journal: JAMA (1967)

June is the month of graduations, and it has become traditional forThe Journalto mark this fact with publication of its annual State Board Number. But June is also the month of weddings, and brides too honor tradition, by wearing "something old, something new, something borrowed, and something blue."The Journalsalutes these two June events with its own version of the old, the new, the borrowed, and the blue. The old is the former medical school at Salerno in Italy, the oldest medical school in Europe, and the first to confer formal degrees. The new is the proposed medical school at Salerno, which is presently being planned to replace the old. The borrowed is the degree of doctor in philosophy and medicine awarded to one Signore Francesco Antonio Candido by Salerno in the Year of Our Lord 1665 and reproduced on this week's cover. And the blue, of
The Number of Glycine Residues Which Limits Intact Absorption of Glycine Oligopeptides in Human Jejunum
Authors: Siamak A. Adibi, Emile L. Morse
Journal: Journal of Clinical Investigation (1977)

Studies were performed to determine whether glycine peptides of four or more glycine residues can be transported by the peptide carrier system, previously shown to transport diglycine and triglycine. When human jejunum was perfused with tetraglycine solutions, the rate of tetraglycine disappearance increased linearly as the concentration was increased over the range of 12.5-50 mM, however, the rate was slow in comparison to diglycine and triglycine disappearance rates.