tbuckley/cabot-search huggingface dataset:
A novel HLA-D/DR-like antigen specific for human B lymphoid cells. Biochemical evidence for similarity to but nonidentity with known HLA-D/DR antigens.
Authors: G E Marti, M C Kuo, S Shaw, C C Chang, R Demars, J A Sogn, J E Coligan, T J Kindt
Journal: The Journal of Experimental Medicine (1983)

The polymorphic human B cell-specific antigen, 33.1, detected by a murine monoclonal antibody, was compared by genetics and structural analysis with known human Ia antigens from a panel of DR homozygous Epstein-Barr virus-transformed B lymphoblastoid cell lines. Cells homozygous for DR 1, 2, 4, 5, and w6 were positive, while cells that are DR3,3 or DR7,7 usually failed to express this antigen. Mutant DR null, DC/MB-positive cells were 33.1 positive while DR null, DC/MB-negative cells failed to express this antigen, suggesting the segregation of 33.1 with the DC antigen. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that 33.1 alpha and beta chains were of lower molecular weights than the DR alpha and beta chains isolated from the same cell line. Partial N-terminal amino acid sequence analyses were carried out for the heavy and light chains of the 33.1 antigen radiolabeled with [3H] phenylalanine. The results of these analyses, in conjunction with previous data on tissue distribution, indicate that the 33.1 antigen is a non-DR but Ia-like antigen closely related to the previously defined I-A homologues, DC and DS.
Smac-Mimetic–Induced Epithelial Cell Death Reduces the Growth of Renal Cysts
Authors: Lucy X. Fan, Xia Zhou, William E. Sweeney, Darren P. Wallace, Ellis D. Avner, Jared J. Grantham, Xiaogang Li
Journal: Journal of the American Society of Nephrology (2013)

Past efforts to pharmacologically disrupt the development and growth of renal cystic lesions focused primarily on normalizing the activity of a specific signaling molecule, but the effects of stimulating apoptosis in the proliferating epithelial cells have not been well studied. Although benign, ADPKD renal cysts created by the sustained proliferation of epithelial cells resemble tumors, and malignant cell death can be achieved by cotreatment with TNF-α and a mimetic of second mitochondria-derived activator of caspase (Smac). Notably, TNF-α accumulates to high levels in ADPKD cyst fluid. Here, we report that an Smac-mimetic selectively induces TNF-α-dependent cystic renal epithelial cell death, leading to the removal of cystic epithelial cells from renal tissues and delaying cyst formation. In vitro, a Smac-mimetic (GT13072) induced the degradation of cIAP1 that is required but not sufficient for cell death. Cotreatment with TNF-α augmented the formation and activation of the RIPK1-dependent death complex and the degradation and cleavage of FLIP, an inhibitor of caspase-8, in renal cystic epithelial cells. This approach produced death specifically in Pkd1 mutant epithelial cells, with no effect on normal renal epithelial cells. Moreover, treatment with the Smac-mimetic slowed cyst and kidney enlargement and preserved renal function in two genetic strains of mice with Pkd1 mutations. Thus, our mechanistic data characterize an apoptotic pathway, activated by the selective synergy of an Smac-mimetic and TNF-α in renal cyst fluid, that attenuates cyst development, providing an innovative translational platform for the rational development of novel therapeutics for ADPKD.
Traumatic humeral articular cartilage shear (THACS) lesion in a professional rugby player: a case report
Authors: I-H Jeon, W A Wallace
Journal: British Journal of Sports Medicine (2004)

A 20 year old male professional rugby player was seen at the clinic for evaluation of shoulder pain after rugby play. Magnetic resonance imaging showed extensive subchondral bone bruising of the humeral head with defect of the articular cartilage. Arthroscopy showed that the inferior half of the humeral head had extensive articular cartilage loss with nearly 70% of the inferior head having lost its cartilage. Sports medicine doctors should be aware that the shoulder joint in young competitive athletes playing contact sports may be exposed to greater risk of this kind of injury.
Transbronchial biopsies in lung cancer: Retrospective review of 116 patients
Authors: Ping Shi Zhu, Charles D. Poirier, Michel Gagnon, Thomas Vandemoortele
Journal: European Respiratory Journal (2014)

Background: Bronchoscopy with transbronchial biopsy (TBB) is an interesting tool in the investigation of lung cancer. We aimed to describe the yield and safety of TBB in the evaluation of pulmonary malignancy.   Methods: We retrospectively reviewed the data of 116 TBB performed to assess lung lesions executed between January 2013 and December 2013 at a tertiary center. We evaluated these procedures in terms of diagnostic yield for neoplasia and complications.   Results: The mean age of the patients was 66 years old (range 26-88), with 55 male (48.9%). The mean number of biopsies was 4.28 (±1.46). The diagnostic yield from TBB alone for lung cancer was 37.9% (44/116), while when combined with other sampling procedures (such as bronchial biopsy, bronchoalveolar lavage or brush), diagnostic yield was 43.1% (50/116). When linear endobronchial ultrasound (EBUS) was performed during the same procedure, diagnostic yield further increased to 58.6% (68/116).  A higher number of biopsies improved the diagnostic yield (72.7% with g 5 biopsies vs 36.7% with 3-5 biopsies vs 0% with 1-2 biopsies; p= 0.015). Diagnostic yield was higher when lesions measured ≥ 30 mm (46.3%; 31/67) compared with nodules l30 mm in diameter (25.6%; 10/39) [p=0.041]. Adjuncts such as radial EBUS (8/116), electromagnetic navigation (19/116), fluoroscopy (17/116) and cryoprobe (4/116) were used in 29 TBB (25%), with no significant effect on diagnostic yield (p=0.659). Only one patient suffered from a small pneumothorax (0.9 %) that did not require chest drainage.   Conclusions:  Efficacy of TBB for the diagnosis of lung cancer is optimized when performed with linear EBUS, g 5 biopsies and larger lung lesion.
Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction
Authors: David Aguilar, Hicham Skali, Lemuel A. Moyé, Eldrin F. Lewis, J.Michael Gaziano, John D. Rutherford, L.Howard Hartley, Otelio S. Randall, Edward M. Geltman, Gervasio A. Lamas, Jean L. Rouleau, Marc A. Pfeffer, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2004)
Dynamics of Polymorphism in a Malaria Vaccine Antigen at a Vaccine-Testing Site in Mali
Authors: Shannon L Takala, Drissa Coulibaly, Mahamadou A Thera, Alassane Dicko, David L Smith, Ando B Guindo, Abdoulaye K Kone, Karim Traore, Amed Ouattara, Abdoulaye A Djimde, Paul S Sehdev, Kirsten E Lyke, Dapa A Diallo, Ogobara K Doumbo, Christopher V Plowe
Journal: PLoS Medicine (2007)

Malaria vaccines based on the 19-kDa region of merozoite surface protein 1 (MSP-1(19)) derived from the 3D7 strain of Plasmodium falciparum are being tested in clinical trials in Africa. Knowledge of the distribution and natural dynamics of vaccine antigen polymorphisms in populations in which malaria vaccines will be tested will guide vaccine design and permit distinction between natural fluctuations in genetic diversity and vaccine-induced selection.Using pyrosequencing, six single-nucleotide polymorphisms in the nucleotide sequence encoding MSP-1(19) were genotyped from 1,363 malaria infections experienced by 100 children who participated in a prospective cohort study in Mali from 1999 to 2001. The frequencies of 14 MSP-1(19) haplotypes were compared over the course of the malaria transmission season for all three years, in three age groups, and in consecutive infections within individuals. While the frequency of individual MSP-1(19) haplotypes fluctuated, haplotypes corresponding to FVO and FUP strains of P. falciparum (MSP-1(19) haplotypes QKSNGL and EKSNGL, respectively) were most prevalent during three consecutive years and in all age groups with overall prevalences of 46% (95% confidence interval [CI] 44%-49%) and 36% (95% CI 34%-39%), respectively. The 3D7 haplotype had a lower overall prevalence of 16% (95% CI 14%-18%). Multiplicity of infection based on MSP-1(19) was higher at the beginning of the transmission season and in the oldest individuals (aged > or =11 y). Three MSP-1(19) haplotypes had a reduced frequency in symptomatic infections compared to asymptomatic infections. Analyses of the dynamics of MSP-1(19) polymorphisms in consecutive infections implicate three polymorphisms (at positions 1691, 1700, and 1701) as being particularly important in determining allele specificity of anti-MSP-1(19) immunity.Parasites with MSP-1(19) haplotypes different from that of the leading vaccine strain were consistently the most prevalent at a vaccine trial site. If immunity elicited by an MSP-1-based vaccine is allele-specific, a vaccine based on either the FVO or FUP strain might have better initial efficacy at this site. This study, to our knowledge the largest of its kind to date, provides molecular information needed to interpret population responses to MSP-1-based vaccines and suggests that certain MSP-1(19) polymorphisms may be relevant to cross-protective immunity.
Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
Authors: Xinyan Zhao, Eszter Deak, Kelly Soderberg, Melissa Linehan, David Spezzano, Jia Zhu, David M. Knipe, Akiko Iwasaki
Journal: The Journal of Experimental Medicine (2003)

Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c+ DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFNγ secretion from HSV-specific CD4+ T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b+ DCs, and the CD8α+ lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b+ submucosal DCs, but not Langerhans cell–derived or CD8α+ DCs, presented viral antigens to CD4+ T cells and induced IFNγ secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases.
Discussing Bad News in the Outpatient Oncology Clinic: Rethinking Current Communication Guidelines
Authors: Susan Eggly, Louis Penner, Terrance L. Albrecht, Rebecca J.W. Cline, Tanina Foster, Michael Naughton, Amy Peterson, John C. Ruckdeschel
Journal: Journal of Clinical Oncology (2006)

Aware that his pancreatic cancer had metastasized to his liver, Mr B and his adult son and daughter traveled several hundred miles to see an oncologist at a regional comprehensive cancer center. As the oncologist explained the treatment options, Mr B and his family occasionally interrupted with questions, statements, or expressions of emotion. During the interaction, Mr B and his family learned that surgery was not a treatment option, as they had hoped. They also learned that Mr B was not eligible for any clinical trials. The only available option was chemotherapy, but it carried the potential for severe adverse effects, had less than a 10% chance of shrinking the tumor, and had no chance of “melting the tumor away.” In response to one of the son’s questions, the oncologist said that complementary or alternative medicines were not available at this center. As part of his response to the daughter’s question about the urgency of a treatment decision, the oncologist mentioned that the cancer had been in Mr B’s body for a number of years. Mr B and both of his children asked several questions about this piece of information, indicating their surprise and dismay. Mr B shook his head and exclaimed, “And I go to the doctor all the time!” As the discussion concluded, the oncologist provided details about how chemotherapy might be delivered and repeated that there was no urgency to the decision.
Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study
Authors: A. Poprach, T. Pavlik, B. Melichar, I. Puzanov, L. Dusek, Z. Bortlicek, R. Vyzula, J. Abrahamova, T. Buchler
Journal: Annals of Oncology (2012)
Parenting intervention in Sure Start services for children at risk of developing conduct disorder: pragmatic randomised controlled trial
Authors: Judy Hutchings, Tracey Bywater, Dave Daley, Frances Gardner, Chris Whitaker, Karen Jones, Catrin Eames, Rhiannon T Edwards
Journal: BMJ (2007)

Objective To evaluate the effectiveness of a parenting programme as a preventive intervention with parents of preschool children considered to be at risk of developing conduct disorder. Design Pragmatic randomised controlled trial using a block design with allocation by area. Setting Eleven Sure Start areas in north and mid-Wales. Participants 153 parents from socially disadvantaged areas, with children aged 36-59 months at risk of conduct disorder defined by scoring over the clinical cut off on the Eyberg child behaviour inventory. Participants were randomised on a 2:1 basis, 104 to intervention and 49 to remaining on the wait listing (control). Twenty (13%) were lost to follow-up six months later, 18 from the intervention group. Intervention The Webster-Stratton Incredible Years basic parenting programme, a 12 week group based intervention. Main outcome measures Problem behaviour in children and parenting skills assessed by self reports from parents and by direct observation in the home. Parents' self reported parenting competence, stress, and depression. Standardised and well validated instruments were used throughout. Results At follow-up, most of the measures of parenting and problem behaviour in children showed significant improvement in the intervention group. The intention to treat analysis for the primary outcome measure, the Eyberg child behaviour inventory, showed a mean difference between groups of 4.4 points (95% confidence interval 2.0 to 6.9, P<0.001) on the problem scale with an effect size of 0.63, and a mean difference of 25.1 (14.9 to 35.2, P<0.001) on the intensity scale with an effect size of 0.89. Conclusion This community based study showed the effectiveness of an evidence based parenting intervention delivered with fidelity by regular Sure Start staff. It has influenced policy within Wales and provides lessons for England where, to date, Sure Start programmes have not been effective. Trial registration ISRCTN46984318
Pulmonary Alveolar Proteinosis
Authors: John F. Seymour, Jeffrey J. Presneill
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Section:ChooseTop of pageAbstract <<Table of ContentsDESCRIPTION OF A “NEW” DI...NATURE OF THE ACCUMULATED...PUBLISHED FEATURES OF PAT...DIAGNOSTIC PROCEDURESHISTOPATHOLOGYPATHOGENESIS AND CLASSIFI...DEVELOPMENT OF EFFECTIVE ...RESPONSE TO THERAPEUTIC L...GM-CSF THERAPY IN ACQUIRE...SECONDARY INFECTIONSSURVIVAL AND CAUSE OF DEA...POTENTIAL PROGNOSTIC FACT...SPONTANEOUS RESOLUTIONReferencesCITING ARTICLES
Multicentric Castleman's disease associated with rheumatoid arthritis: a possible role of hepatitis B antigen.
Authors: E Ben-Chetrit, D Flusser, E Okon, Z Ackerman, A Rubinow
Journal: Annals of the Rheumatic Diseases (1989)

A patient with seropositive rheumatoid arthritis and a carrier of hepatitis B surface antigen developed angiofollicular hyperplasia (multicentric Castleman9s disease). The hepatitis B virus and the rheumatoid factor may have had a role in the aetiology of this lymphatic disorder. The development of Castleman9s disease in association with these factors may provide another clue supporting the reactive nature of this disease.
Species-Specific Features of DARC, the Primate Receptor for Plasmodium vivax and Plasmodium knowlesi
Authors: A. Demogines, K. A. Truong, S. L. Sawyer
Journal: Molecular Biology and Evolution (2011)

The DARC (Duffy antigen/receptor for chemokines) gene, also called Duffy or FY, encodes a membrane-bound chemokine receptor. Two malaria parasites, Plasmodium vivax and Plasmodium knowlesi, use DARC to trigger internalization into red blood cells. Although much has been reported on the evolution of DARC null alleles, little is known about the evolution of the coding portion of this gene or the role that protein sequence divergence in this receptor may play in disease susceptibility or zoonosis. Here, we show that the Plasmodium interaction domain of DARC is nearly invariant in the human population, suggesting that coding polymorphism there is unlikely to play a role in differential susceptibility to infection. However, an analysis of DARC orthologs from 35 simian primate species reveals high levels of sequence divergence in the Plasmodium interaction domain. Signatures of positive selection in this domain indicate that species-specific mutations in the protein sequence of DARC could serve as barriers to the transmission of Plasmodium between primate species.
Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1)
Authors: Arthur A.M Wilde, Rosalie J.E Jongbloed, Pieter A Doevendans, Donald R Düren, Richard N.W Hauer, Irene M van Langen, J.Peter van Tintelen, Hubert J.M Smeets, Henk Meyer, Jan L.M.C Geelen
Journal: Journal of the American College of Cardiology (1999)
Galectin-1 Drives Pancreatic Carcinogenesis through Stroma Remodeling and Hedgehog Signaling Activation
Authors: Neus Martínez-Bosch, Maite G. Fernández-Barrena, Mireia Moreno, Elena Ortiz-Zapater, Jessica Munné-Collado, Mar Iglesias, Sabine André, Hans-Joachim Gabius, Rosa F. Hwang, Françoise Poirier, Carolina Navas, Carmen Guerra, Martin E. Fernández-Zapico, Pilar Navarro
Journal: Cancer Research (2014)

Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC stroma, but its roles there have not been studied. Here we report functions and molecular pathways of Gal1 that mediate its oncogenic properties in this setting. Genetic ablation of Gal1 in a mouse model of PDAC (EIa-myc mice) dampened tumor progression by inhibiting proliferation, angiogenesis, desmoplasic reaction and by stimulating a tumor-associated immune response, yielding a 20% increase in relative lifesplan. Cellular analyses in vitro and in vivo suggested these effects were mediated through the tumor microenvironment. Importantly, acinar-to-ductal metaplasia, a crucial step for initiation of PDAC, was found to be regulated by Gal1. Mechanistic investigations revealed that Gal1 promoted Hedgehog pathway signaling in PDAC cells and stromal fibroblasts as well as in Ela-myc tumors. Taken together, our findings establish a function for Gal1 in tumor-stroma crosstalk in PDAC and provide a preclinical rationale for Gal1 targeting as a microenvironment-based therapeutic strategy.
Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus
Authors: Sharon A. Chung, Elizabeth E. Brown, Adrienne H. Williams, Paula S. Ramos, Celine C. Berthier, Tushar Bhangale, Marta E. Alarcon-Riquelme, Timothy W. Behrens, Lindsey A. Criswell, Deborah Cunninghame Graham, F. Yesim Demirci, Jeffrey C. Edberg, Patrick M. Gaffney, John B. Harley, Chaim O. Jacob, M. Ilyas Kamboh, Jennifer A. Kelly, Susan Manzi, Kathy L. Moser-Sivils, Laurie P. Russell, Michelle Petri, Betty P. Tsao, Tim J. Vyse, Raphael Zidovetzki, Matthias Kretzler, Robert P. Kimberly, Barry I. Freedman, Robert R. Graham, Carl D. Langefeld
Journal: Journal of the American Society of Nephrology (2014)

Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci.
US managed care: has the UK anything to learn?
Authors: J. Le Grand
Journal: BMJ (1998)

A few years ago at an international conference the American health economist, Uwe Reinhardt, said that we were all about to enter an era of “fishbowl medicine.” Clinical freedom was disappearing. Clinicians would be increasingly subject to inspection. Instead of exercising their professional judgment about appropriate treatment, they would be required to follow protocols and guidelines and they would be held accountable for their decisions, especially if they departed from those guidelines. A new book by Ray Robinson and Andrea Steiner of Southampton University suggests that Reinhardt was right—at least about the United States.1

Based on a report prepared for the Department of Health, the book is a systematic review of the US experience of managed care and an analysis of what lessons, if any, the United Kingdom can learn. It paints an extraordinary picture of the US situation. Managed care institutions such as health …
Parapneumonic effusion and empyema
Authors: H Hamm, RW Light
Journal: European Respiratory Journal (1997)

Parapneumonic effusions account for about one third of all pleural effusions. Approximately 40% of patients with pneumonia develop a concomitant effusion, which is associated with an increased morbidity and mortality. In order to select the most appropriate therapy for the individual patient, the effusion should be categorized as being in the exudative, fibropurulent, or organizational stage, and all necessary information should be compiled to decide whether the effusion is likely to take an uncomplicated or a complicated course. There is a considerable variation in the aggressiveness and course of parapneumonic effusions, and, therefore, the spectrum of the appropriate therapy may vary from a conservative approach in uncomplicated effusions to aggressive surgical intervention in advanced multiloculated empyemas. This review discusses current diagnostic and therapeutic options and offers guidelines for treating the various stages of parapneumonic effusions and empyemas.