tbuckley/cabot-search huggingface dataset:
Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily.
Authors: R L Idzerda, C J March, B Mosley, S D Lyman, T Vanden Bos, S D Gimpel, W S Din, K H Grabstein, M B Widmer, L S Park
Journal: The Journal of Experimental Medicine (1990)

IL-4, a pleiotropic cytokine produced by T lymphocytes, plays an important role in immune responsiveness by regulating proliferation and differentiation of a variety of lymphoid and myeloid cells via binding to high affinity receptors. In this report we describe the isolation and functional expression of a human IL-4-R cDNA. When transfected into COS-7 cells, the cDNA encodes a 140-kD cell-surface protein. After transfection into a murine T cell line, the cDNA encodes a protein that binds human IL-4 with high affinity and can confer responsiveness to human IL-4. The predicted extracellular domain of the IL-4-R exhibits significant amino acid sequence homology with the beta subunit of the IL-2-R (p75), and the receptors for IL-6, erythropoietin, and prolactin. These receptors comprise a novel superfamily with extracellular domains characterized by four conserved cysteine residues and a double tryptophan-serine (WSXWS) motif located proximal to the transmembrane region.
Clinical features and race-specific incidence/prevalence rates of systemic lupus erythematosus in a geographically complete cohort of patients.
Authors: N D Hopkinson, M Doherty, R J Powell
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To assess race-specific incidence and prevalence rates for systemic lupus erythematosus (SLE) using 1991 National Census data and to ascertain the frequency of clinical/laboratory features of a geographically complete cohort of patients with SLE. METHODS--Multiple methods of retrieval were used to ascertain SLE patients including screening request cards for immunology investigations. Patients were classified according to the revised ARA criteria. Multiple logistic regression analysis was used to study the effects of age at diagnosis on the frequency of clinical/laboratory SLE features. RESULTS--The overall one year period prevalence rate for SLE was 24.7 (age adjusted, 95% CI: 20.7-28.8)/100,000. Highest rates were seen in Afro-Caribbeans (207 (111-302)/100,000), followed by Asians (48.8 (10.5-87.1)/100,000), and then Whites (20.3 (16.6-24.0)/100,000). The mean age at diagnosis of SLE was 40.9 years (range: 11-83) with a mean interval between first definite SLE symptom and diagnosis of 61 months (0-518). In 85% of patients the first definite lupus feature was musculoskeletal and/or cutaneous. In this SLE cohort renal disease (22%) was observed less commonly than in previous studies and the 9classic9 butterfly rash was present in only 30% of patients. Malar rash, thrombocytopaenia, positive anti-dsDNA antibodies, hypocomplementaemia (C4), and positive IgG anticardiolipin antibodies were all seen less commonly with increasing age at diagnosis. CONCLUSIONS--A closer estimate of the true frequency of clinical/laboratory SLE manifestations is likely from this geographically complete cohort of patients compared with studies that may be skewed by referral patterns.
Necrotizing Sweet syndrome: A new variant of neutrophilic dermatosis mimicking necrotizing fasciitis
Authors: Daniela Kroshinsky, Allireza Alloo, Brian Rothschild, Jordan Cummins, Jennifer Tan, Rafael Montecino, Mai P. Hoang, Lyn Duncan, Martin Mihm, Alireza Sepehr
Journal: Journal of the American Academy of Dermatology (2012)
Generalised non-reactive tuberculosis: a clinicopathological study of four patients.
Authors: R Singh, R C Joshi, J Christie
Journal: Thorax (1989)

Non-reactive tuberculosis is a histopathological entity characterised by foci of necrosis surrounded by normal parenchyma and absence of epithelioid cell granulomas. The clinical presentation and necropsy findings in four patients are described and the pathogenesis of the disease discussed.
Protection against two spontaneous mouse leukemias conferred by immunogenic variants obtained by mutagenesis.
Authors: A Van Pel, F Vessière, T Boon
Journal: The Journal of Experimental Medicine (1983)

Two spontaneous mouse leukemias were adapted to culture. In agreement with most reported observations on spontaneous tumors, injection of irradiated cells of the malignant culture cell lines failed to protect mice against these leukemias. These cell lines were treated in vitro with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine and stable immunogenic variants (tum-) were obtained, that failed to form progressive tumors in syngeneic CBA/Ht mice. Mice that had rejected tum- variants showed a significant degree of resistance to challenge not only with the original malignant cell line but also with the original transplantable tumor. No protection was observed against syngeneic tumor cells other than those of the parental tumor. These results indicate that these two spontaneous leukemias carry a specific transplantation antigen that can be the target of a rejection response by syngeneic mice. In confirmation of this, we found that lymphocytes of CBA/Ht mice that had rejected tum- variants could be restimulated in vitro so as to develop a cytolytic activity directed against an antigen that was specific for the original tumor cell line.
Can Communication Skills Training Alter Physicians' Beliefs and Behavior in Clinics?
Authors: Valerie Jenkins, Lesley Fallowfield
Journal: Journal of Clinical Oncology (2002)

PURPOSE: 

To measure the psychosocial attitudes and beliefs of physicians working within oncology in the United Kingdom and to examine whether beliefs alter after communication skills training. Additionally, to investigate whether physicians' attitudes are reflected in communication behaviors with patients during interviews.

METHODS: 

Ninety-three physicians completed a 32-item Physician Psychosocial Belief (PPSB) questionnaire at baseline (T1) before randomization to attendance at a 3-day residential communication skills course (n = 48) or a control group (n = 45). Three months later (T2), both groups completed another PPSB and a self-assessment questionnaire recording perceived changes in communication with patients. At both time points, physicians' consultations with two consenting patients were videotaped. Communication behaviors were measured using the Medical Interaction Processing System.

RESULTS: 

Physicians who attended the course showed significantly improved attitudes and beliefs toward psychosocial issues compared with controls (P =.002). This improvement was reflected in the analysis of the videotaped recordings of their communication behaviors with patients. Expressions of empathy were more likely for the course group at T2 than the controls (P =.02), as were open questions (P =.001), appropriate responses to patient cues (P =.005), and psychosocial probing (P =.041). These objective findings were supported by physicians' self report of changes in communication style during interviews with patients.

CONCLUSION: 

Our results show that a communication skills training intervention using behavioral, cognitive, and affective components not only increases potentially beneficial and more effective interviewing styles but can also alter attitudes and beliefs, thus increasing the likelihood that such skills will be used in the clinical setting.
Influence of age of onset and patient's sex on the prevalence and severity of manifestations of Behcet's syndrome.
Authors: H Yazici, Y Tüzün, H Pazarli, S Yurdakul, Y Ozyazgan, H Ozdoğan, S Serdaroğlu, M Ersanli, B.Y Ulkü, A.U Müftüoğlu
Journal: Annals of the Rheumatic Diseases (1984)

Eye disease, arthritis, folliculitis, and thrombophlebitis were more common among males, and erythema nodosum among females, in 297 patients with Behćet syndrome (BS) at their first visit despite an identical disease duration. Younger males and females (age of onset 24 years or less) had a higher prevalence of eye disease and total clinical activity than did the older patients (age of onset 25 years or more). Among the 51 patients followed up for 52 months (SD 7 months) the total clinical activity became significantly less (p less than 0.05) in the whole group at the end of this period. This was particularly true for older females. While male sex and a younger age of onset are associated with more severe disease in BS, overall, the syndrome ran an improving or stable course over 4 1/2 years.
If it was good enough for Aristotle......
Authors: T. M. Maher, A. U. Wells
Journal: Thorax (2011)

‘If you want to understand today you have to search yesterday’ wrote the American novelist Pearl Buck, and such is the challenge facing those who hope to disentangle the pathogenesis of idiopathic pulmonary fibrosis (IPF). The disease is characterised by the insidious but progressive development of fibrosis that culminates in respiratory failure and death, usually within 5 years of diagnosis. Despite recent advances in pathogenetic understanding, IPF remains a disease in need of effective treatments.

Following the reclassification of the idiopathic interstitial pneumonias 10 years ago,1 our understanding of the natural history of IPF has increased exponentially. Yet there remain lacunae in our knowledge of the disease: what does the earliest lesion of IPF look like and, even more importantly, what triggers its development and early progression? In most cases of IPF, extensive fibrosis is already established at the time of diagnosis. Much in the same way that cosmologists strive to infer the origins of the universe from modern-day movements of stars and planets, researchers hoping to understand the initiating events in pulmonary fibrosis have to do so by studying events that occur in established disease.

At a molecular level, IPF is characterised by the apparently unopposed activation of multiple profibrotic pathways involved in wound healing.2 The purpose of the normal wound healing process is to restore tissue integrity, structure and function following injury. In early wound healing, tissue expansion is associated with migration to the site of injury of fibroblasts that then proliferate, transform into myofibroblasts and rapidly synthesise extracellular matrix.3 In healthy individuals, the profibrotic phase of tissue repair then switches off and resorption of the extracellular matrix, with fibroblast apoptosis and architectural remodelling of tissue, occurs. In IPF, in contrast, several strands of evidence point strongly to a pivotal role for repetitive alveolar epithelial injury, resulting …
<i>FBW7</i> mutations in leukemic cells mediate NOTCH pathway activation and resistance to γ-secretase inhibitors
Authors: Jennifer O'Neil, Jonathan Grim, Peter Strack, Sudhir Rao, Deanne Tibbitts, Christopher Winter, James Hardwick, Markus Welcker, Jules P. Meijerink, Rob Pieters, Giulio Draetta, Rosalie Sears, Bruce E. Clurman, A. Thomas Look
Journal: The Journal of Experimental Medicine (2007)

γ-secretase inhibitors (GSIs) can block NOTCH receptor signaling in vitro and therefore offer an attractive targeted therapy for tumors dependent on deregulated NOTCH activity. To clarify the basis for GSI resistance in T cell acute lymphoblastic leukemia (T-ALL), we studied T-ALL cell lines with constitutive expression of the NOTCH intracellular domain (NICD), but that lacked C-terminal truncating mutations in NOTCH1. Each of the seven cell lines examined and 7 of 81 (8.6%) primary T-ALL samples harbored either a mutation or homozygous deletion of the gene FBW7, a ubiquitin ligase implicated in NICD turnover. Indeed, we show that FBW7 mutants cannot bind to the NICD and define the phosphodegron region of the NICD required for FBW7 binding. Although the mutant forms of FBW7 were still able to bind to MYC, they do not target it for degradation, suggesting that stabilization of both NICD and its principle downstream target, MYC, may contribute to transformation in leukemias with FBW7 mutations. In addition, we show that all seven leukemic cell lines with FBW7 mutations were resistant to the MRK-003 GSI. Most of these resistant lines also failed to down-regulate the mRNA levels of the NOTCH targets MYC and DELTEX1 after treatment with MRK-003, implying that residual NOTCH signaling in T-ALLs with FBW7 mutations contributes to GSI resistance.
Pattern of Lyme arthritis in Europe: report of 14 cases.
Authors: J P Huaux, G Bigaignon, S Stadtsbaeder, P F Zangerle, C Nagant de Deuxchaisnes
Journal: Annals of the Rheumatic Diseases (1988)

Fourteen cases of Lyme arthritis are reported. The most frequent picture was that of oligoarthritis appearing in that part of the leg where the cutaneous or neurological complications, or both, of Lyme disease had developed before the arthritis. In most cases recovery followed a single 10 day course of intravenous (IV) penicillin therapy. Arthritis was the presenting feature of Lyme disease in three cases.
High Rates of Molecular Evolution in Hantaviruses
Authors: C. Ramsden, F. L. Melo, Luiz. M. Figueiredo, E. C. Holmes, P. M.A. Zanotto
Journal: Molecular Biology and Evolution (2008)

Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae, and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10−7 nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the 3 rodent subfamilies: Araraquara virus (Sigmodontinae), Dobrava virus (Murinae), Puumala virus (Arvicolinae), and Tula virus (Arvicolinae). Our results reveal that hantaviruses exhibit short-term substitution rates of 10−2 to 10−4 substitutions/site/year and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent–hantavirus codivergence suggests that the codivergence hypothesis may need to be reevaluated.
Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components
Authors: M. Dougados, B. Combe, A. Cantagrel, P. Goupille, P. Olive, M. Schattenkirchner, S Meusser, L Paimela, R. Rau, H. Zeidler, M. Leirisalo-Repo, K. Peldan
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> To investigate the potential clinical benefit of a combination therapy. <h3>METHODS</h3> 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying anti-rheumatoid drugs previously, with an early (⩽1 year duration), active (Disease Activity Score (DAS) &gt; 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). <h3>RESULTS</h3> The mean changes in the DAS during the one year follow up of the study was −1.15, −0.87, −1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). <h3>CONCLUSION</h3> This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.
Measles campaign's “historic victory” for global public health
Authors: Peter Moszynski
Journal: BMJ (2007)

Deaths from measles have fallen by 60% worldwide since 1999, an achievement that campaigners describe as “a major public health success.” Progress against measles—one of the world's most infectious diseases and a big killer of children—has exceeded the United Nations' goal to halve deaths from the disease between 1999 and 2005, largely because of an “unprecedented decline” in Africa. 

The World Health Organization, Unicef, and partners in the Measles Initiative—the American Red Cross, the US Centers for Disease Control and Prevention, and the United Nations Foundation—made the announcement last …
IgE antibody screening in children
Authors: A. W. Van Toorenenbergen, A. P. Oranje, A. M. Vermeulen, R. S. R. Aarsen
Journal: Allergy (1991)

With 200 sera from children, results of the Phadiatop Paediatric test were compared with results of the combination “Phadiatop + mixed‐food‐RAST”. The Phadiatop Paediatric test was found to be efficient for IgE antibody screening in young children, when the results of this test were not solely given as “positive” or “negative”, but also as “sample/reference – ratio”. Clinical documentation could be obtained retrospectively for 171 children and revealed that 99% of the children with atopic disease were found positive in the Phadiatop Paediatric. 17% of the children who were considered non‐atopic on clinical grounds, were positive both in the Phadiatop Paediatric and in the combination “Phadiatop + mixed‐food‐RAST”. It is concluded that an atopic immune response is not always associated with current symptoms.
Patients' opinions, feelings, and attitudes after a campaign to promote the Di Bella therapy
Authors: Rodolfo Passalacqua, Francesco Campione, Caterina Caminiti, Stefania Salvagni, Alessandro Barilli, Mariangela Bella, Sandro Barni, Gemma Barsanti, Orazio Caffo, Paolo Carlini, Giuseppa Cinquemani, Francesco Di Costanzo, Lucio Giustini, Roberto Labianca, Antonio Mazzei, Nina Olmeo, Adriano Paccagnella, Lucia Toscano, Giorgio Cocconi
Journal: The Lancet (1999)
Deregulation of the tumour suppressor genes p14<sup>ARF</sup>, p15<sup>INK4b</sup>, p16<sup>INK4a</sup>and p53 in basal cell carcinoma
Authors: P. Kanellou, A. Zaravinos, M. Zioga, D.A. Spandidos
Journal: British Journal of Dermatology (2009)

Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes and is mostly seen in older members of the population.To determine the involvement of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in BCC.We investigated the integrity of the CDKN2A locus in 15 BCC samples by analysing the presence of allelic imbalance/loss of heterozygosity (LOH). Moreover, we studied the mRNA expression levels of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in the BCC samples and compared them with mRNA levels in the corresponding normal tissue. The presence of mutations was examined by sequencing for exons 1a and 2 of p16(INK4a).We found LOH in one BCC sample for the marker D9S1748. A polymorphism (G442A) of exon 2 was detected in three cases. p14(ARF), p15(INK4b) and p53 presented high expression levels, whereas p16(INK4a) exhibited low mRNA levels compared with the corresponding normal tissue. Significant correlations were detected among the genes studied.Our results demonstrate a different expression profile between p16(INK4a) and p14(ARF), p15(INK4b) and p53 in BCC. Moreover, we found a low percentage of LOH and of a polymorphic sequence variant (Ala148Thr) for the CDKN2A locus.
Re: Vitamin A Analogue for Breast Cancer Prevention: a Grade of F or Incomplete?
Authors: Umberto Veronesi, Giuseppe De Palo, Ettore Marubini, Alberto Costa, Luigi Mariani, Franca Formelli, Andrea Decensi
Journal: JNCI Journal of the National Cancer Institute (2000)

Author(s): Veronesi, U; De Palo, G; Marubini, E; Costa, A; Mariani, L; Formelli, F; Decensi, A
The Mechanical Stress–Activated Serum-, Glucocorticoid-Regulated Kinase 1 Contributes to Neointima Formation in Vein Grafts
Authors: Jizhong Cheng, Ying Wang, Yewei Ma, Bonita Tak-yee Chan, Min Yang, Anlin Liang, Liping Zhang, Huihua Li, Jie Du
Journal: Circulation Research (2010)

Rationale: Mechanical stress plays an important role in proliferation of venous smooth muscle cells (SMCs) in neointima, a process of formation that contributes to failure of vein grafts. However, it is unknown what intracellular growth signal leads to proliferation of venous SMCs. Objective: The objective of this study is to identify mechanisms of mechanical stretch on neointima formation. Methods and Results: By a microarray analysis, we found that mechanical cyclic stretch (15% elongation) stimulated the transcription of SGK-1 (serum-, glucocorticoid-regulated kinase-1). Mechanical stretch–induced SGK-1 mRNA expression was blocked by actinomycin D. The mechanism for the SGK-1 expression involved MEK1 but not p38 or JNK signaling pathway. SGK-1 activation in response to stretch is blocked by insulin-like growth factor (IGF)-1 receptor inhibitor and mammalian target of rapamycin complex (mTORC)2 inhibitor (Ku-0063794) but not mTORC1 inhibitor (rapamycin). Mechanical stretch–induced bromodeoxyuridine incorporation was reduced by 83.5% in venous SMCs isolated from SGK-1 knockout mice. In contrast, inhibition of Akt, another downstream signal of PI3K resulted in only partial inhibition of mechanical stretch–induced proliferation of venous SMCs. Mechanical stretch also induced phosphorylation and nuclear exportation of p27 kip1 , whereas knockout of SGK-1 attenuated this effect of mechanical stretch on p27 kip1 . In vivo, we found that placement of a vein graft into artery increased SGK-1 expression. Knockout of SGK-1 effectively prevented neointima formation in vein graft. There is significant lower level of p27 kip1 located in the nucleus of neointima cells in SGK-1 knockout mice compared with that of wild-type vein graft. In addition, we also found that wire injury of artery or growth factors in vitro increased expression of SGK-1. Conclusions: These results suggest that SGK-1 is an injury-responsive kinase that could mediate mechanical stretch–induced proliferation of vascular cells in vein graft, leading to neointima formation.
The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development
Authors: Susanne Gessert, Michael Kühl
Journal: Circulation Research (2010)

Abstract : Understanding heart development on a molecular level is a prerequisite for uncovering the causes of congenital heart diseases. Therapeutic approaches that try to enhance cardiac regeneration or that involve the differentiation of resident cardiac progenitor cells or patient-specific induced pluripotent stem cells will also benefit tremendously from this knowledge. Wnt proteins have been shown to play multiple roles during cardiac differentiation and development. They are extracellular growth factors that activate different intracellular signaling branches. Here, we summarize our current understanding of how these factors affect different aspects of cardiogenesis, starting from early specification of cardiac progenitors and continuing on to later developmental steps, such as morphogenetic processes, valve formation, and establishment of the conduction system.