tbuckley/cabot-search huggingface dataset:
Hormone Receptor Status of a Contralateral Breast Cancer Is Independent of the Receptor Status of the First Primary in Patients Not Receiving Adjuvant Tamoxifen
Authors: G. Arpino, H.L. Weiss, G.M. Clark, S.G. Hilsenbeck, C.K. Osborne
Journal: Journal of Clinical Oncology (2005)

To determine whether the hormone receptor status of the primary breast cancer (PBC) is predictive of the hormone receptor status of the subsequent contralateral breast cancer (CBC).We identified patients in our database with known estrogen receptor (ER; n = 193) and/or progesterone receptor (PgR; n = 178) status in their PBC and in their subsequent CBC. One hundred twenty-six of these patients had received no adjuvant therapy, 34 had received adjuvant tamoxifen, and 33 had received adjuvant chemotherapy alone. The median interval between the first diagnosis of PBC and the development of the subsequent CBC was 3 years. ER and PgR assays were assessed biochemically in two central reference laboratories using identical quality-controlled ligand-binding methods.Among systemically untreated patients (n = 126), 88% of patients with ER-positive PBC and 75% of patients with ER-negative PBC developed an ER-positive CBC (P = .11). Among the tamoxifen-treated patients, those with an ER-positive PBC were almost equally likely to develop an ER-positive (47%) or ER-negative (53%) CBC (P = .99). PgR status was similar. In the untreated group (n = 112), 59% of patients with a PgR-positive PBC and 66% with a PgR-negative PBC developed a PgR-positive CBC (P = .48). Among tamoxifen-treated patients (n = 33), 50% of patients with a PgR-positive PBC versus 27% of patients with a PgR-negative PBC developed a PgR-positive CBC (P = .28).ER and PgR status of the primary tumor does not predict the hormone receptor status of the subsequent CBC in the absence of selective pressure of adjuvant therapy. Thus, other reasons should be considered to clarify the failure of tamoxifen to reduce the incidence of CBC in patients with a receptor-negative PBC.
Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial
Authors: Jesús F San-Miguel, Vânia T M Hungria, Sung-Soo Yoon, Meral Beksac, Meletios Athanasios Dimopoulos, Ashraf Elghandour, Wieslaw Wiktor Jedrzejczak, Andreas Günther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Paolo Corradini, Suporn Chuncharunee, Je-Jung Lee, Robert L Schlossman, Tatiana Shelekhova, Kwee Yong, Daryl Tan, Tontanai Numbenjapon, Jamie D Cavenagh, Jian Hou, Richard LeBlanc, Hareth Nahi, Lugui Qiu, Hans Salwender, Stefano Pulini, Philippe Moreau, Krzysztof Warzocha, Darrell White, Joan Bladé, WenMing Chen, Javier de la Rubia, Peter Gimsing, Sagar Lonial, Jonathan L Kaufman, Enrique M Ocio, Ljupco Veskovski, Sang Kyun Sohn, Ming-Chung Wang, Jae Hoon Lee, Hermann Einsele, Monika Sopala, Claudia Corrado, Bourras-Rezki Bengoudifa, Florence Binlich, Paul G Richardson
Journal: The Lancet Oncology (2014)
Structural studies on the murine Ia alloantigens. V. Evidence that the structural gene for the I-E/C beta polypeptide is encoded within the I-A subregion.
Authors: R G Cook, E S Vitetta, J W Uhr, J D Capra
Journal: The Journal of Experimental Medicine (1979)

The E/C alpha- and beta-subunits of intra-I-region recombinants were analyzed for primary structural variation by comparative tryptic peptide mapping. The E/C alpha-polypeptides from B10.A, B10.A (3R) and B10.A (5R) showed complete coincident elution of peptides; the E/C beta-chains from B10.A and 3R (or 5R) were approximately 40% different. This suggests that the structural gene for the E/C beta-polypeptide is within the I-A subregion.
Reduction in incidence of exacerbations in patients with Alpha 1 antitrypsin deficiency (A1ATD) treated with concentrates of Alpha 1 antitrypsin (A1AT): REXA study
Authors: Maria L. Torres Duran, Juan Carlos Barros Tizon
Journal: European Respiratory Journal (2011)

Introduction: Augmentation therapy with plasma derived Alpha 1 Antitrypsin represents the only specific treatment for patients with Alpha 1 Antitrypsin Deficiency. The aim of this study was to demonstrate that augmentation therapy can reduce the number of exacerbations in patients with A1ATD.

Material and methods: Retrospective multicentric study. We included 127 patients who received augmentation therapy for 18 months and with clinical follow-up for 18 months before treatment. We compared the incidence of exacerbations into the two periods.

Results: 127 patients, 63% male, age:52y, former smokers:79,4%, never smokers:17,4%, PiZZ:93.6%. Basal FEV1:1.24L (±0.5). Patients were treated with Prolastin® (53.5%) or Trypsone® (46.5%), 78% every 21 days. 52 patients did not present exacerbations in pretreatment period.

Augmentation therapy was associated with reduction of 2.4 exacerbations for every ten treated patients in total population and 6 exacerbations for every 10 treated patients in those with previous exacerbations.(Figure 1) Untreated patients have between 1.4 and 4 times more risk of exacerbation than treated patients.

We didn't observe differences between both available A1AT products.

![Figure][1] 



Conclusions: Augmentation therapy in the A1ATD reduces the total number of exacerbations with low frecuency of adverse events.

Study realized with Grifols support.

 [1]: pending:yes
Neutralizing antibodies to HIV-1 induced by immunization
Authors: Laura E. McCoy, Robin A. Weiss
Journal: The Journal of Experimental Medicine (2013)

Most neutralizing antibodies act at the earliest steps of viral infection and block interaction of the virus with cellular receptors to prevent entry into host cells. The inability to induce neutralizing antibodies to HIV has been a major obstacle to HIV vaccine research since the early days of the epidemic. However, in the past three years, the definition of a neutralizing antibody against HIV has been revolutionized by the isolation of extremely broad and potent neutralizing antibodies from HIV-infected individuals. Considerable hurdles remain for inducing neutralizing antibodies to a protective level after immunization. Meanwhile, novel technologies to bypass the induction of antibodies are being explored to provide prophylactic antibody-based interventions. This review addresses the challenge of inducing HIV neutralizing antibodies upon immunization and considers notable recent advances in the field. A greater understanding of the successes and failures for inducing a neutralizing response upon immunization is required to accelerate the development of an effective HIV vaccine.
Short Communication: Asymmetric Dimethylarginine Impairs Angiogenic Progenitor Cell Function in Patients With Coronary Artery Disease Through a MicroRNA-21–Dependent Mechanism
Authors: Felix Fleissner, Virginija Jazbutyte, Jan Fiedler, Shashi K. Gupta, Xiaoke Yin, Qingbo Xu, Paolo Galuppo, Susanne Kneitz, Manuel Mayr, Georg Ertl, Johann Bauersachs, Thomas Thum
Journal: Circulation Research (2010)

The endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) is increased in patients with coronary artery disease and may regulate function of circulating angiogenic progenitor cells (APCs) by small regulatory RNAs.To study the role of microRNAs in ADMA-mediated impairment of APCs.By using microarray analyses, we established microRNA expression profiles of human APCs. We used ADMA to induce APC dysfunction and found 16 deregulated microRNAs. We focused on miR-21, which was 3-fold upregulated by ADMA treatment. Overexpression of miR-21 in human APCs impaired migratory capacity. To identify regulated miR-21 targets, we used proteome analysis, using difference in-gel electrophoresis followed by mass spectrometric analysis of regulated proteins. We found that transfection of miR-21 precursors significantly repressed superoxide dismutase 2 in APCs, which resulted in increased intracellular reactive oxygen species concentration and impaired nitric oxide bioavailability. MiR-21 further repressed sprouty-2, leading to Erk Map kinase-dependent reactive oxygen species formation and APC migratory defects. Small interference RNA-mediated superoxide dismutase 2 or sprouty-2 reduction also increased reactive oxygen species formation and impaired APC migratory capacity. ADMA-mediated reactive oxygen species formation and APC dysfunction was rescued by miR-21 blockade. APCs from patients with coronary artery disease and high ADMA plasma levels displayed >4-fold elevated miR-21 levels, low superoxide dismutase 2 expression, and impaired migratory capacity, which could be normalized by miR-21 antagonism.We identified a novel miR-21-dependent mechanism of ADMA-mediated APC dysfunction. MiR-21 antagonism therefore emerges as an interesting strategy to improve dysfunctional APCs in patients with coronary artery disease.
Basic and Translational Concepts of Immune-Mediated Glomerular Diseases
Authors: William G. Couser
Journal: Journal of the American Society of Nephrology (2012)

Genetically modified immune responses to infections and self-antigens initiate most forms of GN by generating pathogen- and danger-associated molecular patterns that stimulate Toll-like receptors and complement. These innate immune responses activate circulating monocytes and resident glomerular cells to release inflammatory mediators and initiate adaptive, antigen-specific immune responses that collectively damage glomerular structures. CD4 T cells are needed for B cell-driven antibody production that leads to immune complex formation in glomeruli, complement activation, and injury induced by both circulating inflammatory and resident glomerular effector cells. Th17 cells can also induce glomerular injury directly. In this review, information derived from studies in vitro, well characterized experimental models, and humans summarize and update likely pathogenic mechanisms involved in human diseases presenting as nephritis (postinfectious GN, IgA nephropathy, antiglomerular basement membrane and antineutrophil cytoplasmic antibody-mediated crescentic GN, lupus nephritis, type I membranoproliferative GN), and nephrotic syndrome (minimal change/FSGS, membranous nephropathy, and C3 glomerulopathies). Advances in understanding the immunopathogenesis of each of these entities offer many opportunities for future therapeutic interventions.
Radiological anatomy after pyloroplasty
Authors: D. K. M. Toye, J. F. K. Hutton, J. A. Williams
Journal: Gut (1970)

The radiological anatomy of the pyloro-duodenal area after pyloroplasty is described. The deformity produced by pyloroplasty is shown in the patient with a normal pylorus and duodenum and in the patient with a duodenal ulcer and stenosis. From a study of 24 asymptomatic patients after pyloroplasty it is possible to recognize the radiological features that indicate a successful operation.
American Cancer Society Guidelines for the Early Detection of Cancer, 2003
Authors: R. A. Smith, V. Cokkinides, H. J. Eyre
Journal: CA A Cancer Journal for Clinicians (2003)

Each January, the American Cancer Society (ACS) publishes a summary of existing recommendations for early cancer detection, including updates, and/or emerging issues that are relevant to screening for cancer. In 2002, the ACS assembled expert groups to update guidelines for cervical cancer screening and breast cancer screening, and to evaluate new technology for colorectal cancer screening. In November 2002, updated guidelines for cervical cancer screening were published in this journal, and breast cancer screening guidelines will be updated in 2003. In this issue, there is a report of a workshop held to review emerging technology for colorectal cancer screening that resulted in a modification of current previous recommendations for fecal occult blood tests, and revised recommendations for the "cancer-related check-up" in which clinical encounters provide case-finding and health-counseling opportunities. Finally, we provide an update of the most recent data pertaining to participation rates in cancer screening by age, gender, and ethnicity from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS).
Accuracy of comparing bone quality to chocolate bars for patient information purposes: observational study
Authors: Phil Jones, Sarah Jones, Debbie Stone
Journal: BMJ (2007)

<b>Objective</b> To test whether standard information for patients using Crunchie and Aero chocolate bars to explain bone health and risk of fracture is robust. <b>Design</b> Observational study. <b>Setting</b> Domestic kitchen in rural west Wales. <b>Participants</b> 10 Crunchie bars and 10 Aero bars. <b>Main outcome measure</b> Fracture after falls from varying heights. <b>Results</b> Both Crunchie and Aero bars exhibited the same T and Z scores for bone density. Crunchie bars had a lower chocolate mass index than the Aero bars. Crunchie bars are more liable to fracture. <b>Conclusions</b> Using Crunchie and Aero chocolate bars to explain bone structure to patients may be visually attractive but oversimplifies the situation.
Effect of Reye's syndrome serum on isolated chinchilla liver mitochondria.
Authors: J H Tonsgard, G S Getz
Journal: Journal of Clinical Investigation (1985)

A general impairment of liver mitochondrial enzymes is central to Reye's syndrome (RS). The respiration of isolated liver mitochondria was measured after the addition of concentrated normal serum or RS serum derived from 12 patients. RS serum stimulates oxygen consumption in isolated rat liver mitochondria. This effect is due to the oxidation of uric acid by peroxisomes contaminating the preparation and a stimulation of mitochondrial respiration (1.05 +/- 0.14 nmol of O2/min X mg of protein; control 0.30 +/- 0.08 nmol O2/min X mg). The stimulation of respiration occurs in the presence of all respiratory substrates, is dependent on the amount of serum added, and represents an uncoupling of oxidative phosphorylation. RS serum reduces ATP formation by 15-76%. The uncoupling effect correlates with the amount of free fatty acid in the serum sample and resembles the effect induced by the addition of a dicarboxylic fatty acid. Dicarboxylic fatty acids, especially long-chain dicarboxylic acids, impair ATP formation. Dicarboxylic acids were found in the serum of all RS patients and comprised as much as 54% of the total serum free fatty acids. 90% of the serum dicarboxylic acids were of 16-18 carbon lengths. The amount of dicarboxylic acids in the RS serum corresponded directly with the reduction in ATP formation by the RS serum. This demonstrates that dicarboxylic acids occur in RS and may be important in the general impairment of mitochondrial function in RS and other disorders where they are present.
Internal fixation of closed tibial fractures for the management of sports injuries.
Authors: A Abdel-Salam, K S Eyres, J Cleary
Journal: British Journal of Sports Medicine (1991)

From 1985 to 1988, 90 closed tibial fractures were prospectively studied to assess the morbidity of such injuries to sports people and how this can be influenced by treatment regimens. All fractures were sustained during rugby or football matches. After random selection, 45 fractures were openly reduced and internally fixed (group A), and 45 fractures were manipulated under general anaesthesia and a long-leg plaster applied (group B). For patients in group A, below-knee plasters were used for 3 to 4 weeks, with immediate weight-bearing when tolerated. A total of 44 (98%) tibiae united clinically and radiologically within 14-18 weeks. Within 4 months of surgery 28 (62%) patients had returned to work and were able to play again by the following season. By 6 months 17 (38%) patients had resumed normal activities. In group B, only 24 (53%) tibiae united in a mean time of 16 weeks (range 12-40 weeks). Six (13%) patients required bone grafting for non-union, and one patient subsequently developed osteomyelitis. Only ten (22%) patients were back to work and playing sport again within 6 months of initial injury. It is concluded that internal fixation of closed tibial fractures as a primary procedure following low velocity sports injuries can be safely performed. It leads to a faster return to normal activities with fewer complications than does conservative treatment in plaster using contemporary methods.
Neuropeptides: Metabolism to Bioactive Fragments and the Pharmacology of Their Receptors
Authors: Mathias Hallberg
Journal: Medicinal Research Reviews (2014)

Abstract The proteolytic processing of neuropeptides has an important regulatory function and the peptide fragments resulting from the enzymatic degradation often exert essential physiological roles. The proteolytic processing generates, not only biologically inactive fragments, but also bioactive fragments that modulate or even counteract the response of their parent peptides. Frequently, these peptide fragments interact with receptors that are not recognized by the parent peptides. This review discusses tachykinins, opioid peptides, angiotensins, bradykinins, and neuropeptide Y that are present in the central nervous system and their processing to bioactive degradation products. These well‐known neuropeptide systems have been selected since they provide illustrative examples that proteolytic degradation of parent peptides can lead to bioactive metabolites with different biological activities as compared to their parent peptides. For example, substance P, dynorphin A, angiotensin I and II, bradykinin, and neuropeptide Y are all degraded to bioactive fragments with pharmacological profiles that differ considerably from those of the parent peptides. The review discusses a selection of the large number of drug‐like molecules that act as agonists or antagonists at receptors of neuropeptides. It focuses in particular on the efforts to identify selective drug‐like agonists and antagonists mimicking the effects of the endogenous peptide fragments formed. As exemplified in this review, many common neuropeptides are degraded to a variety of smaller fragments but many of the fragments generated have not yet been examined in detail with regard to their potential biological activities. Since these bioactive fragments contain a small number of amino acid residues, they provide an ideal starting point for the development of drug‐like substances with ability to mimic the effects of the degradation products. Thus, these substances could provide a rich source of new pharmaceuticals. However, as discussed herein relatively few examples have so far been disclosed of successful attempts to create bioavailable, drug‐like agonists or antagonists, starting from the structure of endogenous peptide fragments and applying procedures relying on stepwise manipulations and simplifications of the peptide structures.
Concomitant Analysis of Salivary Tumor Markers—A New Diagnostic Tool for Oral Cancer
Authors: Rafael Nagler, Gideon Bahar, Thomas Shpitzer, Raphael Feinmesser
Journal: Clinical Cancer Research (2006)

Oral squamous cell carcinoma (OSCC) is a common human malignancy. Circulatory epithelial tumor markers were previously investigated in the serum of OSCC patients but almost never in their saliva, in spite of the fact that there is a direct contact between the saliva and the oral cancer lesion. The purpose of the current study was to examine tumor markers in the saliva of OSCC patients.We measured the concentrations of the six most studied epithelial serum circulatory tumor markers in the saliva of OSCC (tongue) patients.Significant increases (of 400%) in salivary concentrations of Cyfra 21-1, tissue polypeptide antigen, and CA125 were shown. Salivary concentrations of CA19-9, SCC, and carcinoembryonic antigen were increased without statistical significance. A concurrent analysis of the three significantly increased markers revealed sensitivity, specificity, and negative and positive predictive values of 71%, 75%, 71%, and 75%, respectively.The increase reported in salivary tumor markers may be used as a diagnostic tool, especially when a concurrent analysis for significantly increased markers is done. Salivary testing is noninvasive, making it an attractive, effective alternative to serum testing, and the possibility of developing home testing kits would further facilitate it as a diagnostic aid, enabling patients to monitor their own health at home and is important for those who live far from their treatment centers and especially for those at risk of developing OSCC.
Case report: Achalasia-like dysmotility secondary to oesophageal involvement of sarcoidosis
Authors: A. J. Bredenoord, J. Jafari, S. Kadri, D. E. Simcock, D. Sifrim, S. L. Preston
Journal: Gut (2010)

We present a case of a patient with sarcoidosis and who subsequently developed dysphagia for solids, and some difficulty in swallowing liquids. High-resolution manometry of the oesophagus showed absent peristalsis in the oesophageal body and incomplete relaxation of the lower oesophageal sphincter. The diagnosis of sarcoidosis with oesophageal involvement was made and treatment with prednisolone 30 mg OD initiated. The patient improved symptomatically and high-resolution manometry was repeated showing complete recovery of oesophageal peristalsis and a deeper relaxation of the lower oesophageal sphincter. This is thus the first description of high-resolution manometry in sarcoidosis-induced changes of the oesophagus and of the effect treatment has on these motility changes. Oesophageal involvement of sarcoidosis is extremely rare and only a few cases have been reported. The symptoms and manometric pattern of this disorder mimics that of achalasia. However, we show that treatment with prednisolone results in a completely disappearance of the symptoms of dysphagia and subsequently lead to a large improvement of oesophageal motility.
Hereditary Colorectal Cancer
Authors: Henry T. Lynch, Albert de la Chapelle
Journal: New England Journal of Medicine (2003)

The question, "Is cancer hereditary?" has been answered beyond any doubt through the discovery of germ-line cancer-causing mutations in a subset of colorectal cancers (CRCs). Clearly, this authentication of the role of genetics was not solely dependent on molecular genetic studies, since hereditary cancer syndromes such as familial adenomatous polyposis (FAP) had been known for at least 100 years, but molecular advances are clarifying and refining clinical impressions. Have clinicians acted on the importance of hereditary factors in cancer so that this knowledge might be translated into patient benefit? Data showing that 59% of patients with FAP still die of metastatic CRC suggest that the answer is no.
The ARTHROPATHIC DYSTROPHIES
Authors: T. A. Clinch
Journal: BMJ (1898)

9 i 2 s which I had the privilege of seeing in the London' Hospital.Sometimes both upper, limbs with adjacent portions of the: thorax in the form .of a "vest" are affected, but it is dis-'tinctly.exceptionalto have the sensory disturbance general-.'ised over the whole body, though such cases have been'reported.