tbuckley/cabot-search huggingface dataset:
Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects
Authors: Kelly A McGowan, Jun Z Li, Christopher Y Park, Veronica Beaudry, Holly K Tabor, Amit J Sabnis, Weibin Zhang, Helmut Fuchs, Martin Hrabé de Angelis, Richard M Myers, Laura D Attardi, Gregory S Barsh
Journal: Nature Genetics (2008)
Durable complete response in a patient with metastatic melanoma following adoptive transfer of autologous T cells recognizing 10 mutated tumor antigens
Authors: Todd D Prickett, Jessica S Crystal, Jared J Gartner, Yao Xin, Pasetto Anna, Alena Gros, Yong-Chen Lu, Yong Li, Mona El-Gamil, Steven A Rosenberg, Paul Robbins
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Durable complete response rates of 20% have been observed in clinical trials of patients with metastatic melanoma employing adoptive cell transfer (ACT) of patient derived tumor infiltrating lymphocytes (TIL). Here we provide a detailed analysis of the response of TIL administered
RAST in the Diagnosis of Dog Dander Allergy
Authors: T. Vanto, M. Viander, A. Koivikko, B. Schwartz, H. Løwenstein
Journal: Allergy (1982)

The results of the skin, bronchial or conjunctival provocation tests and of the radioallergosorbent test (RAST) with dog dander and hair extract preparations from two different producers were compared, 202 asthmatic children were included in the study. The clinical tests, Al‐RAST and paper RAST. were performed using only one allergen preparation (Hu 073), while two allergen preparations (e2 and e5) were used in Phadebas® RAST. A good correlation was generally found between the results of the clinical diagnostic tests, the clinical history and the results of RAST. Phadebas RAST e2 was the most specific but the least sensitive: it gave a class 0 result in 18% and class 3–4 in 34.5% of the subjects with a positive provocation test. The corresponding numbers for e5 RAST were 6.0% and 70.2%, respectively. Al‐RAST was equally sensitive, but had lower specificity than Phadebas RAST e5. The correlation between Phadebas RAST e5 and paper RAST Hu 073 was excellent, which indicates a remarkable similarity between these allergen extracts. Using sensitive, immunochemically standardized Phadebas RAST e5 or Al‐RAST methods, classes 0–1 can be regarded as negative, class 2 as doubtful and classes 3–4 as clinically positive results.
Effects of genetic obesity on rat upper airway muscle and diaphragm contractile properties
Authors: E van Lunteren
Journal: European Respiratory Journal (1996)

The contractile properties of pharyngeal respiratory muscle are altered in sleep apnoea and in conditions associated with sleep apnoea, such as ageing. We hypothesized that the contractile properties of the pharyngeal musculature are also altered by obesity, another factor associated with sleep apnoea. Studies compared a pharyngeal muscle, the sternohyoid, with the diaphragm. These were chosen as representative muscles whose contraction has opposing effects on upper airway patency. Both muscles were removed from nine lean and nine obese male Zucker rats (a genetic model of obesity), and isometric contractile properties were studied in vitro at 37 degrees C. For the sternohyoid muscle, in obese compared to lean animals there were no significant differences in isometric contraction time (15.2 +/- 0.3 vs 14.2 +/- 0.6 ms, respectively), half-relaxation time (13.6 +/- 0.5 vs 12.6 +/- 0.9 ms, respectively), twitch-to-tetanic tension ratio (0.22 +/- 0.02 vs 0.24 +/- 0.02, respectively), force-frequency relationship, fatigue resistance (2 min fatigue index 0.20 +/- 0.03 vs 0.18 +/- 0.02, respectively), or maximal degree of force potentiation during repetitive stimulation (52 +/- 11 vs 74 +/- 20% increase, respectively). For the diaphragm, the only significant effect of obesity was a lowering of the twitch-to-tetanic tension ratio (0.25 +/- 0.01 vs 0.29 +/- 0.02, respectively). In obese, as in lean animals, the sternohyoid had faster isometric twitch kinetics, a larger degree of force potentiation, and lower resistance to fatigue, than the diaphragm. In lean, but not obese, animals the sternohyoid twitch-to-tetanic tension ratio was lower than and the force frequency relationship was located to the right of that of the diaphragm. In this study, genetic obesity in rats was not associated with any significant alterations in the contractile properties of the pharyngeal muscle, and only small changes in the relationship between the contractile properties of the sternohyoid and diaphragm muscle.
Chronic Renal Failure Accelerates Atherogenesis in Apolipoprotein E–Deficient Mice
Authors: Susanne Bro, Jacob F. Bentzon, Erling Falk, Claus B. Andersen, Klaus Olgaard, Lars B. Nielsen
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Cardiovascular mortality is 10 to 20 times increased in patients with chronic renal failure (CRF). Risk factors for atherosclerosis are abundant in patients with CRF. However, the pathogenesis of cardiovascular disease in CRF remains to be elucidated. The effect of CRF on the development of atherosclerosis in apolipoprotein E–deficient male mice was examined. Seven-week-old mice underwent 5/6 nephrectomy (CRF, n = 28), unilateral nephrectomy (UNX, n = 24), or no surgery (n = 23). Twenty-two weeks later, CRF mice showed increased aortic plaque area fraction (0.266 ± 0.033 versus 0.045 ± 0.006; P < 0.001), aortic cholesterol content (535 ± 62 versus 100 ± 9 nmol/cm2 intimal surface area; P < 0.001), and aortic root plaque area (205,296 ± 22,098 versus 143,662 ± 13,302 μm2; P < 0.05) as compared with no-surgery mice; UNX mice showed intermediate values. The plaques from uremic mice contained CD11b-positive macrophages and showed strong staining for nitrotyrosine. Systolic BP and plasma homocysteine concentrations were similar in uremic and nonuremic mice. Plasma urea and cholesterol concentrations were elevated 2.6-fold (P < 0.001) and 1.5-fold (P < 0.001) in CRF compared with no-surgery mice. Both variables correlated with aortic plaque area fraction (r2 = 0.5, P < 0.001 and r2 = 0.3, P < 0.001, respectively) and with each other (r2 = 0.5, P < 0.001). On multiple linear regression analysis, only plasma urea was a significant predictor of aortic plaque area fraction. In conclusion, the present findings suggest that uremia markedly accelerates atherogenesis in apolipoprotein E–deficient mice. This effect could not be fully explained by changes in BP, plasma homocysteine levels, or total plasma cholesterol concentrations. Thus, the CRF apolipoprotein E–deficient mouse is a new model for studying the pathogenesis of accelerated atherosclerosis in uremia. E-mail: [email protected]
Immunoglobulin Class Switch Recombination Is Impaired in <i>Atm</i>-deficient Mice
Authors: Joanne M. Lumsden, Thomas McCarty, Lisa K. Petiniot, Rhuna Shen, Carrolee Barlow, Thomas A. Wynn, Herbert C. Morse, Patricia J. Gearhart, Anthony Wynshaw-Boris, Edward E. Max, Richard J. Hodes
Journal: The Journal of Experimental Medicine (2004)

Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining switch regions and repair of these breaks by nonhomologous end-joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by examining ATM-deficient mice. In response to T cell–dependent antigen (Ag), Atm−/− mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, and IgG3, and less total IgE than Atm+/+ controls. To determine whether Atm−/− B cells have an intrinsic defect in their ability to undergo CSR, we analyzed in vitro responses of purified B cells. Atm−/− cells secreted substantially less IgA, IgG1, IgG2a, IgG3, and IgE than wild-type (WT) controls in response to stimulation with lipopolysaccharide, CD40 ligand, or anti-IgD plus appropriate cytokines. Molecular analysis of in vitro responses indicated that WT and Atm−/− B cells produced equivalent amounts of germline IgG1 and IgE transcripts, whereas Atm−/− B cells produced markedly reduced productive IgG1 and IgE transcripts. The reduction in isotype switching by Atm−/− B cells occurs at the level of genomic DNA recombination as measured by digestion–circularization PCR. Analysis of sequences at CSR sites indicated that there is greater microhomology at the μ–γ1 switch junctions in ATM B cells than in wild-type B cells, suggesting that ATM function affects the need or preference for sequence homology in the CSR process. These findings suggest a role of ATM in DNA DSB recognition and/or repair during CSR.
Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial
Authors: Isis Amer-Wåhlin, Charlotte Hellsten, Håkan Norén, Henrik Hagberg, Andreas Herbst, Ingemar Kjellmer, Håkan Lilja, Claes Lindoff, Maivi Månsson, Laila Mårtensson, Per Olofsson, Anna-Karin Sundström, Karel Maršál
Journal: The Lancet (2001)
Treatment-related improvement in physical function varies with duration of rheumatoid arthritis: a pooled analysis of clinical trial results
Authors: D Aletaha, V Strand, J S Smolen, M M Ward
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physical function, we analysed responsiveness of HAQ scores in patient populations with differing RA durations in randomised controlled trials (RCTs). <h3>Methods:</h3> Data from all RCTs published between 1980 and 2005 that reported changes from baseline in HAQ at 6 and/or 12 months were analysed. Treatments were grouped as "biologics", or "traditional" disease modifying antirheumatic drugs (DMARDs), and "placebo". We computed effect sizes of HAQ in each trial, and contrasted the association between these effects and duration of RA among treatment groups using regression models. <h3>Results:</h3> We identified 42 RCTs with complete data for the statistical models. The models indicate that discrimination of functional improvement between active drug groups and placebo is reduced in patients with a longer duration of RA (p = 0.02 for the change in discrimination over time). The placebo-adjusted HAQ responses decreased on average by 0.37 per year of RA duration. <h3>Conclusion:</h3> Responsiveness in HAQ scores is inversely associated with mean disease duration in RA. This impacts assessment of physical function, a key outcome measure in RCTs and practice, and impacts the ability to discriminate active treatment from placebo.
Role of peptidoglycan subtypes in the pathogenesis of bacterial cell wall arthritis
Authors: E Šimelyte, M Rimpiläinen, X Zhang, P Toivanen
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Bacterial cell wall (CW) arthritis develops in susceptible strains of rats after a single intraperitoneal injection of the CW from certain bacterial species, both pathogenic and non-pathogenic. For the development of chronic bacterial CW arthritis, the structure of the bacterial peptidoglycan (PG) has been found to be decisive. <b>Objective:</b> To define the role of PG subtypes in the pathogenesis of chronic bacterial CW arthritis. <b>Method:</b> Arthritis was induced with CWs of <i>Lactobacillus plantarum</i>, <i>L casei</i> B, <i>L casei</i> C, and <i>L fermentum</i>. Gas chromatography-mass spectrometry was used to measure the presence of CW derived muramic acid in the liver and to determine PG subtypes. CWs were also tested for their resistance to lysozyme in vitro. <b>Results:</b> These results and those published previously indicate that PGs of CWs which induce chronic arthritis, no matter whether they were derived from strains of <i>Streptococcus</i>, <i>Bifidobacterium</i>, <i>Collinsella</i>, or <i>Lactobacillus</i>, all have lysine as the third amino acid of the PG stem peptide, representing PG subtypes A3α and A4α. Those strains which induce only transient acute arthritis or no arthritis at all do not have lysine in this position, resulting in different PG subtypes. <b>Conclusions:</b> In vivo degradation of only those PGs with the subtypes A3α and A4α leads to the occurrence of large CW fragments, which persist in tissue and have good proinflammatory ability. CWs with other PG subtypes, even if they are lysozyme resistant, do not cause chronic arthritis, because the released fragments are not phlogistic. It is emphasised that a variety of microbial components not causing inflammation have been found in animal and human synovial tissue.
Delivery systems for siRNA drug development in cancer therapy
Authors: Cong-fei Xu, Jun Wang
Journal: Asian Journal of Pharmaceutical Sciences (2014)

Since the discovery of the Nobel prize-winning mechanism of RNA interference (RNAi) ten years ago, it has become a promising drug target for the treatment of multiple diseases, including cancer. There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection. However, significant barriers still exist on the road to clinical applications of siRNA drugs, including poor cellular uptake, instability under physiological conditions, off-target effects and possible immunogenicity. The successful application of siRNA for cancer therapy requires the development of clinically suitable, safe and effective drug delivery systems. Herein, we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy, including chemical modifications, lipid-based nanovectors, polymer-mediated delivery systems, conjugate delivery systems, and others.
Early Corticosteroids in Severe Influenza A/H1N1 Pneumonia and Acute Respiratory Distress Syndrome
Authors: Christian Brun-Buisson, Jean-Christophe M. Richard, Alain Mercat, Anne C. M. Thiébaut, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Despite their controversial role, corticosteroids are often administered to patients with adult respiratory distress syndrome (ARDS) secondary to viral pneumonia.To analyze the impact of corticosteroid therapy on outcomes of patients having ARDS associated with influenza A/H1N1 pneumonia.Patients from the French registry of critically ill patients with influenza A/H1N1v 2009 infection were selected if fulfilling criteria for ARDS, excluding patients having other indication for corticosteroids, or decompensated underlying disease as the primary cause for intensive care unit admission. Survival to hospital discharge was analyzed using Cox regression, accounting for the time to administration of steroids, and after adjustment on the propensity for receiving steroid therapy.Of 208 patients with ARDS, 83 (39.9%) received corticosteroids (median initial dose of 270 mg equivalent hydrocortisone per day for a median of 11 d). Steroid therapy was associated with death, both in crude analysis (33.7 vs. 16.8%; hazard ratio, 2.4; 95% CI, 1.3-4.3; P = 0.004) and after propensity score-adjusted analysis (adjusted hazard ratio, 2.82; 95% CI, 1.5-5.4; P = 0.002), controlling for an admission severity Simplified Acute Physiology Score, version 3, greater than 50, initial administration of vasopressors, and immunodepression. Early therapy (≤ 3 d of mechanical ventilation) appeared more strongly associated with mortality than late administration. Patients receiving steroids had more acquired pneumonia and a trend to a longer duration of ventilation.Our study provides no evidence of a beneficial effect of corticosteroids in patients with ARDS secondary to influenza pneumonia, but suggests that very early corticosteroid therapy may be harmful.
Patterns of care and survival for patients with glioblastoma multiforme diagnosed during 2006
Authors: K. R. Yabroff, L. Harlan, C. Zeruto, J. Abrams, B. Mann
Journal: Neuro-Oncology (2012)

Standard treatment for glioblastoma multiforme (GBM) changed in 2005 when addition of temozolomide (TMZ) to maximal surgical resection followed by radiation therapy (RT) was shown to prolong survival in a clinical trial. In this study, we assessed treatment patterns and survival of patients with GBM in community settings in the United States. Patients with newly diagnosed GBM who were aged ≥20 years in 2006 (n = 1202) were identified as part of the National Cancer Institute 's Patterns of Care Studies. We assessed treatment patterns, and in the subset of patients who received total or partial surgical resection, we used multivariable regression analysis to assess patient, clinical, and health system factors associated with receipt of adjuvant chemotherapy and RT and survival through 2008. Approximately 65% of patients with GBM received total or partial surgical resection, and approximately 70% of these patients received adjuvant TMZ and RT. Receipt of adjuvant therapy was associated with patient age, marital status, health insurance, and tumor location. Median survival in all patients was 10 months (95% confidence interval [CI], 9–11 months). Receipt of adjuvant therapy following resection was associated with a lower risk of dying in adjusted analyses for patients who received TMZ and RT (hazard ratio [HR], 0.25; 95% CI, 0.18–0.35) and other adjuvant therapies (HR, 0.55; 95% CI, 0.37–0.81), compared with no adjuvant therapy. We observed rapid diffusion of a new standard of treatment, adjuvant and concurrent TMZ with RT, among adult patients with newly diagnosed GBM in the community setting following publication of a pivotal clinical trial.
Inferior outcomes in immunosuppressed patients with high-risk cutaneous squamous cell carcinoma of the head and neck treated with surgery and radiation therapy
Authors: Bindu V. Manyam, Brian Gastman, Alexandra Y. Zhang, Chandana A. Reddy, Brian B. Burkey, Joseph Scharpf, Daniel S. Alam, Michael A. Fritz, Allison T. Vidimos, Shlomo A. Koyfman
Journal: Journal of the American Academy of Dermatology (2015)
Plasma concentrations of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell patients but do not increase further during painful crisis
Authors: Precious P. Landburg, Tom Teerlink, Frits A.J. Muskiet, Ashley J. Duits, John‐John B. Schnog
Journal: American Journal of Hematology (2008)

Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in the clinically asymptomatic state of sickle cell disease (SCD). However, the role of ADMA during vaso-occlusive complications has not been defined. ADMA concentrations were determined in HbSS (n = 43) and HbSC (n = 25) patients with healthy blood donors (HbAA) as controls. In the clinically asymptomatic state ADMA concentrations were elevated in sickle cell patients as compared to healthy controls (HbSS 0.70 micromol/L, HbSC 0.54 micromol/L, HbAA 0.39 micromol/L) (P < 0.001). Yet plasma ADMA concentrations did not increase further at presentation with a painful crisis implicating no role of primary importance during vaso-occlusive crises.
Palivizumab, pneumococcal and influenza vaccination in cystic fibrosis
Authors: Mukta Jain, Anne H Thomson
Journal: Journal of the Royal Society of Medicine (2009)

Respiratory exacerbations of cystic fibrosis (CF) lung disease have been associated with increased mortality, hospitalization, antibiotic administration, health costs and diminished quality of life. Preventive strategies such as vaccination against common respiratory pathogens have been developed to reduce the frequency of pulmonary exacerbations.1

Children with CF are vaccinated as per the normal childhood vaccination schedule. They are equally at risk from the common childhood diseases but are particularly susceptible to respiratory complications. Young children with CF may miss out on the normal immunizations schedule through illness and general practitioners need to be aware that cough is not a reason to withhold or delay vaccination. Adults may be more susceptible to infections despite being vaccinated in infancy as immunity reduces over time. The extent of damage caused by vaccine preventable diseases in CF is not known.2 The potential benefit of supplemental vaccination strategies is discussed below.
BLOOD CHEMICAL CHANGES IN EXPERIMENTAL STREPTOCOCCUS SEPTICEMIA
Authors: Richard W. Linton
Journal: The Journal of Experimental Medicine (1931)

The following changes have been found to occur in rabbits given fatal intravenous doses of Streptococcus hemolyticus: The blood sugar concentration drops at a constant rate throughout the disease, but does not reach a condition of hypoglycemia. Glycogen is present in the liver at death. The CO(2) capacity is lowered markedly at first, then returns to a somewhat higher level, at which it continues until the terminal stage of the disease, when the acidosis becomes very marked. Inorganic phosphorus is markedly increased in concentration at the terminus of the disease. This increase is greater in animals showing an acute course than in those in which the disease is of the fulminating type. Calcium also shows terminal changes, decreases occurring in both groups. In the acutely infected rabbits the decrease is less than in the fulminating group, although in both a pathological level is reached. Non-protein nitrogen and creatinine are greatly increased in the terminal stages, in both groups of animals. It is suggested that these observations can be explained on the assumption of a large amount of acid production by the streptococcus in vivo.
Ocular Associations of Diabetes Other Than Diabetic Retinopathy
Authors: V. Swetha E. Jeganathan, Jie Jin Wang, Tien Yin Wong
Journal: Diabetes Care (2008)

Diabetic retinopathy is the most well-known ocular complication of diabetes and the leading cause of blindness among people 20–64 years of age in the U.S. (1). Up to 4 million Americans with diabetes, 40 years of age and older, have retinopathy, and nearly 1 million have sight-threatening retinopathy (2). In major clinical trials, tight control of blood glucose and blood pressure has been demonstrated to reduce the risk of retinopathy and associated blindness (3).

A range of ocular diseases is also associated with diabetes, which may lead to vision loss. However, some of these ocular conditions may not be familiar to noneye clinicians (4–6). In this review, we aim to highlight the frequencies, clinical presentations, natural histories, and management of these ocular conditions. Physicians who manage patients with diabetes may benefit from knowledge of these associated conditions and are thus able to ensure adequate and timely referral and treatment. Routine eye screening for retinopathy of individuals with diabetes offers the opportunity to detect these other ocular diseases early, many of which are sight threatening. Physician education remains an important public health strategy in the prevention of vision loss in patients with diabetes.

### 1. Cataracts and cataract surgery

Cataract is a major cause of vision impairment in people with diabetes. Numerous studies have documented an association between diabetes and cataracts. This association is supported by an abundance of data from clinical epidemiological studies and basic science studies (7–22). Both cross-sectional and prospective data from three population-based studies, the Beaver Dam Eye Study, the Blue Mountains Eye Study, and the Visual Impairment Project, have documented associations between diabetes and both prevalent and incident posterior subcapsular cataract and, less consistently, with prevalent and incident cortical cataracts but not nuclear cataract (8–12,14–19,23,25). The Blue …