tbuckley/cabot-search huggingface dataset:
Activated B-RAF Is an Hsp90 Client Protein That Is Targeted by the Anticancer Drug 17-Allylamino-17-Demethoxygeldanamycin
Authors: Silvy da Rocha Dias, Frank Friedlos, Yvonne Light, Caroline Springer, Paul Workman, Richard Marais
Journal: Cancer Research (2005)

Abstract Hsp90 is a ubiquitously expressed molecular chaperone that folds, stabilizes, and functionally regulates many cellular proteins. The benzoquinone ansamysin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is an anticancer drug that disrupts Hsp90 binding to its clients, causing their degradation through the ubiquitin-dependent proteasomal pathway. The protein kinase B-RAF is mutated in ∼7% of human cancers. The most common mutation (∼90%) is V600EB-RAF, which has constitutively elevated kinase activity, stimulates cancer cell proliferation, and promotes survival. Here, we show that V600EB-RAF is an Hsp90 client protein that requires Hsp90 for its folding and stability. V600EBRAF is more sensitive to degradation by 17-AAG treatment than WTB-RAF and we show that the majority of the other mutant forms of B-RAF are also sensitive to 17-AAG–mediated proteasomal degradation. Our data show that B-RAF is an important target for 17-AAG in human cancer.
Renal responses of the cardiac-denervated nonhuman primate to blood volume expansion.
Authors: T V Peterson, C E Jones
Journal: Circulation Research (1983)

Experiments were performed to determine whether total, specific cardiac denervation affects the renal responses of the nonhuman primate to acute intravascular volume expansion. Adult male Macaca fascicularis monkeys underwent chronic intrapericardial cardiac denervation or sham surgery. After a 14- to 30-day recovery period, each animal was anesthetized with sodium pentobarbital and estimated blood volume was volume-expanded 20% with 6% dextran in isotonic saline. Control renal excretory function did not differ between the two groups, and both groups had similar increases in urine flow, sodium and potassium excretion, osmolar clearance, free water clearance, and renal plasma flow after volume expansion. The times to peak diuresis and natriuresis also were similar in both groups. These results demonstrate that the cardiac-denervated monkey shows unattenuated renal excretory responses to volume expansion. This could indicate that either cardiac receptors do not play a major role in eliciting these responses in the primate or that eliminating a role of cardiac afferents is compensated for by redundant afferents from arterial baroreceptors.
Species identification of Aspergillus, Fusarium and Mucorales with direct surface analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry
Authors: E. De Carolis, B. Posteraro, C. Lass-Flörl, A. Vella, A.R. Florio, R. Torelli, C. Girmenia, C. Colozza, A.M. Tortorano, M. Sanguinetti, G. Fadda
Journal: Clinical Microbiology and Infection (2011)
HIV Infection and Risk for Incident Pulmonary Diseases in the Combination Antiretroviral Therapy Era
Authors: Kristina Crothers, Laurence Huang, Joseph L. Goulet, Matthew Bidwell Goetz, Sheldon T. Brown, Maria C. Rodriguez-Barradas, Krisann K. Oursler, David Rimland, Cynthia L. Gibert, Adeel A. Butt, Amy C. Justice
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era.To determine the incidence of pulmonary diseases in HIV-infected persons compared with HIV-uninfected persons.We analyzed data from the Veterans Aging Cohort Study Virtual Cohort, consisting of 33,420 HIV-infected veterans and 66,840 age, sex, race and ethnicity, and site-matched HIV-uninfected veterans. Using Poisson regression, incidence rates and adjusted incidence rate ratios were calculated to determine the association of HIV with pulmonary disease. The Virtual Cohort was merged with the 1999 Veterans Large Health Survey to adjust for self-reported smoking in a nested sample (14%).Incident chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis, as well as pulmonary infections, were significantly more likely among HIV-infected patients compared with uninfected patients in adjusted analyses, although rates of asthma did not differ by HIV status. Bacterial pneumonia and chronic obstructive pulmonary disease were the two most common incident pulmonary diseases, whereas opportunistic pneumonias were less common. Absolute rates of most pulmonary diseases increased with age, although the relative differences between those with and without HIV infection were greatest in younger persons. Chronic obstructive pulmonary disease and asthma, as well as pulmonary infections, were less likely in those with lower HIV RNA levels and use of ART at baseline.Pulmonary diseases among HIV-infected patients receiving care within the Veterans Affairs Healthcare System in the combination ART era reflect a substantial burden of non-AIDS-defining and chronic conditions, many of which are associated with aging.
Missed opportunity following diagnosis of gout.
Authors: S O'Reilly, M Doherty
Journal: Annals of the Rheumatic Diseases (1995)

Case reportA self employed decorator developed his first attack of gout, affecting his first metatarsophalangeal (MTP) joint, at age 40.Risk factors were regular beer drinking and a family history of gout in his father; he had no history of urolithiasis, was not obese, and his blood pressure was normal.His general practitioner diagnosed classic podagra, confirmed an increased serum uric acid concentration of 540 imol/l (normal range in males 100-400 pimol/l), and advised reduction of beer intake.
Annular pancreas: a clinical, endoscopic, and immunohistochemical study.
Authors: J F Dowsett, J Rode, R C Russell
Journal: Gut (1989)

White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion by <i>q</i>-space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The human myelin map could be obtained within 10 min with a 3 T MR scanner. Use of the myelin map was practical for visualizing white matter and it sensitively detected reappearance of myelin signals after demyelination, possibly reflecting remyelination in MS patients. Our results together suggest that the myelin map, a kurtosis-related heat map obtainable with time-saving QSI, may be a novel and clinically useful means of visualizing myelin in the human CNS. <b>SIGNIFICANCE STATEMENT</b> Myelin abnormalities in the CNS have been gaining increasing attention in various neurological and psychiatric diseases. However, appropriate methods with which to monitor CNS myelin in daily clinical practice have been lacking. In the current study, we introduced a novel MRI modality that produces the "myelin map." The myelin map accurately depicted myelin status in mice and nonhuman primates and in a pilot clinical study of multiple sclerosis patients, suggesting that it is useful in detecting possibly remyelinated lesions. A myelin map of the human brain could be obtained in &lt;10 min using a 3 T scanner and it therefore promises to be a powerful tool for researchers and clinicians examining myelin-related diseases.
Biker's scapula: an ergonomic implication of biking
Authors: Shantanu Sharma, Ram Prabhu, Mrigank Aggarwal
Journal: British Journal of Sports Medicine (2010)

Introduction There are emerging trends of designing motor bikes with sporty looks. These bikes are especially popular among youth due to the speed that it can gain. There are bikers who complain of pain after biking for long distances. This is generally a case with heavy, non-cruiser bikes. The purpose of this poster is to depict the biomechanical and ergonomical basis of this pain felt at the superior angle of the scapula along with the diagnosis and treatment. Description: (1) Pain: the pain (dull and aching type) occurs at the superior angle of the scapula. After driving a bike, the pain stops but the soreness remains for 4–5 days. Any activity involving shrugging brought on the pain. (2) Biomechanics and Ergonomics: to streamline the body according to the speed of the bike, the biker pokes his chin, shrugs his shoulder and flexes his elbow. In this position, levator scapulae muscle is been used to shrug the shoulder as well as to maintain the position of the scapula. As this position is dynamic, the position keeps the levator scapulae in a contracted phase for prolonged period which may lead to repetitive stresses and microtrauma at the insertion of levator scapulae and start causing pain. (3) Diagnosis: eight patients were identified and this type of pathology is suspected wherein superior angle of scapula is tender and resisted shoulder shrugging is painful at the same area. However, scapular mobility and arm movements are normal. (4) Treatment: ultrasound therapy is definitely effective in relieving symptoms in two to three sittings after which resisted shrugging is given with mild resistance. However, it was seen that the pain recurs after a week or so if the long distance biking continues. (5) Prevention: To avoid this, bikers must take care of their posture while riding as well as proper selection of bike. It is also advised to use cruiser bikes for long distances. Conclusion In future, the cases with the similar history must be properly assessed and documented so that the further research can be carried out on the causes, permanent treatment and the other ways to prevent it.
Thromboembolism related to a Port-a-Cath device in a patient with cystic fibrosis
Authors: B. Yung, J. S. Elborn, I. A. Campbell, Y. Summers, M. Beckles, A. A. Woodcock
Journal: Thorax (1997)

The case is described of a potentially life threatening complication relating to the use of a totally implantable venous access device (Port-a-Cath) in a 28 year old patient with cystic fibrosis. The device was inserted in 1990 and used repeatedly for antibiotic therapy without any complications. In 1995, during assessment for double lung transplantation, a 3 cm thrombus was found at the tip of the catheter in the right atrium. Embolisation of the thrombus to the pulmonary arteries occurred after the infusion of recombinant tissue plasminogen activator (rt-PA). Thrombus formation may be associated with totally implantable venous access devices and thromboembolism may occur following the use of thrombolytic agents in the treatment of such thrombosis.
CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer’s disease model
Authors: Marius Krauthausen, Markus P. Kummer, Julian Zimmermann, Elisabet Reyes-Irisarri, Dick Terwel, Bruno Bulic, Michael T. Heneka, Marcus Müller
Journal: Journal of Clinical Investigation (2014)

Chemokines are important modulators of neuroinflammation and neurodegeneration. In the brains of Alzheimer’s disease (AD) patients and in AD animal models, the chemokine CXCL10 is found in high concentrations, suggesting a pathogenic role for this chemokine and its receptor, CXCR3. Recent studies aimed at addressing the role of CXCR3 in neurological diseases indicate potent, but diverse, functions for CXCR3. Here, we examined the impact of CXCR3 in the amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model of AD. We found that, compared with control APP/PSI animals, plaque burden and Aβ levels were strongly reduced in CXCR3-deficient APP/PS1 mice. Analysis of microglial phagocytosis in vitro and in vivo demonstrated that CXCR3 deficiency increased the microglial uptake of Aβ. Application of a CXCR3 antagonist increased microglial Aβ phagocytosis, which was associated with reduced TNF-α secretion. Moreover, in CXCR3-deficient APP/PS1 mice, microglia exhibited morphological activation and reduced plaque association, and brain tissue from APP/PS1 animals lacking CXCR3 had reduced concentrations of proinflammatory cytokines compared with controls. Further, loss of CXCR3 attenuated the behavioral deficits observed in APP/PS1 mice. Together, our data indicate that CXCR3 signaling mediates development of AD-like pathology in APP/PS1 mice and suggest that CXCR3 has potential as a therapeutic target for AD.
Pulmonary alveolar proteinosis: two contrasting cases
Authors: H.L. Crocker, J. Pfitzner, I.R Doyle, W.M Hague, B.J. Smith, R.E. Ruffin
Journal: European Respiratory Journal (2000)

Pulmonary alveolar proteinosis is a rare condition characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. Two cases with contrasting modes of presentation, course, and response to therapeutic whole lung lavage are described. Both cases were in hypoxaemic respiratory failure at the time the definitive diagnosis was made, and in both cases the diagnosis was made by segmental bronchoalveolar lavage following negative open lung biopsy. In neither was an underlying causative organism or agent identified. In one case the alveolar proteinosis developed in late pregnancy, a presentation that is previously unreported. Clinical improvement in this case required repeated whole lung lavages and was accompanied by a trend towards normalization of the ratios of surfactant protein-A and surfactant protein-B to disaturated phospholipid, ratios which may be useful as prognostic indicators. The response to therapeutic lavage was markedly different in the two cases, and it is postulated that this may relate to the fact that alveolar proteinosis is a heterogeneous disease and that the course and response to treatment may relate in part to the specific composition of the abnormal proteinaceous fluid.
Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial
Authors: F. Cognetti, E.M. Ruggeri, A. Felici, M. Gallucci, G. Muto, C.F. Pollera, B. Massidda, A. Rubagotti, D. Giannarelli, F. Boccardo, R. Cantiani, M. Aglietta, O. Bertetto, G.L. Cetto, P. Orlandini, E. Ferrazzi, M. Nardi, Sollievo della Sofferenza, L. Manzione, V. Adamo, G. Porcile, M. Lentini, E. Breda, T. Gamucci, D. Tummarello, L. Dogliotti, S. Tumolo, M. Motta, V. Lo Russo, G. De Grande, C. Sacco, F. Gaion, A. Lavarello, A. Nuzzo, M. Clerico, C. Aragona, A. Gernone, F. Morelli, V. Olivito, None Cupini, R. Mattioli, A. Marra, A. Marra, M. Antimi, V. Silingardi, R. Labianca, A. Martoni, V. Bortolussi, M. Luoni, A. Rosabian, F. Di Vito, G. Catalano, N. Gebbia
Journal: Annals of Oncology (2011)
AN ASSAY FOR DETERMINING THE RELATIVE AFFINITY OF TRACE AMOUNTS OF LABELED ANTIBODIES
Authors: Lisa A. Steiner, Herman N. Eisen
Journal: The Journal of Experimental Medicine (1967)

All assay for the binding efficiency or "relative affinity" of trace amounts of radioactively labeled anti-2,4-dinitrophenyl (DNP) antibodies has been developed. The assay measures the relative ability of the labeled antibodies to combine and precipitate with antigen in the presence of a large amount of unlabeled reference antibody of the same specificity. It has been possible to correlate the relative affinity of the labeled antibodies for dinitrophenylated antigens with the association constants of the reference antibodies for simple univalent DNP ligands.
One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles
Authors: Chien-Han Kao, Jaw-Yuan Wang, Kuo-Hsiang Chuang, Chih-Hung Chuang, Ta-Chun Cheng, Yuan-Chin Hsieh, Yun-long Tseng, Bing-Mae Chen, Steve R. Roffler, Tian-Lu Cheng
Journal: Biomaterials (2014)
Carfilzomib-Dependent Selective Inhibition of the Chymotrypsin-like Activity of the Proteasome Leads to Antitumor Activity in Waldenstrom's Macroglobulinemia
Authors: Antonio Sacco, Monette Aujay, Brittany Morgan, Abdel Kareem Azab, Patricia Maiso, Yang Liu, Yong Zhang, Feda Azab, Hai T. Ngo, Ghayas C. Issa, Phong Quang, Aldo M. Roccaro, Irene M. Ghobrial
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Primary Waldenstrom's Macroglobulinemia (WM) cells present with a significantly higher level of the immunoproteasome compared with the constitutive proteasome. It has been demonstrated that selective inhibition of the chymotrypsin-like (CT-L) activity of constitutive-(c20S) and immuno-(i20S) proteasome represents a valid strategy to induce antineoplastic effect in hematologic tumors. We therefore evaluated carfilzomib, a potent selective, irreversible inhibitor of the CT-L activity of the i20S and c20S in WM cells. Experimental Design: We tested the effect of carfilzomib on survival and proliferation of primary WM cells, as well as of other IgM-secreting lymphoma cell lines. Carfilzomib-dependent mechanisms of induced apoptosis in WM cells, and its effect on WM cells in the context of bone marrow (BM) microenvironment have been also evaluated. Moreover, the combinatory effect of carfilzomib and bortezomib has been investigated. In vivo studies have been performed. Results: We demonstrated that carfilzomib targeted the CT-L activity of both i20S and c20S, which led to the induction of toxicity in primary WM cells, as well as in other IgM-secreting lymphoma cells. Importantly, carfilzomib targeted WM cells even in the context of BM milieu. In addition, carfilzomib induced apoptosis through c-jun-N-terminal-kinase activation, caspase cleavage, and initiation of unfolded protein response. Importantly, the combination of carfilzomib and bortezomib synergistically inhibited CT-L activity, as well as caspase-, PARP-cleavage and GRP94 expression. Antitumor activity of carfilzomib has been validated in vivo. Conclusions: These findings suggest that targeting i20S and c20S CT-L activity by carfilzomib represents a valid antitumor strategy in WM and other IgM-secreting lymphomas. Clin Cancer Res; 17(7); 1753–64. ©2011 AACR.
Clinical and Demographic Predictors of Outcomes in Recent Onset Dilated Cardiomyopathy
Authors: Dennis M. McNamara, Randall C. Starling, Leslie T. Cooper, John P. Boehmer, Paul J. Mather, Karen M. Janosko, John Gorcsan, Kevin E. Kip, G. William Dec
Journal: Journal of the American College of Cardiology (2011)
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Authors: J R Mendell
Journal: Annual Review of Medicine (1993)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represents an important acquired condition characterized by progressive, symmetrical, proximal and distal weakness. Muscle stretch reflexes are depressed and sensory loss is variable. Patients may have mild to severe weakness and may require assisted ambulation or wheelchairs. Rarely do patients require respiratory support. Laboratory features include nerve conduction changes and nerve biopsy pathology indicative of demyelination. Cerebrospinal fluid protein is characteristically elevated without pleocytosis. The condition is responsive to immunosuppressive therapy, especially prednisone and plasmapheresis (plasma exchange). CIDP frequently follows a chronic or relapsing course.
Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry
Authors: D Salmon-Ceron, F Tubach, O Lortholary, O Chosidow, S Bretagne, N Nicolas, E Cuillerier, B Fautrel, C Michelet, J Morel, X Puéchal, D Wendling, M Lemann, P Ravaud, X Mariette
Journal: Annals of the Rheumatic Diseases (2010)

Background Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). Objective To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. Methods A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case–control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. Results 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p&lt;0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use &gt;10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). Conclusion Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use &gt;10 mg/day are independently associated with OI.
Peak Expiratory Flow Rate: Relationship to Risk Variables and Mortality
Authors: Barbara E.K. Klein, Scot E. Moss, Ronald Klein, Karen J. Cruickshanks
Journal: Diabetes Care (2001)

OBJECTIVE—To examine correlates of peak expiratory flow rate in people with type 1 diabetes and to evaluate the relationship of peak expiratory flow rate to mortality. RESEARCH DESIGN AND METHODS—A cohort study that was originally designed to determine the prevalence, incidence, and severity of diabetic retinopathy also provided the opportunity to measure peak expiratory flow rate. This was first measured at a 10-year follow-up and was evaluated in regard to risk factors for microvascular complications of diabetes. Mortality during 6 years of follow-up after the measurement was also ascertained. RESULTS—In multivariable analysis, peak expiratory flow rate was associated with sex, age, height, BMI, history of cardiovascular disease, pulse rate, duration of diabetes, glycosylated hemoglobin, and end-stage renal disease. Peak expiratory flow rate was significantly associated with survival in categorical analyses. Even after considering age, sex, renal disease, history of cardiovascular disease, respiratory symptoms, duration of diabetes, cigarette smoking, and hypertension, peak expiratory flow rate was still significantly related to survival (hazard ratio 0.61 [95% CI 0.46–0.82]). CONCLUSIONS—These data indicate that peak expiratory flow rate is associated with risk factors for other complications of diabetes. In addition, peak expiratory flow rate is a significant predictor of survival over even a relatively short period of time (6 years) in patients with younger-onset diabetes.