tbuckley/cabot-search huggingface dataset:
The wrist of the formula 1 driver.
Authors: E H Masmejean, H Chavane, A Chantegret, J J Issermann, J Y Alnot
Journal: British Journal of Sports Medicine (1999)

During formula 1 driving, repetitive cumulative trauma may provoke nerve disorders such as nerve compression syndrome as well as osteoligament injuries. A study based on interrogatory and clinical examination of 22 drivers was carried out during the 1998 formula 1 World Championship in order to better define the type and frequency of these lesions.The questions investigated nervous symptoms, such as paraesthesia and diminishment of sensitivity, and osteoligamentous symptoms, such as pain, specifying the localisation (ulnar side, dorsal aspect of the wrist, snuff box) and the effect of the wrist position on the intensity of the pain. Clinical examination was carried out bilaterally and symmetrically.Fourteen of the 22 drivers reported symptoms. One suffered cramp in his hands at the end of each race and one described a typical forearm effort compartment syndrome. Six drivers had effort "osteoligamentous" symptoms: three scapholunate pain; one medial hypercompression of the wrist; two sequellae of a distal radius fracture. Seven reported nerve disorders: two effort carpal tunnel syndromes; one typical carpal tunnel syndrome; one effort cubital tunnel syndrome; three paraesthesia in all fingers at the end of a race, without any objective signs.This appears to be the first report of upper extremity disorders in competition drivers. The use of a wrist pad to reduce the effects of vibration may help to prevent trauma to the wrist in formula 1 drivers.
Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase
Authors: M. Borrell-Pages
Journal: Journal of Clinical Investigation (2006)

There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin-induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway through formation of clathrin-coated vesicles containing brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy.
Professional Boundaries in the Physician-Patient Relationship
Authors: Glen O. Gabbard
Journal: JAMA (1995)

THE SUBJECT of professional boundaries (and boundary violations) has received a great deal of recent attention in the psychiatric literature.<sup>1-5</sup>The emphasis on defining guidelines for professional conduct has expanded beyond the confines of ethics committees and has worked its way into licensing boards charged with disciplining physicians whose behavior jeopardizes the well-being of patients. The Massachusetts Board of Registration in Medicine,<sup>6</sup>for example, has recently issued detailed guidelines on such matters as self-disclosure, dual relationships, sexual relationships with patients, and other professional boundaries to help define for the public and for the profession the parameters of professional conduct in the practice of psychotherapy by physicians. While specialists in psychiatry have been debating the pros and cons of issuing such guidelines, nonpsychiatric physicians have yet to involve themselves so extensively in similar discussions. In this article, we will provide a conceptual framework for discussion of professional boundaries in
Brief Report: Lysyl Oxidase Is a Potential Biomarker of Fibrosis in Systemic Sclerosis
Authors: Doron Rimar, Itzhak Rosner, Yuval Nov, Gleb Slobodin, Michael Rozenbaum, Katy Halasz, Tharwat Haj, Nizar Jiries, Lisa Kaly, Nina Boulman, Rula Daood, Zahava Vadasz
Journal: Arthritis & Rheumatology (2013)

Fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc). Levels of lysyl oxidase (LOX), an extracellular enzyme that stabilizes collagen fibrils, have been found to be elevated in the skin of SSc patients, but have not been evaluated in the serum or correlated with the clinical parameters. We undertook this study to evaluate serum LOX levels in SSc patients and to correlate these levels with clinical parameters of SSc.SSc patients were evaluated for demographic features, clinical manifestations, routine laboratory tests, serum autoantibodies, serum LOX concentrations, and nailfold capillaroscopy patterns. They underwent pulmonary function testing, echocardiography, and high-resolution computed tomography scans of the lung, assessment of skin fibrosis by the modified Rodnan skin thickness score (MRSS), and assessment of disease severity and activity by the Medsger severity scale and the Valentini activity index.Twenty-six SSc patients were evaluated and compared with 25 healthy controls and with 9 disease control patients with primary myelofibrosis. Almost 62% of the SSc patients (16 of 26) had limited cutaneous SSc (lcSSc), while 38% had diffuse cutaneous SSc (dcSSc) (10 of 26); 31% of the patients (8 of 26) had lung involvement. The LOX concentration in SSc patients was higher than that in healthy controls and similar to that in disease controls (P < 0.0001), and it was significantly higher in patients with dcSSc than in those with lcSSc (P = 0.006). The LOX concentration correlated with the MRSS in patients without lung fibrosis.This study is the first to demonstrate high serum LOX levels in SSc patients that correlate specifically with skin fibrosis. These correlations suggest that LOX levels may serve as a novel biomarker of fibrosis. Future studies are warranted to determine whether LOX is a potential therapeutic target in SSc.
A girl with extensive dissemination of thoracic ecchinococcosus
Authors: Iris Groothuis, C.P. van de Ven, A.W.P.M. Maat, G. Paleru, J.C. de Jongste
Journal: European Respiratory Journal (2011)

A 10 year old girl from Irak was routinely screened for tuberculosis after immigration. She reported chronic cough and chest pain during the past year. A cystic lesion was detected on chest X-ray, and confirmed by a chest CT which also showed some pleural nodules. There was no suspicion of malignancy, tuberculosis was excluded and Echinococcus serology was negative. Bronchoscopy showed no abnormalities, BAL cultures were negative and galactomannan was normal. Abdominal ultrasound excluded cystic lesions in the liver. She was treated with antibiotics and her symptoms dissapeared. Surgery was scheduled to make a final diagnosis and because of the infection risk, with a diagnosis of infected CCAM and pleural adhesions. Before surgery we made an MRI scan which revealed a massive amount of cystic lesions, occupying a large part of her left hemithorax. We now suspected dissiminated thoracic echinococcosus, and repeated serology, wich was now positive. After albendazole pretreatment a left lower lobectomy and resection of a large number of cysts was performed. Retrospectively, she had experienced an episode where she had noticed a salty taste and had expectorated white matter, presumable as a sign of endobronchial rupture of an ecchynococcus cyst. In conclusion, we present a rare case of extensively dissiminated pulmonary and thoracic ecchinococcosus, which might have been prevented by careful medical history taking, which could have detected cyst rupture.
Agonist Anti-CD137 mAb Act on Tumor Endothelial Cells to Enhance Recruitment of Activated T Lymphocytes
Authors: Asís Palazón, Alvaro Teijeira, Iván Martínez-Forero, Sandra Hervás-Stubbs, Carmen Roncal, Iván Peñuelas, Juan Dubrot, Aizea Morales-Kastresana, José Luis Pérez-Gracia, M. Carmen Ochoa, Laura Ochoa-Callejero, Alfredo Martínez, Alfonso Luque, Joseph Dinchuk, Ana Rouzaut, Maria Jure-Kunkel, Ignacio Melero
Journal: Cancer Research (2011)

Abstract Agonist monoclonal antibodies (mAb) to the immune costimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment on the basis of their costimulatory effects on primed T cells and perhaps other cells of the immune system. Here we provide evidence that CD137 is selectively expressed on the surface of tumor endothelial cells. Hypoxia upregulated CD137 on murine endothelial cells. Treatment of tumor-bearing immunocompromised Rag−/− mice with agonist CD137 mAb did not elicit any measurable antiangiogenic effects. In contrast, agonist mAb stimulated tumor endothelial cells, increasing cell surface expression of the adhesion molecules intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin. When adoptively transferred into mice, activated T lymphocytes derived from CD137-deficient animals entered more avidly into tumor tissue after treatment with agonist mAb. This effect could be neutralized with anti–ICAM-1 and anti–VCAM-1 blocking antibodies. Thus, stimulation of CD137 not only enhanced T-cell activation but also augmented their trafficking into malignant tissue, through direct actions on the blood vessels that irrigate the tumor. Our findings identify an additional mechanism of action that can explain the immunotherapeutic effects of agonist CD137 antibodies. Cancer Res; 71(3); 801–11. ©2011 AACR.
Definitive radiation therapy for elderly patients with stage III NSCLC not candidates for combined chemoradiation
Authors: Keith Sigel, Linda Lurslurchachai, Grace Mhango, Ethan Halm, Marcelo Bonomi, Juan Wisniveksy
Journal: European Respiratory Journal (2012)

Purpose: Combined chemoradiation is the treatment of choice for locally advanced (stage IIIA-IIIB), unresectable non-small cell lung cancer (NSCLC). However, elderly patients are frequently unable to tolerate this treatment; the benefit of radiation therapy (RT) alone for the management these patients is not well studied. Using population-based cancer data, we evaluated if use of RT alone is associated with improved survival of unresected stage III elderly NSCLC patients.  Methods: Using the SEER registry linked to Medicare we identified 13,522 patients >65 years of age with unresected stage IIIA-B NSCLC diagnosed between 1992-2009. We excluded cases receiving chemotherapy as well as patients who could not be candidates for RT because they died within 4 weeks of cancer diagnosis. We determined propensity scores for patients receiving RT alone vs. no therapy based on their pre-treatment characteristics. Survival of patients treated with and without RT was compared using Cox regression adjusting for propensity scores. The odds for toxicity requiring hospitalization among patients treated with RT were also estimated, adjusting for propensity scores.  Results: Overall, 7,703 (57%) patients received RT. RT alone was also associated with improved overall survival (HR: 0.76; 95% CI:0.74-0.79) in analyses adjusting for propensity scores. RT treated patients had an increased adjusted risk of hospitalization for pneumonitis (OR: 130; 95% CI:18-928) and esophagitis (OR: 8; 95% CI:4-17).  Conclusions: These data suggest that definitive RT alone is associated with improved survival in elderly patients with unresected stage III NSCLC. RT was also associated with risk of severe toxicity.
Increased rates of duodenal mucosal protein synthesis in vivo in patients with untreated coelia disease.
Authors: I M Nakshabendi, S Downie, R I Russell, M J Rennie
Journal: Gut (1996)

A robust, reproducible method for the measurement of protein synthesis in the gastrointestinal mucosa was applied to investigate possible differences between the rate of duodenal mucosal protein synthesis in coeliac patients and normal control subjects.Eight patients, means (SD) (51 (10) years, 57 (11) kg, 160 (6) cm) with newly diagnosed untreated coeliac disease and seven control subjects (48 (11) years, 71.5 (12) kg, 172 (10) cm) received primed, continuous, intragastric (IG) and intravenous (i.v.) infusions of L-[1-13C]leucine and L-[1-13C]valine after an overnight fast. Distal duodenal biopsy specimens were obtained at endoscopy performed after 240 minutes of infusion. Protein synthesis was calculated from protein labelling relative to intracellular free amino acid enrichment, after appropriate mass spectrometric measurements.Rates of duodenal protein synthesis were significantly greater in coeliac patients than in control subjects (i.v. tracer, coeliac v control, 3.58 (0.45) v 2.26 (0.22)%/h, p< 0.05; IG tracer, 6.25 (0.97) v 2.34 (0.52)%/h respectively, p < 0.01). The rates of mucosal protein synthesis calculated on the basis of the tracer infused via the intragastric route were higher in patients with coeliac disease than in control subjects. Tissue protein/DNA ratios were significantly reduced in coeliac patients (coeliac v control, 9.2 (1.6) mg/micrograms v 13.0 (2.2) mg/micrograms respectively, p < 0.05) suggesting smaller mucosal cell size in coeliac patients.Despite the villous atrophy and reduced cell size observed in coeliac disease, the rates of mucosal protein synthesis are considerably increased. These results suggest that a high rate of protein synthesis may be adaptive to a high rate of protein breakdown or mucosal cell loss in coeliac patients.
Combining protein evolution and secondary structure
Authors: J. L. Thorne, N. Goldman, D. T. Jones
Journal: Molecular Biology and Evolution (1996)

An evolutionary model that combines protein secondary structure and amino acid replacement is introduced. It allows likelihood analysis of aligned protein sequences and does not require the underlying secondary (or tertiary) structures of these sequences to be known. One component of the model describes the organization of secondary structure along a protein sequence and another specifies the evolutionary process for each category of secondary structure. A database of proteins with known secondary structures is used to estimate model parameters representing these two components. Phylogeny, the third component of the model, can be estimated from the data set of interest. As an example, we employ our model to analyze a set of sucrose synthase sequences. For the evolution of sucrose synthase, a parametric bootstrap approach indicates that our model is statistically preferable to one that ignores secondary structure.
Prostaglandin G/H synthase-2 is required for maximal formation of osteoclast-like cells in culture
Authors: Yosuke Okada, Joseph A. Lorenzo, Amanda M. Freeman, Masato Tomita, Scott G. Morham, Lawrence G. Raisz, Carol C. Pilbeam
Journal: Journal of Clinical Investigation (2000)

We examined the effect on osteoclast formation of disrupting the prostaglandin G/H synthase genes PGHS-1 and-2. Prostaglandin E2 (PGE2) production was significantly reduced in marrow cultures from mice lacking PGHS-2 (PGHS-2–/–) compared with wild-type (PGHS-2+/+) cultures. Osteoclast formation, whether stimulated by 1,25-dihydroxyvitamin D3 (1,25-D) or by parathyroid hormone (PTH), was reduced by 60–70% in PGHS-2–/– cultures relative to wild-type cultures, an effect that could be reversed by providing exogenous PGE2. Cultures from heterozygous mice showed an intermediate response. PGHS inhibitors caused a similar drop in osteoclast formation in wild-type cultures. Co-culture experiments showed that supporting osteoblasts, rather than osteoclast precursors, accounted for the blunted response to 1,25-D and PTH. This lack of response appeared to result from reduced expression of RANK ligand (RANKL) in osteoblasts. We cultured spleen cells with exogenous RANKL and found that osteoclast formation was 50% lower in PGHS-2–/– than in wild-type cultures, apparently because the former cells expressed high levels of GM-CSF. Injection of PTH above the calvaria caused hypercalcemia in wild-type but not PGHS-2–/– mice. Histological examination of bone from 5-week-old PGHS-2–/– mice revealed no abnormalities. Mice lacking PGHS-1 were similar to wild-type mice in all of these parameters. These data suggest that PGHS-2 is not necessary for wild-type bone development but plays a critical role in bone resorption stimulated by 1,25-D and PTH.
Metabolic and cellular alterations underlying the exaggerated renal prostaglandin and thromboxane synthesis in ureter obstruction in rabbits. Inflammatory response involving fibroblasts and mononuclear cells.
Authors: T Okegawa, P E Jonas, K DeSchryver, A Kawasaki, P Needleman
Journal: Journal of Clinical Investigation (1983)

Unilateral ureter obstruction in rabbits produced profound changes in endogenous and exogenous renal arachidonic acid metabolism. Isolated perfused hydronephrotic kidneys (removed after 3 or 10 d of ureter obstruction) responded to bradykinin stimulation with a markedly enhanced release of prostaglandin E2 and thromboxane A2. Reversal (3 or 10 d) of the ureter obstruction resulted in a reduction in the vasoactive peptide-induced release of prostaglandin E2 and thromboxane A2 from the perfused hydronephrotic kidney. However, postobstruction reversal of prostaglandin production by the agonist-stimulated perfused kidney was not reflected in the cortical microsomal cyclooxygenase activity, which is greatly enhanced during ureter obstruction and does not decrease after removal of the obstruction. Histological analysis of the renal cortex in rabbits with ureteral obstruction revealed a proliferation of fibroblast-like cells and the presence of mononuclear cells; removal of the obstruction did not result in a disappearance of cortical fibroblasts but did result in a decrease of monocytes. The critical involvement of mononuclear cells in the exaggerated arachidonate metabolism that occurs during hydronephrosis was exhibited by the demonstration that: (a) only the perfused hydronephrotic rabbit kidney responded to administration of endotoxin with a sustained release of prostaglandin E2 and thromboxane A2; (b) the contralateral rabbit kidney, which is devoid of mononuclear cells, did not respond to endotoxin; and (c) the hydronephrotic cat kidney, which exhibits a fibroblast proliferation with a low number of mononuclear cells, did not respond to endotoxin. Thus, proliferation of fibroblast-like cells and the presence of mononuclear cells appear to be involved in the exaggerated prostaglandin and thromboxane production underlying hydronephrosis. The increase in microsomal cyclooxygenase activity is apparently most closely correlated with the increased fibroblastic activation and cellularity, whereas mononuclear cells (possibly via monokines) seem to be critical for the markedly enhanced prostaglandin and thromboxane release induced by endotoxin and bradykinin.
Serum Uric Acid and 1-h Postload Glucose in Essential Hypertension
Authors: Francesco Perticone, Angela Sciacqua, Maria Perticone, Franco Arturi, Paola Elisa Scarpino, Michele Quero, Giorgio Sesti
Journal: Diabetes Care (2011)

Subjects who are normal glucose tolerant (NGT) are considered at low risk, even if a plasma glucose value ≥155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) is able to identify NGT subjects at high risk for type 2 diabetes and subclinical organ damage. Hyperuricemia is associated with several risk factors for cardiovascular diseases such as hypertension, insulin resistance, and diabetes. However, it is unknown whether uric acid (UA) is able to affect 1-h postload plasma glucose in hypertensive NGT subjects.From a cohort of ∼1,200 uncomplicated hypertensive outpatients who underwent OGTT, we selected 955 subjects (548 men and 407 women) aged 45.6 ± 10.1 years. Laboratory evaluations were performed, and estimated glomerular filtration rate was assessed by using the new equation proposed by investigators in the Chronic Kidney Disease Epidemiology Collaboration.Considering different stepwise multivariate linear regression models, UA was the major predictor of 1-h postload glucose in the entire population, with NGT ≥155 subjects, impaired glucose tolerant, and type 2 diabetic patients accounting for 26.0% (P < 0.0001), 25.3% (P < 0.0001), 13.5% (P < 0.0001), and 13.5% (P = 0.003) of its variation in the respective models.We documented that in hypertensive NGT ≥155 subjects, UA is strongly associated with 1-h postload glucose, similarly to what is observed in impaired glucose tolerant and diabetic patients.
Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype
Authors: Heiko Reinold, Seifollah Ahmadi, Ulrike B. Depner, Beate Layh, Cornelia Heindl, May Hamza, Andreas Pahl, Kay Brune, Shuh Narumiya, Ulrike Müller, Hanns Ulrich Zeilhofer
Journal: Journal of Clinical Investigation (2005)

Blockade of prostaglandin (PG) production by COX inhibitors is the treatment of choice for inflammatory pain but is also prone to severe side effects. Identification of signaling elements downstream of COX inhibition, particularly of PG receptor subtypes responsible for pain sensitization (hyperalgesia), provides a strategy for better-tolerated analgesics. Here, we have identified PGE2 receptors of the EP2 receptor subtype as key signaling elements in spinal inflammatory hyperalgesia. Mice deficient in EP2 receptors (EP2–/– mice) completely lack spinal PGE2-evoked hyperalgesia. After a peripheral inflammatory stimulus, EP2–/– mice exhibit only short-lasting peripheral hyperalgesia but lack a second sustained hyperalgesic phase of spinal origin. Electrophysiological recordings identify diminished synaptic inhibition of excitatory dorsal horn neurons as the dominant source of EP2 receptor–dependent hyperalgesia. Our results thus demonstrate that inflammatory hyperalgesia can be treated by targeting of a single PG receptor subtype and provide a rational basis for new analgesic strategies going beyond COX inhibition.
Hydroxypropyl Cellulose Methacrylate as a Photo‐Patternable and Biodegradable Hybrid Paper Substrate for Cell Culture and Other Bioapplications
Authors: Aisha Qi, Siew Pei Hoo, James Friend, Leslie Yeo, Zhilian Yue, Peggy P. Y. Chan
Journal: Advanced Healthcare Materials (2013)

In addition to the choice of appropriate material properties of the tissue construct to be used, such as its biocompatibility, biodegradability, cytocompatibility, and mechanical rigidity, the ability to incorporate microarchitectural patterns in the construct to mimic that found in the cellular microenvironment is an important consideration in tissue engineering and regenerative medicine. Both these issues are addressed by demonstrating a method for preparing biodegradable and photo‐patternable constructs, where modified cellulose is cross‐linked to form an insoluble structure in an aqueous environment. Specifically, hydroxypropyl cellulose (HPC) is rendered photocrosslinkable by grafting with methylacrylic anhydride, whose linkages also render the cross‐linked construct hydrolytically degradable. The HPC is then cross‐linked via a photolithography‐based fabrication process. The feasibility of functionalizing these HPC structures with biochemical cues is verified post‐fabrication, and shown to facilitate the adhesion of mesenchymal progenitor cells. The HPC constructs are shown to be biocompatible and hydrolytically degradable, thus enabling cell proliferation and cell migration, and therefore constituting an ideal candidate for long‐term cell culture and implantable tissue scaffold applications. In addition, the potential of the HPC structure is demonstrated as an alternative substrate to paper microfluidic diagnostic devices for protein and cell assays.