tbuckley/cabot-search huggingface dataset:
High Prevalence of Peripheral Arterial Disease in Persons With Renal Insufficiency
Authors: Ann M. O’Hare, David V. Glidden, Caroline S. Fox, Chi-yuan Hsu
Journal: Circulation (2004)

Although renal insufficiency is a recognized risk factor for coronary artery disease, little is known about the epidemiology of lower-extremity peripheral arterial disease (PAD) in persons with renal insufficiency.We examined the cross-sectional association of PAD, defined as an ankle-brachial index (ABI) <0.9, and renal insufficiency, defined as an estimated creatinine clearance (CRCL) <60 mL. min(-1). 1.73 m(-2), among 2229 eligible participants in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000. An estimated 1.2+/-0.3 million persons >/=40 years old with CRCL <60 mL. min(-1). 1.73 m(-2) (24%) have PAD defined as an ABI <0.9 (versus 3.7% of persons with CRCL >/=60 mL. min(-1). 1.73 m(-2)). The association of ABI <0.9 with renal insufficiency was independent of potential confounders such as age, diabetes, hypertension, coronary artery disease, stroke history, and hypercholesterolemia (OR 2.5, 95% CI 1.2 to 5.1, P=0.011, referent category ABI 1.0 to 1.3).Clinicians should be aware of the remarkably high prevalence of PAD among patients with renal insufficiency. In the clinical setting, accurate identification of patients with renal insufficiency combined with routine ABI measurement in this group would greatly enhance efforts to detect subclinical PAD.
I-J-restricted interactions in the generation of azobenzenearsonate-specific suppressor T cells.
Authors: M Takaoki, M S Sy, A Tominaga, A Lowy, M Tsurufuji, R Finberg, B Benacerraf, M I Greene
Journal: The Journal of Experimental Medicine (1982)

The genetic restrictions of the activation of third-order suppressor cells (Ts3) were studied in mice, using two different types of anti-azobenzenearsonate (ABA)-immune responses, namely delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) generation. Ts2 cells were induced in several different strains of mice by injecting monoclonal T hybridoma molecules or first-order suppressor factors (TsF1) originating in A/J (H-2a, Igh-1e) mice and then testing the TsF2 molecules derived from these Ts2 in A/J and A.By (H-2b, Igh-1e) or (A/J X A.By)F1 (H-2a/b, Igh-1e) and (C57Bl/6 X A/J)F1 (H-2b/a, Igh-1e) mice. It was shown that the activity of TsF2 was restricted to the I-J of the strain in which Ts2 was induced. By genetic analysis, restriction was shown to be due to the requirement of H-2 identity between ABA-coupled cells used for Ts3 activation and the strain of the TsF2 origin. Moreover, by using H-2-congenic ABA-coupled cells, we were also able to precisely map and demonstrate that ABA-coupled cells I-J identical to TsF2 induced in various strains were necessary for effective suppression to occur. This selective activation of Ts3 suggested the existence of I-J-related antigen presentation for suppression as the counterpart of I-A or I-A-I-E-restricted antigen presentation for positive immune responses.
Sports and exercise physicians as medical assessors: Table 1
Authors: Chris Milne, Peter Harcourt, David Bolzonello
Journal: British Journal of Sports Medicine (2012)

To clarify the role of sports and exercise physicians as medical assessors.Group discussion between senior doctors at a previous annual conference of the Australasian College of Sports Physicians, followed by further discussion between the authors. Clarification of the key requirements of insurers, and formulation of practical advice for those performing this work.Our expertise in performing medical assessments for the purpose of fitness to play sport is a transferable skill. It can also be used to provide medical assessments for injured workers. Our expertise in rehabilitation is also of value to insurers and other interested parties.The work is both challenging and rewarding, and can provide additional variety in the working week.
Treating Chemobrain: Rehabilitation Therapies Emerge
Authors: C. McNeil
Journal: JNCI Journal of the National Cancer Institute (2012)

Cancer patients had been reporting problems with cognitive function for years. And for years, clinicians had been stumped about how to handle a problem that has come to be known as chemobrain. But now, more cancer centers have begun testing interventions for chemobrain, including, most notably, cognitive behavioral therapy (CBT). Major cancer centers in the U.S. and Australia, among others, are now recruiting patients for randomized controlled trials of CBT; five of the trials have 2012 launch dates (see sidebar). The growing number of trials reflects accumulating data and changing attitudes. Patricia Ganz, M.D., at UCLA’s Jonsson Comprehensive Cancer Center, traces several stages in the evolution of thinking about cancer and cognition. At first, everyone believed that the blood–brain barrier protected patients from chemotherapy, so patient reports were not taken seriously. As chemotherapy became more common and rigorous, complaints multiplied and researchers began paying attention. Now, more sophisticated imaging methods and animal models have begun to show evidence of brain changes associated with cancer and to suggest mechanisms that could make chemotherapy one of the culprits. “We are chipping away at getting a scientific database to persuade people,” Ganz said. One addition to that database came in March, with the publication of a small controlled study showing that impaired cognitive function after chemotherapy associated with longitudinal changes in the brain’s white matter. Sabine Deprez, M.D., of Belgium’s University Hospital Gasthuisberg, and colleagues showed that changes in the white matter associated with neuropsychological test results and with the patients’ own reports of specific problems, such as word retrieval. The study appeared in the Journal of Clinical Oncology. Subjective Versus Objective Cognition Many chemobrain studies have found no association between patient reports of cognitive problems—“subjective cognition” in psychologists’ terms—and the findings of test results, or “objective cogni tion. ” But Deprez’s study found that structural changes in the brain associated with both
A Gene Duplication/Loss Event in the Ribulose-1,5-Bisphosphate-Carboxylase/Oxygenase (Rubisco) Small Subunit Gene Family among Accessions of Arabidopsis thaliana
Authors: S. Schwarte, R. Tiedemann
Journal: Molecular Biology and Evolution (2011)

Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39), the most abundant protein in nature, catalyzes the assimilation of CO2 (worldwide about 1011 t each year) by carboxylation of ribulose-1,5-bisphosphate. It is a hexadecamer consisting of eight large and eight small subunits. Although the Rubisco large subunit (rbcL) is encoded by a single gene on the multicopy chloroplast genome, the Rubisco small subunits (rbcS) are encoded by a family of nuclear genes. In Arabidopsis thaliana, the rbcS gene family comprises four members, that is, rbcS-1a, rbcS-1b, rbcS-2b, and rbcS-3b. We sequenced all Rubisco genes in 26 worldwide distributed A. thaliana accessions. In three of these accessions, we detected a gene duplication/loss event, where rbcS-1b was lost and substituted by a duplicate of rbcS-2b (called rbcS-2b*). By screening 74 additional accessions using a specific polymerase chain reaction assay, we detected five additional accessions with this duplication/loss event. In summary, we found the gene duplication/loss in 8 of 100 A. thaliana accessions, namely, Bch, Bu, Bur, Cvi, Fei, Lm, Sha, and Sorbo. We sequenced an about 1-kb promoter region for all Rubisco genes as well. This analysis revealed that the gene duplication/loss event was associated with promoter alterations (two insertions of 450 and 850 bp, one deletion of 730 bp) in rbcS-2b and a promoter deletion (2.3 kb) in rbcS-2b* in all eight affected accessions. The substitution of rbcS-1b by a duplicate of rbcS-2b (i.e., rbcS-2b*) might be caused by gene conversion. All four Rubisco genes evolve under purifying selection, as expected for central genes of the highly conserved photosystem of green plants. We inferred a single positive selected site, a tyrosine to aspartic acid substitution at position 72 in rbcS-1b. Exactly the same substitution compromises carboxylase activity in the cyanobacterium Anacystis nidulans. In A. thaliana, this substitution is associated with an inferred recombination. Functional implications of the substitution remain to be evaluated.
The Age-Specific Effect Modification of Male Sex for Ulcerated Cutaneous Melanoma
Authors: Blakely S. Richardson, William F. Anderson, Jill S. Barnholtz-Sloan, Margaret A. Tucker, Meg R. Gerstenblith
Journal: JAMA Dermatology (2014)

<h3>Importance</h3> Tumor ulceration is an important prognostic factor for cutaneous melanoma (CM). Previous studies demonstrated that the proportion of ulcerated to nonulcerated CM rose with increasing tumor depth. These frequency-based studies, however, were not adjusted for the population at risk. <h3>Objective</h3> To determine the absolute incidence of ulcerated CM by tumor depth, stratified by sex and age at diagnosis. <h3>Design, Setting, and Participants</h3> We compared ulcerated CM by tumor thicknesses (≤1.00, 1.01-2.00, 2.01-4.00, and ≥4.01 mm), stratified by sex among younger (10-39 years) and older (40-84 years) non-Hispanic whites in the National Cancer Institute’s Surveillance, Epidemiology, and End Results database from 2004 through 2008. Types of CM included superficial spreading, nodular, and unclassified in 5106 cases among 3206 men and 1900 women. <h3>Main Outcomes and Measures</h3> Incidence of ulcerated CM by tumor depth for younger and older men and women. <h3>Results</h3> The incidence of tumor ulceration was stable across all tumor depths among younger men and older women. Among younger women, it declined for the thickest lesions (0.08 per 100 000 for tumor depth ≥4.01 mm), although the trend was not statistically significant. In contrast, among older men, there was a statistically significant increase in ulceration for CM with a depth of approximately 1.4 per 100 000 for tumor depth of 2.00 mm or thicker. <h3>Conclusions and Relevance</h3> Male sex is an age-specific effect modifier for ulcerated CM by tumor depth. Future studies and staging guidelines should consider the interaction among CM ulceration, thickness, sex, and age at diagnosis.
Acute respiratory failure as the first sign of Arnold-Chiari malformation associated with syringomyelia
Authors: D Alvarez, I Requena, M Arias, L Valdes, I Pereiro, R De la Torre
Journal: European Respiratory Journal (1995)

We report a rare case of acute respiratory failure in a previously asymptomatic patient showing clinical signs of inferior cranial nerve palsy together with weakness and muscular atrophy of the upper limbs. Magnetic resonance imaging revealed Arnold-Chiari malformation associated with platybasia, basilar impression, syringomyelia and Klippel-Feil syndrome. Episodes of apnoea required tracheostomy and recurred upon tentative closure of the tracheostome, but remitted upon decompression of the posterior fossa. This case involved both obstructive mechanisms and dysfunction of the respiratory centre. Patients with respiratory failure not explained by pulmonary pathology should be checked for underlying neurological disease.
Medicine in Europe: Electronic health records: the European scene
Authors: D Kalra
Journal: BMJ (1994)

Commentary: both hospital and community services are needed Although stroke is common few properly designed studies have tested the value ofdifferent approaches to management.But acute stroke units have been shown to confer benefit, and the argument in favour of having an acute stroke unit in every hospital seems to me to be com- pelling.This is not to say that there should not be equally well organised stroke services in the community.We do not yet have data to indicate that a community based stroke rehabilitation service would be effective.But given the huge cost of stroke patients in both financial and social terms such a study seems long overdue.The likely outcome is that there should be a continuum beginning in hospital and then following through when the patient goes home.In the meantime it is important to recognise that some patients are more likely to benefit from rehabilitation than others and resources should be directed at those with the best prog- nosis.-PETERC RUBIN, professor of therapeutics, University ofNottingham focus for the training of medical and non-medical staff and for the development and evaluation of new techniques.Unless stroke care is coordinated from a single centre we will not be able to evaluate new treatments when they become available.Only by concentrating clinical skills in one area can stroke care be effectively coordinated, and only by concentrating stroke patients in one area will appreciable advances be made in knowledge and clinical practice.Stroke units have been shown to provide the most effective service.They should coordinate stroke management until we have a better and cheaper altemative.Without a considerable investment of time and effort, community services are incapable of mounting any form of comprehensive coordinated programme.If it does not become routine policy for stroke patients to be managed in specialist units the quality of stroke management will inevitably decline.
Results of the Post-U.S. Food and Drug Administration-Approval Study With a Continuous Flow Left Ventricular Assist Device as a Bridge to Heart Transplantation
Authors: Randall C. Starling, Yoshifumi Naka, Andrew J. Boyle, Gonzalo Gonzalez-Stawinski, Ranjit John, Ulrich Jorde, Stuart D. Russell, John V. Conte, Keith D. Aaronson, Edwin C. McGee, William G. Cotts, David DeNofrio, Duc Thinh Pham, David J. Farrar, Francis D. Pagani
Journal: Journal of the American College of Cardiology (2011)
Adrenocortical steroids increase renal thiazide diuretic receptor density and response.
Authors: Z Chen, D A Vaughn, P Blakely, D D Fanestil
Journal: Journal of the American Society of Nephrology (1994)

The density of the rat renal pharmacologic receptor for thiazide-type diuretics, as quantitated by the maximal specific binding of (3H)metolazone, decreased to one-third normal after adrenalectomy. Selective glucocorticoid (dexamethasone or RU-28362) replacement increased thiazide receptor density to or above the normal level over the dose range of steroid that decreased thymus weight, which served as a bioassay for glucocorticoid activity. Mineralocorticoid (fludrocortisone or aldosterone), in doses that did not decrease thymus weight, also increased thiazide diuretic receptor density to or above normal. The addition of glucocorticoid (RU-28362) to maximal aldosterone increased thiazide receptor above that produced by aldosterone alone and to threefold normal. Similarly, the addition of aldosterone to high-dose RU-28362 also increased thiazide receptor density above that produced by the glucocorticoid alone and to threefold normal. Hence, the effects of glucocorticoids and mineralocorticoids appeared to be additive. The increase in renal thiazide receptor density produced by fludrocortisone, at a dose that elicited both mineralocorticoid and glucocorticoid effects, was unrelated to the basal (prethiazide) renal excretion of sodium, potassium, chloride, or calcium. However, fludrocortisone-pretreated animals responded to bendroflumethiazide with a greater natriuresis than did controls. In addition, the magnitudes of the thiazide-elicited natriuresis and chloriuresis correlated significantly with thiazide receptor. It was concluded that both the density of the renal thiazide receptor and the quantity of sodium and chloride reabsorbed by the thiazide-sensitive Na-Cl cotransporter in the kidney are under adrenocortical regulation.
Combining Portable Raman Probes with Nanotubes for Theranostic Applications
Authors: Ashwinkumar A. Bhirde, Gang Liu, Albert Jin, Ramiro Iglesias-Bartolome, Alioscka A. Sousa, Richard D. Leapman, J. Silvio Gutkind, Seulki Lee, Xiaoyuan Chen
Journal: Theranostics (2011)

Recently portable Raman probes have emerged along with a variety of applications, including carbon nanotube (CNT) characterization.Aqueous dispersed CNTs have shown promise for biomedical applications such as drug/gene delivery vectors, photo-thermal therapy, and photoacoustic imaging.In this study we report the simultaneous detection and irradiation of carbon nanotubes in 2D monolayers of cancer cells and in 3D spheroids using a portable Raman probe.A portable handheld Raman instrument was utilized for dual purposes: as a CNT detector and as an irradiating laser source.Single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) were dispersed aqueously using a lipid-polymer (LP) coating, which formed highly stable dispersions both in buffer and cell media.The LP coated SWCNT and MWCNT aqueous dispersions were characterized by atomic force microscopy, transmission electron microscopy, dynamic light scattering, Fourier transform infrared spectroscopy and Raman spectroscopy.The cellular uptake of the LP-dispersed SWCNTs and MWCNTs was observed using confocal microscopy, and fluorescein isothiocyanate (FITC)-nanotube conjugates were found to be internalized by ovarian cancer cells by using Z-stack fluorescence confocal imaging.Biocompatibility of SWCNTs and MWCNTs was assessed using a cell viability MTT assay, which showed that the nanotube dispersions did not hinder the proliferation of ovarian cancer cells at the dosage tested.Ovarian cancer cells treated with SWCNTs and MWCNTs were simultaneously detected and irradiated live in 2D layers of cancer cells and in 3D environments using the portable Raman probe.An apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay carried out after laser irradiation confirmed that cell death occurred only in the presence of nanotube dispersions.We show for the first time that both SWCNTs and MWCNTs can be selectively irradiated and detected in cancer cells using a simple handheld Raman instrument.This approach could potentially be used to treat various diseases, including cancer.
Heart involvement in systemic sclerosis: an ultrasonic tissue characterisation study
Authors: C. Ferri, V. Di Bello, A. Martini, D. Giorgi, F. A A Storino, M. Bianchi, A. Bertini, M. Paterni, C. Giusti, G. Pasero
Journal: Annals of the Rheumatic Diseases (1998)

<h3>BACKGROUND</h3> Clinicoepidemiological findings indicate that symptomatic heart involvement in patients with systemic sclerosis (SSc) predicts a very poor prognosis. At necropsy studies, SSc heart involvement without significant coronary lesions is characterised by patchy myocyte necrosis and contraction band necrosis with collagen replacement leading to myocardial fibrosis. There is a discrepancy between the frequency of clinically evident myocardial disease (25%) and autoptical myocardial fibrosis (81%). <h3>OBJECTIVE</h3> The aim of this study was to detect preclinical myocardial alterations in SSc patients by ultrasonic videodensitometric analysis. <h3>METHODS</h3> Thirty five SSc patients (three male, aged 48.6 (11) SD years, range 22–65) with normal ventricular function and 25 age and sex matched healthy controls were studied. All patients had a negative maximal exercise stress; in all cases arterial hypertension, renal involvement, and diabetes were excluded. Echocardiographic images were digitised by a real time videodigitiser (Tomtec Imaging Systems). Quantitative texture analysis was performed on data from the septum and the posterior wall, obtaining mean gray level histogram (MGL) at both end-diastole (d) and end-systole (s). The cyclic variation index (CVI), was calculated according to the formula ((MGLd−MGLs)/MGLd) × 100. Left ventricular mass (LVM), body surface corrected, was calculated according to Penn convention. <h3>RESULTS</h3> Comparable systolic and diastolic blood pressure, LVM, diastolic and systolic function were recorded in both SSc patients and controls. In contrast, in SSc patients the CVI, which is the expression of the intrinsic myocardial structural function, was significantly lower than in controls (septum: −18 (28)%<i>v</i> 35 (10)%, p&lt;0.0001; and posterior wall: −13 (32)%<i>v</i> 50 (20)%, p&lt;0.0001). Changes in cyclic echo amplitude, probably related to myocardial fibrosis, were detected in the large majority of SSc patients (88%). <h3>CONCLUSIONS</h3> Ultrasonic videodensitometric analysis represents a non-invasive, feasible method that can detect early myocardial changes in SSc patients, which could be related to both fibrosis and microcirculatory abnormalities. Their potential evolution towards ventricular dysfunction and their link with cardiac sudden death, because of severe conduction system or rhythm disturbancies, should be further investigated.
TLR4 signaling in effector CD4+ T cells regulates TCR activation and experimental colitis in mice
Authors: José M. González-Navajas, Sean Fine, Jason Law, Sandip K. Datta, Kim P. Nguyen, Mandy Yu, Maripat Corr, Kyoko Katakura, Lars Eckman, Jongdae Lee, Eyal Raz
Journal: Journal of Clinical Investigation (2010)

TLRs sense various microbial products. Their function has been best characterized in DCs and macrophages, where they act as important mediators of innate immunity. TLR4 is also expressed on CD4+ T cells, but its physiological function on these cells remains unknown. Here, we have shown that TLR4 triggering on CD4+ T cells affects their phenotype and their ability to provoke intestinal inflammation. In a model of spontaneous colitis, Il10-/-Tlr4-/- mice displayed accelerated development of disease, with signs of overt colitis as early as 8 weeks of age, when compared with Il10-/- and Il10-/-Tlr9-/- mice, which did not develop colitis by 8 months. Similar results were obtained in a second model of colitis in which transfer of naive Il10-/-Tlr4-/- CD4+ T cells into Rag1-/- recipients sufficient for both IL-10 and TLR4 induced more aggressive colitis than the transfer of naive Il10-/- CD4+ T cells. Mechanistically, LPS stimulation of TLR4-bearing CD4+ T cells inhibited ERK1/2 activation upon subsequent TCR stimulation via the induction of MAPK phosphatase 3 (MKP-3). Our data therefore reveal a tonic inhibitory role for TLR4 signaling on subsequent TCR-dependent CD4+ T cell responses.
DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes
Authors: Dvir Aran, Sivan Sabato, Asaf Hellman
Journal: Genome biology (2013)

Abstract Background Abnormal epigenetic marking is well documented in gene promoters of cancer cells, but the study of distal regulatory siteshas lagged behind.We performed a systematic analysis of DNA methylation sites connected with gene expression profilesacross normal and cancerous human genomes. Results Utilizing methylation and expression data in 58 cell types, we developed a model for methylation-expression relationships in gene promoters and extrapolated it to the genome. We mapped numerous sites at which DNA methylation was associated with expression of distal genes. These sites bind transcription factors in a methylation-dependent manner, and carry the chromatin marks of a particular class of transcriptional enhancers. In contrast to the traditional model of one enhancer site per cell type, we found that single enhancer sites may define gradients of expression levels across many different cell types. Strikingly, the identified sites were drastically altered in cancers: hypomethylated enhancer sites associated with upregulation of cancer-related genes and hypermethylated sites with downregulation. Moreover, the association between enhancer methylation and gene deregulation in cancerwas significantly stronger than the association of promoter methylationwith gene deregulation. Conclusions Methylation of distal regulatory sites is closely related to gene expression levels across the genome. Single enhancers may modulate ranges of cell-specific transcription levels, from constantlyopen promoters. In contrast to the remote relationships between promoter methylation and gene dysregulation in cancer, altered methylation of enhancer sites is closely related to gene expression profiles of transformed cells.