tbuckley/cabot-search huggingface dataset:
Polymorphisms in the<i>HBB</i>gene relate to individual cardiorespiratory adaptation in response to endurance training
Authors: Z He, Y Hu, L Feng, Y Lu, G Liu, Y Xi, L Wen, X Xu, K Xu
Journal: British Journal of Sports Medicine (2006)

The crucial role of haemoglobin in endurance performance has been well documented. We examined whether polymorphisms in the HBB gene modified aerobic capacity.102 recruits were trained by running 5000 m three times per week for 18 weeks. Exercise intensity progressively increased from an initial heart rate corresponding to 95% of the individual baseline ventilatory threshold during the first 10 weeks to 105% during the last 8 weeks. The phenotypes measured were running economy and VO(2)max. Running economy was determined by measuring submaximal VO(2) for 5 min at a constant running speed of 12 km.h(-1) and VO(2)max was obtained during an incremental test to exhaustion. Genomic DNA was extracted from white cells of peripheral blood and the -551C/T, intron2,+16C/G and +340 A/T genotypes were examined relative to the TAA site variants by PCR-RFLP.Genotype distributions were in Hardy-Weinberg equilibrium at three loci. None of the running economy and VO(2)max-related traits were associated with the three polymorphisms or haplotypes at baseline, while the training response of running economy was associated with -551C/T and intron2,+16C/G polymorphisms. Subjects homozygous for intron2,+16C/C or -551C/C had decreased oxygen cost of running compared to the other individuals.It was concluded that the -551C/C or intron2,+16C/C genotype might explain part of the individual variation in the cardiorespiratory adaptation to endurance training.
Rhinovirus Infection Is Associated With Changes In The Airway Microbiome
Authors: Kirsten Kloepfer, Valeriy Poroyko, Rose Vrtis, Tressa Pappas, Theresa Kang, Wai-Ming Lee, Michael D. Evans, Ronald E. Gangnon, Yury Bochkov, Robert F. Lemanske, James E. Gern
Journal: Journal of Allergy and Clinical Immunology (2014)
Translating the Brain-Machine Interface
Authors: Nitish V. Thakor
Journal: Science Translational Medicine (2013)

Brain-machine and brain-computer interface technologies hold great promise for use in the recovery of sensory and motor functions lost as a result of nervous-system injuries or limb amputations. This Perspective describes the current state of noninvasive and invasive technologies with a view to potential applications. The scientific and technological challenges and barriers to translation are critically analyzed for a variety of approaches.
Evaluation of DNA from the Papanicolaou Test to Detect Ovarian and Endometrial Cancers
Authors: Isaac Kinde, Chetan Bettegowda, Yuxuan Wang, Jian Wu, Nishant Agrawal, Ie-Ming Shih, Robert Kurman, Fanny Dao, Douglas A. Levine, Robert Giuntoli, Richard Roden, James R. Eshleman, Jesus Paula Carvalho, Suely Kazue Nagahashi Marie, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Luis A. Diaz
Journal: Science Translational Medicine (2013)

Mutant DNA from ovarian and endometrial tumors can be detected in Pap smear specimens through massively parallel sequencing.
Use of Nondisclosure Agreements in Medical Malpractice Settlements by a Large Academic Health Care System
Authors: William M. Sage, Joseph S. Jablonski, Eric J. Thomas
Journal: JAMA Internal Medicine (2015)

Honesty and transparency are essential aspects of health care, including in physicians' and hospitals' responses to medical error. Biases and habits associated with medical malpractice litigation, however, may work at cross-purposes with compassion in clinical care and with efforts to improve patient safety.To determine the frequency of nondisclosure agreements in medical malpractice settlements and the extent to which the restrictions in these agreements seem incompatible with good patient care.We performed a retrospective review of medical malpractice claim files, including settlement agreements, for claims closed before (fiscal year 2001-2002), during (fiscal year 2006-2007), and after (fiscal years 2009-2012) the implementation of tort reform in Texas. We studied The University of Texas System, which self-insures malpractice claims that involve 6000 physicians at 6 medical campuses in 5 cities.Nondisclosure provisions in medical malpractice settlements.During the 5 study years, The University of Texas System closed 715 malpractice claims and made 150 settlement payments. For the 124 cases that met our selection criteria, the median compensation paid by the university was $100,000 (range, $500-$1.25 million), and the mean compensation was $185,372. A total of 110 settlement agreements (88.7%) included nondisclosure provisions. All the nondisclosure clauses prohibited disclosure of the settlement terms and amount, 61 (55.5%) prohibited disclosure that the settlement had been reached, 51 (46.4%) prohibited disclosure of the facts of the claim, 29 (26.4%) prohibited reporting to regulatory agencies, and 10 (9.1%) prohibited disclosure by the settling physicians and hospitals, not only by the claimant. Three agreements (2.7%) included specific language that prohibited the claimant from disparaging the physicians or hospitals. The 50 settlement agreements signed after tort reform took full effect in Texas (2009-2012) had stricter nondisclosure provisions than the 60 signed in earlier years: settlements after tort reform were more likely to prohibit disclosure of the event of settlement (36 [72.0%] vs 25 [41.7%]; P < .001), to prohibit disclosure of the facts of the claims (31 [62.0%] vs 20 [33.3%]; P = .003), and to prohibit reporting to regulatory bodies (25 [50.0%] vs 4 [6.7%]; P < .001).An academic health system with a declared commitment to patient safety and transparency used nondisclosure clauses in most malpractice settlement agreements but with little standardization or consistency. The scope of nondisclosure was often broader than seemed needed to protect physicians and hospitals from disparagement by the plaintiff or to avoid publicizing settlement amounts that might attract other claimants. Some agreements prohibited reporting to regulatory agencies, a practice that the health system changed in response to our findings.
Bortezomib Is Active in Patients With Untreated or Relapsed Waldenström's Macroglobulinemia: A Phase II Study of the National Cancer Institute of Canada Clinical Trials Group
Authors: Christine I. Chen, C. Tom Kouroukis, Darrell White, Michael Voralia, Edward Stadtmauer, A. Keith Stewart, John J. Wright, Jean Powers, Wendy Walsh, Elizabeth Eisenhauer
Journal: Journal of Clinical Oncology (2007)

To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenström's macroglobulinemia (WM).Symptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m2 intravenously days 1, 4, 8, and 11 on a 21-day cycle until two cycles past complete response (CR), stable disease (SD) attained, progression (PD), or unacceptable toxicity. Responses were based on both paraprotein levels and bidimensional disease measurements.Twenty-seven patients were enrolled. A median of six cycles (range, two to 39) of bortezomib were administered. Twenty-one patients had a decrease in immunoglobulin M (IgM) of at least 25%, with 12 patients (44%) reaching at least 50% IgM reduction. Using both IgM and bidimensional criteria, responses included seven partial responses (PRs; 26%), 19 SDs (70%), and one PD (4%). Total response rate was 26%. IgM reductions were prompt, with nodal responses lagging. Hemoglobin levels increased by at least 10 g/L in 18 patients (66%). Most nonhematologic toxicities were grade 1 to 2, but 20 patients (74%) developed new or worsening peripheral neuropathy (five patients with grade 3, no grade 4), a common cause for dose reduction. Onset of neuropathy was within two to four cycles and reversible in the majority. Hematologic toxicities included grade 3 to 4 thrombocytopenia in eight patients (29.6%) and neutropenia in five (19%). Toxicity led to treatment discontinuation in 12 patients (44%), most commonly because of neuropathy.Bortezomib has efficacy in WM, but neurotoxicity can be dose limiting. The slower response in nodal disease may require prolonged therapy, perhaps with a less intensive dosing schedule to avoid early discontinuation because of toxicity. Future studies of bortezomib in combination with other agents are warranted.
Digital Disease Detection — Harnessing the Web for Public Health Surveillance
Authors: John S. Brownstein, Clark C. Freifeld, Lawrence C. Madoff
Journal: New England Journal of Medicine (2009)

The Internet has become a critical medium for clinicians, public health practitioners, and laypeople seeking health information. Data about diseases and outbreaks are disseminated not only through online announcements by government agencies but also through informal channels, ranging from press reports to blogs to chat rooms to analyses of Web searches (see Digital Resources for Disease Detection). Collectively, these sources provide a view of global health that is fundamentally different from that yielded by the disease reporting of the traditional public health infrastructure.1 Digital Resources for Disease Detection.Sample Web-based data sourcesProMED-mail, www.promedmail.orgGlobal Public Health Intelligence Network (GPHIN), . . .
Hyperactivity and altered mRNA isoform expression of the Cl−/HCO3− anion-exchanger in the hypertrophied myocardium
Authors: G Chiappe de Cingolani
Journal: Cardiovascular Research (2001)

Objective: The aim was to examine the regulation of the cardiac Na+-independent Cl−/HCO3− exchanger (AE) mRNA isoform expression in association to the enhanced AE activity in the hypertrophied myocardium of spontaneously hypertensive rats (SHR). Methods: AE activity was determined by the initial rates of the pHi recovery from imposed intracellular alkalinization (forward mode of exchange) and the pHi rise induced by Cl− removal (reverse mode). Net HCO3− (JHCO3−) efflux and influx were respectively determined. AE mRNA isoforms were analyzed by Northern blot with specific probes to detect AE1, AE2 and AE3 mRNAs. Results: Initial JHCO3− efflux after imposed alkaline load (pHi7.5) was higher in SHR than in normotensive WKY rats (3.01±0.33, n=7, vs. 0.64±0.29 mM/min, n=5, P<0.05). JHCO3− influx induced by Cl− deprivation was also increased in SHR, 4.24±0.56 mM/min (n=10) versus 2.31±0.26 (n=10, P<0.05) in WKY. In arbitrary units, the 4.1-kb AE1 mRNA decreased in SHR (0.15±0.01, n=7) compared to WKY (0.29±0.06, n=7, P<0.05), whereas the 3.6-kb mRNA did not change. AE2 mRNAs were similarly expressed in WKY and SHR. Cardiac specific AE3 (cAE3) mRNA decreased in SHR, 1.10±0.16 arbitrary units (n=8) versus 1.79±0.24, (n=8, P<0.05) in WKY. Full length AE3 (flAE3) mRNA increased from 0.69±0.06 (WKY, n=8) to 1.25±0.19 arbitrary units in SHR (n=8, P<0.05). Conclusions: The increase in flAE3 mRNA expression in cardiac tissue from the SHR is an adaptive change of the hypertrophied myocardium that might be in connection with the increased activity of the AE.
Persistent Latent Tuberculosis Reactivation Risk in United States Immigrants
Authors: Nicholas D. Walter, John Painter, Matthew Parker, Phillip Lowenthal, Jennifer Flood, Yunxin Fu, Redentor Asis, Randall Reves
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<MethodsResultsDiscussionConclusionsReferencesCITING ARTICLES
Fixation with Carnov's fluid reduces the number of chymase‐positive mast cells: not all chvmase‐Dositive mast cells are also posithe for iryptase
Authors: A. KleinJan, T. Godthelp, H. M. Blom, W. J. Fokkens
Journal: Allergy (1996)

Mast cells in the nasal mucosa can be studied by means of monoclonal antibodies (mAb) against tryptase (T + MC) and chymase (C + MC). Fixation with acetone gives more positive cells than does fixation with Carnoy's fluid. In frozen biopsy specimens of allergic nasal mucosa fixed with acetone, the number of T + MC equals that of C + MC. When fixed with Carnoy's fluid, however, the number of T + MC is larger than the number of C + MC. The decrease in both T + MC and C + MC resulting from fixation with Carnoy's fluid is time‐related and depends on the type of mAb used. Carnoy fixation time gives a decrease in the number of C + MC within 1 min, whereas the number of T + MC decreases only after 10 min. Within 1 min, the number of C + MC decreases to a level where continued fixation no longer gives further decreases in the number of cells. Two populations of mast cells can be distinguished here: one sensitive and the other insensitive to Carnoy's fluid. When double‐staining is used, fixation with acetone gives three populations of mast cells: one positive for tryptase (T + C ‐ MC), another positive for tryptase and chymase (T + C + MC), and a third one positive for chymase (T ‐ C + MC). These three populations were found in lymph node, spleen, thymus, dermis, lung parenchyma, small intestinal submucosa, and nasal mucosa.
The predominance of IgG3 and IgM isotype antimitochondrial autoantibodies against recombinant fused mitochondrial polypeptide in patients with primary biliary cirrhosis
Authors: Charles D. Surh, Anne E. Cooper, Ross L. Coppel, Patrick Leung, Aftab Ahmed, Rolland Dickson, Eric M. Gershwin
Journal: Hepatology (1988)

Autoantibodies against inner mitochondrial membrane proteins are a hallmark of primary biliary cirrhosis. Specifically, these antimitochondrial autoantibodies recognize two polypeptides of approximately 70 and 52 kD, respectively. Although the specificity of antimitochondrial autoantibodies has been studied for the past 2 decades, the complementary DNA encoding the major primary biliary cirrhosis-specific 70 kD antigen has only recently been cloned. The availability of the recombinant autoantigen has resulted in the development of a highly sensitive and specific ELISA to detect antimitochondrial autoantibodies and to determine their immu-noglobulin isotypes. We report herein that IgG3 is the predominant isotype of antimitochondrial autoantibodies in a group of 74 primary biliary cirrhosis patients. This finding is significant in light of the genomic im-munoglobulin in heavy chain gene arrangement. Ninety-three per cent of primary biliary cirrhosis patients possessed IgG3 antimitochondrial autoantibodies with ti-ters of 1:10 3 or higher; 32% of these patients possessed titers of 10 4 , 29% at 10 3 and 7% at 10 6 . IgM antimitochondrial autoantibodies were next most prevalent; 63% of the patients were positive and 50% of these patients showed titers of 10 3 , 43% at 10 4 and 6% at 10 5 . Other isotypes were present but in much lower titer and occurrence. Isotypes of antimitochondrial autoantibodies reactive to the 52 kD antigen were also determined using immunoblotting techniques. The predominance of IgG3 and IgM were similarly observed. Finally, the serum immunoglobulin isotype levels of primary biliary cirrhosis patients were compared with healthy normal adults by radial immunodiffusion. Serum IgG3 and IgM were very elevated in primary biliary cirrhosis; with IgG3 at 5.5-fold and IgM at 4.3-fold above normals. Moreover, IgG3 comprised an average of 17.4% of the total serum IgG in primary biliary cirrhosis compared to 4.5% in the normal population. These results are noteworthy because experimental and naturally occurring viral infections likewise lead to a predominance of IgG3 antibodies.
Energizing the Search to Target <i>LKB1</i>-Mutant Tumors
Authors: Adam I. Marcus, Fadlo R. Khuri
Journal: Cancer Discovery (2013)

Abstract Summary: LKB1 is the third most frequently mutated gene in non–small cell lung cancer and serves as a master regulator of cell metabolism and polarity across a variety of model organisms. Recent studies are beginning to identify therapeutics that exploit defects associated with LKB1 loss. The work presented here by Liu and colleagues shows that deoxythymidylate kinase is a new potential target in LKB1-deficient tumors and highlights the possibility of a new therapeutic option for this subset of patients with cancer. Cancer Discov; 3(8); 843–5. ©2013 AACR. See related article by Liu et al., p. 870
Ischemia-Induced K-<i>ras</i> Mutations in Human Colorectal Cancer Cells: Role of Microenvironmental Regulation of MSH2 Expression
Authors: Siranoush Shahrzad, Lindsay Quayle, Courtney Stone, Claire Plumb, Senji Shirasawa, Janusz W. Rak, Brenda L. Coomber
Journal: Cancer Research (2005)

Abstract Mutation of the K-ras gene is one of the most common genetic alterations in solid tumors, including colorectal cancer. The relatively late emergence of K-ras mutations in colorectal cancer is particularly striking in the class of mismatch repair–deficient tumors associated with early-onset microsatellite instability. We, therefore, tested the hypothesis that the microsatellite instability phenotype itself does not efficiently trigger K-ras mutations in colorectal cancer cells, but rather that tumor-associated microenvironmental conditions (e.g., hypoxia and hypoglycemia) contribute to this event by modulating genetic instability. We examined K-rasG13D mutation using PCR-RFLP analysis in two different microsatellite instability colorectal cancer cell lines (HCT116 and DLD-1) and their variants in which the mutant (but not the wild-type) K-ras allele has been genetically disrupted (Hkh-2 and Dks-8). We found K-rasG13D mutation to occur at far greater incidence in cells derived from xenografted tumors or exposed to conditions of combined hypoxia and hypoglycemia in vitro. Interestingly, this mutagenesis was neither enhanced by induced oxidative damage nor prevented by the antioxidant vitamin E. Moreover, the accumulation of K-ras mutations was paralleled by down-regulation of the key mismatch repair protein MSH2 in xenografted tumors, particularly in hypoperfused areas and under hypoglycemic conditions (in vitro). In contrast, the microsatellite stable colorectal cancer cell line Caco-2 neither accumulated K-ras mutations nor showed down-regulation of MSH2 under these conditions. Thus, our study suggests that ischemia may not simply select for, but can actually trigger, increased mutation rate in crucial colorectal cancer oncoproteins. This finding establishes a novel linkage between genetic instability, tumor ischemia, and genetic tumor progression and carries important implications for applying anticancer therapies involving tumor hypoxia (e.g., antiangiogenesis) in microsatellite instability cancers.
In vivo functional brain mapping in a conditional mouse model of human tauopathy (taup301l) reveals reduced neural activity in memory formation structures
Authors: Pablo D Perez, Gabrielle Hall, Tetsuya Kimura, Yan Ren, Rachel M Bailey, Jada Lewis, Marcelo Febo, Naruhiko Sahara
Journal: Molecular Neurodegeneration (2013)

Abstract Background Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI) to investigate basal levels of brain activity in the rTg4510 and control mice. Results Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Conclusion Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tau P301L -induced neurodegeneration.
AN INTEGRATED VIEW OF β-CELL DYSFUNCTION IN TYPE-II DIABETES
Authors: Vincent Poitout, D, R. Paul Robertson, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Type-II (non-insulin-dependent) diabetes mellitus (NIDDM) is a heterogeneous disease resulting from insulin resistance and β-cell dysfunction. β-Cell dysfunction in Type-II diabetes is characterized by a specific lack of first-phase glucose-induced insulin secretion. This defect is readily reversible upon normalization of blood glucose levels. Chronic hyperglycemia itself is harmful to the β-cell and affects both insulin biosynthesis and exocytosis. No unique intracellular defect has been demonstrated to be responsible for all common forms of the disease. However, mutations of the glucokinase gene have been identified in maturity onset diabetes in the young, a particular form of NIDDM.
Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanosomiasis.
Authors: B A Arrick, O W Griffith, A Cerami
Journal: The Journal of Experimental Medicine (1981)

With the expectation that trypanosomal glutathione (GSH) plays a major protective role against the endogenous oxidant stress that results form high intracellular levels of H2O2, we sought to deplete Trypanosoma brucei brucei of their GSH through inhibition of its biosynthesis. Administration of buthionine sulfoximine (BSO), a reversible inhibitor of gamma-glutamylcysteine synthetase, to parasitemic mice resulted in a progressive decrease in trypanosome GSH content, such that parasites isolated after 5 h or BSO treatment contained 50% of normal values. When BSO administration was continued for 18 h (intraperitoneal injection of 4 mmol/kg every 1.5 h), parasitemias temporarily cleared. When inhibitory plasma levels of BSO were maintained for about 27 h, two out of six infected mice were cured and the rest had significantly prolonged survival. These findings demonstrate the potential value of GSH depletion for the treatment of trypanosomiasis.
Time of day of prednisolone administration in rheumatoid arthritis.
Authors: I C Kowanko, R Pownall, M S Knapp, A J Swannell, P G Mahoney
Journal: Annals of the Rheumatic Diseases (1982)

Twelve patients with rheumatoid arthritis took low dosage prednisolone, mean 5.6 mg daily, at either 0800 h, 1300 h or 2300 h in a double-blind within-patient controlled trial. Each patient was studied on each of the 3 regimens to assess control of symptoms and side effects and also to examine circadian rhythms in signs and symptoms. For several days during each drug regimen patients collected urine at each micturition and self-assessed their signs and symptoms. Circadian rhythms of finger joint swelling and of grip strength were determined, and were similar on all regimens, with morning peaks of symptoms and signs. Subjective and objective assessments showed no differences in effectiveness between the 3 times of administration of prednisolone. Urinary excretion patterns were similar to those observed in untreated people. The quantity and circadian pattern of 11-hydroxycorticosteroids excreted were similar to those in healthy patients, providing no evidence of adrenal cortical suppression at the dose levels studied, even when this dose was taken in the evening. A single morning dose of prednisolone appears in many patients to be as effective as a single evening dose or divided doses. It is therefore reasonable to initiate therapy with a morning-only regimen, because adrenopituitary suppression should be minimised.