tbuckley/cabot-search huggingface dataset:
Population Structure and Population History of Anopheles dirus Mosquitoes in Southeast Asia
Authors: Catherine Walton, Jane M. Handley, Willoughby Tun-Lin†, Frank H. Collins, Ralph E. Harbach, Visut Baimai, Roger K. Butlin
Journal: Molecular Biology and Evolution (2000)

Separating the confounding effects of long-term population history from gene flow can be difficult. Here, we address the question of what inferences about gene flow can be made from mitochondrial sequence data in three closely related species of mosquitoes, Anopheles dirus species A, C, and D, from southeast Asia. A total of 84 sequences of 923 bp of the mitochondrial cytochrome oxidase I gene were obtained from 14 populations in Thailand, Myanmar, and Bangladesh. The genealogy of sequences obtained from two populations of AN: dirus C indicates no contemporary gene flow between them. The F(ST) value of 0.421 therefore probably represents a recent common history, perhaps involving colonization events. Anopheles dirus A and D are parapatric, yet no differentiation was seen either within or between species. The starlike genealogy of their haplotypes, smooth unimodal mismatch distributions, and excess of low frequency mutations indicate population expansion in An. dirus A and D. This, rather than widespread gene flow, explains their low within-species F(ST) values (0.018 and 0.022). The greater genetic diversity of An. dirus D suggests that expansion occurred first in species D and subsequently in species A. The current geographical separation and low hybrid fitness of these species also argue against ongoing interspecific gene flow. They suggest instead either historical introgression of mtDNA from An. dirus D into species A followed by independent range expansions, or a selective sweep of mtDNA that originated in An. dirus D. While not excluding contemporary gene flow, historical population processes are sufficient to explain the data in An. dirus A and D. The genealogical relationships between haplotypes could not be used to make inferences of gene flow because of extensive homoplasy due to hypervariable sites and possibly also recombination. However, it is concluded that this approach, rather than the use of fixation indices, is required in the future to understand contemporary gene flow in these mosquitoes. The implications of these results for understanding gene flow in another important and comparable group of malaria vector mosquitoes in Africa, the An. gambiae complex, are also discussed.
Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study
Authors: James C Jackson, Pratik P Pandharipande, Timothy D Girard, Nathan E Brummel, Jennifer L Thompson, Christopher G Hughes, Brenda T Pun, Eduard E Vasilevskis, Alessandro Morandi, Ayumi K Shintani, Ramona O Hopkins, Gordon R Bernard, Robert S Dittus, E Wesley Ely
Journal: The Lancet Respiratory Medicine (2014)
Endocrine disorders remain undetected and untreated in India
Authors: G. Mudur
Journal: BMJ (1999)

Endocrine disorders in several million children and adults in India remain undetected and untreated because of inadequate professional expertise and a lack of reliable diagnostic services, according to a report presented in New Delhi last week.

“Therapeutic benefits are not available to millions suffering from endocrine diseases in this country,” Dr Narayanapanicker Kochupillai, head of endocrinology and metabolism at the All India Institute of Medical Sciences in New Delhi, reported to a national symposium on endocrine disorders.

Undetected endocrine disorders include neonatal hypothyroidism, adrenal deficiency after tuberculosis, and …
Cryptogenic fibrosing alveolitis: prediction of fibrogenic activity from immunohistochemical studies of collagen types in lung biopsy specimens.
Authors: E D Bateman, M Turner-Warwick, P L Haslam, B C Adelmann-Grill
Journal: Thorax (1983)

Collagen immunofluorescence studies were performed on biopsy specimens from 25 patients with cryptogenic fibrosing alveolitis. We studied the relationship of these results to the clinical, radiological, and physiological assessments of disease activity during six-month periods before and after the lung biopsy; to the appearances on routine histological examination; to the inflammatory cell proportions in bronchoalveolar lavage fluid; and to the response to treatment. Positive associations were observed between the presence of type III collagen and disease activity before (p less than 0.015) and after (p less than 0.02) lung biopsy. These were independent of clinical and routine histological features. The type-III-positive group also contained nine of the 11 responding to treatment. None of the type-III-positive patients had a quiescent or stable course. In contrast, most patients with no type-III-collagen fluorescence had a stable course over the time of this study and did not improve on treatment. It is suggested that collagen typing may be an additional useful method of assessing potentially reversible disease in cryptogenic fibrosing alveolitis.
Specific and dose-dependent enzyme induction by omeprazole in human beings
Authors: Karl Ludwig Rost, Herbert Brösicke, Gerhard Heinemeyer, Ivar Roots
Journal: Hepatology (1994)

Omeprazole induces hepatic cytochrome P-4501A2. In a previous study this effect was shown to be significant in vivo in 6 poor metabolizers, including 1 intermediate metabolizer, but not in 12 extensive metabolizers of S-mephenytoin after 7 days of treatment with 40 mg/day omeprazole. In this study, the specificity of the inducing potential of omeprazole was investigated in these volunteers. Furthermore, in eight of the extensive metabolizers the dose-dependence of cytochrome P-450 1A2 induction was evaluated. Cytochrome P-450 1A2 activity was monitored by means of the 13C-[N3-methyl]caffeine breath test and by means of plasma caffeine clearance before omeprazole treatment with 120 mg/day, on the seventh day of dosage and after a 7-day washout. Omeprazole plasma concentration was measured. Results were compared with those after 40 mg. gamma-Glutamyltransferase activity in serum, as well as urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol, were measured on the same study days in all study groups (n = 26). In the eight extensive metabolizers the breath test indicated a dose-dependent increase of cytochrome P-450 1A2 activity of 8.5% +/- 15.0% (40 mg, mean +/- SD, NS) and 27.2% +/- 16.5% (120 mg, p = 0.002). Caffeine clearance was increased by 31.6% +/- 20.7% (p < 0.001) with the higher dose. None of the study groups exhibited a significant increase of gamma-glutamyltransferase activity or urinary excretion of D-glucaric acid or 6 beta-hydroxycortisol. This was in contrast to the phenobarbital-type induction observed after treatment with antiepileptic drugs. Induction by omeprazole seems to be restricted to cytochrome P-450 1A enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of Cell Death of Chronic Lymphocytic Leukemia Lymphocytes by RNA-Directed Agent, 8-NH2-Adenosine
Authors: Kumudha Balakrishnan, William G. Wierda, Michael J. Keating, Varsha Gandhi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine if RNA-directed nucleoside analogue, 8-NH2-adenosine, induces cell death and if that is accompanied with transcription inhibition of the key survival factors of chronic lymphocytic leukemia (CLL) cells. Experimental Design: Primary lymphocytes from CLL patients were incubated with 10 μmol/L 8-NH2-adenosine for 2, 4, and 6 or 8 hours. The accumulation of analogue triphosphate and the decline in endogenous ATP pool were analyzed by high-performance liquid chromatography. Inhibition of global RNA and protein synthesis was measured and correlated with specific decline in transcript and protein levels of MCL-1, XIAP, and BCL-2, the key survival factors of CLL. These biochemical and molecular end points were related to cell death of these quiescent lymphocytes. Results: In vitro incubations of CLL lymphocytes with 8-NH2-adenosine resulted in rapid but heterogeneous accumulation of 8-NH2-ATP (390-680 μmol/L), with a concomitant decline in endogenous ATP (median, &amp;gt;50% by 4 hour). Global RNA synthesis was decreased in all samples and was associated with a decline in MCL-1, XIAP, and BCL-2 transcripts. There was a parallel decrease in the protein level of MCL-1 and XIAP but not BCL-2. These biochemical changes were accompanied by apoptosis. Conclusion: The evidence of CLL cell death with complementary changes in the expression of survival proteins provides a molecular rationale for using 8-NH2-adenosine as a therapeutic agent for this indolent leukemia.
Studies on Left Atrial Automaticity in Dogs
Authors: M. MIROWSKI, SUN H. LAU, GUSTAVUS A. BOBB, CHARLES STEINER, ANTHONY N. DAMATO
Journal: Circulation Research (1970)

The site of origin and the sequence of atrial activation were studied in 21 open-chested dogs anesthetized with sodium pentobarbital. Bipolar plunge electrodes were used to record atrial electrograms simultaneously with surface lead II and His bundle electrogram. In sinus rhythm the sinus node was activated first, followed sequentially by Bachmann's bundle, right atrial appendix, left atrial appendix, posterior left atrium, and the proximal portion of the coronary sinus. In 15 dogs left atrial beats and rhythms of various rate were recorded, including instances of left atrial exit block and of rapid left atrial rhythms. In such beats one of the left atrial electrodes was activated first and was followed by Bachmann's bundle, sinus node, proximal portion of the coronary sinus, and by right atrial appendix. Left atrial beats were observed occurring (1) spontaneously; (2) as a result of vagal stimulation; (3) after destruction of the sinus node; (4) during ventricular pacing. Left atrial pacing through the electrode recording initial activity reproduced the sequence and configuration of atrial electrogram similar to that seen in the ectopic left atrial beats. These results demonstrate that in dogs ectopic activity frequently originates in the left atrium.
Evidence for clonal selection of gamma/delta T cells in response to a human pathogen.
Authors: K Uyemura, R J Deans, H Band, J Ohmen, G Panchamoorthy, C T Morita, T H Rea, R L Modlin
Journal: The Journal of Experimental Medicine (1991)

T cells bearing gamma/delta antigen receptors comprise a resident population of intraepithelial lymphocytes in organs such as skin, gut, and lungs, where they are strategically located to contribute to the initial defense against infection. An important unsolved question about antigen-driven gamma/delta T cell responses regards the breadth of their T cell receptor (TCR) repertoire, since many specific epithelial compartments in mice display limited diversity. We have examined the diversity of TCR delta gene expression among human gamma/delta T cells from skin lesions induced by intradermal challenge with Mycobacterium leprae. We show that the vast majority of gamma/delta cells from M. leprae lesions use either V delta 1-J delta 1 or V delta 2-J delta 1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity. This contrasts markedly with the extensive diversity of gamma/delta T cells from peripheral blood of these same individuals, as well as skin from normal donors. These results indicate that the gamma/delta response to M. leprae involves the selection of a limited number of clones from among a diverse repertoire, probably in response to specific mycobacterial and/or host antigens.
Too Soon to Give Up: Re-examining the Value of Advance Directives
Authors: Benjamin H. Levi, Michael J. Green
Journal: The American Journal of Bioethics (2010)

In the face of mounting criticism against advance directives, we describe how a novel, computer-based decision aid addresses some of these important concerns. This decision aid, Making Your Wishes Known: Planning Your Medical Future, translates an individual's values and goals into a meaningful advance directive that explicitly reflects their healthcare wishes and outlines a plan for how they wish to be treated. It does this by (1) educating users about advance care planning; (2) helping individuals identify, clarify, and prioritize factors that influence their decision-making about future medical conditions; (3) explaining common end-of-life medical conditions and life-sustaining treatment; (4) helping users articulate a coherent set of wishes with regard to advance care planning—in the form of an advance directive readily interpretable by physicians; and (5) helping individuals both choose a spokesperson, and prepare to engage family, friends, and health care providers in discussions about advance care planning.
Effect of theophylline on exercise performance in patients with severe chronic obstructive pulmonary disease.
Authors: G Fink, C Kaye, J Sulkes, U Gabbay, S A Spitzer
Journal: Thorax (1994)

BACKGROUND--Theophylline is a well known bronchodilator which has been used for more than 50 years in the treatment of obstructive pulmonary diseases. In patients with severe chronic obstructive pulmonary disease whose cardiopulmonary performance is limited by their ventilatory capacity the administration of theophylline may improve exercise performance. METHODS--A randomised, placebo controlled, double blind, crossover trial was conducted in 22 patients with severe but stable disease. The patients (mean age 68 years) were studied before and after one month of placebo and one month of treatment with a sustained release preparation of theophylline administered orally. The theophylline dose was adjusted until a blood level above 55.5 mumol/l was achieved. The two treatments were administered in random order and separated by a two week washout period. After theophylline was administered for one month a mean level of 68.2 mumol/l was achieved. Pulmonary function tests, arterial blood gas measurements, maximal voluntary ventilation (MVV), and an incremental exercise test were performed before (baseline) and at the end of the first and second month of treatment. RESULTS--Pulmonary function tests showed no improvement in the flow parameters but showed an improvement in MVV after treatment with theophylline. Pulmonary gas exchange was improved after theophylline (resting arterial PO2 8.91 v 8.59 kPa, PCO2 5.38 v 5.56 kPa). The incremental exercise study showed improvement in maximal work rate (86.5 v 75.0 watts) and maximal ventilation (VEmax) (46.7 v 43.01/min). The dyspnoea index on maximal effort (VEmax/MVV), anaerobic threshold, and oxygen pulse remained unchanged. Resting and exercise heart rate were higher after theophylline. CONCLUSIONS--Theophylline improved cardiorespiratory performance in these patients with severe chronic obstructive pulmonary disease mainly by increasing the ventilatory capacity.
Can We Predict Type 1 Diabetes in the General Population?
Authors: Mikael Knip
Journal: Diabetes Care (2002)

Diabetes-associated autoantibodies have been shown to be useful in the assessment of diabetes risk among first-degree relatives of subjects with type 1 diabetes (1–3), whereas their predictive characteristics are poorly defined in the general population, from which ∼90% of the newly diagnosed patients are derived (4). In a simulation study based on the combination of cross-sectional data from children with newly diagnosed type 1 diabetes and unaffected schoolchildren, Bingley et al. (5) reported earlier that positivity for multiple diabetes-associated autoantibodies was associated with reasonable sensitivity and a relatively high positive predictive value for clinical disease in schoolchildren. In this issue of Diabetes Care , LaGasse et al. (6) confirm the utility of disease-associated autoantibodies in the prediction of type 1 diabetes in the general population, represented by 4,505 schoolchildren from Washington state aged 12–18 years at initial sampling. The authors conclude that teens with at least two defined autoantibodies, i.e., antibodies to insulin, the 65-kDa isoform of GAD, and/or to the protein tyrosine phosphatase-related IA-2/islet cell autoantibody (ICA)-512 molecule, are characterized by a high risk of progression to overt diabetes, and that a screening strategy based on the analysis of insulin autoantibodies and GAD and IA-2 antibodies is highly successful in the assessment of type 1 diabetes risk in adolescents.

The conclusions are based on information obtained by recontacting 3,000 of the aforementioned 4,505 schoolchildren (67%) 6–11 years later, with a median interval of 8 years. All but 4 of the 141 children who initially tested positive for at least one autoantibody were reached. Six subjects presented with type 1 diabetes within a median interval of 2.8 years after the initial test, and …
Renal and Brain Isoforms of WNK3 Have Opposite Effects on NCCT Expression
Authors: Mark Glover, Annie Mercier Zuber, Kevin M. O’Shaughnessy
Journal: Journal of the American Society of Nephrology (2009)

Mutations in the WNK kinases WNK1 and WNK4 cause a rare familial form of hypertension (Gordon syndrome) by increasing expression of the thiazide-sensitive co-transporter NCCT in the kidney. Regulation of NCCT expression involves a scaffold of proteins composed of several kinases, including the third member of the WNK kinase family, WNK3. This protein, expressed in several tissues including kidney and brain, displays splice variation around exons 18 and 22. We expressed these proteins in Xenopus oocytes and found that the renal isoform of WNK3 increased but the brain isoform decreased NCCT expression and activity. Introduction of a kinase-inactivating mutation into renal WNK3 reversed its action on NCCT, and the same mutation in the brain isoforms led to loss of function. We also studied the effect of phosphorylation of a key NCCT threonine (T58) on the effects of WNK3/4 coexpression; NCCT mutants with a T58A or T58D substitution had the same surface expression as T58 but had significantly altered transporter activity; however, both isoforms of WNK3 as well as WNK4 still modulated expression of these NCCT mutants. Finally, experiments using kinase-dead STE20/SPS1-related proline/alanine-rich kinase (SPAK), a putative downstream target for WNKs, revealed that brain WNK3 acts in tandem with SPAK, whereas renal WNK3 seems to upregulate NCCT through a SPAK-independent pathway. Taken together, these results suggest that the C-terminal motifs contributed by exons 18 and 22 play an important role in the actions of WNK3 isoforms on NCCT.
Validation of computed tomographic lung densitometry for monitoring emphysema in 1-antitrypsin deficiency
Authors: David Parr, BC Stoel, J Stolk, Robert Stockley
Journal: Thorax (2006)

<b>Background:</b> Lung densitometry derived from computed tomographic images offers an opportunity to quantify emphysema non-invasively, but a pathological standard cannot be applied to validate its use in longitudinal monitoring studies. Consequently, forced expiratory volume in 1 second (FEV<sub>1</sub>) remains the standard against which new methods must be judged. We related progression of densitometry (15th percentile point and voxel index, threshold −950 Hounsfield units) to disease stage and FEV<sub>1</sub> decline in two studies of subjects with α<sub>1</sub>-antitrypsin deficiency (PiZ). <b>Methods:</b> Consistency of progression, measured using densitometry and FEV<sub>1</sub>, was assessed in relation to disease stage in a 2 year study of 74 subjects grouped according to the FEV<sub>1</sub> criteria employed in the GOLD guidelines. In the second study of a subgroup of subjects with extended data (n = 34), summary statistics were applied to measurements performed annually over 3 years and the rate of progression of densitometry was related to FEV<sub>1</sub> decline. <b>Results:</b> The progression of percentile point was consistent across a wide spectrum of disease severity, but voxel index progression varied in association with disease stage (p = 0.004). In the second study, FEV<sub>1</sub> decline correlated with progression of lung densitometry (percentile point: <i>r</i><sub>S</sub> = 0.527, p = 0.001; voxel index: <i>r</i><sub>S</sub> = −0.398, p = 0.012). <b>Conclusions:</b> 15th percentile point is a more consistent measure of lung density loss across a wide range of physiological impairment than voxel index. However, both methods are valid for use in longitudinal and interventional studies in which emphysema is the major outcome target.
Observer agreement in the assessment of narrowband imaging system surface patterns in Barrett’s esophagus: a multicenter study
Authors: M. Singh, A. Bansal, W. Curvers, M. Kara, S. Wani, L. Alvarez Herrero, C. Lynch, M. van Kouwen, F. Peters, J. Keighley, A. Rastogi, K. Pondugula, R. Kim, V. Singh, S. Gaddam, J. Bergman, P. Sharma
Journal: Endoscopy (2011)

<b>Background and study aims: </b> The clinical utility of narrow-band imaging (NBI) for Barrett's esophagus is limited by the multiplicity of classification schemes. We evaluated the interobserver agreement and accuracy of a new consensus-driven simplified binary classification of NBI surface patterns. <b>Patients and methods:</b> NBI images from macroscopically normal areas in patients with Barrett's esophagus were retrieved from endoscopy databases and were randomized for review by seven endoscopists (three experts, four nonexperts). A simplified binary classification of NBI mucosal and vascular patterns was used: (1) regular pattern (nondysplastic Barrett's esophagus); (2) irregular pattern (dysplastic Barrett's esophagus). Agreement in relation to surface patterns and predicted histology (dysplasia vs. no dysplasia) was calculated using κ statistics. <b>Results:</b> A total of 252 NBI images from 75 patients with Barrett's esophagus were assessed: 93 showed intestinal metaplasia, 91 low-grade dysplasia, and 68 high-grade dysplasia/esophageal adenocarcinoma. The median score for image quality was 4 (very good). Interobserver agreement for mucosal and vascular patterns and dysplasia prediction was fair: κ = 0.40 (95%CI: 0.37–0.42), 0.36 (95%CI: 0.33–0.38), and 0.39 (95%CI: 0.36–0.41) respectively, with comparable results for experts and nonexperts. Intraobserver agreement was substantially better among experts than among nonexperts, with mucosal κ = 0.63 vs. 0.49, vascular κ = 0.58 vs. 0.43, and predicted histology κ = 0.68 vs. 0.54 (all <i>P</i> < 0.005). Mean sensitivity and specificity of NBI surface patterns for predicting dysplasia were 47% (95%CI: 44%–55%) and 72% (95%CI: 69%–76%) respectively. <b>Conclusions:</b> Using a consensus-driven simplified classification of NBI surface patterns for Barrett's esophagus, the interobserver agreement was fair with suboptimal sensitivity and specificity. Significant improvements in NBI interpretation are needed prior to the routine use of NBI surface patterns for the assessment of Barrett's esophagus. <i>Results of this study were presented in part at DDW 2008</i>