tbuckley/cabot-search huggingface dataset:
Essential Roles of an Intercalated Disc Protein, mXinβ, in Postnatal Heart Growth and Survival
Authors: Qinchuan Wang, Jenny Li-Chun Lin, Benjamin E. Reinking, Han-Zhong Feng, Fu-Chi Chan, Cheng-I. Lin, Jian-Ping Jin, Elisabeth A. Gustafson-Wagner, Thomas D. Scholz, Baoli Yang, Jim Jung-Ching Lin
Journal: Circulation Research (2010)

The Xin repeat-containing proteins mXinalpha and mXinbeta localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinalpha directly interacts with beta-catenin, p120-catenin, and actin filaments. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinbeta in mXinalpha-deficient hearts suggests a partial compensation.The essential roles of mXinbeta in cardiac development and intercalated disc maturation were investigated.Ablation of mXinbeta led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinalpha. Postnatal upregulation of mXinbeta in wild-type hearts, as well as altered apoptosis and proliferation in mXinbeta-null hearts, suggests that mXinbeta is required for postnatal heart remodeling. The mXinbeta-null hearts exhibited a misorganized myocardium as detected by histological and electron microscopic studies and an impaired diastolic function, as suggested by echocardiography and a delay in switching off the slow skeletal troponin I. Loss of mXinbeta resulted in the failure of forming mature intercalated discs and the mislocalization of mXinalpha and N-cadherin. The mXinbeta-null hearts showed upregulation of active Stat3 (signal transducer and activator of transcription 3) and downregulation of the activities of Rac1, insulin-like growth factor 1 receptor, protein kinase B, and extracellular signal-regulated kinases 1 and 2.These findings identify not only an essential role of mXinbeta in the intercalated disc maturation but also mechanisms of mXinbeta modulating N-cadherin-mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival.
Origin and Domestication of the Fungal Wheat Pathogen Mycosphaerella graminicola via Sympatric Speciation
Authors: E. H. Stukenbrock, S. Banke, M. Javan-Nikkhah, B. A. McDonald
Journal: Molecular Biology and Evolution (2006)

The Fertile Crescent represents the center of origin and earliest known place of domestication for many cereal crops. During the transition from wild grasses to domesticated cereals, many host-specialized pathogen species are thought to have emerged. A sister population of the wheat-adapted pathogen Mycosphaerella graminicola was identified on wild grasses collected in northwest Iran. Isolates of this wild grass pathogen from 5 locations in Iran were compared with 123 M. graminicola isolates from the Middle East, Europe, and North America. DNA sequencing revealed a close phylogenetic relationship between the pathogen populations. To reconstruct the evolutionary history of M. graminicola, we sequenced 6 nuclear loci encompassing 464 polymorphic sites. Coalescence analyses indicated a relatively recent origin of M. graminicola, coinciding with the known domestication of wheat in the Fertile Crescent around 8,000–9,000 BC. The sympatric divergence of populations was accompanied by strong genetic differentiation. At the present time, no genetic exchange occurs between pathogen populations on wheat and wild grasses although we found evidence that gene flow may have occurred since genetic differentiation of the populations.
Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry
Authors: Raúl J. Andrade, Isabel M. Lucena, Neil Kaplowitz, Beatriz García-Muņoz, Yolanda Borraz, Ketevan Pachkoria, Miren García-Cortés, Carmen M. Fernández, Gloria Pelaez, Luis Rodrigo, José A. Durán, Joan Costa, Ramón Planas, Anabel Barriocanal, Carlos Guarner, Manuel Romero-Gomez, Teresa Muņoz-Yagüe, Javier Salmerón, Ramón Hidalgo
Journal: Hepatology (2006)

A chronic adverse reaction may occur in some instances of drug-induced liver injury (DILI), even despite drug cessation. In our study, we obtained records from a Spanish registry and evaluated cases of DILI with biochemical evidence of long-term damage. Chronic outcome was defined as a persistent biochemical abnormality of hepatocellular pattern of damage more than 3 months after drug withdrawal or more than 6 months after cholestatic/mixed damage. Data on 28 patients with a chronic clinical evolution (mean follow-up 20 months) between November 1995 and October 2005 were retrieved (18 female; overall mean age 55 yr) and accounted for 5.7% of total idiosyncratic DILI cases (n = 493) submitted to the registry. The main drug classes were cardiovascular and central nervous system (28.5% and 25%, respectively), which, in contrast, represented only 9.8% and 13%, respectively, of all DILI cases. The most frequent causative drugs were amoxicillin–clavulanate (4 of 69 cases), bentazepam (3 of 7 cases), atorvastatin (2 of 7 cases), and captopril (2 of 5 cases). Patients with cholestatic/mixed injury (18 of 194 cases [9%]) were more prone to chronicity than patients with hepatocellular injury (10 of 240 cases; P &lt; .031). In the case of chronic hepatocellular injury, 3 patients progressed to cirrhosis and 2 to chronic hepatitis. In the cholestatic/mixed group, liver biopsy indicated cirrhosis in 1 patient and ductal lesions in 3 patients. In conclusion , cholestatic/mixed type of damage is more prone to become chronic while, in the hepatocellular pattern, the severity is greater. Cardiovascular and central nervous system drugs are the main groups leading to chronic liver damage.
Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation
Authors: E Crisafulli, S Costi, F Luppi, G Cirelli, C Cilione, O Coletti, L M Fabbri, E M Clini
Journal: Thorax (2008)

Chronic obstructive pulmonary disease (COPD) is often associated with other chronic diseases. These patients are often admitted to hospital based rehabilitation programmes.To determine the prevalence of chronic comorbidities in patients with COPD undergoing pulmonary rehabilitation and to assess their influence on outcome.Observational retrospective cohort study.A single rehabilitation centre.2962 inpatients and outpatients with COPD (73% male, aged 71 (SD 8) years, forced expiratory volume in 1 s (FEV(1)) 49.3 (SD 14.8)% of predicted), graded 0, 1 or >/=2 according to the comorbidity categories and included in a pulmonary rehabilitation programme.The authors analysed the number of self-reported comorbidities and recorded the Charlson Index. They then calculated the percentage of patients with a predefined positive response to pulmonary rehabilitation (minimum clinically important difference (MCID)), as measured by improvement in exercise tolerance (6 min walking distance test (6MWD)), dyspnoea (Medical Research Council scale) and/or health related quality of life (St George's Respiratory Questionnaire (SGRQ)).51% of the patients reported at least one chronic comorbidity added to COPD. Metabolic (systemic hypertension, diabetes and/or dyslipidaemia) and heart diseases (chronic heart failure and/or coronary heart disease) were the most frequently reported comorbid combinations (61% and 24%, respectively) among the overall diseases associated with COPD. The prevalence of patients with MCID was different across the comorbidity categories and outcomes. In a multiple categorical logistic regression model, the Charlson Index (OR 0.72 (96% CI 0.54 to 0.98) and 0.51 (96% CI 0.38 to 0.68) vs 6MWD and SGRQ, respectively), metabolic diseases (OR 0.57 (96% CI 0.49 to 0.67) vs 6MWD) and heart diseases (OR 0.67 (96% CI 0.55 to 0.83) vs SGRQ) reduced the probability to improve outcomes of rehabilitation.Most patients with COPD undergoing pulmonary rehabilitation have one or more comorbidities. Despite the fact that the presence of comorbidities does not preclude access to rehabilitation, the improvement in exercise tolerance and quality of life after rehabilitation may be reduced depending on the comorbidity.
Human keratinocytes contain mRNA indistinguishable from monocyte interleukin 1 alpha and beta mRNA. Keratinocyte epidermal cell-derived thymocyte-activating factor is identical to interleukin 1.
Authors: T S Kupper, D W Ballard, A O Chua, J S McGuire, P M Flood, M C Horowitz, R Langdon, L Lightfoot, U Gubler
Journal: The Journal of Experimental Medicine (1986)

Keratinocytes produce an IL-1 like factor termed epidermal cell-derived thymocyte-activating factor (ETAF). In this study, we show that ETAF and IL-1 are identical by the following criteria: Both normal and malignant human keratinocytes contain mRNAs identical to monocytic IL-1 alpha and IL-1 beta mRNA, as determined by an S1 nuclease protection assay; and IL-1 activity in medium conditioned by these cells can be neutralized by antibodies specific for human IL-1. The IL-1 alpha and IL-1 beta mRNAs can be identified in cultured human keratinocytes in the absence of identifiable stimulation; this basal level of mRNA can be further induced to accumulate with certain defined stimuli. Cultured normal human keratinocytes (HFKs) contain 2-4 times more IL-1 alpha than IL-1 beta mRNA; in contrast, human peripheral blood monocytes contain 10-20 times more IL-1 beta than IL-1 alpha mRNA. The IL-1 activity released by these HFK can be neutralized by an antibody that neutralizes both alpha and beta IL-1, but not by an antibody that neutralizes only IL-1 beta. While human monocytes produce a large excess of IL-1 beta after appropriate stimulation, these data suggest that IL-1 alpha is a major (and may be the predominant) form of IL-1 produced by human keratinocytes.
Reply to M.C. Chamberlain
Authors: Mark R. Gilbert, James Dignam, Stephanie Pugh, Terri S. Armstrong, Jeffrey S. Wefel, Ken Aldape, Roger Stupp, Monika Hegi, Minhee Won, Walter J. Curran, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2014)

patients for whom the benefit of prolonged maintenance TMZ is unclear.Nonetheless, the use of 12 cycles of post-RT TMZ in patients with newly diagnosed GBM is a common practice, notwithstanding the lack of evidence to support prolonged maintenance TMZ.These comments are not meant to diminish the significant efforts by the RTOG study group but rather to ask whether this study is practice changing?No, although we should acknowledge the substudy of net clinical benefit contained within RTOG 0525 that highlights a hitherto neglected dimension of treatment effect and that will likely become a new standard assessment instrument in randomized trials of gliomas. 7Are the results sufficiently different than currently used therapies?No, RT plus TMZ remains the standard of care for protocol eligible young patients with newly diagnosed GBM.Might there be an opportunity to further refine the approach to GBM? Absolutely, but the challenge has been how and with what novel therapy.
Secreted phospholipases A2, a new class of HIV inhibitors that block virus entry into host cells
Authors: David Fenard, Gérard Lambeau, Emmanuel Valentin, Jean-Claude Lefebvre, Michel Lazdunski, Alain Doglio
Journal: Journal of Clinical Investigation (1999)

Mammalian and venom secreted phospholipases A2 (sPLA2s) have been associated with a variety of biological effects. Here we show that several sPLA2s protect human primary blood leukocytes from the replication of various macrophage and T cell–tropic HIV-1 strains. Inhibition by sPLA2s results neither from a virucidal effect nor from a cytotoxic effect on host cells, but it involves a more specific mechanism. sPLA2s have no effect on virus binding to cells nor on syncytia formation, but they prevent the intracellular release of the viral capsid protein, suggesting that sPLA2s block viral entry into cells before virion uncoating and independently of the coreceptor usage. Various inhibitors and catalytic products of sPLA2 have no effect on HIV-1 infection, suggesting that sPLA2 catalytic activity is not involved in the antiviral effect. Instead, the antiviral activity appears to involve a specific interaction of sPLA2s to host cells. Indeed, of 11 sPLA2s from venom and mammalian tissues assayed, 4 venom sPLA2s were found to be very potent HIV-1 inhibitors (ID50 < 1 nM) and also to bind specifically to host cells with high affinities (K0.5 < 1 nM). Although mammalian pancreatic group IB and inflammatory-type group IIA sPLA2s were inactive against HIV-1 replication, our results could be of physiological interest, as novel sPLA2s are being characterized in humans.
Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining
Authors: N. Gul, M. Bogels, S. Grewal, A. J. van der Meer, L. B. Rojas, D. M. Fluitsma, M. P. van den Tol, K. A. Hoeben, J. van Marle, H. E. de Vries, R. H. J. Beelen, M. van Egmond
Journal: Gut (2011)

<h3>Objective</h3> Resection of primary colorectal cancer is associated with enhanced risk of development of liver metastases. It was previously demonstrated that surgery initiated an early inflammatory response resulting in elevated tumour cell adhesion in the liver. Because reactive oxygen species (ROS) are shown to be produced and released during surgery, the effects of ROS on the liver vascular lining and tumour cell adhesion were investigated. <h3>Methods</h3> Human endothelial cell monolayers (human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells of the lung (HMEC-1s)) were exposed to ROS production, after which electrical impedance, cellular integrity and tumour cell adhesion were investigated. Furthermore, surgery-induced tumour cell adhesion as well as the role of ROS and liver macrophages (Kupffer cells) in this process were studied in vivo. <h3>Results</h3> Production of ROS decreased cellular impedance of endothelial monolayers dramatically. Moreover, formation of intercellular gaps in endothelial monolayers was observed, exposing subendothelial extracellular matrix (ECM) on which colon carcinoma cells adhered via integrin molecules. Endothelial damage was, however, prevented in the presence of ROS-scavenging enzymes. Additionally, surgery induced downregulation of both rat and human liver tight junction molecules. Treatment of rats with the ROS scavenger edaravone prevented surgery-induced tumour cell adhesion and downregulation of tight junction proteins in the liver. Interestingly, depletion of Kupffer cells prior to surgery significantly reduced the numbers of adhered tumour cells and prevented disruption of expression of tight junction proteins. <h3>Conclusions</h3> In this study it is shown that surgery-induced ROS production by macrophages damages the vascular lining by downregulating tight junction proteins. This leads to exposure of ECM, to which circulating tumour cells bind. In light of this, perioperative therapeutic intervention, preventing surgery-induced inflammatory reactions, may reduce the risk of developing liver metastases, thereby improving the clinical outcome of patients with colorectal cancer.
Some Recent Results from the Study of Labour by Means of Frozen Sections and Casts
Authors: A. H. F. Barbour
Journal: BMJ (1890)

left apex are coarser, and moist rales, diminishing in distinctness, are heard down to the very base of the lung.December 1st, 1889 (eighth day of illness).The rdla at the back of the lung are less distinct to-day.Bowels moved; motions loose and pale, but not offensive.December 3rd, 1889 (tenth day of illness).At the left apex the dulness is more pronounced, and the movements there are distinctly diminished.For the last two nights the patient.who has been inclined to wander slightly all along, has been markedly de- lirious, talking constantly, and he has had very little sleep.The tongue is dry, coated, brownish, and tremulous.December 4th, 1889 (eleventh day of illness).Bowels moved last night, the motion being solid, and nearly of the natural colour.December 8th, 1889 (fifteenth day of illness).Patient's getieral condition is somewhat worse.He rambles constantly night and day, and sleeps very little.The hands tremble, and he occasinally fumbles with the bedclothes.The albumen, although dimin- ished, is still present in the urine.December 11th, 1889 (eighteenth day of illness).The rdles have almost entirely disappeared from the front of the left lung, but they are abundant at the base posteriorly, and very similar in cha- racter to those which were at the apex.At the right base there is now some dulness on percussion, and an abundant, fine, subcrepi- tant rdle is heard.December 13th, 1889 (twentieth day of illness).On the right side a suberepitant rdle has now appeared at the level of the nipple.On the left side a sonorous rdle is heard in the supra- clavicular, and a few faint mucous and sibilant rale8 in the infra- clavicular, region.December 17th, 1889 (twenty-fourth day of illness).With the exception of a slight sibilus at the right base, the rdles have en- tirely disappeared from the chest.Slight delirium still persists, although the temperature has for some days been subnormal.Patient is very drowsy, and sleeps constantly, being, however, easily aroused to take nourishment.The album.n in the urine is no longer present.December 21st, 1889 (twenty-eighth day).All physical signs of disease have disappeared from the chest, and all special treatment by drugs has been stopped.He remains very prostrate, and there is still occasionally slight delirium.December 27th, 1889 (thirty-fourth day).Though still very weak, he is picking up flesh and strength considerably, and is now perfectly conscious and observant of what is going on around him.January 7th, 1890 (forty-fifth day).He has been steadily and rapidly improving and gaining strength, and has today been allowed, for the first time, to rise for an hour.On January 23rd, 1890, I requested my colleague, Professor Gairdner, to examine this patient's chest.which he kindly agreed to do, and in a letter to me he says: "I I have examined G. H., and find that there is nothing that can be very definitely stated as abnormal in the physical signs in his chest.
Non-pharmacological factors for the emergence of drug resistance in patients of pulmonary tuberculosis: An Indian overview
Authors: J.K. Samaria, Satyadeo Chaubey
Journal: European Respiratory Journal (2012)

Aim: to evaluate the impact of or non pharmacological factors on the emergence of drug resistant tuberculosis in eastern Uttar Pradesh.  Material and methods:150 diagnosed cases of drug resistance pulmonary tuberculosis via culture and sensitivity were evaluated of their socio-economic background with special reference to their literacy, annual income, housing, reason of discontinuation of treatment, migration status etc. Data was collected and analysed statistically.  Observation: prevalence of drug resistance was more in large families(76%), with lower housing area per person(62%), with at least one migration history(75.33%), having at least one member previously sputum positive(65.33%) and lower annual income(66%). Also was more in illiterates(58%). The reason of discontinuation were adverse effect(18%), resolution of basic symptoms/ early asymptomatics(40%), advised by unqualified doctors(12%), social stigma(8%), and non affordable private treatment(15.33%).  Conclusion: role of socioeconomic factors can9t be denied in emergence of drug resistance. Patient centered approach especially proper counselling may help in this regard.
Intensive educational course in allergy and immunology
Authors: A. Elizalde, E. E. Perez, P. Sriaroon, D. Nguyen, R. F. Lockey, M. J. Dorsey
Journal: Allergy (2012)

Abstract A one‐day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows‐in‐training.
Evidence of the Limitations of Water as a Freely Diffusible Tracer in Brain of the Rhesus Monkey
Authors: JOHN O. EICHLING, MARCUS E. RAICHLE, ROBERT L. GRUBB, MICHEL M. TER-POGOSSIAN
Journal: Circulation Research (1974)

The extraction of 15 O-labeled water by the brain during a single capillary transit was studied in vivo in 20 adult rhesus monkeys by external detection of the time course of the tracer subsequent to the internal carotid injection of 0.2 ml of whole blood labeled with H 2 15 O. The data showed that labeled water does not freely equilibrate with the exchangeable water in the brain when the mean cerebral blood flow exceeds 30 ml/100 g min -1 . At the normal cerebral blood flow in the rhesus monkey (∼50 ml/100 g min -1 ), only 90% of the H 2 15 O is extracted during a single capillary transit. In addition, cerebral blood flow was determined with H 2 15 O and 133 Xe in these monkeys using residue detection and employing the central volume principle. The data supported the hypothesis that a diffusible tracer, H 2 15 O, need not be in complete equilibrium between the phases of a system for the application of the central volume principle to be valid. Finally, the brain capillary permeability-surface area product was computed from these data; it was approximately 0.023 cm 3 /sec g -1 .
Prognosis of Depression in Elderly Community and Primary Care Populations: A Systematic Review and Meta-Analysis
Authors: M G Cole, F Bellavance, A Mansour
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to determine the prognosis of depression in elderly community and primary care populations.MEDLINE and PsycINFO were searched for potentially relevant articles published from January 1981 to November 1996 and from January 1984 to November 1996, respectively. The bibliographies of relevant articles were searched for additional references. Twelve studies met the following five inclusion criteria: original research, published in English or French, study population of community residents or primary care patients, subjects' mean age 60 years and over, and reported affective state as an outcome. The validity of the studies was assessed according to the criteria for prognostic studies described by the Evidence-Based Medicine Working Group. Information about the population, proportion of depressed subjects detected and treated by primary care physicians, length of follow-up, outcomes, and prognostic factors was systematically abstracted from each report.All of the studies had some methodologic limitations. A meta-analysis of outcomes at 24 months estimated that 33% of subjects were well, 33% were depressed, and 21% had died. There was statistically significant heterogeneity in the outcomes across studies. The length of follow-up and lower age limit for enrollment explained part of the heterogeneity for the percent well but not for the other outcomes. Physical illness, disability, cognitive impairment, and more severe depression were associated with worse outcomes but inconsistently so.Depression in elderly community and primary care populations has a poor prognosis, is perhaps chronic or relapsing or both, and is probably undertreated. Despite the methodologic limitations of the studies and this meta-analysis, these findings seem to support efforts to develop detection and treatment programs for depression in these populations.