tbuckley/cabot-search huggingface dataset:
Modulation of Cytokine-Induced Cardiac Myocyte Apoptosis by Nitric Oxide, Bak, and Bcl-x
Authors: Douglas J. Ing, Jie Zang, Victor J. Dzau, Keith A. Webster, Nanette H. Bishopric
Journal: Circulation Research (1999)

Abstract —Cytokine-induced NO production depresses myocardial contractility and has been shown to be cytotoxic to cardiac myocytes. However, the mechanisms of cytokine-induced cardiac myocyte cell death are unclear. To analyze these mechanisms in detail, we treated neonatal cardiac myocytes in serum-free culture with a combination of the macrophage-derived cytokines interleukin-1β, tumor necrosis factor-α, and interferon-γ. These cytokines caused a time-dependent induction of cardiac myocyte apoptosis, but not necrosis, beginning 72 hours after treatment, as determined by nuclear morphology, DNA internucleosomal cleavage, and cleavage of poly(ADP-ribose) polymerase, reflecting caspase activation. Apoptosis was preceded by a &gt;50-fold induction of inducible NO synthase mRNA and the release of large amounts (5 to 8 nmol/μg protein) of NO metabolites (NOx) into the medium. Cell death was completely blocked by an NO synthase inhibitor and attenuated by antioxidants ( N -acetylcysteine and DTT) and the caspase inhibitor ZVAD-fmk. Cytokines also mediated an NO-dependent, sustained increase in myocyte expression of the Bcl-2 homologs Bak and Bcl-x(L). The NO donor S -nitrosoglutathione also induced apoptosis and cell levels of Bak, but not of Bcl-x(L). All effects of cytokines, including poly(ADP-ribose) polymerase cleavage, could be attributed to interleukin-1β; interferon-γ and tumor necrosis factor-α had no independent effects on apoptosis or on NOx production. We conclude that cytokine toxicity to neonatal cardiac myocytes results from the induction of NO and subsequent activation of apoptosis, at least in part through the generation of oxygen free radicals. The rate and extent of this apoptosis is modulated by alterations in the cellular balance of Bak and Bcl-x(L), which respond differentially to cytokine-induced and exogenous NO and by the availability of oxidant species.
Body mass index, chronological age and hormonal status are better predictors of biological skin age than arm skin autofluorescence in healthy women who have never smoked
Authors: A.C. Randag, R. Graaff, M.M. Dreise, A. Vierkötter, P.M.N. Werker, M.W. Stenekes
Journal: British Journal of Dermatology (2015)

As life expectancy is increasing and healthy ageing becomes more and more important, skin ageing is a growing topic of interest from both a medical and a commercial point of view. The urgency to unravel the causes of skin ageing is rising. However, there is a lack of objective, simple, noninvasive methods to assess biological skin age – a term introduced to describe how old someone looks, covering both the appearance and function of the skin. A rapid, noninvasive assessment of biological skin age would greatly facilitate the execution of the studies required to find the causes of skin ageing. To find an objective, easy‐to‐apply method to assess biological skin age. Skin age score (SAS) was compared with skin autofluorescence, a measure of advanced glycation end products in the skin, and several subject characteristics in 32 healthy, white women with little sun‐exposed skin and no history of smoking. A moderate, positive correlation (R2 = 0·32, P = 0·001) between SAS and skin autofluorescence‐based biological skin age was found. However, the variation in biological skin age according to SAS could be explained better by body mass index, chronological age and hormonal status (R2 = 0·86, P < 0·001). In the current setting skin autofluorescence did not contribute better to the prediction of biological skin age than chronological age. Biological skin age was best predicted by body mass index, chronological age and hormonal status, and this approach provides a considerable simplification of the application of biological skin age.
Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study
Authors: Virginia Devonshire, Eva Havrdova, Ernst Wilhelm Radue, Paul O'Connor, Lixin Zhang-Auberson, Catherine Agoropoulou, Dieter Adrian Häring, Gordon Francis, Ludwig Kappos
Journal: The Lancet Neurology (2012)
AN UNUSUAL CASE OF APPENDICITIS
Authors: E. W. M. H. Phillips
Journal: BMJ (1914)

Jackson's pericolic mnembrane, on the ether hand, may give rise to svmptoms simulating chr(onic appendicitis.This occasional membrane is a congenital abnormality, and takes oriain from the primitive riglht lateral process of the great omentum.Wllen only a limited band persists as a relic of the membrane, constriction of the ascending colon may result, tlhouglh often the symptoms resembling chronic appendicitis are due to an associated abnormal mobility of the proximal colon.
A defined xeno-free and feeder-free culture system for the derivation, expansion and direct differentiation of transgene-free patient-specific induced pluripotent stem cells
Authors: Hong Fang Lu, Chou Chai, Tze Chiun Lim, Meng Fatt Leong, Jia Kai Lim, Shujun Gao, Kah Leong Lim, Andrew C.A. Wan
Journal: Biomaterials (2014)
Tumor-Specific Methylation in Saliva: A Promising Biomarker for Early Detection of Head and Neck Cancer Recurrence
Authors: Christian Adrien Righini, Florence de Fraipont, Jean-François Timsit, Claire Faure, Elisabeth Brambilla, Emile Reyt, Marie-Christine Favrot
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Our goal was to define tumor and saliva gene methylation profile of head and neck squamous cell carcinoma and to evaluate its prognostic significance and its biomarker potential for early detection of relapse. Experimental Design: We prospectively analyzed 11 genes by methylation-specific PCR on primary tumors, histologically normal adjacent mucosa, and saliva from 90 French patients at diagnosis and during follow-up as well as on 30 saliva specimens from control-matched patients with nonmalignant head and neck pathology. Five additional genes were analyzed on 50 tumors of the series. Results: Methylation of TIMP3, ECAD, p16, MGMT, DAPK, and RASSF1 was the most frequently observed in tumors and paired saliva samples were analyzed at diagnosis, with an excellent agreement between both samples. At least one of these six genes was methylated in &amp;gt;75% of the samples without additional positive samples when other genes were analyzed. Methylation profile was similar in newly diagnosed and second primary cancers. Aberrant methylation was not associated with a worse prognosis. Ninety percent of normal adjacent mucosa and all control saliva samples were negative. Twenty-two patients were followed after treatment; abnormal methylation was detectable in the saliva of five patients few months before clinical and 2-deoxy-2[18F]fluoro-d-glucose-positron emission tomography signs of relapse, allowing curable surgery. Saliva samples were negative for the 17 other patients: 16 were in remission and only 1 relapsed. Conclusions: Gene methylation in saliva is a promising biomarker for the follow-up and early detection of still curable relapses of head and neck squamous cell carcinoma patients.
The kd/kd Mouse Is a Model of Collapsing Glomerulopathy
Authors: Laura Barisoni, Michael P. Madaio, Maria Eraso, David L. Gasser, Peter J. Nelson
Journal: Journal of the American Society of Nephrology (2005)

Collapsing glomerulopathy (CG) is associated with disorders that markedly perturb the phenotype of podocytes. The kd/kd mouse has been studied for immune and genetic causes of microcystic tubulointerstitial nephritis with little attention to its glomerular lesion. Because histologic examination revealed classic morphologic features of CG, the question arises whether podocytes in kd/kd mice exhibit additional phenotypic criteria for CG. Utilizing Tg26 mice as a positive control, immunohistochemical profiling of the podocyte phenotype was conducted simultaneously on both models. Similar to Tg26 kidneys, podocytes in kd/kd kidneys showed de novo cyclin D1, Ki-67, and desmin expression with loss of synaptopodin and WT-1 expression. Electron micrographs showed collapsed capillaries, extensive foot process effacement, and dysmorphic mitochondria in podocytes. These results indicate that the kd/kd mouse is a model of CG and raise the possibility that human equivalents of the kd susceptibility gene may exist in patients with CG.
Autosomal recessive retinitis pigmentosa E150K opsin mice exhibit photoreceptor disorganization
Authors: Ning Zhang, Alexander V. Kolesnikov, Beata Jastrzebska, Debarshi Mustafi, Osamu Sawada, Tadao Maeda, Christel Genoud, Andreas Engel, Vladimir J. Kefalov, Krzysztof Palczewski
Journal: Journal of Clinical Investigation (2012)

The pathophysiology of the E150K mutation in the rod opsin gene associated with autosomal recessive retinitis pigmentosa (arRP) has yet to be determined. We generated knock-in mice carrying a single nucleotide change in exon 2 of the rod opsin gene resulting in the E150K mutation. This novel mouse model displayed severe retinal degeneration affecting rhodopsin's stabilization of rod outer segments (ROS). Homozygous E150K (KK) mice exhibited early-onset retinal degeneration, with disorganized ROS structures, autofluorescent deposits in the subretinal space, and aberrant photoreceptor phagocytosis. Heterozygous (EK) mice displayed a delayed-onset milder retinal degeneration. Further, mutant receptors were mislocalized to the inner segments and perinuclear region. Though KK mouse rods displayed markedly decreased phototransduction, biochemical studies of the mutant rhodopsin revealed only minimally affected chromophore binding and G protein activation. Ablation of the chromophore by crossing KK mice with mice lacking the critical visual cycle protein LRAT slowed retinal degeneration, whereas blocking phototransduction by crossing KK mice with GNAT1-deficient mice slightly accelerated this process. This study highlights the importance of proper higher-order organization of rhodopsin in the native tissue and provides information about the signaling properties of this mutant rhodopsin. Additionally, these results suggest that patients heterozygous for the E150K mutation should be periodically reevaluated for delayed-onset retinal degeneration.
Detecting lung infections in breathprints: empty promise or next generation diagnosis of infections
Authors: Hossam Haick, Sylvia Cohen-Kaminsky
Journal: European Respiratory Journal (2014)

A wide spectrum of diagnostic technologies and tools are used to identify the agents causing infectious diseases [1–3]. It is increasingly recognised that an improved diagnostic tool should evolve into a personalised approach, fully taking into account 1) identification of individuals at risk of developing diseases; 2) interpretation of diagnostic tests; 3) providing prognostic information; and 4) predicting and following the efficacy of therapies [4]. A new noninvasive and potentially inexpensive frontier in the diagnosis of infectious diseases relies on the detection of volatile organic compounds (VOCs), which are organic compounds that have a high vapour pressure in ordinary room-temperature conditions, from exhaled breath [5–8]. A discussion of evidence on the link between breathprints of bacterial lung infections and the immune response <http://ow.ly/DgOOb>
A unified mixed-model method for association mapping that accounts for multiple levels of relatedness
Authors: Jianming Yu, Gael Pressoir, William H Briggs, Irie Vroh Bi, Masanori Yamasaki, John F Doebley, Michael D McMullen, Brandon S Gaut, Dahlia M Nielsen, James B Holland, Stephen Kresovich, Edward S Buckler
Journal: Nature Genetics (2005)
Fluorescence Versus White-Light Bronchoscopy for Detection of Preneoplastic Lesions: a Randomized Study
Authors: F. R. Hirsch, S. A. Prindiville, Y. E. Miller, W. A. Franklin, E. C. Dempsey, J. R. Murphy, P. A. Bunn, T. C. Kennedy
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: There are no currently approved methods for the screening and early detection of lung cancer. We compared the ability of conventional white-light bronchoscopy (WLB) and laser-induced fluorescence endoscopy (LIFE) to detect preneoplastic lung lesions in a randomized trial in which both the order of the procedures and the bronchoscopists were randomly assigned. Methods: The study included high-risk subjects enrolled because of a cigarette smoking history of at least 30 pack-years, an air-flow obstruction, and either an abnormal sputum cytology (n = 48) or a previous or suspected lung cancer (n = 7). LIFE and WLB were performed on all patients. Biopsy specimens were assessed for histologic abnormalities, including the presence of angiogenic squamous dysplasia. All statistical tests were two-sided. Results: A total of 391 biopsy specimens were taken from the 55 patients. Thirty-two patients (58%; 95% confidence interval [CI] = 44% to 71%) had at least one biopsy with moderate or severe dysplasia, and 19 (59%; 95% CI = 41% to 76%) of these patients could be diagnosed based solely on the results of LIFE. LIFE was statistically significantly more sensitive than WLB for detecting moderate dysplasia or worse (68.8% versus 21.9%, respectively) (difference = 46.9%; 95% CI = 25% to 68%; P<.001). The relative sensitivities (WLB = 1.0) were 3.1 (95% CI = 1.6 to 6.3) for LIFE and 3.7 (95% CI = 1.9 to 7.3) for LIFE and WLB combined. LIFE was less specific than WLB (69.6% versus 78.3%, respectively; P = .45), but the difference was not statistically significant. The relative specificities (WLB = 1.0) were 0.9 for LIFE (95% CI = 0.6 to 1.3) and 0.6 (95% CI = 0.4 to 1.0) for LIFE and WLB combined. The results were similar regardless of the order of the procedures or the order of the bronchoscopists. Also, LIFE was better at identifying angiogenic squamous dysplasia lesions than WLB (detection ratio [DR], which indicates the relative likelihood of getting a positive result in a sample with dysplasia compared with one without, for LIFE = 1.39 [95% CI = 1.17 to 1.65] versus DR for WLB = 0.67 [95% CI = 0.38 to 1.21]). Conclusion: LIFE was more sensitive than WLB in detecting preneoplastic bronchial changes in high-risk subjects. The prognostic implication of this finding is not yet clear.
Two dimensional protein patterns of bronchoalveolar lavage fluid from non-smokers, smokers, and subjects exposed to asbestos.
Authors: M. Lindahl, T. Ekstrom, J. Sorensen, C. Tagesson
Journal: Thorax (1996)

BACKGROUND: Bronchoalveolar lavage (BAL) fluid contains a large number of proteins which comprise a potential resource for studying respiratory effects due to occupational and environmental exposures. A study was undertaken to compare protein patterns of BAL fluid from non-smokers, smokers, and subjects exposed to asbestos. METHODS: BAL fluid samples were analysed with two dimensional gel electrophoresis (2-DE). The separated proteins were detected, quantified, and pattern-matched between different individuals with a computerised imaging system designed for evaluations of 2-DE patterns. RESULTS: About 200 different protein spots were detected in each sample of BAL fluid. As is the case with blood plasma, the BAL fluid samples contained large amounts of albumin, transferrin, and immunoglobulins. Higher levels of basic proteins were found in smokers than in non-smokers, while subjects exposed to asbestos had increased amounts of several high molecular weight proteins as well as basic proteins. Lower levels of albumin and higher levels of immunoglobulins were found in smokers than in non-smokers, while higher levels of transferrin were found in asbestos exposed subjects than in unexposed subjects. Moreover, in the group exposed to asbestos differences were found between patients with pleuritis and patients with pleural plaque, and one protein spot was found only in two patients with progressive pleural disease. CONCLUSION: These results suggest that both smokers and asbestos exposed subjects have significant changes in their airway protein expression compared with non-smokers and unexposed subjects. It is inferred that analysis of protein patterns in the BAL fluid with 2-DE may be used to detect and characterise, at a molecular level, respiratory effects due to occupational and environmental exposures.
Sympathetic Nerve Activity Is Inappropriately Increased in Chronic Renal Disease
Authors: Inge H.H.T. Klein, Gerry Ligtenberg, Jutta Neumann, P. Liam Oey, Hein A. Koomans, Peter J. Blankestijn
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The hypothesis that in hypertensive patients with renal parenchymal disease sympathetic activity is "inappropriately" elevated and that this overactivity is a feature of renal disease and not of a reduced number of nephrons per se is addressed. Fifty seven patients with renal disease (various causes, no diabetes, all on antihypertensive medication) were studied, age range 18 to 62, creatinine clearance 10 to 114 ml/min per 1.73 m2. Antihypertensives were stopped, but diuretics were allowed, to prevent overhydration. Matched control subjects were also studied. The effect of changes in fluid status was examined in seven patients while on and after stopping diuretics and in eight control subjects while on low- and high-sodium diet. Seven kidney donors were studied before and after unilateral nephrectomy. Sympathetic activity was quantified as muscle sympathetic nerve activity (MSNA) in the peroneal nerve. Mean arterial pressure, MSNA, and plasma renin activity were higher in patients than in control subjects, respectively (115 ± 12 and 88 ± 11 mmHg, 31 ± 15 and 18 ± 10 bursts/min, and 500 [20 to 6940] and 220 [40 to 980] fmol/L per s; P < 0.01 for all items). Extracellular fluid volume (bromide distribution) did not differ. Seven patients were studied again after stopping diuretics. MSNA decreased from 34 ± 18 to 19 ± 18 bursts/min (P < 0.01). Eight healthy subjects were studied during low- and high-sodium diet. MSNA was 26 ± 12 and 13 ± 7 bursts/min (P < 0.01). The curves relating extracellular fluid volume to MSNA were parallel in the two groups but shifted to a higher level of MSNA in the patients. In the kidney donors, creatinine clearance reduced by 25%, but MSNA was identical before and after donation. It is concluded that in hypertensive patients with renal parenchymal disease, sympathetic activity is inappropriately high for the volume status and that reduction of nephron number in itself does not influence sympathetic activity.
Inverse Prognostic Impact of Angiogenic Marker Expression in Tumor Cells versus Stromal Cells in Non–Small Cell Lung Cancer
Authors: Tom Donnem, Samer Al-Saad, Khalid Al-Shibli, Marit P. Delghandi, Magnus Persson, Marit N. Nilsen, Lill-Tove Busund, Roy M. Bremnes
Journal: Clinical Cancer Research (2007)

The vascular endothelial growth factors (VEGF-A, -C, -D) and the VEGF receptors (VEGFR-1, -2, and -3) are important molecular markers in angiogenesis and lymphangiogenesis. This study elucidates the prognostic significance of these molecular markers in tumor cells as well as in the tumor stroma of resected non-small cell lung cancer tumors.Tumor tissue samples from 335 resected patients with stage I to IIIA disease were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and surrounding stromal tissue from each resected specimen. Immunohistochemistry was used to evaluate the expression of each molecular marker. Microvessel density was assessed by CD34 immunohistochemical staining.In univariate analyses, high tumor cell expression of VEGF-A (P = 0.0005), VEGFR-1 (P = 0.013), VEGFR-2 (P = 0.006), and VEGFR-3 (P = 0.0003) were negative prognostic indicators for disease-specific survival (DSS). In tumor stroma, however, high expression of VEGF-A (P = 0.017), VEGF-C (P = 0.003), VEGF-D (P = 0.009), VEGFR-1 (P = 0.01), and VEGFR-2 (P = 0.019) correlated with good prognosis. There was no significant correlation between microvessel density and DSS. In multivariate analyses, high expression in tumor cells of VEGFR-3 (P = 0.007) was an independent negative prognostic factor for DSS, whereas in stromal cells, high VEGF-C (P = 0.004) expression had an independent positive survival impact.These are the first tissue microarray data in non-small cell lung cancers showing a positive prognostic impact by highly expressed angiogenic markers in tumor stroma, with VEGF-C as a major independent prognostic indicator.
Management of the Patient With Implantable Cardioverter-Defibrillator Lead Failure
Authors: Gautham Kalahasty, Kenneth A. Ellenbogen
Journal: Circulation (2011)

A 52-year-old man was brought to the emergency department because of multiple implantable cardioverterdefibrillator (ICD) shocks.His existing dual-chamber pacemaker was upgraded from a biventricular ICD 4 years ago.The ECG in the emergency department showed sinus tachycardia with left bundle-branch block at a rate of 135 bpm.In the emergency department, the patient received 5 additional shocks without a change in rhythm.A donut magnet was placed over the ICD.Interrogation revealed evidence of a lead fracture, and tachycardia therapies were disabled.The high-voltage lead was a Medtronic Sprint Fidelis ICD lead.Admission to the hospital was recommended for definitive correction of his problem.
Lowering Effect on Postprandial Glycemic Response of Nopales Added to Mexican Breakfasts
Authors: Montserrat Bacardi-Gascon, Dulce Dueñas-Mena, Arturo Jimenez-Cruz
Journal: Diabetes Care (2007)

The burden of diabesity is increasing rapidly in Mexico (1). Culturally based diets with low glycemic index and glycemic load might be a low-cost approach for a population with a high index of socioeconomic marginality. Mixed meals are the usual manner of food intake, and they are different among regions of Mexico. Consumption of nopales (prickly pear cactus pads) in middle and low socioeconomic populations of central and southern Mexico is generally three times weekly. Nopales can be purchased at any food market in Mexico. The purpose of this study was to estimate the glycemic index of three usual Mexican breakfasts and to measure the effect of adding cactus pads (nopales) on postprandial glucose response in type 2 diabetic subjects.

Thirty six volunteers with type 2 diabetes (47–72 years of age) were recruited. Their mean ± SD fasting blood glucose was 8.0 ± 2 mmol/l. All subjects were treated with glibenclamide, metformin, or both. None of the patients were treated with insulin. Their mean ± SD BMI was 24.86 ± 3.76 kg/m2. All participants gave informed consent, and the study was approved by the Nutrition Institute of Baja California Ethics Committee.

Subjects were randomly assigned to eat one of the three test breakfast meals with and without nopales. Ten subjects were assigned to …