tbuckley/cabot-search huggingface dataset:
Selectin adhesion molecules in Behcet's disease
Authors: S. Haznedaroglu
Journal: Annals of the Rheumatic Diseases (2000)

The pathogenesis of Behçet's disease (BD) is closely related to endothelial cells, leucocyte functions and autoimmunity. The aim of this study was to investigate circulating selectin adhesion molecules, which are known to play a significant part in the immune response especially by regulating interactions of the leucocytes with endothelium, in BD.Plasma E-, L-, and P-selectin concentrations were evaluated in 11 patients with widespread BD (group I), 10 cases with merely mucocutaneous involvement (group II) and 15 age and sex matched healthy control subjects. The patients were newly or previously diagnosed cases not taking any drug for BD.Plasma concentrations of all selectins were significantly higher in group I compared with group II. E-selectin and P-selectin were significantly increased in each subgroup of patients compared with the healthy controls. L-selectin concentrations were higher than the controls only in group I.Increases in the selectins in BD may be a direct consequence of the leucocyte, endothelium and platelet activations observed during the disease process. However, abnormal/increased selectin expression to various triggers should also be considered. More prominent increases in patients with extensive disease suggest that circulating selectin concentrations are related to disease severity.
Prostate cancer genomics: can we distinguish between indolent and fatal disease using genetic markers?
Authors: Fredrik Wiklund
Journal: Genome Medicine (2010)

Prostate cancer is one of the most heritable cancers in men, and recent genome-wide association studies have revealed numerous genetic variants associated with disease. The risk variants identified using case-control designs that compared unaffected individuals with all types of patients with prostate cancer show little or no ability to discriminate between indolent and fatal forms of this disease. This suggests different genetic components are involved in the initiation as compared with the prognosis of prostate cancer. Future studies contrasting patients with more and less aggressive disease, and exploring association with disease progression and prognosis, should be more effective in detecting genetic risk factors for prostate cancer outcome.
Mortality in End-Stage Renal Disease
Authors: EDWARD F. VONESH, JOHN MORAN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Recent registry studies comparing mortality between peritoneal dialysis (PD) and hemodialysis (HD) patients show conflicting results. The purpose of this study is to determine whether previously published results showing higher mortality for patients treated with PD versus HD in the United States continue to hold true over the period 1987-1993. National mortality rates for PD and HD were extracted from the U.S. Renal Data System (USRDS) annual reports for the cohort periods: 1987-1989, 1988-1990, 1989-1991, 1990-1992, and 1991-1993. Using Poisson regression, death rates per 100 patient years were compared between PD and HD for each cohort period controlling for age, gender, race, and cause of end-stage renal disease (diabetes versus nondiabetes). When incident patients and patients with a prior transplant were included in the analysis, starting with the 1989-1991 cohort, we found little or no difference in the relative risk (RR PD:HD) of death between PD and HD (1987-1989: RR = 1.17, P &lt; 0.001; 1988-1990: RR = 1.12, P &lt; 0.001; 1989-1991: RR = 1.06, P = NS; 1990-1992: RR = 1.06, P = NS; 1991-1993: RR = 1.08, P = 0.043). After a test for goodness-of-fit, separate analyses for diabetic patients and nondiabetic patients were done to examine unexplained variation in death rates. For nondiabetic patients, there was less than a 1% difference in the adjusted 1-yr survival between PD and HD from 1989-1993 (1989-1991: RR = 1.05, P = NS; 1990-1992: RR = 1.04, P = NS; 1991-1993: RR = 1.07, P &lt; 0.01). Among diabetic patients, the PD:HD death rate ratio varied significantly according to gender and age. For the average male diabetic patient, there was little or no difference in risk between PD and HD from 1989-1993 (1989-1991: RR = 1.02, P = NS; 1990-1992: RR = 1.05, P = NS; 1991-1993: RR = 1.08, P &lt; 0.01). For diabetic patients under the age of 50, those treated with PD had a significantly lower risk of death than those treated with HD (1989-1993: 0.84 ≤ RR ≤ 0.89, P &lt; 0.005). Over the same period, female diabetic patients treated with PD had a higher risk, on average, than HD (1.18 ≤ RR ≤ 1.19, P &lt; 0.001) as did diabetic patients over the age 50 (1.28 ≤ RR ≤ 1.30, P &lt; 0.001). Unlike previously published results that were restricted to prevalent-only patients, this national study of both prevalent and incident patients found little or no difference in overall mortality between PD and HD. The recent trends in mortality likely reflect the inclusion of incident patients, but they may also reflect changes in case-mix differences and/or improved PD practice. Additional incident-based studies that allow for additional case-mix adjustments are needed to better compare outcomes between HD and PD.
Exhaled breath condensate biomarkers in COPD
Authors: Z. L. Borrill, K. Roy, D. Singh
Journal: European Respiratory Journal (2008)

Biomarkers in chronic obstructive pulmonary disease may be useful in aiding diagnosis, defining specific phenotypes of disease, monitoring exacerbations and evaluating the effects of drugs. Exhaled breath condensate is a noninvasive means of sampling the airways, allowing biomarkers of airway inflammation and oxidative stress to be measured. In the present review, the use of exhaled breath condensate biomarkers in chronic obstructive pulmonary disease is explored and potential applications in diagnosis, disease phenotyping, exacerbation monitoring and clinical trials are considered. Exhaled breath condensate biomarkers are comprehensively reviewed in terms of method validation, reproducibility, disease specificity and sensitivity to detect changes in airway inflammation. The commonly used exhaled breath condensate methodologies in chronic obstructive pulmonary disease patients are shown to have considerable variability, due to technical issues concerning both sample collection and analysis. Despite these issues, there is still data to support the use of exhaled breath condensate biomarkers for monitoring chronic obstructive pulmonary disease exacerbations and the response to pharmacological intervention. Further improvements to sample collection and analysis methods will improve the sensitivity of these biomarkers. The use of cytokine arrays, mass spectrometry and nuclear magnetic resonance profiling of exhaled breath condensate has opened a new avenue for analysis, as hypothesis generation from such profiling may lead to further selection of biomarkers for specific analysis.
Lack of myocardial lipid peroxidation during acute reperfusion injury in perfused guinea pig hearts
Authors: P. L Barrington, E. Lai, P. B McCay
Journal: Cardiovascular Research (1993)

Journal Article Lack of myocardial lipid peroxidation during acute reperfusion injury in perfused guinea pig hearts Get access Peggy L Barrington, Peggy L Barrington Molecular Toxicology Division, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA: E Lai, P B McCay; Department of Pharmacology, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA: P L Barrington. Correspondence to Dr Barrington. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward Lai, Edward Lai Molecular Toxicology Division, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA: E Lai, P B McCay; Department of Pharmacology, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA: P L Barrington. Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul B McCay Paul B McCay Molecular Toxicology Division, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA: E Lai, P B McCay; Department of Pharmacology, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA: P L Barrington. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 7, July 1993, Pages 1339–1345, https://doi.org/10.1093/cvr/27.7.1339 Published: 01 July 1993 Article history Received: 15 October 1992 Accepted: 22 January 1993 Published: 01 July 1993
Risk of aggressive periodontitis in adolescent carriers of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans in Morocco: a prospective longitudinal cohort study
Authors: Dorte Haubek, Oum-Keltoum Ennibi, Knud Poulsen, Michael Væth, Sven Poulsen, Mogens Kilian
Journal: The Lancet (2008)
HISTOGENESIS OF SEBACEOUS GLAND CARCINOMAS PRODUCED IN RATS BY 2-ACETYLAMINOFLUORENE
Authors: Stanley C. Skoryna, Roderick C. Ross, L. A. Rudis
Journal: The Journal of Experimental Medicine (1951)

1. Tumors of the external auditory canal region were produced by oral administration of 2-acetylaminofluorene in 71 rats out of 124 which survived a 6 month period of administration of the compound. In 12 animals the tumors were bilateral. Tumors in other locations, such as the liver, breast, etc., were less frequent. 2. Tumors were found to originate in the compound sebaceous gland located at the medial end of the external auditory canal. 3. Histologically the tumors were sebaceous or keratinizing squamous-cell carcinomas. 4. The tumors were found to arise in cystic lobules of the gland, produced by stasis of secretion. 5. Cystic lesions of the sebaceous glands appear to be a frequent condition in older rats. The outward bulging of the tympanic membrane with interference in drainage from the gland seems to be a promoting factor in the stasis of sebum. 6. The localizing effect of the preexisting cystic lesions in the sebaceous glands on the carcinogenic action of 2-acetylaminofluorene is discussed.
P62 Are we missing opportunities to obtain a microbiological diagnosis of TB?
Authors: Z. Al-Nakeeb, V. Gupta, C. Bell, M. Woodhead
Journal: Thorax (2010)

<h3>Introduction</h3> TB incidence is rising in the UK, with drug resistance becoming increasingly problematic. Diagnosis with microbiological culture and confirmation of sensitivity is therefore vital. This study investigated how often we are not achieving microbiological diagnosis at our centre, what factors influence this and whether opportunities to obtain microbiological samples were missed. <h3>Methods</h3> A retrospective study of all 156 cases (adult and paediatric) diagnosed with TB at Central Manchester Teaching Hospitals in 2009 was carried out. Demographic details, site of disease, types of specimens and results of TB culture were recorded. Cases where there were no specimens or cultures were negative were analyzed in detail. <h3>Results</h3> Most disease was pulmonary (n=69). Other disease sites included lymph node (n=34), ocular (n=12) and pleura (n=10). 128 (82%) patients had samples sent for microbiology. 92 (59%) patients were culture positive and 36 (23%) were culture negative. 28 (18%) patients had no specimens sent for culture. Factors which were associated with whether samples were sent for culture included site of disease (p&lt;0.0001), with ocular disease being the least likely to be sampled, and age of patients (p=0.002). 45% patients &lt;17 years did not have samples sent compared with 12.5 % patients 17–64. Ethnicity did not influence the frequency of sampling. A negative culture result was related to the specimen type (p&lt;0.0001) and patient9s age (p=0.019), with fewer paediatric samples positive. Site of disease or ethnicity did not affect culture results. In 25/28 cases with no microbiological specimens it was considered reasonable that specimens were not sent, as most of these were either ocular (n=12) or paediatric (n=9). In 3/28 (11%) samples could have been sent and all involved adult patients not born in the UK who had procedures whereby specimens were sent only for histology. 32/36 culture negative cases were considered to have been managed appropriately. 4/36 (11%) culture negative cases were potential missed opportunities for further sampling and were all due to patients with pleural TB not having pleural biopsies. <h3>Conclusion</h3> In our centre, despite a microbiology negative rate of 41%, reasonable opportunities to obtain a microbiological diagnosis are seldom missed.
Unusual cutaneous features associated with a heterozygous gain-of-function mutation in<i>IFIH1</i>: overlap between Aicardi-Goutières and Singleton-Merten syndromes
Authors: A.-C. Bursztejn, T.A. Briggs, Y. del Toro Duany, B.H. Anderson, J. O'Sullivan, S.G. Williams, C. Bodemer, S. Fraitag, F. Gebhard, B. Leheup, I. Lemelle, A. Oojageer, E. Raffo, E. Schmitt, G.I. Rice, S. Hur, Y.J. Crow
Journal: British Journal of Dermatology (2015)

Cutaneous lesions described as chilblain lupus occur in the context of familial chilblain lupus or Aicardi-Goutières syndrome. To date, seven genes related to Aicardi-Goutières syndrome have been described. The most recently described encodes the cytosolic double-stranded RNA receptor IFIH1 (also known as MDA5), a key component of the antiviral type I interferon-mediated innate immune response. Enhanced type I interferon signalling secondary to gain-of-function mutations in IFIH1 can result in a range of neuroinflammatory phenotypes including classical Aicardi-Goutières syndrome. It is of note that none of the patients with a neurological phenotype so far described with mutations in this gene was reported to demonstrate cutaneous involvement. We present a family segregating a heterozygous pathogenic mutation in IFIH1 showing dermatological involvement as a prominent feature, variably associated with neurological disturbance and premature tooth loss. All three affected individuals exhibited increased expression of interferon-stimulated genes in whole blood, and the mutant protein resulted in enhanced interferon signalling in vitro, both in the basal state and following ligand stimulation. Our results further extend the phenotypic spectrum associated with mutations in IFIH1, indicating that the disease can be confined predominantly to the skin, while also highlighting phenotypic overlap with both Aicardi-Goutières syndrome and Singleton-Merten syndrome.
Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study
Authors: Sylvie Castaigne, Cécile Pautas, Christine Terré, Emmanuel Raffoux, Dominique Bordessoule, Jean-Noel Bastie, Ollivier Legrand, Xavier Thomas, Pascal Turlure, Oumedaly Reman, Thierry de Revel, Lauris Gastaud, Noémie de Gunzburg, Nathalie Contentin, Estelle Henry, Jean-Pierre Marolleau, Ahmad Aljijakli, Philippe Rousselot, Pierre Fenaux, Claude Preudhomme, Sylvie Chevret, Hervé Dombret
Journal: The Lancet (2012)
Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients
Authors: Samy L Habib
Journal: Molecular Cancer (2009)

The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phopho-tuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients.
Year in review in intensive care medicine, 2004. I. Respiratory failure, infection, and sepsis
Authors: Peter Andrews, Elie Azoulay, Massimo Antonelli, Laurent Brochard, Christian Brun-Buisson, Geoffrey Dobb, Jean-Yves Fagon, Herwig Gerlach, Johan Groeneveld, Jordi Mancebo, Philipp Metnitz, Stefano Nava, Jerome Pugin, Michael Pinsky, Peter Radermacher, Christian Richard, Robert Tasker, Benoit Vallet
Journal: Intensive Care Medicine (2004)
Pattern of 24 hour intragastric acidity in active duodenal ulcer disease and in healthy controls.
Authors: H S Merki, C J Fimmel, R P Walt, K Harre, J Rohmel, L Witzel
Journal: Gut (1988)

Twenty four hour intragastric acidity was measured by continuous recording using intragastric combined glass electrodes in 46 duodenal ulcer patients within 48 hours of endoscopic confirmation of active ulceration. Acidity during predefined time periods was compared with that measured in 40 healthy controls without gastrointestinal disease: it was significantly higher in duodenal ulcer patients at all times, but 25% of ulcer patients had median 24 hour acidity within the interquartile range of the normal group. During the evening (18,00 to 22,00 h) ulcer patients had considerable acidity with a median of 39.8 (63.1-31.6) mmol/l (interquartile range) compared with 5.6 (22.3-0.4) mmol/l of controls. It is suggested that antisecretory treatment be directed to decrease this period of unbuffered acidity, as well as during the night, which is presently considered of prime importance.
Deletion of Protein Kinase C-ε Signaling Pathway Induces Glomerulosclerosis and Tubulointerstitial Fibrosis In Vivo
Authors: Matthias Meier, Jan Menne, Joon-Keun Park, Marcel Holtz, Faikah Gueler, Thorsten Kirsch, Mario Schiffer, Michael Mengel, Carsten Lindschau, Michael Leitges, Hermann Haller
Journal: Journal of the American Society of Nephrology (2007)

Protein kinase C (PKC), a family of 12 distinct serine-threonine kinases, is an important intracellular signaling pathway involved in various cellular functions, such as proliferation, hypertrophy, apoptosis, and adhesion. PKC-epsilon, a novel PKC isoform that is activated in the diabetic kidney, has been demonstrated to have a central role in the underlying signaling infrastructure of myocardial ischemia and hypertrophy. The renal phenotype of PKC-epsilon(-/-) mice was studied with regard to renal hypertrophy and fibrosis. PKC-epsilon(-/-) deficient knockout mice were generated and then killed after 6, 16, and 26 wk of life. Kidney/body weight ratio did not show any significant group difference compared with appropriate wild-type controls. Urinary albumin/creatinine ratio remained normal in wild-type mice, whereas PKC-epsilon(-/-) mice after 6 and 16 wk showed elevated albuminuria. Masson-Goldner staining revealed that tubulointerstitial fibrosis and mesangial expansion were significantly increased in PKC-epsilon(-/-) mice. However, this profibrotic phenotype was not observed in other organs, such as liver and lung. Immunohistochemistry of the kidneys from PKC-epsilon(-/-) mice showed increased renal fibronectin and collagen IV expression that was further aggravated in the streptozotocin-induced diabetic stress model. Furthermore, TGF-beta(1), phospho-Smad2, and phospho-p38 mitogen-activate protein kinase expression was increased in PKC-epsilon(-/-) mice, suggesting a regulatory role of PKC-epsilon in TGF-beta(1) and its signaling pathway in the kidney. These results indicate that deletion of PKC-epsilon mediates renal fibrosis and that TGF-beta1 and its signaling pathway might be involved. Furthermore, these data suggest that activation of PKC-epsilon in the diabetic state may rather represent a protective response to injury than be a mediator of renal injury.
Toward Systems Neuroscience of ADHD: A Meta-Analysis of 55 fMRI Studies
Authors: Samuele Cortese, Clare Kelly, Camille Chabernaud, Erika Proal, Adriana Di Martino, Michael P. Milham, F. Xavier Castellanos
Journal: American Journal of Psychiatry (2012)

The authors performed a comprehensive meta-analysis of task-based functional MRI studies of attention deficit hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, EMBASE, Web of Science, ERIC, CINAHAL, and NeuroSynth for studies published through June 30, 2011. Significant differences in brain region activation between individuals with ADHD and comparison subjects were detected using activation likelihood estimation meta-analysis. Dysfunctional regions in ADHD were related to seven reference neuronal systems. The authors performed a set of meta-analyses focused on age groups (children and adults), clinical characteristics (history of stimulant treatment and presence of psychiatric comorbidities), and specific neuropsychological tasks (inhibition, working memory, and vigilance/attention). Fifty-five studies were included (39 for children and 16 for adults). In children, hypoactivation in ADHD relative to comparison subjects was observed mostly in systems involved in executive function (frontoparietal network) and attention (ventral attentional network). Significant hyperactivation in ADHD relative to comparison subjects was observed predominantly in the default, ventral attention, and somatomotor networks. In adults, ADHD-related hypoactivation was predominant in the frontoparietal system, while ADHD-related hyperactivation was present in the visual, dorsal attention, and default networks. Significant ADHD-related dysfunction largely reflected task features and was detected even in the absence of comorbid mental disorders or a history of stimulant treatment. A growing literature provides evidence of ADHD-related dysfunction in multiple neuronal systems involved in higher-level cognitive functions but also in sensorimotor processes, including the visual system, and in the default network. This meta-analytic evidence extends early models of ADHD pathophysiology that were focused on prefrontal-striatal circuits.