tbuckley/cabot-search huggingface dataset:
Fibronectin gene polymorphisms are associated with the development of B-cell lymphoma in type II mixed cryoglobulinemia
Authors: M Fabris, L Quartuccio, S Salvin, G Pozzato, V De Re, C Mazzaro, C Ferri, C Baldini, S De Vita
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To analyse fibronectin (FN) gene polymorphisms in type II mixed cryoglobulinemic syndrome (MCsn), an immune-complex mediated systemic vasculitis linked to hepatitis C virus (HCV) infection and characterised by rheumatoid factor (RF) positive B-cell proliferation at high risk for the progression into non-Hodgkin's lymphoma (NHL). <h3>Methods:</h3> Samples from 74 patients with MCsn (type II serum cryoglobulins and clinical signs of vasculitis) were studied. In all, 58 (78.4%) patients were HCV-positive. In total, 21 (28.4%) patients developed a B-cell NHL during the course of MCsn. A total of 72 patients with HCV-negative and MC-unrelated NHL and 110 healthy blood donors (HBDs) were taken as controls. HaeIIIb and MspI FN gene polymorphisms were analysed by PCR and specific restriction enzyme digestions, following reported procedures. Plasma FN levels were analysed by ELISA, whenever possible. <h3>Results:</h3> HaeIIIb and MspI allele and genotype frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI (OR = 5.99; CI 1.77–20.261, p = 0.0039) and the AA-HaeIIIb (OR = 4.82, CI 1.42–16.39, p = 0.0176) homozygosis appeared significantly associated with the development of B-cell NHL in MCsn patients, with the HaeIIIb A allele possibly conferring an increased risk of NHL in the general population (OR = 1.72, CI 1.128–2.635, p = 0.0133). None of the other MCsn-related clinical manifestations were significantly associated with a particular genetic pattern. No association between FN plasma levels and FN genotypes was found. <h3>Conclusion:</h3> Genotyping for MspI and HaeIIIb FN gene polymorphisms may be clinically relevant to define the risk of lymphoma development in MCsn.
Mitogen-Activated Protein Kinase Phosphatase-1 Is Overexpressed in Non-Small Cell Lung Cancer and Is an Independent Predictor of Outcome in Patients
Authors: Silvestre Vicent, Mercedes Garayoa, José M. López-Picazo, María D. Lozano, Gemma Toledo, Frederik B. J. M. Thunnissen, Ramón G. Manzano, Luis M. Montuenga
Journal: Clinical Cancer Research (2004)

Abstract Purpose: An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH2-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). This study was designed to examine the involvement of CL100/MKP-1 and stress-related MAPKs in lung cancer. Experimental Design: We assessed the expression of CL100/MKP-1 and the activation of the MAPKs in a panel of 18 human cell lines [1 primary normal bronchial epithelium, 8 non-small cell lung cancer (NSCLC), 7 small cell lung cancer (SCLC), and 2 carcinoids] and in 108 NSCLC surgical specimens. Results: In the cell lines, CL100/MKP-1 expression was substantially higher in NSCLC than in SCLC. P-ERK, P-JNK, and P-p38 were activated in SCLC and NSCLC, but the degree of their activation was variable. Immunohistochemistry in NSCLC resection specimens showed high levels of CL100/MKP-1 and activation of the three MAPK compared with normal lung. In univariate analysis, no relationship was found among CL100/MKP-1 expression and P-ERK, P-JNK, or P-p38. Interestingly, high CL100/MKP-1 expression levels independently predicted improved survival in multivariate analysis. JNK activation associated with T1–2 and early stage, whereas ERK activation correlated with late stages and higher T and N. Neither JNK nor ERK activation were independent prognostic factors when studied for patient survival. Conclusions: Our data indicate the relevance of MAPKs and CL100/MKP-1 in lung cancer and point at CL100/MKP-1 as a potential positive prognostic factor in NSCLC. Finally, our study supports the search of new molecular targets for lung cancer therapy within the MAPK signaling pathway.
An Official American Thoracic Society Clinical Practice Guideline: Exercise-induced Bronchoconstriction
Authors: Jonathan P. Parsons, Teal S. Hallstrand, John G. Mastronarde, David A. Kaminsky, Kenneth W. Rundell, James H. Hull, William W. Storms, John M. Weiler, Fern M. Cheek, Kevin C. Wilson, Sandra D. Anderson
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Section:ChooseTop of pageAbstract <<ContentsExecutive SummaryIntroductionMethodsPathogenesisRole of the EnvironmentDiagnosisTreatmentScreening for EIBExercise, Asthma, and Dop...ReferencesCITING ARTICLES
Signal in Noise: Evaluating Reported Reproducibility of Serum Proteomic Tests for Ovarian Cancer
Authors: K. A. Baggerly, J. S. Morris, S. R. Edmonson, K. R. Coombes
Journal: JNCI Journal of the National Cancer Institute (2005)

Proteomic profiling of serum initially appeared to be dramatically effective for diagnosis of early-stage ovarian cancer, but these results have proven difficult to reproduce. A recent publication reported good classification in one dataset using results from training on a much earlier dataset, but the authors have since reported that they did not perform the analysis as described. We examined the reproducibility of the proteomic patterns across datasets in more detail. Our analysis reveals that the pattern that enabled successful classification is biologically implausible and that the method, properly applied, does not classify the data accurately. We show that the method used in previously published studies does not establish reproducibility and performs no better than chance for classifying the second dataset, in part because the second dataset is easy to classify correctly. We conclude that the reproducibility of the proteomic profiling approach has yet to be established.
GLUTEAL HERPES AND MALARIA.
Authors: JAMES H. SEQUEIRA
Journal: British Journal of Dermatology (1933)

Journal Article GLUTEAL HERPES AND MALARIA. Get access JAMES H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S. JAMES H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 45, Issue 10, 1 October 1933, Page 425, https://doi.org/10.1111/j.1365-2133.1933.tb10116.x Published: 01 October 1933
Myocardial K <sub>ATP</sub> Channels in Preconditioning
Authors: Brian O’Rourke
Journal: Circulation Research (2000)

Abstract —We are on the brink of harnessing the cell’s natural defenses against ischemia and reperfusion injury after years of research into the destructive and protective mechanisms involved. Since the discovery of ischemic preconditioning, the surface receptors and signal transduction pathways underlying this phenomenon have been clarified, but many questions remain about the downstream targets that ultimately protect the cell. ATP-sensitive K + (K ATP ) channels are thought to play a role in protection, but their mechanism of action has been unclear. Accumulating evidence now suggests that the location of the K ATP channels relevant to cytoprotection may be on the mitochondrial inner membrane instead of on the sarcolemma of the cardiac cell. This review discusses recent findings and unanswered questions about the role of K ATP channels in preconditioning and protection.
Alcohol alters skeletal muscle heat shock protein gene expression in rats: these effects are moderated by sex, raised endogenous acetaldehyde, and starvation
Authors: Tatsuo Nakahara, Ross Hunter, Makoto Hirano, Hideyuki Uchimura, Ann McArdle, Caroline S. Broome, Michael Koll, Colin R. Martin, Victor R. Preedy
Journal: Metabolism (2006)
Reproductive Period and Risk of Dementia in Postmenopausal Women
Authors: Mirjam I. Geerlings
Journal: JAMA (2001)

ContextExogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied.ObjectiveTo determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause.Design and SettingThe Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands.ParticipantsA total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia.Main Outcome MeasuresIncidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause.ResultsDuring 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD. After adjusting for age, dementia was not clearly associated with length of reproductive period. However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with &gt;39 reproductive years [highest quartile] compared with &lt;34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84). The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08). For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively. Risk of dementia associated with a longer reproductive period was most pronounced in APOE ∊4 carriers (adjusted RR for &gt;39 reproductive years compared with &lt;34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed.ConclusionOur findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.
STRUCTURE AND FUNCTION OF THE SMALL INTESTINE IN DERMATITIS HERPETIFORMIS
Authors: N. G. FRASER, D. MURRAY, J. O'D. Alexander
Journal: British Journal of Dermatology (1967)

Journal Article STRUCTURE AND FUNCTION OF THE SMALL INTESTINE IN DERMATITIS HERPETIFORMIS Get access N. G. FRASER, M.B.Glasg., M.R.C.P.E., N. G. FRASER, M.B.Glasg., M.R.C.P.E. Dermatological Registrar Search for other works by this author on: Oxford Academic Google Scholar D. MURRAY, M.B., B.Sc.Glasg., D. MURRAY, M.B., B.Sc.Glasg. Lecturer, University Department of Pathology Search for other works by this author on: Oxford Academic Google Scholar J. O'D. Alexander, M.B.Birm., M.R.C.P.G. J. O'D. Alexander, M.B.Birm., M.R.C.P.G. Consultant Dermatologist, Glasgow Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 10, 1 October 1967, Pages 509–518, https://doi.org/10.1111/j.1365-2133.1967.tb11405.x Published: 01 October 1967
Is deprivation associated with hospitalisation for upper gastrointestinal haemorrhage? a nationwide study of hospital admissions
Authors: C. J. Crooks, T. Card, J. West
Journal: Gut (2011)

<h3>Introduction</h3> Socioeconomic variation has previously been observed with upper gastrointestinal haemorrhage in a small study in the west of Scotland1 and this was assumed to be related to <i>H. pylori</i> acquisition. However, it is not known whether variceal haemorrhage admissions vary with socioeconomic indicators despite gradients in alcohol intake and body mass index. We therefore studied the national hospitalisation rates of both non variceal and variceal upper gastrointestinal haemorrhage according to socioeconomic status. <h3>Methods</h3> We used hospital episode statistics which contain all admissions within England, and identified upper gastrointestinal bleeds according to ICD 10 codes between 2001 and 2007. Population denominators were derived from Office of National Statistics mid-year population estimates by lower super output area (approximately 400 homes). Deprivation scores were generated from 1 (least deprived) to 5 (most deprived) according to quintiles of super output areas ranked by the Index of Multiple Deprivation (2007). Hospitalisation rates per deprivation score were adjusted for age and sex using Poisson regression. <h3>Results</h3> 237,139 non variceal haemorrhage admissions and 8,291 variceal admissions were identified between 2001 and 2007. Rates of hospitalisation for non variceal haemorrhage were 2-fold greater (incidence rate ratio 2.02, 95% confidence interval 1.99–2.04) among those from the most deprived areas compared to least deprived. The differences for variceal haemorrhage hospitalisation rates were even more pronounced (incidence rate ratio 2.49, 95% Confidence interval 2.32–2.67). These differences were present in every region of the country (figure 1, only non-variceal shown). Adjusting for age and sex increased the disparity between deprived and affluent in each region. 28-day mortality did not have a similar gradient. <h3>Conclusion</h3> We found that for both variceal and non-variceal haemorrhage hospitalisation rates vary widely by the socioeconomic status of the area of a person9s residence. The association was present through all areas of the country and in all age bands and was of greater magnitude than any regional differences. The existence of such a steep gradient suggests that there are opportunities to reduce overall admission rates to those of the least deprived areas and avoid almost 10,000 admissions and over 1000 deaths a year.
Endothelin mediates pulmonary vascular remodelling in a canine model of chronic embolic pulmonary hypertension
Authors: H. Kim, G.L. Yung, J.J. Marsh, R.G. Konopka, C.A. Pedersen, P.G. Chiles, T.A. Morris, R.N. Channick
Journal: European Respiratory Journal (2000)

It is well known that endothelin (ET)-1 mediates vascular remodelling in various kinds of clinical and experimental pulmonary hypertension. The aim of this study was to investigate whether ET-1 is associated with the development of pulmonary vascular remodelling in a canine model of chronic embolic pulmonary hypertension. Pulmonary hypertension was induced in 10 mongrel dogs by repeated embolization with ceramic beads. In five of the dogs, bosentan, a nonselective ET receptor antagonist, was administered throughout the study. Haemodynamic measurements and plasma ET-1 assays were performed every 2 months. Eight months after initial embolization, computer-assisted morphometry and immunohistochemistry were performed on the lung tissue including that from three control dogs. Pulmonary arterial pressure and pulmonary vascular resistance were increased in all embolized dogs, compared to baseline. In nontreated embolized dogs, plasma ET-1 concentration and pulmonary arterial wall thickness were increased compared to control animals, and ET-1 immunoreactivity was detected in thickened pulmonary arteries. In bosentan treated dogs, pulmonary arterial walls were not significantly thickened. Pulmonary vascular remodelling, associated with elevated plasma endothelin-1 levels and positive endothelin-1 immunoreactivity in lung tissue is attenuated by the endothelin receptor antagonist, bosentan. These findings suggest that endothelin mediates pulmonary vascular remodelling in a canine model of chronic embolic pulmonary hypertension.
Metastatic pulmonary calcification after renal transplantation
Authors: M Murris-Espin, L Lacassagne, A Didier, JJ Voigt, JM Cisterne, J Giron, D Durand, P Leophonte
Journal: European Respiratory Journal (1997)

Metastatic pulmonary calcifications, unlike dystrophic calcifications, occur in the normal healthy lung. The radiological pattern is quite specific. The disease is commonly described in chronic renal failure with calcium disorders. The prognosis is totally unpredictable. In 1992, a 50 yr old man underwent a successful renal transplantation during the final stage of chronic renal failure. He subsequently developed asymptomatic diffuse nodular opacities, that were discovered in 1995. An open lung biopsy confirmed the diagnosis of metastatic pulmonary calcification. There was no calcium disorder in this patient. In contrast to the benign course of pulmonary calcification in most patients, some fulminant pulmonary calcifications complicating renal transplantation or hypercalcaemia have been described. Radiographic identification of such entities is important to permit correction of calcium disorders. Otherwise, the condition is a potentially progressive and fatal cause of respiratory failure.
Is Maximal Lung Recruitment Worth It?
Authors: João Batista Borges Sobrinho, Carlos Roberto Ribeiro de Carvalho, Marcelo Britto Passos Amato
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

In their recent article, Borges and colleagues nicely show by computed tomography (CT) that nearly complete lung recruitment may be achieved in most mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome (ALI/ ARDS) (1). Unfortunately, the authors failed to prove that their maximal lung recruitment strategy is safe. To obtain full recruitment, which was defined as PaO2 PaCO2 400 mm Hg, they use an aggressive strategy consisting of a sequential increase in inspiratory pressures up to 60 cm H2O if necessary. However, the extreme values of PaCO2 and pH observed during recruitment can hardly be considered as safe. Furthermore, the minimal gain in reversing collapse beyond 45 cm H2O (Figure 2 of their article) indicates that unnecessarily high distending pressures were probably used. The low rates of barotrauma and hyperinflation on CT do not exclude overdistension, which is easily identified in their data by the increase in PaCO2 and the decrease in cardiac output. More important, overdistension may worsen lung injury, release inflammatory mediators, and induce distant organ failure and death (2, 3). In fact, despite the low number of patients, the 57% mortality rate is unexpectedly high compared with most recent trials and with previous data of the same group. Decades of research have moved us toward a more gentle and rational ventilation (4). Overdistension may be a high price to pay for maximal recruitment.
Gastric mucosal barrier: evidence for Helicobacter pylori ingesting gastric surfactant and deriving protection from it.
Authors: B A Hills
Journal: Gut (1993)

Ultrastructural examination by electron microscopy has been undertaken on human oxyntic mucosa from biopsy specimens obtained during diagnostic endoscopy from patients in whom infection by Helicobacter pylori was subsequently confirmed. A novel fixation procedure was used that avoided conventional fixatives based upon glutaraldehyde, which can destroy the hydrophobic lining of surfaces such as gastric mucosa. The resulting electron micrographs show densely osmiophilic inclusions of varying sizes in Helicobacter, some of which can be resolved and identified as lamellar bodies and their partially digested states. This finding indicates that Helicobacter may act as an aggressive agent by ingesting a gastric mucosal barrier of gastric surfactant, exposing the surface to attack by acid while simultaneously rendering it less hydrophobic. There is also evidence that Helicobacter pylori avoid their own digestion by coating themselves with essentially the same barrier of gastric surfactant, probably derived from the host. This is a possible explanation for the apparent absence of these bacteria in the duodenum.
The College of General Practitioners
Authors: D. Carney, J. St. L. O'Dea, J. J. McCann, E. A. O'Reilly, A. E. H. O'Byrne, D. S. Kearon, R. O'Meara, L. Masterson, J. Fleetwood, J. F. O'Grady, N. McNally, A. Ryan
Journal: BMJ (1953)
Short-Term Intensive Therapy in Newly Diagnosed Type 2 Diabetes Partially Restores Both Insulin Sensitivity and β-Cell Function in Subjects With Long-Term Remission
Authors: Yun Hu, Lirong Li, Yu Xu, Tingting Yu, Guoyu Tong, Hong Huang, Yan Bi, Jianping Weng, Dalong Zhu
Journal: Diabetes Care (2011)

To examine the effect of intensive glycemic control therapy (IT) on insulin sensitivity and β-cell function in newly diagnosed type 2 diabetic patients compared with subjects with normal glucose tolerance (NGT) and those with impaired glucose tolerance (IGT).Forty-eight newly diagnosed type 2 diabetic patients were randomly assigned to IT for 2 weeks and followed up for 1 year. Intravenous glucose tolerance tests were conducted in NGT, IGT, and diabetic subjects. Blood glucose and insulin were measured before and after IT and at the 1-year follow-up.IT lowered the homeostasis model assessment (HOMA) for insulin resistance (IR) significantly, from 3.12 ± 1.4 (mean ± SD) to 1.72 ± 0.8, a level comparable to the IGT (1.96 ± 1.1) and NGT (1.37 ± 0.6) subjects in the remission group; however, no HOMA-IR improvement was observed in nonremission subjects. HOMA-β in the remission group was improved (mean, interquartile range) from 18.4 (8.3-28.5) to 44.6 (32.1-69.1) and acute insulin response of insulin (AIRins) from 1.50 ± 0.22 to 1.83 ± 0.19 μIU/mL after IT, but was still significantly lower than those in NGT individuals (HOMA-β: 86.4 [56.7-185.2], P < 0.01; AIRins: 2.54 ± 0.39 μIU/mL, P < 0.01). After IT and at 1 year, the hyperbolic relationship between HOMA-β and HOMA sensitivity of remission subjects shifted close to that of IGT subjects.IT in newly diagnosed type 2 diabetes not only partially restored β-cell function but also greatly restored insulin sensitivity. Compared with IGT and NGT subjects, β-cell function was less restored than insulin sensitivity after IT in the remission subjects.
Preeclampsia: a link between trophoblast dysregulation and an antiangiogenic state
Authors: Roberto Romero, Tinnakorn Chaiworapongsa
Journal: Journal of Clinical Investigation (2013)

A 24-year-old nulliparous woman developed mildly elevated blood pressure (140–150/90–100 mmHg) without proteinuria (20 mg protein in a 24-hour urine collection) at 306/7 weeks of gestation. The fetus was small for gestational age (estimated fetal weight under the fifth percentile). At 325/7 weeks of gestation, the patient complained of epigastric pain, blood pressure was 180/110 mmHg, proteinuria was documented (780 mg protein in a 24-hour urine collection), schistocytes were detected in the peripheral smear, platelet count was 60,000 cells per mm3, and serum glutamic oxaloacetic transaminase was 234 U/l. The patient was diagnosed with severe preeclampsia/HELLP syndrome. Antenatal steroids were administered to induce fetal lung maturity. She and her family want to know the causes of this condition, what treatment is available, and whether there are any long-term implications of this diagnosis.
Human migrating myoelectric complex in relation to gastrointestinal transit of a meal.
Authors: J L Madsen, K Dahl
Journal: Gut (1990)

Feeding interrupts the migrating myoelectric complex in most mammals. This study aimed to assess whether resumption of the migrating myoelectric complex in the human duodenum after eating was related to the gastrointestinal transit of the meal. Five healthy subjects participated in the study. After eating a radiolabelled test meal consisting of mixed liquid and solids, duodenal myoelectric activity and gastrointestinal transit of the meal were determined simultaneously. In spite of considerable variation in entire gastric emptying time between subjects (range 2.5-5.0 hours), significant correlation was found between the completion of gastric emptying and the resumption of duodenal phase III activity within subjects (p less than 0.01). A new technique for recording the duodenal myoelectric activity was used.