tbuckley/cabot-search huggingface dataset:
Incidence of Basal Cell and Squamous Cell Carcinomas in a Population Younger Than 40 Years
Authors: Leslie J. Christenson
Journal: JAMA (2005)

The incidence of nonmelanoma skin cancer is increasing rapidly among elderly persons, but little is known about its incidence in the population younger than 40 years.To estimate the sex- and age-specific incidences of basal cell carcinoma and squamous cell carcinoma in persons younger than 40 years in Olmsted County, Minnesota, and to evaluate change in incidence over time; to describe the clinical presentation, rate of recurrence and metastasis, and histologic characteristics of these tumors in this population-based sample.Population-based retrospective incidence case review.Residents of Olmsted County, Minnesota, a population with comprehensive medical records captured through the Rochester Epidemiology Project.Patients younger than 40 years with basal cell carcinoma or squamous cell carcinoma diagnosed between 1976 and 2003.Incident basal cell carcinomas and squamous cell carcinomas and change in incidence of these tumors over time.During the study period, 451 incident basal cell carcinomas were diagnosed in 417 patients and 70 incident squamous cell carcinomas were diagnosed in 68 patients. Of these tumors, 328 were histologically confirmed basal cell carcinomas and 51 were histologically confirmed squamous cell carcinomas. Overall, the age-adjusted incidence of basal cell carcinoma per 100,000 persons was 25.9 (95% confidence interval [CI], 22.6-29.2) for women and 20.9 (95% CI, 17.8-23.9) for men. The incidence of basal cell carcinoma increased significantly during the study period among women (P<.001) but not men (P = .19). Nodular basal cell carcinoma was the most common histologic subtype; 43.0% of tumors were solely nodular basal cell carcinoma and 11.0% had a mixed composition, including the nodular subtype. The incidence of squamous cell carcinoma was similar in men and women, with an average age- and sex-adjusted incidence per 100 000 persons of 3.9 (95% CI, 3.0-4.8); the incidence of squamous cell carcinoma increased significantly over the study period among both women (P = .01) and men (P = .04).This population-based study demonstrated an increase in the incidence of nonmelanoma skin cancer among young women and men residing in Olmsted County, Minnesota. There was a disproportionate increase in basal cell carcinoma in young women. This increase may lead to an exponential increase in the overall occurrence of nonmelanoma skin cancers over time as this population ages, which emphasizes the need to focus on skin cancer prevention in young adults.
The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study
Authors: Harvey O Coxson, Asger Dirksen, Lisa D Edwards, Julie C Yates, Alvar Agusti, Per Bakke, Peter MA Calverley, Bartolome Celli, Courtney Crim, Annelyse Duvoix, Paola Nasute Fauerbach, David A Lomas, William MacNee, Ruth J Mayer, Bruce E Miller, Nestor L Müller, Stephen I Rennard, Edwin K Silverman, Ruth Tal-Singer, Emiel FM Wouters, Jørgen Vestbo
Journal: The Lancet Respiratory Medicine (2013)
Clinician's Guide to Helicobacter pylori
Authors: I. Forgacs
Journal: Gut (1996)

<h3>SUMMARY</h3> A single region of the <i>Pseudomonas putida</i> genome, designated the flagellar cluster, includes 59 genes potentially involved in the biogenesis and function of the flagellar system. Here we combine bioinformatics and <i>in vivo</i> gene expression analyses to clarify the transcriptional organization and regulation of the flagellar genes in the cluster. We have identified eleven flagellar operons and characterized twenty-two primary and internal promoter regions. Our results indicate that synthesis of the flagellar apparatus and core chemotaxis machinery is regulated by a three-tier cascade in which <i>fleQ</i> is a Class I gene, standing at the top of the transcriptional hierarchy. FleQ- and <i>σ</i><sup>54</sup>-dependent Class II genes encode most components of the flagellar structure, part of the chemotaxis machinery and multiple regulatory elements, including the flagellar <i>σ</i> factor FliA. FliA activation of Class III genes enables synthesis of the filament, one stator complex and completion of the chemotaxis apparatus. Accessory regulatory proteins and an intricate operon architecture add complexity to the regulation by providing feedback and feed-forward loops to the main circuit. Because of the high conservation of the gene arrangement and promoter motifs, we believe that the regulatory circuit presented here may also apply to other environmental pseudomonads. <h3>ORIGINALITY-SIGNIFICANCE STATEMENT</h3> This is the first integrative study of the flagellar transcriptional cascade in <i>Pseudomonas putida</i>. Our results provide a new transcriptional organization featuring several operons with a nested architecture, detailed regulatory characterization of twenty-two flagellar promoters and a novel hierarchy for the regulatory circuit of the flagellar transcriptional cascade. The results presented represent a significant departure from previous models for other related bacteria. High conservation of flagellar gene organization and promoter sequences suggest that our observations may be relevant to other pseudomonads.
The influence of acute bronchiolitis in infancy on later quality of life
Authors: Leif Bjarte Rolfsjord, Håvard Ove Skjerven, Petter Mowinckel, Kai-Håkon Carlsen, Egil Bakkeheim, Bente Kvenshagen, Karen-Eline Stensby Høstmark, Jon Olav Hunderi, Teresa Løvold Berents, Karin Cecilie Lødrup Carlsen
Journal: European Respiratory Journal (2013)

Stress and reduced quality of life is associated with later allergic disease, with acute bronchiolitis as an asthma risk factor.   Aims:  To evaluate the role of acute bronchiolitis for quality of life (QoL) nine months later.   Methods:  An infant QoL questionnaire (ITQOL™) with 13 domains was sent to 644 and received from parents of 415 children, mean age (standard deviation) 5.2 (3.3) months, 209 who were hospitalised with acute bronchiolitis and a control group (mean ages 4.0 (2.8) and 6.4 (3.4) months, respectively). Analyses by robust regression included age at hospitalisation, gender, hospitalisation for bronchiolitis and severity given by length of hospital stay, nasogastric tube feeding, oxygen therapy, ventilation support and clinical score.   Results:  Hospitalisation was associated with significantly reduced QoL in four domains (overall health, general behaviour, general health and change in health) (all p   Conclusion:  Acute bronchiolitis and disease severity are associated with reduced QoL nine months later.
CXCL5 Drives Neutrophil Recruitment in TH17-Mediated GN
Authors: Erik M. Disteldorf, Christian F. Krebs, Hans-Joachim Paust, Jan-Eric Turner, Geraldine Nouailles, André Tittel, Catherine Meyer-Schwesinger, Gesa Stege, Silke Brix, Joachim Velden, Thorsten Wiech, Udo Helmchen, Oliver M. Steinmetz, Anett Peters, Sabrina B. Bennstein, Anna Kaffke, Chrystel Llanto, Sergio A. Lira, Hans-Willi Mittrücker, Rolf A.K. Stahl, Christian Kurts, Stefan H.E. Kaufmann, Ulf Panzer
Journal: Journal of the American Society of Nephrology (2014)

Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in TH17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen- and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic TH17/IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in TH17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens.
Asthma and atopy: has peak prevalence been reached?
Authors: D. Nowak, C. Suppli Ulrik, E. von Mutius
Journal: European Respiratory Journal (2004)

Numerous studies have been published concerning the changing epidemiology of asthma and atopy, and studies from “western countries” have consistently shown a dramatic increase in prevalence over the last two to three decades. However, in this issue of the European Respiratory Journal , Braun-FahrlAnder et al. 1 report interesting new evidence concerning the prevalence rates of asthma and atopy in a group of Swiss teenagers. Their repeated cross-sectional survey of 14‐yr-old children shows that the prevalence of asthma and current asthmatic symptoms remained constant between 1992 and 2000. Likewise, no further increase was found in hay fever rates and allergic sensitisation during the same period. Asthma and hay fever diagnoses were based on written and/or video questionnaires, and sensitisation was determined by multiscreen SX1 tests (and afterwards confirmed by measurements of specific immunoglobulin E levels). Therefore, although additional years of data collection are necessary to confirm a change in trend, their observations clearly suggest that the increase in asthma and atopy may have come to an end, at least in some societies.

These data are in line with some recently published studies showing a plateau in the prevalence of both childhood asthma 2–4, including asthma attack prevalence in the past 12 months and hospitalisations …
Measurement of In Vivo BCR-ABL Kinase Inhibition to Monitor Imatinib-Induced Target Blockade and Predict Response in Chronic Myeloid Leukemia
Authors: Deborah White, Verity Saunders, Andrew Grigg, Chris Arthur, Robin Filshie, Michael F. Leahy, Kevin Lynch, L. Bik To, Timothy Hughes
Journal: Journal of Clinical Oncology (2007)

Purpose Intrinsic sensitivity to imatinib, based on measurement of inhibitory concentration 50% for imatinib, is variable in untreated patients with chronic myeloid leukemia (CML). This suggests that patient-tailored dosing may be more rational than a fixed dose for all. Dose optimization potentially could be based on accurate measurement of the level of BCR-ABL kinase inhibition achieved in vivo. Patients and Methods In vivo kinase inhibition was measured by calculating the reduction in protein (p) -Crkl level in mononuclear blood cells taken from 49 CML patients at weekly intervals after imatinib therapy was commenced. Results Greater than 50% inhibition (&gt; 50% reduction in p-Crkl from baseline) was achieved by 21% of patients by days 7 to 14 (and maintained in all patients on days 21 to 28) and an additional 24% of patients achieved more than 50% inhibition by days 21 to 28. Thus, overall 45% of patients achieved more than 50% inhibition. All of these patients achieved major molecular responses by 24 months compared with 56% of the patients who failed to achieve 50% kinase inhibition (P &lt; .001). Patients with less than 50% kinase inhibition were also more likely to have suboptimal responses. Conclusion In vivo BCR-ABL kinase inhibition can be assessed in the first month of imatinib therapy and may provide a valuable guide to optimization of dosage. The extent of BCR-ABL kinase inhibition is an excellent predictor of cytogenetic and molecular response. These observations suggest that dose adjustment based on in vivo measurements of drug-induced target inhibition could be applied in settings beyond imatinib and may be a more effective approach than using one dose for all patients in targeted anticancer therapy.
TRAF6-Mediated SM22α K21 Ubiquitination Promotes G6PD Activation and NADPH Production, Contributing to GSH Homeostasis and VSMC Survival In Vitro and In Vivo
Authors: Li-Hua Dong, Liang Li, Yu Song, Zhi-Li Duan, Shao-Guang Sun, Yan-Ling Lin, Sui-Bing Miao, Ya-Juan Yin, Ya-Nan Shu, Huan Li, Peng Chen, Li-Li Zhao, Mei Han
Journal: Circulation Research (2015)

Rationale: Vascular smooth muscle cell (VSMC) survival under stressful conditions is integral to promoting vascular repair, but facilitates plaque stability during the development of atherosclerosis. The cytoskeleton-associated smooth muscle (SM) 22α protein is involved in the regulation of VSMC phenotypes, whereas the pentose phosphate pathway plays an essential role in cell proliferation through the production of dihydronicotinamide adenine dinucleotide phosphate. Objective: To identify the relationship between dihydronicotinamide adenine dinucleotide phosphate production and SM22α activity in the development and progression of vascular diseases. Methods and Results: We showed that the expression and activity of glucose-6-phosphate dehydrogenase (G6PD) are promoted in platelet-derived growth factor (PDGF)-BB–induced proliferative VSMCs. PDGF–BB induced G6PD membrane translocation and activation in an SM22α K21 ubiquitination–dependent manner. Specifically, the ubiquitinated SM22α interacted with G6PD and mediated G6PD membrane translocation. Furthermore, we found that tumor necrosis factor receptor–associated factor (TRAF) 6 mediated SM22α K21 ubiquitination in a K63-linked manner on PDGF-BB stimulation. Knockdown of TRAF6 decreased the membrane translocation and activity of G6PD, in parallel with reduced SM22α K21 ubiquitination. Elevated levels of activated G6PD consequent to PDGF-BB induction led to increased dihydronicotinamide adenine dinucleotide phosphate generation through stimulation of the pentose phosphate pathway, which enhanced VSMC viability and reduced apoptosis in vivo and in vitro via glutathione homeostasis. Conclusions: We provide evidence that TRAF6-induced SM22α ubiquitination maintains VSMC survival through increased G6PD activity and dihydronicotinamide adenine dinucleotide phosphate production. The TRAF6–SM22α–G6PD pathway is a novel mechanism underlying the association between glucose metabolism and VSMC survival, which is beneficial for vascular repair after injury but facilitates atherosclerotic plaque stability.
Prognostic Impact of Micrometastatic Tumor Cells in the Lymph Nodes and Bone Marrow of Patients With Completely Resected Stage I Non–Small-Cell Lung Cancer
Authors: Toshihiro Osaki, Tsunehiro Oyama, Chun-Dong Gu, Toshihiro Yamashita, Tomoko So, Mitsuhiro Takenoyama, Kenji Sugio, Kosei Yasumoto
Journal: Journal of Clinical Oncology (2002)

This study was designed to substantiate the prognostic impact of occult micrometastatic tumor cells in the lymph nodes (LNs) and bone marrow (BM) in stage I non-small-cell lung cancer (NSCLC) patients using cytokeratin (CK) as a micrometastatic marker and the relationship between the micrometastases in the LNs and BM.A total of 2,432 hilar and mediastinal LNs were removed during surgery from 115 patients with completely resected stage I NSCLC. The LNs were analyzed for micrometastasis using immunohistochemistry with the biclonal anti-CK antibody AE1/AE3. BM aspirates from 115 patients were immunocytochemically stained with the monoclonal anti-CK antibody CK2.CK-positive (CK+) cells were detected in 42 (1.7%) of 2,432 LNs, in 32 (27.8%) of 115 patients, and in 32 (27.8%) of 115 BM aspirates. There was no relationship between the frequencies of CK+ cells in the LNs and in the BM. The patients with CK+ cells in the LNs had a poor prognosis by both univariate (P =.008) and multivariate analyses (P =.01), whereas the presence of CK+ cells in the BM did not allow prediction of survival (P =.32). The prognostic impact of LNs micrometastasis was independent even after adjusting for the status of BM micrometastasis.The detection of lymph nodal micrometastatic tumor cells provides an accurate assessment of tumor staging and has powerful prognostic implications for completely resected stage I NSCLC patients.
Projecting the Future Diabetes Population Size and Related Costs for the U.S.
Authors: Elbert S. Huang, Anirban Basu, Michael O'Grady, James C. Capretta
Journal: Diabetes Care (2009)

OBJECTIVE We developed a novel population-level model for projecting future direct spending on diabetes. The model can be used in the federal budget process to estimate the cost implications of alternative policies. RESEARCH DESIGN AND METHODS We constructed a Markov model simulating individuals' movement across different BMI categories, the incidence of diabetes and screening, and the natural history of diabetes and its complications over the next 25 years. Prevalence and incidence of obesity and diabetes and the direct spending on diabetes care and complications are projected. The study population is 24- to 85-year-old patients characterized by the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey and National Health Interview Survey. RESULTS Between 2009 and 2034, the number of people with diagnosed and undiagnosed diabetes will increase from 23.7 million to 44.1 million. The obesity distribution in the population without diabetes will remain stable over time with ∼65% of individuals of the population being overweight or obese. During the same period, annual diabetes-related spending is expected to increase from $113 billion to $336 billion (2007 dollars). For the Medicare-eligible population, the diabetes population is expected to rise from 8.2 million in 2009 to 14.6 million in 2034; associated spending is estimated to rise from $45 billion to $171 billion. CONCLUSIONS The diabetes population and the related costs are expected to at least double in the next 25 years. Without significant changes in public or private strategies, this population and cost growth are expected to add a significant strain to an overburdened health care system.
Adrenergic inhibition of endogenous acetylcholine release on postganglionic cardiac vagal nerve terminals
Authors: T Akiyama
Journal: Cardiovascular Research (2000)

Objective: The aim was to examine the adrenergic modulation of endogenous acetylcholine (ACh) release from vagal nerve terminals in the in vivo heart. Methods: Using dialysis technique in anesthetized cats, we investigated the influence of exogenous noradrenaline on dialysate ACh response. Dialysis probes were implanted in the left ventricular myocardium and perfused with Krebs–Henseleit buffer containing eserine (10−4 M) at 3 μl/min. Dialysate ACh concentration was measured as an index of ACh release from cardiac vagal nerve terminals. The dialysate ACh response to vagal nerve stimulation was examined before and after local administration of noradrenaline (10−5 M) through dialysis probes. Results: Noradrenaline significantly attenuated the dialysate ACh response to vagal nerve stimulation (10 Hz) from 9.5±1.8 to 5.4±1.2 nM (n=7). In the presence of the α-adrenergic antagonist phentolamine (10−4 M), noradrenaline did not attenuate the dialysate ACh response (from 9.8±2.7 to 9.4 ±2.8 nM, n=6). The N-type Ca2+ channel blocker ω-conotoxin GVIA (10−5 M) significantly attenuated the dialysate ACh response from 9.6±1.2 to 4.5±0.7 nM (n=8). In the presence of ω-conotoxin GVIA, noradrenaline did not attenuate the dialysate ACh response (from 3.8±1.4 to 3.5±1.3 nM, n=7). Conclusions: Our results suggest the presynaptic adrenergic inhibition of ACh release on postganglionic cardiac vagal nerve terminals. Adrenergic inhibition of Ca2+ influx through the N-type Ca2+ channels could play a predominant role in the decrease in ACh release.
Circulating and intra-articular immune complexes in rheumatoid arthritis: a comparative study of the C1q binding and monoclonal rheumatoid factor assays.
Authors: P J Roberts-Thomson, S H Neoh, J Bradley, S C Milazzo
Journal: Annals of the Rheumatic Diseases (1980)

The C1q binding assay and the nephelometric monoclonal rheumatoid factor assay were able to discriminate 79% and 57% respectively of rheumatoid arthritis (RA) patients from healthy blood donors. In addition these assays could distinguish those patients with active arthritis from those with inactive disease, and the C1q binding assay correlated significantly with other laboratory indices of the rheumatoid process, including the erythrocyte sedimentation rate, low molecular weight or 7S IgM, and the rheumatoid factor titre. High levels of C1q binding were also seen in rheumatoid vasculitis. Both assays gave higher mean values in synovial fluid compared with the corresponding serum, but it appeared from ultracentrifugal analysis and from a lack of a consistent correlation between these assays that each assay was measuring different forms of immunecomplex-like material which may be involved in the immunopathogenesis of this disease. The C1q binding assay is of some value in the laboratory assessment of rheumatoid arthritis and appears to offer greater advantages than the monoclonal rheumatoid factor assay, although the usefulness of this latter assay may be very dependent on the monoclonal rheumatoid factor used.
Bile salt sequestration induces hepatic<i>de novo</i>lipogenesis through farnesoid X receptor- and liver X receptorα-controlled metabolic pathways in mice
Authors: Hilde Herrema, Maxi Meissner, Theo H. van Dijk, Gemma Brufau, Renze Boverhof, Maaike H. Oosterveer, Dirk-Jan Reijngoud, Michael Müller, Frans Stellaard, Albert K. Groen, Folkert Kuipers
Journal: Hepatology (2009)

Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through signaling pathways involving farnesoid X receptor (FXR) and liver X receptor α (LXRα). We quantitatively assessed kinetic parameters of bile salt metabolism in lean C57Bl/6J and in obese, diabetic db/db mice upon bile salt sequestration using colesevelam HCl (2% wt/wt in diet) and related these to quantitative changes in hepatic lipid metabolism. As expected, bile salt sequestration reduced intestinal bile salt reabsorption. Importantly, bile salt pool size and biliary bile salt secretion remained unchanged upon sequestrant treatment due to compensation by de novo bile salt synthesis in both models. Nevertheless, lean and db/db mice showed increased, mainly periportally confined, hepatic TG contents, increased expression of lipogenic genes, and increased fractional contributions of newly synthesized fatty acids. Lipogenic gene expression was not induced in sequestrant-treated Fxr −/− and Lxr α−/− mice compared with wild-type littermates, in line with reports indicating a regulatory role of FXR and LXRα in bile salt–mediated regulation of hepatic lipid metabolism. Conclusion: Bile salt sequestration by colesevelam induces the lipogenic pathway in an FXR- and LXRα-dependent manner without affecting the total pool size of bile salts in mice. We speculate that a shift from intestinal reabsorption to de novo synthesis as source of bile salts upon bile salt sequestration affects zonation of metabolic processes within the liver acinus. (Hepatology 2010.)