tbuckley/cabot-search huggingface dataset:
Evidence That Gsta4 Modifies Susceptibility to Skin Tumor Development in Mice and Humans
Authors: Erika L. Abel, Joe M. Angel, Penny K. Riggs, Laura Langfield, Herng-Hsiang Lo, Maria D. Person, Yogesh C. Awasthi, Li-E Wang, Sara S. Strom, Qingyi Wei, John DiGiovanni
Journal: JNCI Journal of the National Cancer Institute (2010)

The incidence of nonmelanoma skin cancer (NMSC) is equivalent to that of all other cancers combined. Previously, we mapped the 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion susceptibility locus, Psl1, to distal chromosome 9 in crosses of sensitive DBA/2 mice with relatively resistant C57BL/6 mice. Here, we used the mouse two-stage skin carcinogenesis model to identify the gene(s) responsible for the effects of Psl1. Interval-specific congenic mouse strains (n ≥ 59 mice per strain) were used to more precisely map the Psl1 locus. Having identified glutathione S-transferase α4 (Gsta4) as a candidate tumor promotion susceptibility gene that mapped within the delimited region, we analyzed Gsta4-deficient mice (n = 62) for susceptibility to skin tumor promotion by TPA. We used quantitative polymerase chain reaction, western blotting, and immunohistochemistry to verify induction of Gsta4 in mouse epidermis following TPA treatment and biochemical assays to associate Gsta4 activity with tumor promotion susceptibility. In addition, single-nucleotide polymorphisms (SNPs) in GSTA4 were analyzed in a case–control study of 414 NMSC patients and 450 control subjects to examine their association with human NMSC. Statistical analyses of tumor studies in mice were one-sided, whereas all other statistical analyses were two-sided. Analyses of congenic mice indicated that at least two loci, Psl1.1 and Psl1.2, map to distal chromosome 9 and confer susceptibility to skin tumor promotion by TPA. Gsta4 maps to Psl1.2 and was highly induced (mRNA and protein) in the epidermis of resistant C57BL/6 mice compared with that of sensitive DBA/2 mice following treatment with TPA. Gsta4 activity levels were also higher in the epidermis of C57BL/6 mice following treatment with TPA. Gsta4-deficient mice (C57BL/6.Gsta4-/- mice) were more sensitive to TPA skin tumor promotion (0.8 tumors per mouse vs 0.4 tumors per mouse in wild-type controls; difference = 0.4 tumors per mouse; 95% confidence interval = 0.1 to 0.7, P = .007). Furthermore, inheritance of polymorphisms in GSTA4 was associated with risk of human NMSC. Three SNPs were found to be independent predictors of NMSC risk. Two of these were associated with increased risk of NMSC (odds ratios [ORs] = 1.60 to 3.42), while the third was associated with decreased risk of NMSC (OR = 0.63). In addition, a fourth SNP was associated with decreased risk of basal cell carcinoma only (OR = 0.44). Gsta4/GSTA4 is a novel susceptibility gene for NMSC that affects risk in both mice and humans.
COMPENSATORY HYPERTROPHY OF THE SPLEEN
Authors: Eaton M. MacKay, W. Scott Polland
Journal: The Journal of Experimental Medicine (1931)

Following the removal of half of the spleen in young adult rats there is a compensatory enlargement of the remaining portion of about 50 per cent while in mature rabbits no such compensatory hypertrophy follows a similar procedure. It is uncertain whether this difference is due to a difference in the function of the spleen in the two species or to the fact that the rats were infected with Bartonella muris while the rabbits were not.
Persistent systemic inflammatory response after stent insertion in patients with malignant bile duct obstruction
Authors: A B Ballinger, J A Woolley, M Ahmed, H Mulcahy, E M Alstead, J Landon, M L Clark, M J G Farthing
Journal: Gut (1998)

Surgery in patients with malignant bile duct obstruction is associated with high postoperative morbidity and mortality. Tumour necrosis factor alpha (TNF-alpha) plays a key role in the pathogenesis of these complications.To determine the effect of biliary drainage on plasma concentrations of TNF-alpha, its soluble circulating receptors (sTNFr), and other proinflammatory cytokines.Plasma concentrations of TNF-alpha, sTNFr-P75, interleukin 6 (IL-6), and IL-1 alpha were measured in 25 patients with malignant bile duct obstruction before and after endoscopic stent insertion.Mean serum bilirubin was 157 mumol/l before stent insertion and 35.2 mumol/l one week post stent insertion. There was complete relief of jaundice in 77% of patients by four weeks. Plasma concentrations of TNF-alpha and IL-1 alpha were below the detection limit of the assays in all samples. Median plasma sTNFr-P75 in the cancer patients was 960 ng/l (range 400-6600), before stent insertion and remained unchanged at one and four weeks after stenting. Plasma sTNFr-P75 in cancer patients was significantly higher (p < 0.01) than in healthy controls (250 (200-650) ng/l). Before stent insertion, plasma IL-6 concentrations were detectable (above 5 ng/l) in 17 (68%) patients. After relief of biliary obstruction IL-6 levels fell from a prestent median of 13.2 to less than 5 ng/l at one week after stent insertion. Plasma concentrations of IL-6 were undetectable in 76% of patients at this time.Activation of the TNF/sTNFr complex is unchanged after biliary drainage in patients with malignant bile duct obstruction. This may explain why preoperative drainage does not influence the high morbidity and mortality associated with surgery in these patients.
In situ validation of an intestinal stem cell signature in colorectal cancer
Authors: Jennifer L Ziskin, Debra Dunlap, Murat Yaylaoglu, Imola K Fodor, William F Forrest, Rajesh Patel, Nianfeng Ge, Gordon G Hutchins, James K Pine, Philip Quirke, Hartmut Koeppen, Adrian M Jubb
Journal: Gut (2012)

<h3>Objective</h3> Wnt/Tcf, Lgr5, Ascl2 and/or Bmi1 signalling is believed to define the mouse intestinal stem cell niche(s) from which adenomas arise. The aim of this study was to determine the relevance of these putative intestinal stem cell markers to human colorectal cancer. <h3>Design</h3> 19 putative intestinal stem cell markers, including Ascl2 and Lgr5, were identified from published data and an evaluation of a human colorectal gene expression database. Associations between these genes were assessed by isotopic in situ hybridisation (ISH) in 57 colorectal adenocarcinomas. Multiplex fluorescent ISH and chromogenic non-isotopic ISH were performed to confirm expression patterns. The prognostic significance of Lgr5 was assessed in 891 colorectal adenocarcinomas. <h3>Results</h3> Ascl2 and Lgr5 were expressed in 85% and 74% of cancers respectively, and expression was positively correlated (p=0.003). Expression of Bmi1 was observed in 47% of cancers but was very weak in 98% of cases with expression. Both Ascl2 and/or Lgr5 were positively correlated with the majority of genes in the signature but neither was correlated with Cdk6, Gpx2, Olfm4 or Tnfrsf19. Lgr5 did not have prognostic significance. <h3>Conclusion</h3> These data suggest that 74–85% of colorectal cancers express a Lgr5/Ascl2 associated signature and support the hypothesis that they derive from Lgr5<sup>+</sup>/Ascl2<sup>+</sup> crypt stem cells, not Bmi1<sup>+</sup> stem cells. However, Olfm4 was not found to be a useful marker of Lgr5<sup>+</sup> cells in normal colon or tumours. In this large series, Lgr5 expression is not associated with increased tumour aggressiveness, as might be expected from a cancer stem cell marker.
A Model of Cardiac Muscle Dynamics
Authors: EDWARD S. GROOD, ROBERT E. MATES, HERMAN FALSETTI
Journal: Circulation Research (1974)

A mathematical model is presented describing the time- and length-dependent behavior of cardiac muscle. The model describes a wider variety of experimental data than do previously published models. It incorporates a modification of the Hill equation describing the force-velocity relation. Based on the sliding filament theory, the revised equation includes the effects of finite cross-bridge compliance proposed by A. F. Huxley. The essential simplicity of the Hill equation is retained; however, the model successfully predicts force development during both isometric and isotonic contractions, observed deactivation of the contractile element during isotonic shortening, and the apparent dependence of series elastic stiffness on time after stimulation during quick-release and quick-stretch experiments.
Whooping cough in school age children with persistent cough: prospective cohort study in primary care
Authors: Anthony Harnden, Cameron Grant, Timothy Harrison, Rafael Perera, Angela B Brueggemann, Richard Mayon-White, David Mant
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To estimate the proportion of school age children with a persistent cough who have evidence of a recent <i>Bordetella pertussis</i> infection. <b>Design</b> Prospective cohort study (October 2001 to March 2005). <b>Setting</b> General practices in Oxfordshire, England. <b>Participants</b> 172 children aged 5-16 years who presented to their general practitioner with a cough lasting 14 days or more who consented to have a blood test. <b>Main outcome measures</b> Serological evidence of a recent <i>Bordetella pertussis</i> infection; symptoms at presentation; duration and severity of cough; sleep disturbance (parents and child). <b>Results</b> 64 (37.2%, 95% confidence interval 30.0% to 44.4%) children had serological evidence of a recent <i>Bordetella pertussis</i> infection; 55 (85.9%) of these children had been fully immunised. At presentation, children with whooping cough were more likely than others to have whooping (odds ratio 2.85, 95% confidence interval 1.39 to 5.82), vomiting (4.35, 2.04 to 9.25), and sputum production (2.39, 1.14 to 5.02). Children with whooping cough were also more likely to still be coughing two months after the start of their illness (85% <i>v</i> 48%; P = 0.001), continue to have more than five coughing episodes a day (P = 0.049), and cause sleep disturbance for their parents (P = 0.003). <b>Conclusions</b> For school age children presenting to primary care with a cough lasting two weeks or more, a diagnosis of whooping cough should be considered even if the child has been immunised. Making a secure diagnosis of whooping cough may prevent inappropriate investigations and treatment.
Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study
Authors: Marco Mura, Maria A. Porretta, Elena Bargagli, Gianluigi Sergiacomi, Maurizio Zompatori, Nicola Sverzellati, Amedeo Taglieri, Fabrizio Mezzasalma, Paola Rottoli, Cesare Saltini, Paola Rogliani
Journal: European Respiratory Journal (2012)

The natural history of idiopathic pulmonary fibrosis (IPF) is not well defined and its clinical course is variable. We sought to investigate the survival and incidence of acute exacerbations (AEs) and their significant predictors in newly diagnosed patients. 70 patients newly diagnosed with IPF were prospectively followed for at least 3 yrs. Baseline evaluation included Medical Research Council dyspnoea score (MRCDS), 6-min walk test, pulmonary function tests, all of which were repeated at 6 months, and high-resolution computed tomography. A retrospective cohort of 68 patients was used for confirmation. Mean survival from the time of diagnosis was 30 months, with a 3-yr mortality of 46%. A Risk stratificatiOn ScorE (ROSE) based on MRCDS &gt;3, 6-min walking distance ≤72% predicted and composite physiologic index &gt;41 predicted 3-yr mortality with high specificity. 6-month progression of ROSE predicted rapid progression. 3-yr incidence of AE was 18.6%, mostly occurring in the first 18 months; risk factors for AE were concomitant emphysema and low diffusing coefficient of the lung for carbon monoxide. Results were confirmed in an independent cohort of patients. In newly diagnosed IPF, advanced disease at presentation, rapid progression and AEs are the determinants of 3-yr survival. The purpose of the multifactorial ROSE is to risk-stratify patients in order to predict survival and detect rapid disease progression.
Role of the Cytosolic Chaperones Hsp70 and Hsp90 in Maturation of the Cardiac Potassium Channel hERG
Authors: Eckhard Ficker, Adrienne T. Dennis, Lu Wang, Arthur M. Brown
Journal: Circulation Research (2003)

The human ether-a-gogo-related gene (hERG) encodes the alpha subunit of the cardiac potassium current IKr. Several mutations in hERG produce trafficking-deficient channels that may cause hereditary long-QT syndrome and sudden cardiac death. Although hERG currents have been studied extensively, little is known about the proteins involved in maturation and trafficking of hERG. Using immunoprecipitations, we show that the cytosolic chaperones heat shock protein (Hsp) 70 and Hsp90, but not Grp94, interact with hERG wild type (WT) during maturation. The specific Hsp90 inhibitor geldanamycin prevents maturation and increases proteasomal degradation of hERG WT, while reducing hERG currents in heterologous expression systems. In ventricular myocytes, inhibition of Hsp90 also decreases IKr, whereas geldanamycin had no effect on IKs or heterologously expressed Kv2.1 and Kv1.5 currents. Both Hsp90 and Hsp70 interact directly with the core-glycosylated form of hERG WT present in the endoplasmic reticulum but not the fully glycosylated, cell-surface form. For the trafficking-deficient LQT2 mutants, hERG R752W and hERG G601S, interactions with Hsp90 and Hsp70 are increased as both mutants remained tightly associated with Hsp90 and Hsp70 in the endoplasmic reticulum. Incubation at lower temperature for R752W or with the hERG blocker astemizole for G601S dissociates channel-chaperone complexes and restores trafficking. In contrast, nonfunctional but trafficking-competent hERG G628S is released from chaperone complexes during maturation comparable to WT. We conclude that Hsp90 and Hsp70 are crucial for the maturation of hERG WT as well as the retention of trafficking-deficient LQT2 mutants. The full text of this article is available online at http://www.circresaha.org.
The Impact of Adding Taxanes to Gemcitabine and Platinum Chemotherapy for the First-Line Therapy of Advanced or Metastatic Urothelial Cancer: A Systematic Review and Meta-analysis
Authors: Patrizia Giannatempo, Gregory R. Pond, Guru Sonpavde, Daniele Raggi, Gurudatta Naik, Matthew D. Galsky, Joaquim Bellmunt, Andrea Necchi
Journal: European Urology (2015)
A comparison between criteria for diagnosing atopic eczema in infants
Authors: H. Johnke, W. Vach, L.A. Norberg, C. Bindslev-Jensen, A. Host, K.E. Andersen
Journal: British Journal of Dermatology (2005)

Journal Article A comparison between criteria for diagnosing atopic eczema in infants Get access H. Jøhnke, H. Jøhnke Departments of Dermato‐venereology and Paediatrics, Odense University Hospital, University of Southern Denmark, DK‐5000 Odense, Denmark Hanne Jøhnke. E‐mail: hj@dadlnet.dk Search for other works by this author on: Oxford Academic Google Scholar W. Vach, W. Vach Department of Statistics, University of Southern Denmark, Odense, Denmark Search for other works by this author on: Oxford Academic Google Scholar L.A. Norberg, L.A. Norberg Departments of Dermato‐venereology and Paediatrics, Odense University Hospital, University of Southern Denmark, DK‐5000 Odense, Denmark Search for other works by this author on: Oxford Academic Google Scholar C. Bindslev‐Jensen, C. Bindslev‐Jensen Departments of Dermato‐venereology and Paediatrics, Odense University Hospital, University of Southern Denmark, DK‐5000 Odense, Denmark Search for other works by this author on: Oxford Academic Google Scholar A. Høst, A. Høst Departments of Dermato‐venereology and Paediatrics, Odense University Hospital, University of Southern Denmark, DK‐5000 Odense, Denmark Search for other works by this author on: Oxford Academic Google Scholar K.E. Andersen K.E. Andersen Departments of Dermato‐venereology and Paediatrics, Odense University Hospital, University of Southern Denmark, DK‐5000 Odense, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 2, 1 August 2005, Pages 352–358, https://doi.org/10.1111/j.1365-2133.2005.06491.x Published: 01 August 2005 Article history Accepted: 09 October 2004 Published: 01 August 2005
Several Classes of New Drugs Emerging for Parkinson Disease
Authors: Pat Phillips
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Redistribution of Renal Blood Flow Produced by Furosemide and Ethacrynic Acid
Authors: A. G. BIRTCH, R. M. ZAKHEIM, L. G. JONES, A. C. BARGER
Journal: Circulation Research (1967)

Outer medullary blood flow ( 85 Kr method) is markedly reduced by furose-mide and ethacrynic acid injected into the renal artery of unanesthetized dogs; juxtamedullary cortical flow is also decreased. Anatomic localization of the redistribution was verified by autoradiography and by silastic injection studies. The injected specimens demonstrated a relative increase in the resistance of the peritubular capillaries of the juxtamedullary cortex and outer medulla, the blood supply of the juxtamedullary tubules, Henle's loops and collecting ducts; the vasa recta were dilated. Total renal blood flow (Doppler Flowmeter) decreased 10% 1 min after injection, and then gradually began to increase at 2 to 3 min, reaching levels 25 to 30% above control as cortical blood flow increased. The vasodilatation in the cortex is probably localized in the pars radiata. The onset of the diuresis coincided with the decrease in renal blood flow, and persisted after total renal blood flow returned to control value. Thus, the time course of the dicresis correlated more closely with the sustained decrease in juxtameduiary and outer medullary blood flow.
Performance of Immuno–Positron Emission Tomography with Zirconium-89-Labeled Chimeric Monoclonal Antibody U36 in the Detection of Lymph Node Metastases in Head and Neck Cancer Patients
Authors: Pontus K.E. Börjesson, Yvonne W.S. Jauw, Ronald Boellaard, Remco de Bree, Emile F.I. Comans, Jan C. Roos, Jonas A. Castelijns, Maria J.W.D. Vosjan, J. Alain Kummer, C. René Leemans, Adriaan A. Lammertsma, Guus A.M.S. van Dongen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Immuno–positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 (89Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with 89Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases. Experimental Design: Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq 89Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with 18F-fluoro-2-deoxy-d-glucose. Immuno-PET scans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis. Results: Immuno-PET detected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumor-involved neck levels and sides, immuno-PET and 18F-fluoro-2-deoxy-d-glucose PET gave comparable diagnostic results. Conclusion: In this study, immuno-PET with 89Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.
Beneficial effects of treatment of early subclinical rejection
Authors: D Rush, P Nickerson, J Gough, R McKenna, P Grimm, M Cheang, K Trpkov, K Solez, J Jeffery
Journal: Journal of the American Society of Nephrology (1998)

The prevalence of subclinical rejection, by the Banff criteria, is approximately 30% in the first 3 mo in renal transplant recipients. A randomized study was performed to determine whether the treatment of subclinical rejection with corticosteroids was associated with improved outcomes in these patients. Seventy-two patients, stratified by donor source, were randomized to biopsies at 1, 2, 3, 6, and 12 mo (Biopsy group), or to 6- and 12-mo biopsies only (Control group). Patients were analyzed by "intent to treat" and were followed for a minimum of 2 yr. Patients in the Biopsy arm of the study had a significant decrease in early (months 2 and 3) and late (months 7 to 12) acute rejection episodes, a reduced chronic tubulointerstitial score at 6 mo, and a lower serum creatinine at 24 mo than did patients in the Control arm. There was a trend toward an increase in infectious morbidity, but no increase in mortality, in the patients randomized to the Biopsy group. The results of this study suggest that early protocol biopsies and the treatment of subclinical rejection with corticosteroids may lead to better histologic and functional outcomes in renal transplant recipients.
Pulmonary arterial hypertension in systemic sclerosis: a distinctive endotheliopathy?
Authors: S. E. Orfanos, D. Langleben
Journal: European Respiratory Journal (2009)

To the Editors: 

We read with great interest the recent article by Overbeek et al. 1 on the histological differences in pulmonary vessels from patients with pulmonary arterial hypertension (PAH) related to systemic sclerosis (SSc) versus idiopathic PAH (IPAH). The study demonstrates that pulmonary pathological features in patients suffering from limited cutaneous SSc (lcSSc) differ from the ones seen in IPAH, in relation to the occurrence of small vessel intimal fibrosis, the presence of pulmonary veno-occlusive disease-like lesions, and the absence of plexiform lesions in the former group. Overbeek et al. 1 correctly suggest that their findings point to the presence of a distinct vasculopathy in the SSc cohort that may contribute to the lower transfer factor of the lung for …