tbuckley/cabot-search huggingface dataset:
S72 Clinical Prediction Models For Malignancy In Solitary Pulmonary Nodules - A Validation Study In A Uk Population
Authors: A. Al-Ameri, P. Malhotra, H. Thygesen, S. Vaidyanathan, P. Plant, S. Karthik, A. Scarsbrook, M. Callister
Journal: Thorax (2014)

<h3>Background</h3> Management of solitary pulmonary nodules (SPNs) depends critically on the pre-test probability of malignancy. Several quantitative prediction models have been developed using clinical and radiological criteria. Three models include CT criteria (Mayo, Veterans Association, Brock University) with a fourth model (Herder) incorporating FDG avidity on CT-PET scan in addition. These models have not been validated in a UK population, and the current study aimed to compare their performance in a population of patients recruited from a UK teaching hospital. <h3>Methods</h3> Patients with SPNs (4–30 mm) were retrospectively identified from the lung cancer MDT and a nodule follow-up clinic (n = 246). All patients had a final diagnosis confirmed by histology or radiological stability on a 2-year follow up. For each patient, the probability of the pulmonary nodule being malignant was calculated using the four models described. The models were used both in a restricted cohort of patients based on their respective exclusion criteria, and in the total cohort of patients. The accuracy of each model was assessed by calculating the area under the receiver operating characteristic (ROC) curve. <h3>Results</h3> The median age of the patient population was 69 years (range 32–94) and 50% were male. The prevalence of malignancy was 40.6% (33.3% primary lung cancer, 7.3% metastatic disease). Figure 1 shows the distribution of the probabilities of malignancy according to the four different models. The areas under the ROC curves for the cohorts restricted by respective exclusion criteria were (AUC, 95% CI): Mayo 0.892 (0.847–0.937); VA 0.736 (0.672–0.801); Brock 0.901 (0.855–0.947) and Herder 0.924 (0.875–0.974). For the total cohort, the AUC values were Mayo 0.873, VA 0.736, Brock 0.867 and Herder 0.916. There was no statistical difference between the Mayo and Brock models, but both were significantly better than VA (AUC difference of 0.14 and 0.13 respectively, p ≤ 0.0001 for both). The Herder model performed significantly better than both Mayo and Brock models (AUC difference of 0.10 and 0.14 respectively, p ≤ 0.01). <h3>Conclusion</h3> Both the Mayo and the Brock models perform well in a UK population, but accuracy is improved by incorporating CT-PET findings using the Herder prediction model.
Identification of a Cholangiocarcinoma-Like Gene Expression Trait in Hepatocellular Carcinoma
Authors: Hyun Goo Woo, Jeong-Hoon Lee, Jung-Hwan Yoon, Chung Yong Kim, Hyo-Suk Lee, Ja June Jang, Nam-Joon Yi, Kyung-Suk Suh, Kuhn Uk Lee, Eun Sung Park, Snorri S. Thorgeirsson, Yoon Jun Kim
Journal: Cancer Research (2010)

Abstract Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major adult liver cancers. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. Here, we applied an integrative oncogenomic approach to address the clinical and functional implications of the overlapping phenotype between these tumors. By performing gene expression profiling of human HCC, CHC, and CC, we identified a novel HCC subtype, i.e., cholangiocarcinoma-like HCC (CLHCC), which expressed cholangiocarcinoma-like traits (CC signature). Similar to CC and CHC, CLHCC showed an aggressive phenotype with shorter recurrence-free and overall survival. In addition, we found that CLHCC coexpressed embryonic stem cell–like expression traits (ES signature) suggesting its derivation from bipotent hepatic progenitor cells. By comparing the expression of CC signature with previous ES-like, hepatoblast-like, or proliferation-related traits, we observed that the prognostic value of the CC signatures was independent of the expression of those signatures. In conclusion, we suggest that the acquisition of cholangiocarcinoma-like expression traits plays a critical role in the heterogeneous progression of HCC. Cancer Res; 70(8); 3034–41. ©2010 AACR.
Bone development and inflammatory disease is regulated by AP-1 (Fos/Jun)
Authors: E F Wagner
Journal: Annals of the Rheumatic Diseases (2009)

The Fos and Jun proteins are members of the AP-1 transcription factor complex, which is a central regulator for many cellular functions. This paper summarises the important functions of Fos proteins in bone development, with special emphasis on the Fos-related proteins Fra-1 and Fra-2. These factors determine the functions of osteoblasts and osteoclasts and regulate cytokine signalling during bone development. Likewise, the Jun proteins control the expression of cytokines and chemokines and are probably causally involved in inflammatory skin diseases such as psoriasis. Investigations into the molecular mechanisms responsible for skin inflammation have revealed that Jun proteins control cytokine expression, such as granulocyte colony-stimulating factor, IL-6 and tumour necrosis factor alpha by transcriptional and posttranscriptional pathways. Finally, the paper discusses the relevance of the Jun-dependent mouse model for psoriasis for preclinical studies in the field of anti-angiogenic therapies.
HSP90 Inhibition Is Effective in Breast Cancer: A Phase II Trial of Tanespimycin (17-AAG) Plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab
Authors: Shanu Modi, Alison Stopeck, Hannah Linden, David Solit, Sarat Chandarlapaty, Neal Rosen, Gabriella D'Andrea, Maura Dickler, Mary E. Moynahan, Steven Sugarman, Weining Ma, Sujata Patil, Larry Norton, Alison L. Hannah, Clifford Hudis
Journal: Clinical Cancer Research (2011)

HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer.We enrolled patients with metastatic HER2(+) breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m(2) intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 17 months (95% CI: 16-28).This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted.
Quality-of-Life of Food Allergic Adults Improves after Double-Blind Placebo-Controlled Food Challenge: Preliminary results
Authors: B.M.J. Flokstra - de Blok, G.N. van der Meulen, J.N.G. Oude Elberink, B.J. Vlieg - Boerstra, A. DunnGalvin, J.O.B. Hourihane, E.J. Duiverman, A.E.J. Dubois
Journal: Journal of Allergy and Clinical Immunology (2009)
Ultrastructural and functional properties of cultured lung cancer-associated myofibroblasts
Authors: Siri Lehtonen, Henna Karvonen, Raija Sormunen, Elisa Lappi-Blanco, Magnus Sköld, Riitta Kaarteenaho
Journal: European Respiratory Journal (2013)

Cancer-associated stromal cells are important regulators of tumor progression. Our aim was to culture and characterize these cells.

Cells were cultured from 13 adeno-, 6 squamous cell and 2 other carcinomas. For comparison, the cells were cultured from tumor-free lung tissue of the same patients (4 non-smokers, 9 smokers and 8 smokers with COPD). The cultured cells were analysed by immunocytochemistry, transmission electron microscopy (TEM), immunoelectron microscopy (IEM), Western and gel contraction assay.

Cultured cells from both cancer and tumor-free lung were mixtures of fibroblasts and myofibroblasts. Cancer associated cells contained more alpha smooth muscle actin (αSMA) (p=0.006) and cancer associated myofibroblasts exhibited more αSMA labeling by IEM (p=0.01) than the cells cultured from tumor-free lung (fig 1). Amount of αSMA was lower in smokers’ cells cultured both from tumor and tumor-free lung than those from non-smokers (fig 1). Cells from lung cancers and smokers with COPD were more contractive than those from non-involved lung. Extracellular component of fibronexus by TEM associated with the contraction capacity of the cells.

![Figure][1] 



Our study shows that cultured cancer-associated myofibroblasts differ both structurally and functionally from cells of non-involved lung and this difference is maintained to some extent during prolonged cell culture. Smoking and COPD affected also the properties of the cells.

 [1]: pending:yes
Autoantibodies to Isolated Human Hepatocyte Plasma Membranes in Chronic Active Hepatitis. Ii. Specificity of Antibodies
Authors: Nigel R. Swanson, William D. Reed, Linda J. Yarred, Keith B. Shilkin, Richard A. Joske
Journal: Hepatology (1990)

The fine specificity of autoantibodies to human hepatocyte plasma membranes in autoimmune chronic active hepatitis was determined by one-dimensional immunoblotting. Sera from 12 patients with "classical" autoimmune chronic active hepatitis contained autoantibodies recognizing many human hepatocyte plasma membrane polypeptides in the 15 to 220 kD range. Many of these autoantibodies titrated beyond 1:80,000 and some may be potentially "pathological." In particular, one band with an apparent molecular weight of 60 kD was a dominant and consistent finding in all patients with autoimmune chronic active hepatitis by immunoblotting. Serum absorption studies showed this band to be predominantly liver-specific. Control sera from patients with chronic persistent hepatitis, nonhepatic autoimmune disease and normal healthy subjects possessed low titer reactivity that most likely represented "natural" autoantibodies. Anti-human hepatocyte plasma membranes in autoimmune chronic active hepatitis consisted of all three immunoglobulin isotypes (G,M and A) and their presence was not caused by nonspecific reactions as a consequence of hypergammaglobulinemia. Autoantibodies were shown to be specific by virtue of their absorption and exhaustion on titration. Many were directed at species nonspecific determinants, however, some autoantibodies recognized human-specific polypeptides. The majority of anti-human hepatocyte plasma membranes appeared to be organ-specific as sera from patients with autoimmune chronic active hepatitis reacted only weakly with polypeptides of kidney plasma membranes. Of the activity detected, few bands corresponded with those obtained using polypeptides of human hepatocyte plasma membranes. Our results show that patients with autoimmune chronic active hepatitis possess an array of liver-specific autoantibodies to polypeptide subunits of human hepatocyte plasma membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Estradiol and Testosterone Secretion by Human, Simian, and Canine Testes, in Males with Hypogonadism and in Male Pseudohermaphrodites with the Feminizing Testes Syndrome
Authors: R. P. Kelch, M. R. Jenner, R. Weinstein, S. L. Kaplan, M. M. Grumbach
Journal: Journal of Clinical Investigation (1972)

The role of the human testis in the production of 17beta-estradiol (E(2)) was investigated by determining the concentration of E(2) and testosterone in peripheral and spermatic vein plasma samples. Specimens were obtained from eight normal men, three men with hypogonadism, and two patients with the incomplete form of the feminizing testes syndrome. For comparison, similar studies were performed in four monkeys, 10 mongrel dogs, and 4 additional dogs who were given 1000 IU of human chorionic gonadotropin/day for 5 days. Plasma E(2) was measured by radioimmunoassay utilizing sheep anti-E(2) serum preceded by ether extraction and thin layer chromatographic separation of plasma steroids. Procedural blanks, which were subtracted from all reported values were 14.1+/-0.74 (SEM) pg for deionized water and 13.1+/-0.66 pg for charcoaladsorbed pooled male plasma. Pooled male and pooled female control plasmas averaged 17+/-0.71 pg/ml and 95+/-6.9 pg/ml, respectively; individual adult male specimens ranged between 8 and 28 with a mean of 18+/-1.4 pg/ml. In the eight normal men, the mean peripheral vein E(2) concentration was 20+/-1.6 pg/ml, while the spermatic vein concentration was 50 times as great, 1049+/-57 pg/ml. All three patients with testicular abnormalities had low spermatic vein E(2) concentrations (160, 280, and 416 pg/ml). Lesser E(2) gradients were found across the simian (3-fold) and canine (approximately 12-fold) testes. Testicular testosterone gradients (human 110-, simian 10-, and canine 77-fold) were greater than the E(2) gradients in all three species. In four dogs, HCG treatment elicited a 6-fold increase in peripheral and a 9-fold increase in spermatic vein testosterone concentrations; however, peripheral and spermatic vein E(2) concentrations did not differ from control values. Spermatic vein E(2) concentrations were > 4600 and 2210 pg/ml (post-HCG) in two patients with the incomplete form of the feminizing testes syndrome. Postorchiectomy, peripheral E(2) and testosterone concentrations fell precipitously in both patients, confirming the major contribution of the testes, in this syndrome, to circulating E(2) and testosterone. These studies provide direct evidence that the human testic secretes estradiol.
Dermatologists, Imiquimod, and Treatment of Molluscum Contagiosum in Children
Authors: Kenneth A. Katz
Journal: JAMA Dermatology (2015)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
Assessment of the rapid pullthrough technique in oesophageal manometry.
Authors: R J Goodall, D J Hay, J G Temple
Journal: Gut (1980)

The lower oesophageal sphincter pressure was measured by infusion manometry using the rapid pullthrough technique in two studies designed to evaluate this technique. The first study performed was an assessment of its reproducibility in individual subjects on separate occasions. We conclude that the rapid pullthrough technique does not give reproducible results. The second study compared the lower oesophageal sphincter pressure obtained by this technique with that by the standard station pullthrough technique. We conclude that the results are not comparable.
Edging Closer to Early Optimal Patient Management With High-Sensitivity Cardiac Troponin Assay
Authors: Fred S. Apple
Journal: Circulation (2011)

T hese are exciting times in the evolution of cardiac biomarkers.In the past 12 years, we have witnessed the transition from creatine kinase-MB to cardiac troponin I (cTnI) and T (cTnT) as the standard biomarkers to aid in the diagnosis of acute myocardial infarction (MI).This is evidenced by the overwhelming endorsement through recommendations from laboratory medicine, 1 cardiology, 2 and emergency medicine. 3At present, the biomarker field is moving forward with an analytic advancement of technologies to be able to measure both cTnT and cTnI for the precise measurement at concentrations within normal reference subjects.High-sensitivity cardiac troponin assays show great promise for earlier diagnostic accuracy for detection of MI, 4 improved triage of patients to allow for better outcomes assessment of low-risk acute coronary syndrome patients, 5 and to address a role in primary prevention as a necessary tool to assist clinicians in all cardiovascular evaluations. 6,7What distinguishes these new high-sensitivity assays from their predecessors is the ability to measure very low cTnT and cTnI concentrations (1 to 20 pg/mL, which equals 0.001 to 0.020 g/L, well below the limit of detection of the sensitive and contemporary assays used in clinical practice today), with an excellent imprecision (coefficient of variation Յ10%) at and below the assay's 99th percentile value.This added sensitivity allows high-sensitivity cardiac troponin assays to reliably measure concentrations in almost 100% of healthy individuals.Contemporary assays can typically measure cardiac troponin values in only 10% to 20% of individuals from the general, apparently healthy population.
Leukotoxin and its diol induce neutrophil chemotaxis through signal transduction different from that of fMLP
Authors: Y Totani, Y Saito, T Ishizaki, F Sasaki, S Ameshima, I Miyamori
Journal: European Respiratory Journal (2000)

When injected into animals, leukotoxin (Lx) causes acute lung injury which is associated with neutrophils infiltrating the lung tissues. However, the effect of Lx on neutrophils is still unknown, and recently it has been reported that Lx diol, a hydrolyzed metabolite, should be more potent than Lx in vitro. In this study, the authors examined the effect of Lx and its diol on human neutrophils by assessing their chemotactic response, expression of adhesion molecules, and production of peroxides. Both Lx and its diol induced chemotaxis in human neutrophils via an involvement of pertussis toxin-sensitive G-proteins, but they did not influence the expression of adhesion molecules or the production of peroxides. Furthermore, Lx synergistically affected chemotaxis with N-formyl-methionyl-leucyl-phenylalanine (fMLP), but not with endothelin-1. Neutrophil chemotaxis induced by both Lx and its diol was inhibited by phosphatidylinositol-3-kinase (PI3-K) inhibitors, but not by protein tyrosine kinase (PTK) inhibitors or by protein kinase C (PKC) inhibitors, whereas fMLP-induced chemotaxis was inhibited by PTK inhibitors, but not by PI3-K inhibitors or by PKC inhibitors. These results suggest that neutrophil chemotaxis induced by both Lx and its diol involves pathways different from those induced by fMLP. In conclusion, both leukotoxin and its diol metabolite induce chemotaxis in human neutrophils in a unique way and may act as important bioactive lipids when considering the pathological mechanism of acute lung injury.
A Systematic Investigation of 16 Cases of Neonaticide
Authors: M G Spinelli
Journal: American Journal of Psychiatry (2001)

Neonaticide, or infant murder on the day of birth, is often preceded by denial of pregnancy. The preponderance of case reports of neonaticide describes a pattern of pregnancy denial, dissociation, and ego disorganization. The author systematically investigated the clinical characteristics of 16 women charged with homicide in the United States after alleged neonaticides.The women received a psychiatric evaluation and were administered the Dissociative Experiences SCALE:Nearly all of the women reported similar precipitants and symptoms, including depersonalization, dissociative hallucinations, and intermittent amnesia at delivery.The characteristics of the women in the study were similar to those reported in the literature on neonaticide. The existence of this common pattern suggests that treatment strategies can be designed for women at risk for neonaticide.
Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry
Authors: R J Haidry, M A Butt, J M Dunn, A Gupta, G Lipman, H L Smart, P Bhandari, L Smith, R Willert, G Fullarton, M Di Pietro, C Gordon, I Penman, H Barr, P Patel, N Kapoor, J Hoare, R Narayanasamy, Y Ang, A Veitch, K Ragunath, M Novelli, L B Lovat
Journal: Gut (2014)

<h3>Background</h3> Barrett9s oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. <h3>Methods</h3> We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008–2010 and 2011–2013). Durability of successful treatment and progression to OAC were also evaluated. <h3>Results</h3> 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p&lt;0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p&lt;0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). <h3>Conclusions</h3> Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2–4% at 1 year in these high-risk patients. <h3>Trial registration number</h3> ISRCTN93069556.