tbuckley/cabot-search huggingface dataset:
Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer
Authors: P Langer, P H Kann, V Fendrich, N Habbe, M Schneider, M Sina, E P Slater, J T Heverhagen, T M Gress, M Rothmund, D K Bartsch
Journal: Gut (2009)

<h3>Objective:</h3> Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme. <h3>Aim:</h3> To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years. <h3>Methods:</h3> HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography. <h3>Results:</h3> Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1). <h3>Conclusions:</h3> In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.
PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY
Authors: J. S. Najarian, J. D. Feldman
Journal: The Journal of Experimental Medicine (1963)

Passive transfer of homograft immunity was successfully achieved by injection of the supernatant obtained from tissue-sensitized lymphoid cells disrupted by sonic vibration. The effective substance destroyed specific skin homografts within 6 days but did not reject non-specific skin grafts in this time. No evidence of transferred antigen or of transfer factor was found when the effective material was passed to irradiated recipients carrying test grafts. By a variety of physiochemical procedures the "soluble substance" behaved like a gamma globulin and was considered to be a transplantation antibody.
Reduction in Myocardial Collagen Cross-Linking Parallels Left Ventricular Dilatation in Rat Models of Systolic Chamber Dysfunction
Authors: A. J. Woodiwiss, O. J. Tsotetsi, S. Sprott, E. J. Lancaster, T. Mela, E. S. Chung, T. E. Meyer, G. R. Norton
Journal: Circulation (2001)

The transition from compensated left ventricular hypertrophy (LVH) to heart failure is associated with alterations in the myocardial interstitium. We hypothesized that LV dilatation is associated with modifications in collagen cross-linking.We studied 2 rat models of LV dilatation: (1) pressure-overload hypertrophy with heart failure (POH-F) induced by suprarenal abdominal aortic banding and (2) LVH induced by 7 months of isoproterenol (ISO, 0.04 mg x kg(-1) x d(-1)) administration. In POH-F rats and in rats receiving ISO, LV dilatation and a reduced systolic chamber performance were noted. Myocardial hydroxyproline concentrations ([HPRO]) were increased in the POH-F rats, whereas in rats receiving ISO, [HPRO] was decreased. In POH-F rats, the ratio of myocardial collagen type I to type III was increased, but in rats receiving ISO, myocardial collagen I/III was unchanged. In contrast to the diverse changes in myocardial collagen concentrations and phenotypes observed in the 2 models of LV dilatation, the ratio of myocardial insoluble to soluble (relationship between cross-linked and non-cross-linked) collagen was decreased in both the POH-F and ISO groups. Moreover, administration of captopril (0.22 mmol x kg(-1) x d(-1)), which inhibited the ISO-induced reduction in myocardial insoluble/soluble collagen but not the reduction in [HPRO], prevented the ISO-induced alterations in LV dimensions and performance.Because decreases in the ratio of myocardial insoluble to soluble collagen parallel LV dilatation in rats, reductions in myocardial collagen cross-linking may be an important mechanism contributing to LV dilatation in heart disease.
Accumulation of protoporphyrin IX from delta-aminolevulinic acid in bovine skin fibroblasts with hereditary erythropoietic protoporphyria. A gene-dosage effect.
Authors: S Sassa, S Schwartz, G Ruth
Journal: The Journal of Experimental Medicine (1981)

Bovine skin fibroblasts accumulated protoporphyrin IX when incubated in culture with the porphyrin-heme precursor, delta-aminolevulinic acid (ALA). Fibroblasts from cattle homozygous for erythropoietic protoporphyria (EPP) and with the clinical symptoms of the disease accumulated approximately sixfold greater amounts of protoporphyrin IX than cells from normal control animals. Cells from obligatory heterozygous animals, which are clinically normal, accumulated an intermediate level of protoporphyrin IX. When these cells were incubated with ALA and CaMg EDTA, all types of cells accumulated approximately the same amount of protoporphyrin IX (approximately 500 nmol/mg protein), suggesting that ferrochelatase activity was equally low after inhibition by treatment with CaMg EDTA in all cells. Thus the ratio of protoporphyrin IX accumulation from ALA in cultures treated with CaMg EDTA compared with controls treated with ALA alone was greatest in normal cells, least in EPP cells, and intermediate in the heterozygote cells. These findings suggest that the amount of protoporphyrin IX accumulation from ALA reflects the extent of deficiency of ferrochelatase and is proportional to the dosage of abnormal EPP gene in cultured fibroblasts. Similarly, stimulation of porphyrin accumulation by CaMg EDTA reflects diminished ferrochelatase activity in these cells. Thus, the results of this study demonstrate the usefulness of estimating protoporphyrin IX formation from ALA for the detection of an EPP gene defect in cultured bovine skin fibroblasts.
An audit of microbiological investigations performed on patients admitted with community acquired pneumonia
Authors: J.R. Wilson, J.M. Sloan, C.L. Griffin, M.E.M. Wilkie, J.D. Chalmers, S. Schembri
Journal: European Respiratory Journal (2012)

Introduction   The British Thoracic Society (BTS) guidelines suggest that blood and sputum culture be performed in patients with moderately severe community-acquired pneumonia (CAP). Atypical testing and viral PCR are recommended in severe CAP.  The aim was to identify whether the appropriate microbiological investigations are being performed on patients with CAP.   Method   This was a retrospective audit. CAP was defined as a clinical diagnosis of pneumonia in a patient with a new radiographic infiltrate. Microbiology investigations performed in CAP patients were compared against the same data collected in 94 CAP patients in 2008. The 2009 BTS guidelines served as the audit standard.   Results   210 patients were included. 55% had blood cultures taken, with bacteraemia confirmed in 15 patients. This compared with 70% having blood cultures in 2008,p=0.02.  16% (34) had sputum culture compared with 25% (24) in 2008, p=0.06.  11% had legionella antigen analysis compared with 16% in 2008. 10% had atypical serology carried out in 2011 and 22% in 2008. 12% had viral PCR compared to 5% in 2008.  In total, only 2.4% of patients had all of the recommended microbiology investigations (2.1% in 2008). 35.2% had no microbiology testing (21% in 2008,p=0.02).   Conclusions   Recommended microbiology investigations are underutilised in CAP patients. There has been a reduction in microbiological testing in comparison with 2008 figures.
Activin-A: active in inflammation in COPD
Authors: N. P. Tania, M. Schmidt, R. Gosens
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow limitation in which chronic inflammation of the airways plays a major role. The persistent inflammation is triggered by inhaled toxic substances, such as cigarette smoke. Accumulating evidence indicates the involvement of developmental pathways in chronic lung diseases, including COPD [1]. Signalling pathways such as transforming growth factor (TGF)-β, WNT and Sonic hedgehog have all been linked to COPD, either because of genetic associations or because of differential gene and protein expression in lung tissue [2–4]. Although these pathways were originally primarily known for their role in development, it is now increasingly clear that these pathways also play crucial regulatory roles in tissue inflammation and repair, providing a plausible explanation for the involvement of these pathways in COPD [3].

Activin-A, a member of the TGF-β superfamily, is an important regulator of embryonic development, haematopoiesis and a broad range of tightly regulated biological processes, including immunity and tissue repair [5]. Dysregulation of activin-A may contribute to the development of disease. Recently, increased expression of activin-A has been demonstrated in pulmonary hypertension [6], acute lung …
Radiofrequency Catheter Ablation of Atrial Fibrillation: A Cause of Silent Thromboembolism?
Authors: Fiorenzo Gaita, Domenico Caponi, Martina Pianelli, Marco Scaglione, Elisabetta Toso, Federico Cesarani, Carlo Boffano, Giovanni Gandini, Maria Consuelo Valentini, Roberto De Ponti, Franck Halimi, Jean François Leclercq
Journal: Circulation (2010)

Radiofrequency left atrial catheter ablation has become a routine procedure for treatment of atrial fibrillation. The aim of this study was to assess with preprocedural and postprocedural cerebral magnetic resonance imaging the thromboembolic risk, either silent or clinically manifest, in the context of atrial fibrillation ablation. The secondary end point was the identification of clinical or procedural parameters that correlate with cerebral embolism.A total of 232 consecutive patients with paroxysmal or persistent atrial fibrillation who were candidates for radiofrequency left atrial catheter ablation were included in the study. Pulmonary vein isolation or pulmonary vein isolation plus linear lesions plus atrial defragmentation with the use of irrigated-tip ablation catheters was performed. All of the patients underwent preprocedural and postablation cerebral magnetic resonance imaging. A periprocedural symptomatic cerebrovascular accident occurred in 1 patient (0.4). Postprocedural cerebral magnetic resonance imaging was positive for new embolic lesions in 33 patients (14). No clinical parameters such as age, hypertension, diabetes mellitus, previous history of stroke, type of atrial fibrillation, and preablation antithrombotic treatment showed significant correlation with ischemic cerebral embolism. Procedural parameters such as activated clotting time value and, in particular, electric or pharmacological cardioversion to sinus rhythm correlated with an increased incidence of cerebral embolism. Cardioversion was also associated with an increased risk of 2.75 (95 confidence interval, 1.29 to 5.89; P=0.009).Radiofrequency left atrial catheter ablation carries a low risk of symptomatic cerebral ischemia but is associated with a substantial risk of silent cerebral ischemia detected on magnetic resonance imaging. Independent risk factors for cerebral thromboembolism are the level of activated clotting time and, in particular, the electric or pharmacological cardioversion to sinus rhythm during the procedure.
Heat Shock Protein 90α Recruits FLIPS to the Death-Inducing Signaling Complex and Contributes to TRAIL Resistance in Human Glioma
Authors: Amith Panner, Joseph C. Murray, Mitchel S. Berger, Russell O. Pieper
Journal: Cancer Research (2007)

Heat shock protein 90 (HSP90) is a molecular chaperone that contributes to the proper folding and stability of target proteins. Because HSP90 has been suggested to interact with FLIP(S), the key regulator of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in glioma cells, we examined the role HSP90 played in controlling TRAIL response. HSP90alpha was found to associate with FLIP(S) in resting cells in a manner dependent on the ATP-binding NH2-terminal domain of HSP90alpha. Following TRAIL exposure, HSP90alpha and the client FLIP(S) protein were recruited to the death-inducing signaling complex (DISC). Short interfering RNA-mediated suppression of HSP90alpha did not alter the total cellular levels of FLIP(S), but rather inhibited the recruitment of FLIP(S) and other antiapoptotic proteins such as RIP and FLIP(L) to the DISC, and sensitized otherwise resistant glioma cells to TRAIL-induced apoptosis. These results show that HSP90alpha, by localizing FLIP(S) to the DISC, plays a key role in the resistance of tumor cells to TRAIL, and perhaps other proapoptotic agents. The results also define a novel means of apoptotic control by a HSP90alpha that may in turn help explain the global antiapoptotic effects of this protein.
Comparison of Clinical and Immunological Effects of Intravenous and Intradermal Administration of α-GalactosylCeramide (KRN7000)-Pulsed Dendritic Cells
Authors: Andrew J. Nicol, Andrea Tazbirkova, Mie Nieda
Journal: Clinical Cancer Research (2011)

Human Vα24+Vβ11+ natural killer T-cells (NKT cells) have antitumor activity via direct cytotoxicity and by induction of antitumor actions of T and NK cells. Activation of NKT cells is crucial for their antitumor activity and is induced by α-galactosylceramide (α-GalCer, KRN7000) presented by CD1d on dendritic cells (DC). We conducted a phase I clinical trial of therapy with α-GalCer-pulsed DC to determine safety, tolerability, immune effects and an optimal dose, and administration route.Twelve subjects (3 cohorts) with metastatic malignancy received 4 treatments of α-GalCer-pulsed DC, 2 treatments intravenously (IV), and 2 treatments intradermally (ID). Each successive cohort received a log higher cell dose. Clinical and immunological outcomes were evaluated, including secondary effects on NK and T cells.Substantial effects on peripheral blood NKT cells were observed but were greater following IV treatment. Secondary immune effects including activation of T and NK cells, increases in T- and NK-cell cytoplasmic interferon-γ, and increases in serum interferon-γ levels were seen after IV but not after ID treatment. Therapy was well tolerated, but 9 of 12 subjects had tumor flares with clinical findings consistent with transient tumor inflammation. Disease response (minor) or stabilization of disease progressing up to enrollment was observed in 6 of the 12 subjects. Stabilization of previously progressive disease lasted for at least one year in three subjects.We conclude that therapy with α-GalCer-pulsed DC induced clinically beneficial immune responses that are highly dependent on cell dose and administration route.
Terminal‐deoxynucleotidyl‐transferase immunofluorescence on bone marrow smears: Serial studies on 28 patients
Authors: William M. Miller, Sanford A. Stass, Harold R. Schumacher, Frederick J. Bollum
Journal: American Journal of Hematology (1981)

Terminal-deoxynucleotidyl-transferase (TdT) activity determinations, using the indirect immunofluorescence technique, were performed on 28 consecutive leukemia patients. Fifteen patients with acute lymphoblastic leukemia had 38 bone marrow smears examined. TdT-positive cells were a good indicator of disease activity in acute lymphoblastic leukemia in that numbers were increased at the time of diagnosis, normal during remission, and increased during relapse. Ten patients with acute myeloid leukemias had 42 smears studied. The number of TdT-positive cells did not reflect the activity of the disease, except for two patients with acute myelomonocytic leukemia in which TdT-positive cells were mildly increased during relapse. Three patients with chronic myelogenous leukemia had eight smears studied. The number of positive cells seemed meaningful only in following the course of lymphoid blast crisis. It would therefore appear that TdT determinations seem to be of value in lymphoblastic leukemia, but of limited value in myeloid leukemias.
Interaction of calcium and pentagastrin on gastric acid secretion in man
Authors: J. Christiansen, L. Hendel
Journal: Gut (1972)

In a recent report based on the study of a single human subject calcium was found to potentiate the action of pentagastrin on gastric acid secretion. To elucidate this problem gastric acid secretion was studied in five patients during stimulation with pentagastrin and during stimulation with pentagastrin and calcium. No potentiation between the two agents was found.
Vascular Structural and Functional Changes in Type 2 Diabetes Mellitus
Authors: Ian Schofield, Rayaz Malik, Ashley Izzard, Clare Austin, Anthony Heagerty
Journal: Circulation (2002)

Background— To further investigate vascular morphology and function in type 2 (non–insulin-dependent) diabetes mellitus (type 2D), small arteries were examined in vitro from carefully defined cohorts of patients with or without concomitant hypertension and the results compared with those from selected normotensive nondiabetic control subjects and a group of untreated patients with essential hypertension (EH). Methods and Results— Blood vessels were studied through the use of pressure myography to determine vascular morphology, mechanics, and myogenic responsiveness, together with testing of constrictor and dilator function. Small arteries from patients with EH demonstrated eutrophic inward remodeling and an increased distensibility. Vessels from type 2D patients demonstrated hypertrophy, a further increase in distensibility, and a highly significant loss of myogenic responsiveness compared with patients with EH and control patients. Vasoconstrictor function to norepinephrine was normal in patients with type 2D and type 2D+H and EH. Endothelium-dependent dilation was normal in patients with EH but abnormal in patients with type 2D and type 2D+H. There was a significant correlation between dilator impairment and the degree of dyslipidemia recorded in all groups. Conclusions— These results demonstrate vascular hypertrophy in small arteries from patients with type 2D. This could be a consequence of impaired myogenic responsiveness, which will increase wall stress for a given intraluminal pressure, which may be a stimulus for vascular hypertrophy. A substantial proportion of endothelial dysfunction can be attributed to an effect of the abnormal lipid profile seen in such patients.
Host factors and failure of interferon-α treatment in hepatitis C virus
Authors: Bin Gao, Feng Hong, Svetlana Radaeva
Journal: Hepatology (2004)

Failure of interferon-α (IFN-α) treatment in patients with chronic hepatitis C virus (HCV) infection is a challenging obstacle for clinical and experimental hepatology. Both viral and host factors have been implicated in reducing responsiveness to IFN-α therapy. The role of viral factors has been studied extensively and has been summarized in several review articles; however, much less attention has been paid to host factors. In this paper, we review evidence of host factor involvement in IFN-α treatment failure. We discuss possible underlying mechanisms responsible for these effects. Potential therapeutic strategies to enhance the effectiveness of IFN-α therapy for HCV are also proposed. (Hepatology 2004;39:880ndash;890.)
Lung function tests and risk factors for pneumonia in adults with chickenpox
Authors: A H Mohsen, R J Peck, Z Mason, L Mattock, M W McKendrick
Journal: Thorax (2001)

Varicella is 25 times more likely to be complicated by pneumonia in adults than in children. Data on changes in lung function following pneumonia are limited. This study was undertaken to describe the epidemiological factors associated with pneumonia and to investigate lung function up to 1 year following chickenpox.Thirty eight consecutive suitable patients admitted to a university hospital were enrolled in the study; 19 had pneumonia and 19 did not. Epidemiological data and density of rash were recorded, spirometric tests were performed, and carbon monoxide transfer factor was measured.Varicella pneumonia was associated with the presence of respiratory symptoms (p=0.006), current smoking (p=0.003), and history of close contact (p=0.009). There was a trend towards patients with pneumonia having a more severe rash. No association was observed between pneumonia and age or sex. Current smokers had a higher mean number of spots than non-smokers (p=0.005). Carbon monoxide transfer factor at hospital discharge was reduced in 27 patients (71%), more markedly in the group with pneumonia (p=0.009). Nine patients (seven with pneumonia) still had a reduced carbon monoxide transfer factor (mean reduction 36%) at 12 months.Chickenpox may result in a defect in carbon monoxide transfer factor for at least a year after acute illness.
Frequent Silencing of the Candidate Tumor Suppressor <i>PCDH20</i> by Epigenetic Mechanism in Non–Small-Cell Lung Cancers
Authors: Issei Imoto, Hiroyuki Izumi, Sana Yokoi, Hiroshi Hosoda, Tatsuhiro Shibata, Fumie Hosoda, Misao Ohki, Setsuo Hirohashi, Johji Inazawa
Journal: Cancer Research (2006)

Abstract Protocadherins are a major subfamily of the cadherin superfamily, but little is known about their functions and intracellular signal transduction. We identified a homozygous loss of protocadherin 20 (PCDH20, 13q21.2) in the course of a program to screen a panel of non–small-cell lung cancer (NSCLC) cell lines (1 of 20 lines) for genomic copy number aberrations using an in-house array-based comparative genomic hybridization. PCDH20 mRNA was expressed in normal lung tissue but was not expressed in the majority of NSCLC cell lines without a homozygous deletion of this gene (10 of 19 lines, 52.6%). Expression of PCDH20 mRNA was restored in gene-silenced NSCLC cells after treatment with 5-aza 2′-deoxycytidine. The DNA methylation status of the PCDH20 CpG-rich region correlated inversely with the expression of the gene and a putative target region for methylation showed clear promoter activity in vitro. Methylation of this PCDH20 promoter was frequently observed in primary NSCLC tissues (32 of 59 tumors, 54.2%). Among our primary NSCLC cases, the methylated PCDH20 seemed to be associated with a shorter overall survival (P = 0.0140 and 0.0211 in all and stage I tumors, respectively; log-rank test), and a multivariate analysis showed that the PCDH20 methylation status was an independent prognosticator. Moreover, restoration of PCDH20 expression in NSCLC cells reduced cell numbers in colony formation and anchorage-independent assays. These results suggest that epigenetic silencing by hypermethylation of the CpG-rich promoter region of PCDH20 leads to loss of PCDH20 function, which may be a factor in the carcinogenesis of NSCLC. (Cancer Res 2006; 66(9): 4617-26)