tbuckley/cabot-search huggingface dataset:
Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension
Authors: Elaine Soon, Alan M. Holmes, Carmen M. Treacy, Natalie J. Doughty, Laura Southgate, Rajiv D. Machado, Richard C. Trembath, Simon Jennings, Lucy Barker, Paul Nicklin, Christoph Walker, David C. Budd, Joanna Pepke-Zaba, Nicholas W. Morrell
Journal: Circulation (2010)

Background— Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. Methods and Results— We measured levels of serum cytokines (tumor necrosis factor-α, interferon-γ and interleukin-1β, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1β, -2, -4, -6, -8, -10, and -12p70 and tumor necrosis factor-α compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of &gt;9 pg/mL was 30% compared with 63% for patients with levels ≤9 pg/mL ( P =0.008). In this PAH cohort, cytokine levels were superior to traditional markers of prognosis such as 6-minute walk distance and hemodynamics. Conclusions— This study illustrates dysregulation of a broad range of inflammatory mediators in idiopathic and familial PAH and demonstrates that cytokine levels have a previously unrecognized impact on patient survival. They may prove to be useful biomarkers and provide insight into the contribution of inflammation in PAH.
Putative amino acid sequence of HLA-DRB chain contributing to rheumatoid arthritis susceptibility.
Authors: Y Watanabe, K Tokunaga, K Matsuki, F Takeuchi, K Matsuta, H Maeda, K Omoto, T Juji
Journal: The Journal of Experimental Medicine (1989)

The association between HLA-DR4 and rheumatoid arthritis (RA) has been established in many ethnic groups. To clarify the determinant of susceptibility to RA, a polymorphic segment of the HLA-DRB gene was amplified in vitro by polymerase chain reaction and analyzed with oligonucleotide probes specific for the HLA-DR4 DNA sequences. A particular sequence encoding amino acids Gln70-Arg71-Arg72-Ala73-Ala74 showed a strong association with RA (p less than 0.005, relative risk 6.0). This amino acid sequence occurs in the DRB molecules with three RA-associated specificities, DR4/Dw14, DR4/Dw15, and DR1. DR4/Dw4, which is common in Caucasian RA patients, has a strikingly similar amino acid sequence Gln70-Lys71-Arg72-Ala73-Ala74 in terms of polarity and charge profiles. Other RA nonassociated sequences differ from this sequence by at least one amino acid substitution that causes the change of the net charge. The composition of amino acid residues at the positions 70-74 may play a crucial role in the pathogenesis of RA.
GENETICS OF SOMATIC MAMMALIAN CELLS
Authors: T. T. Puck, H. W. Fisher
Journal: The Journal of Experimental Medicine (1956)

The parental HeLa cell population, a morphologically uniform, human cancer cell strain, grown for several years in tissue culture by procedures always involving massive inocula, has been shown to contain different mutant cell types. Two clonal lines have been isolated and established as reliable stock cultures. Both strains exhibit 100 per cent plating efficiency in high or low serum concentrations in the presence of a feeder system. In the absence of a feeder system and in low serum concentrations, the two strains are quantitatively differentiable: S3 still exhibits 100 per cent plating efficiency, while that of S1 lies in the neighborhood of zero. These differences have remained stable throughout 100 successive generations of growth of each strain including 2 single cell isolations. Application of these techniques to studies in the genetics of mammalian somatic cells and to specific cell-cell interactions has been indicated.
Differential Expression of Nephrin According to Glomerular Size in Early Diabetic Kidney Disease
Authors: Jin-Ju Kim, Jin Ji Li, Dong-Sub Jung, Seung-Jae Kwak, Dong-Ryeol Ryu, Tae-Hyun Yoo, Seung Hyeok Han, Hoon Young Choi, Hyung Jong Kim, Dae Suk Han, Shin-Wook Kang
Journal: Journal of the American Society of Nephrology (2007)

Diabetic nephropathy (DN) is clinically characterized by proteinuria. Many studies tried to demonstrate a relationship between proteinuria and changes in nephrin in various forms of glomerular diseases including DN, but the results are not consistent. Glomerular hypertrophy occurs in DN, yet hypertrophy does not develop in all glomeruli concurrently. For investigation of the differences in nephrin expression according to glomerular size, glomeruli were isolated from 10 control and 10 streptozotocin-induced diabetic rats at 6 wk after the induction of diabetes by a sieving technique using sieves with pore sizes of 250, 150, 125, and 75 microm. Glomeruli then were classified into large glomeruli (LG; on the 125-microm sieve) and small glomeruli (SG; on the 75-microm sieve) groups. Glomerular volumes were determined using an image analyzer, and mRNA and protein expression was determined by real-time PCR and Western blot, respectively. The mean volumes of diabetic LG (1.51 +/- 0.06 x 10(6) microm(3)) and control LG (1.37 +/- 0.05 x 10(6) microm(3)) were significantly higher than those of diabetic SG (0.94 +/- 0.03 x 10(6) microm(3)) and control SG (0.87 +/- 0.03 x 10(6) microm(3); P < 0.01). Nephrin mRNA expression was significantly reduced in the diabetic LG group compared with the diabetic SG and control glomeruli groups (P < 0.05). In contrast, nephrin mRNA expression was significantly higher in the diabetic SG group compared with the diabetic LG and control glomeruli groups (P < 0.05). Even after correction for 18s rRNA and Wilms' tumor-1 mRNA expression, the differences in nephrin mRNA expression remained significant. The expression of nephrin protein showed a similar pattern to the mRNA expression. In conclusion, these data suggest that the nephrin gene is differentially expressed according to glomerular size. Furthermore, more hypertrophied glomeruli with lesser nephrin expression may be responsible for albuminuria in the early stage of DN.
Antitumor Effects of a Monoclonal Antibody that Binds Anionic Phospholipids on the Surface of Tumor Blood Vessels in Mice
Authors: Sophia Ran, Jin He, Xianming Huang, Melina Soares, Douglas Scothorn, Philip E. Thorpe
Journal: Clinical Cancer Research (2005)

We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of viable vascular endothelial cells in tumors, possibly in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a monoclonal antibody directed against anionic phospholipids might exert antitumor effects by causing vascular damage in tumors.A new mouse immunoglobulin G3 monoclonal antibody, 3G4, was raised that binds anionic phospholipids in the presence of serum or beta2-glycoprotein I. The antibody was tested for its ability to localize to tumor vessels and exert antitumor effects in mice.3G4 recognized anionic phospholipids on the external membrane of H(2)O(2)-treated endothelial cells and in vitro. It localized specifically to tumor vascular endothelium and to necrotic tumor cells after injection into severe combined immunodeficient mice bearing orthotopic MDA-MB-435 tumors. Treatment with 3G4 retarded the growth of four different tumors in mice. It reduced the growth of established orthotopic MDA-MB-231 and MDA-MB-435 human breast tumors in mice by 75% and 65% respectively, large L540 human Hodgkin's tumors by 50%, and small syngeneic Meth A fibrosarcomas by 90%. Histologic examination revealed vascular damage, a reduction in vascular density, and a reduction in tumor plasma volume. Treatment with 3G4 induced the binding of monocytes to tumor endothelium and infiltration of macrophages into MDA-MB-435 and MDA-MB-231 tumors. No toxicity to the mice was observed.3G4 localizes specifically to complexes of anionic phospholipids and serum proteins on the surface of vascular endothelial cells in tumors in mice. This results in damage to tumor vasculature and suppression of tumor growth.
Culture of Human Endothelial Cells Derived from Umbilical Veins. IDENTIFICATION BY MORPHOLOGIC AND IMMUNOLOGIC CRITERIA
Authors: Eric A. Jaffe, Ralph L. Nachman, Carl G. Becker, C. Richard Minick
Journal: Journal of Clinical Investigation (1973)

Endothelial cells were isolated from freshly obtained human umbilical cords by collagenase digestion of the interior of the umbilical vein. The cells were grown in tissue culture as a homogeneous population for periods up to 5 mo and some lines were subcultured for 10 serial passages. During the logarithmic phase of cell growth, cell-doubling time was 92 h. Light, phase contrast, and scanning electron microscopy demonstrated that cultured human endothelial cells grew as monolayers of closely opposed, polygonal large cells whereas both cultured human fibroblasts and human smooth muscle cells grew as overlapping layers of parallel arrays of slender, spindle-shaped cells. By transmission electron microscopy, cultured endothelial cells were seen to contain cytoplasmic inclusions (Weibel-Palade bodies) characteristic of in situ endothelial cells. These inclusions were also found in endothelial cells lining umbilical veins but were not seen in smooth muscle cells or fibroblasts in culture or in situ. Cultured endothelial cells contained abundant quantities of smooth muscle actomyosin. Cultured endothelial cells also contained ABH antigens appropriate to the tissue donor's blood type; these antigens were not detectable on cultured smooth muscle cells or fibroblasts. These studies demonstrate that it is possible to culture morphologically and immunologically identifiable human endothelial cells for periods up to 5 mo.
Cumulative Risk for Developing End-Stage Renal Disease in the US Population
Authors: Bryce A. Kiberd, Catherine M. Clase
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The individual risk of developing end-stage renal disease (ESRD) and its overall impact on life expectancy is not known. This study’s objectives were to determine the effect of ESRD on life expectancy for a cohort of 20-yr-olds and to compare this impact to that of several cancers for which population-based screening programs exist. A computer simulation, stratified by race (white, black) and by gender was used to calculate cumulative lifetime risk of ESRD, life-years lost to ESRD, and cumulative Medicare payments for ESRD. Similar calculations were made for breast, prostate, and colorectal cancer. The cumulative lifetime risk of ESRD for a 20-yr-old black woman is 7.8%. Equivalent risks for black men are 7.3%, white men 2.5%, and white women 1.8%. Lost years of life attributable to ESRD are 1.09, 1.10, 0.40, and 0.32 yr for black women, black men, white men, and white women, respectively. In blacks, ESRD is responsible for nearly as much loss of life-years as breast cancer in women and more loss of life-years than colorectal or prostate cancer in men. In addition, treatment costs for ESRD in this population are many-fold more expensive than cumulative treatment costs of these cancers. Exploring new screening and treatment strategies may be warranted to prevent ESRD, particularly in the US black population.
Paediatric origins of adult lung disease bullet 1: The contribution of airway development to paediatric and adult lung disease
Authors: S. Stick
Journal: Thorax (2000)

In summary, factors that affect airway growth early in development appear to cause physiological effects that can be persistent. Reduced airway function early in life does not necessarily result in persistent symptoms, but the long term effects and impact on the development of chronic airflow limitation in adults are yet to be determined. Generally, long term sequelae seem to be related to the severity of the initial insult, but the development of persistent increased bronchial responsiveness is an independent risk factor for symptoms and abnormal lung function in later life. In addition, there appear to be separate genetic factors that influence atopy, airway development, and bronchial responsiveness.
The Relative Distribution of Membranous and Cytoplasmic Met Is a Prognostic Indicator in Stage I and II Colon Cancer
Authors: Fiona Ginty, Sudeshna Adak, Ali Can, Michael Gerdes, Melinda Larsen, Harvey Cline, Robert Filkins, Zhengyu Pang, Qing Li, Michael C. Montalto
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The association hepatocyte growth factor receptor (Met) tyrosine kinase with prognosis and survival in colon cancer is unclear, due in part to the limitation of detection methods used. In particular, conventional chromagenic immunohistochemistry (IHC) has several limitations including the inability to separate compartmental measurements. Measurement of membrane, cytoplasm, and nuclear levels of Met could offer a superior approach to traditional IHC. Experimental Design: Fluorescent-based IHC for Met was done in 583 colon cancer patients in a tissue microarray format. Using curvature and intensity-based image analysis, the membrane, nuclear, and cytoplasm were segmented. Probability distributions of Met within each compartment were determined, and an automated scoring algorithm was generated. An optimal score cutpoint was calculated using 500-fold crossvalidation of a training and test data set. For comparison with conventional IHC, a second array from the same tissue microarray block was 3,3′-diaminobenzidine immunostained for Met. Results: In crossvalidated and univariate Cox analysis, the membrane relative to cytoplasm Met score was a significant predictor of survival in stage I (hazard ratio, 0.16; P = 0.006) and in stage II patients (hazard ratio, 0.34; P ≤ 0.0005). Similar results were found with multivariate analysis. Met in the membrane alone was not a significant predictor of outcome in all patients or within stage. In the 3,3′-diaminobenzidine–stained array, no associations were found with Met expression and survival. Conclusions: These data indicate that the relative subcellular distribution of Met, as measured by novel automated image analysis, may be a valuable biomarker for estimating colon cancer prognosis.
Neutrophil-derived S100A12 as novel biomarker of inflammation in familial Mediterranean fever
Authors: T. Kallinich, H. Wittkowski, R. Keitzer, J. Roth, D. Foell
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> Familial Mediterranean fever (FMF) is characterised by recurrent periodic febrile attacks and persistent subclinical inflammation. The damage-associated molecular pattern (DAMP) protein S100A12 has proven to be a sensitive marker for disease activity and inflammation in numerous inflammatory disorders. The aim of this study was to analyse the role of S100A12 in the detection of inflammation in patients with FMF. <h3>Methods</h3> 52 children and adolescents with a clinical and/or genetic diagnosis of FMF were prospectively followed-up over 18 months (in total 196 visits). During clinical visits, erythrocyte sedimentation rate, C reactive protein, serum amyloid A and S100A12 serum concentrations were determined. Patients were categorised into four groups according to the clinical activity of FMF. <h3>Results</h3> Serum concentrations of S100A12 were excessively increased in patients with a mean increase of about 290-fold in active FMF above normal controls. S100A12 decreased significantly after introduction of colchicine therapy. Serum concentrations of S100A12 were significantly higher in patients treated with colchicine with persistent symptoms (mean±SEM, 6260±2120 ng/ml) than in those with clinically controlled disease (440±80 ng/ml, p&lt;0.001). In contrast to classical markers of inflammation, S100A12 was significantly elevated in clinically unaffected homozygous <i>MEFV</i> gene mutation carriers, indicating subclinical inflammation. <h3>Conclusions</h3> S100A12 is a valuable biomarker for monitoring disease activity, inflammation and response to colchicine treatment in patients with FMF. It might even be more sensitive in detecting subclinical inflammation than other available indicators.
A DROPLET CULTURE METHOD FOR FUNGUS ISOLATION, AND A STAINING METHOD FOR DIAGNOSIS OF EPIDERMOPHYTOSIS
Authors: JOHN CURRY
Journal: British Journal of Dermatology (1949)

Journal Article A DROPLET CULTURE METHOD FOR FUNGUS ISOLATION, AND A STAINING METHOD FOR DIAGNOSIS OF EPIDERMOPHYTOSIS Get access JOHN CURRY, M.B., Ch.B JOHN CURRY, M.B., Ch.B Assistant Medical Officer, Manchester and Salford Hospital for Skin Diseases; Assistant Lecturer in Dermatological Mycology, University of Manchester Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 61, Issue 2, 1 February 1949, Pages 54–58, https://doi.org/10.1111/j.1365-2133.1949.tb11318.x Published: 01 February 1949
Validation of information recorded on general practitioner based computerised data resource in the United Kingdom.
Authors: H Jick, S S Jick, L E Derby
Journal: BMJ (1991)

OBJECTIVE--To determine the extent of agreement between clinical information recorded on surgery computers of selected general practitioners and similar information in manual records of letters received from hospital consultants and kept in the general practitioners9 files. DESIGN--Hospital consultants9 letters in the manual records of selected general practitioners were photocopied and the consultants9 clinical diagnoses were compared with diagnoses recorded on computer. SETTING--General practices in the United Kingdom using computers provided by VAMP Health for recording clinical information. SUBJECTS--2491 patients who received one of three non-steroidal anti-inflammatory drugs and who attended 58 practices whose computer recorded data were considered after a preliminary review to be of satisfactory quality. RESULTS--Among 1191 patients for whom consultants9 letters were forwarded a clinical diagnosis reflecting the diagnosis noted on a consultant letter was present on the computer record for 1038 (87%). CONCLUSION--Clinical information available on the computer records of the general practitioners who participated in this study is satisfactory for many clinical studies.
p53 in rheumatoid arthritis synovial fibroblasts at sites of invasion
Authors: C A Seemayer
Journal: Annals of the Rheumatic Diseases (2003)

To analyse the functional response of p53 in rheumatoid arthritis synovial fibroblasts (RASF) in vitro and in vivo and to investigate whether activation of p53 modulates the destructive process of RASF.RASF and controls grown on chamber slides were either directly examined with DO7 anti-p53 antibodies by immunofluorescence or irradiated with 10 Gy x rays and analysed time dependently for the expression of p53. The percentage of positive cells was evaluated by a quantitative scoring system. RASF and normal (N) SF cultured in vitro were co-implanted with human cartilage in SCID mice for 60 days. Consecutively, the invasion score was evaluated, and the number of p53 positive cells was determined at the sites of invasion by immunohistochemistry. In addition, synovial tissues from RA, osteoarthritis, and normal synovia were stained with DO7 antibodies.In vitro the rate of expression of p53 in RASF was low (<5%), but transiently inducible by ionising irradiation (50%). In vitro low p53 expressing RASF disclosed, when invading articular cartilage, a nuclear p53 signal in 20% of the cells, indicating the induction of p53 in a distinct population of RASF during the invasive process.These data suggest an inductive p53 response at sites of cartilage invasion during the destructive process driven by activated RASF.
Immunogenicity and protective efficacy of a tuberculosis DNA vaccine
Authors: Kris Huygen, Jean Content, Olivier Denis, Donna L. Montgomery, Anne M. Yawman, R. Randall Deck, Corrille M. DeWitt, Ian M. Orme, Susan Baldwin, Celine D'Souza, Annie Drowart, Evelyne Lozes, Paul Vandenbussche, Jean-Paul Van Vooren, Margaret A. Liu, Jeffrey B. Ulmer
Journal: Nature Medicine (1996)
Prevention of Nosocomial Infection in Cardiac Surgery by Decontamination of the Nasopharynx and Oropharynx With Chlorhexidine Gluconate
Authors: Patrique Segers, Ron G H Speekenbrink, Dirk T Ubbink, Marc L van Ogtrop, Bas A de Mol
Journal: JAMA (2006)

Nosocomial infections are an important cause of morbidity and mortality after cardiac surgery. Decolonization of endogenous potential pathogenic microorganisms is important in the prevention of nosocomial infections.To determine the efficacy of perioperative decontamination of the nasopharynx and oropharynx with 0.12% chlorhexidine gluconate for reduction of nosocomial infection after cardiac surgery.A prospective, randomized, double-blind, placebo-controlled clinical trial conducted at the Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands, between August 1, 2003, and September 1, 2005. Of 991 patients older than 18 years undergoing elective cardiothoracic surgery during the study interval, 954 were eligible for analysis.Oropharyngeal rinse and nasal ointment containing either chlorhexidine gluconate or placebo.Incidence of nosocomial infection, in addition to the rate of Staphylococcus aureus nasal carriage and duration of hospital stay.The incidence of nosocomial infection in the chlorhexidine gluconate group and placebo group was 19.8% and 26.2%, respectively (absolute risk reduction [ARR], 6.4%; 95% confidence interval [CI], 1.1%-11.7%; P = .002). In particular, lower respiratory tract infections and deep surgical site infections were less common in the chlorhexidine gluconate group than in the placebo group (ARR, 6.5%; 95% CI, 2.3%-10.7%; P = .002; and 3.2%; 95% CI, 0.9%-5.5%; P = .002, respectively). For the prevention of 1 nosocomial infection, 16 patients needed to be treated with chlorhexidine gluconate. A significant reduction of 57.5% in S aureus nasal carriage was found in the chlorhexidine gluconate group compared with a reduction of 18.1% in the placebo group (P<.001). Total hospital stay for patients treated with chlorhexidine gluconate was 9.5 days compared with 10.3 days in the placebo group (ARR, 0.8 days; 95% CI, 0.24-1.88; P = .04).Decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate appears to be an effective method to reduce nosocomial infection after cardiac surgery.clinicaltrials.gov Identifier: NCT00272675.