tbuckley/cabot-search huggingface dataset:
Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure
Authors: Emerson C. Perin, Hans F.R. Dohmann, Radovan Borojevic, Suzana A. Silva, Andre L.S. Sousa, Claudio T. Mesquita, Maria I.D. Rossi, Antonio C. Carvalho, Helio S. Dutra, Hans J.F. Dohmann, Guilherme V. Silva, Luciano Belém, Ricardo Vivacqua, Fernando O.D. Rangel, Roberto Esporcatte, Yong J. Geng, William K. Vaughn, Joao A.R. Assad, Evandro T. Mesquita, James T. Willerson
Journal: Circulation (2003)

Background— This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility. Methods and Results— Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage ≥6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups ( P =0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% ( P =0.003) and a reduction in end-systolic volume ( P =0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments ( P &lt;0.0005) at 4 months after treatment. Conclusions— Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrow–derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function.
Direct evidence for a β1-adrenergic receptor–directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy
Authors: Roland Jahns, Valérie Boivin, Lutz Hein, Sven Triebel, Christiane E. Angermann, Georg Ertl, Martin J. Lohse
Journal: Journal of Clinical Investigation (2004)

Today, dilated cardiomyopathy (DCM) represents the main cause of severe heart failure and disability in younger adults and thus is a challenge for public health. About 30% of DCM cases are genetic in origin; however, the large majority of cases are sporadic, and a viral or immune pathogenesis is suspected. Following the established postulates for pathogenesis of autoimmune diseases, here we provide direct evidence that an autoimmune attack directed against the cardiac β1-adrenergic receptor may play a causal role in DCM. First, we immunized inbred rats against the second extracellular β1-receptor loop (β1-ECII; 100% sequence identity between human and rat) every month. All these rats developed first, receptor-stimulating anti–β1-ECII Ab's and then, after 9 months, progressive severe left ventricular dilatation and dysfunction. Second, we transferred sera from anti–β1-ECII–positive and Ab-negative animals every month to healthy rats of the same strain. Strikingly, all anti–β1-ECII–transferred rats also developed a similar cardiomyopathic phenotype within a similar time frame, underlining the pathogenic potential of these receptor Ab's. As a consequence, β1-adrenergic receptor–targeted autoimmune DCM should now be categorized with other known receptor Ab-mediated autoimmune diseases, such as Graves disease or myasthenia gravis. Although carried out in an experimental animal model, our findings should further encourage the development of therapeutic strategies that combat harmful anti–β1-ECII in receptor Ab–positive DCM patients.
Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection
Authors: Simon Hellier, Angela J. Frodsham, Branwen J.W. Hennig, Paul Klenerman, Suzanne Knapp, Patricia Ramaley, Jack Satsangi, Mark Wright, Lyna Zhang, Howard C. Thomas, Mark Thursz, Adrian V.S. Hill
Journal: Hepatology (2003)

The effect of host genetic variation on the outcome of hepatitis C virus (HCV) infection and its treatment is poorly understood. The chemokine receptors CCR5, CCR2, and CCR3 and their ligands, RANTES, MCP–1, MCP–2, and MIP–1α, are involved in the immune responses and the selective recruitment of lymphocytes to the liver in HCV infection. We studied 20 polymorphisms within these genes and investigated their association with persistent carriage of HCV, severity of liver disease, hepatic inflammation, and response to treatment in a large European cohort. Significant associations were found between CCR5–Δ32 and reduced portal inflammation ( P = .011, odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.09–4.84) and milder fibrosis ( P = .015, OR: 1.97, 95% CI: 1.13–3.42). A promoter polymorphism at position -403 in the RANTES gene was associated with less severe portal inflammation ( P = .004). An amino acid change in MCP2, Q46K, was associated with severity of fibrosis ( P = .018, OR: 2.29, 95% CI: 1.14–4.58). In conclusion, our study suggests a possible role of the polymorphisms CCR5–Δ32, RANTES -403, and MCP–2 Q46K in the outcome of HCV infection.
Serotonin: a new start for an old friend?
Authors: A. Fabre, B. Crestani
Journal: Thorax (2010)

Anterior cruciate ligament (ACL) injuries have been a rising concern in the early years of the women’s Australian Football League (AFLW), eliciting headlines of a ‘knee crisis’ surrounding the league. There has been a focus on female biology as the primary factor driving the high rate of ACL injuries in the AFLW. Emphasising Australian football (AF) as being dangerous predominantly due to female biology may be misrepresenting a root cause of the ACL injury problem, perpetuating gender stereotypes that can restrict physical development and participation of women and girls in the sport. We propose that an approach addressing environmental and sociocultural factors, along with biological determinants, is required to truly challenge the ACL injury problem in the AFLW. Sports science and medicine must therefore strive to understand the whole system of women in AF, and question how to address inequities for the benefit of the athletes.
Subsensitivity to bronchoprotection against adenosine monophosphate challenge following regular once-daily formoterol
Authors: I Aziz, KS Tan, IP Hall, MM Devlin, BJ Lipworth
Journal: European Respiratory Journal (1998)

Regular treatment with inhaled long-acting beta2-agonists leads to subsensitivity to their bronchoprotective effects, although the effect of dosing frequency on this subsensitivity is not known. The aim of this study was to assess whether a once-daily dosing regimen with formoterol might be associated with a lesser degree of subsensitivity. In a randomized placebo-controlled double-blind, double-dummy crossover study 10 asthmatics treated with inhaled steroids (mean age 31 yrs, forced expiratory volume in one second (FEV1) 82% predicted) received 1 week of treatment with: formoterol dry powder 24 microg twice daily (08:00 and 20:00 h); formoterol 24 microg once daily (20:00 h); or identical placebo. Adenosine monophosphate (AMP) bronchial challenge was performed 12 h after the first and the last dose of each treatment. There was significant loss of protection with formoterol twice daily between the first and last dose (geometric mean provocative concentration causing a 20% fall in FEV1 (PC20)): 475 versus 129 mg x mL(-1) (a 3.7-fold loss, p=0.006) and with formoterol once daily: 367 versus 127 mg x mL(-1) (a 2.9-fold loss, p=0.005), compared with placebo: 71 versus 75 mg x ml(-1) (nonsignificant). There was no significant difference in the degree of loss of protection between formoterol once and twice daily. For first-dose protection there was a significant difference between active treatments and placebo, but after the last dose the residual protection between active treatments and placebo was not significant. Thus, in patients taking inhaled corticosteroids, regular formoterol 24 micreog once daily induces a similar degree of subsensitivity to adenosine monophosphate bronchial challenge as with formoterol 24 microg twice daily. This in turn suggests that even with a 24-h dosing interval there is the development of tolerance to formoterol by prolonged occupancy of airway beta2-adrenoceptors.
Prognostic Value of an Activation State Marker for Epidermal Growth Factor Receptor in Tissue Microarrays of Head and Neck Cancer
Authors: Anthony Kong, Pierre Leboucher, Russell Leek, Véronique Calleja, Stuart Winter, Adrian Harris, Peter J. Parker, Banafshé Larijani
Journal: Cancer Research (2006)

Overexpression and mutation of epidermal growth factor receptors (EGFR) have been shown to be important in the prognosis of several cancers, including head and neck cancers. However, our inability to define the activation status of these and other receptors limits our ability to assess the importance of these pathways and to exploit effectively new molecularly targeted treatments directed at their catalytic activities. Here we describe the use of automated, high-throughput fluorescence lifetime imaging microscopy to measure EGFR autophosphorylation status by fluorescence resonance energy transfer (FRET) in head and neck tumors. We have correlated FRET efficiency with the clinical and survival data. The results from head and neck arrays show that high FRET efficiency is correlated with worsening disease-free survival but not with overall survival. This powerful tool could be exploited as a new independent quantitative prognostic factor in clinical decisions and cancer management.
Randomized Phase II Trial of Capecitabine Plus Cisplatin Versus Paclitaxel as First Line Treatment for Metastatic Esophageal Squamous Cell Carcinoma
Authors: Su Jin Lee, Silvia Park, Wonjin Chang, Jung Yong Hong, Moon Ki Choi, Sungmin Kim, Moonjin Kim, Jeeyun Lee, Yeon Hee Park, Young-Hyuck Im, Se Hoon Park
Journal: Annals of Oncology (2013)
Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.
Authors: M S Klempner, C A Dinarello, J I Gallin
Journal: Journal of Clinical Investigation (1978)

The ability of highly purified human leukocytic pyrogen (LP) to induce neutrophil lysosomal protein release is described. Human peripheral blood neutrophils isolated by Ficoll-Hypaque and dextran sedimentation were exposed to purified human LP. The specific granule-associated proteins, lysozyme and lactoferrin were selectively released, whereas primary granule (beta-glucuronidase) and cytoplasmic (lactic dehydrogenase) enzyme markers were not. Optimum release was observed after 45 min in the presence of Ca++ and Mg++. Cytochalasin B (5 microgram/ml) had no effect on LP-induced lysosomal enzyme release. Since the pyrogenicity of LP is dependent on prostaglandin synthesis, the effect of two potent inhibitors of prostaglandin synthesis on lysozyme release was studied. Both indomethacin and naproxen failed to inhibit specific granule protein release. These observations suggest that the concommitance of fever, elevated serum or urine lysozyme and hypoferremia may, in part, be explained by the interaction of LP and peripheral blood neutrophils.
Analysis of MUC1, MUC 16 and TAG 72 expression in ovarian cancer: Antigens for multi-targeted antibody guided therapy
Authors: Subhash C. Chauhan, Namita Vinayek, Katrina Dunham, Yuhlong Lio, Michael D. Koch, Meena Jaggi
Journal: Clinical Cancer Research (2006)

B36  Objective: Approximately 16,000 women die in United States every year due to lack of an effective therapy for advanced stage ovarian cancer. Existing chemotherapy and surgical procedures employed for the treatment of ovarian cancer have their own limitations. The single antigen directed intraperitoneal radioimmunotherapy (IRIT) for ovarian cancer has shown only a limited success due to the heterogeneous presentation of tumor associated antigens (TAAs). To increase the therapeutic efficacy, a multi-targeting approach appears logical. Therefore, the expression of MUC1, MUC16 and TAG72 in alone and in combination was analyzed for developing an effective multi-targeted antibody guided therapy for ovarian cancer.Methods: Ovarian cancer tissue microarray slides were used containing 92 spots, including 72 various cancer types and 20 benign/non-neoplastic tissue samples. Using immunohistochemical analysis, we studied the expression of MUC1, MUC 16 and TAG 72 individually with Vectastain Elite ABC kit. Biocare medical chromagen staining kit was used for double and triple staining. The staining intensity and percent positive cells were recorded by a pathologist to calculate the mean composite scores. Paired t-test statistical analyses were performed to determined correlation between antigen expression with early and advanced stage.Results: In the majority of the ovarian cancer samples, TAG72, MUC1 and MUC16 showed a heterogeneous expression. Among all ovarian cancer types, 72, 61 and 50 percent samples showed immunoreactivity for TAG72, MUC1 and MUC16, respectively. Of the 48 epithelial ovarian cancer samples, TAG72, MUC1 and MUC16 expression was present in 89.5, 87.5 and 73 percent of cases, respectively. While upon combining the three markers, 98% of ovarian cancer samples were targeted. Expression of these antigens was significantly (p
Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or <i>PTPN22</i> susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis
Authors: C Potter, K L Hyrich, A Tracey, M Lunt, D Plant, D P M Symmons, W Thomson, J Worthington, P Emery, A W Morgan, A G Wilson, J Isaacs, A Barton
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To determine whether rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, or carriage of shared epitope (SE) and <i>PTPN22</i> genetic susceptibility variants predict response to therapy in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) agents. <h3>Methods:</h3> UK-wide multicentre collaborations were established to recruit a large cohort of patients treated with anti-TNF drugs for RA. Serum RF, anti-CCP antibody and SE status were determined using commercially available kits. <i>PTPN22</i> R620W genotyping was performed by Sequenom MassArray. Linear regression analyses were performed to investigate the role of these four factors in predicting response to treatment by 6 months, defined as the absolute change in 28-joint Disease Activity Score (DAS28). <h3>Results:</h3> Of the 642 patients analysed, 46% received infliximab, 43% etanercept and 11% adalimumab. In all, 89% and 82% of patients were RF and anti-CCP positive, respectively. Patients that were RF negative had a 0.48 (95% CI 0.08 to 0.87) greater mean improvement in DAS28 compared to patients that were RF positive. A better response was also seen among patients that were anti-CCP negative. No association was demonstrated between drug response and SE or <i>PTPN22</i> 620W carriage. <h3>Conclusion:</h3> The presence of RF or anti-CCP antibodies was associated with a reduced response to anti-TNF drugs. However, these antibodies only account for a small proportion of the variance in treatment response. It is likely that genetic factors will contribute to treatment response, but these do not include the well established RA susceptibility loci, SE and <i>PTPN22</i>.
Early human development. VIDEO
Authors: A H Sathananthan, S S Ratnam, A O Trounson, R G Edwards
Journal: Human Reproduction Update (1999)

This presentation covers original research conducted since 1977 on excess human embryos obtained from several invitro fertilization (IVF) centres around the world. Most of the embryos portrayed were developed from normal, monospermic, bipronuclear ova or from dispermic, tripronuclear ova, after fertilization. With respect to morphology, early dispermic embryos resemble normally fertilized embryos, although they are genetically triploid. The process of human fertilization has been already presented on CD-ROM. Two visual atlases have been published recently on human IVF and embryo development (Sathananthan et al., 1991; Sathananthan, 1996). The preimplantation development of the human embryo begins at fertilization and ends at the implantation of the blastocyst in the uterine endometrium on day 6 after fertilization. Preimplantation development occurs in the Fallopian tube or oviduct and in the uterus during which time the embryo cleaves by repeated mitosis to form a hollow blastocyst. There is little growth and differentiation during cleavage and the embryo is partly dependent on the secretions produced by the oviduct and uterus, since the human egg has no yolk. The embryonic genome is thought to be activated between the 4–8-cell stages of development and the first signs of cell differentiation are evident in the blastocyst, when an outer trophoblast and an inner cell mass or embryoblast have formed. Recent work suggests that somatic and germline cells may be allocated from the 4-cell stage (Edwards and Beard, 1997). The blastocyst finally hatches out from the zona pellucida, or shell, within the uterus and immediately invades the uterine endometrium by means of its trophoblast, after which it is dependent on the mother’s blood for sustenance and eventually develops a placenta. Molecular events during human implantation, especially those involving embryonic interleukins and epithelial β3 integrins, are described by Simon et al. (1998). Human embryos can be developed to blastocysts and even to hatching in vitro. This process of hatching is one of the wondrous events of early development. Embryos are normally developed to the 2–4-cell stages for embryo transfer during IVF and are replaced either in the uterus or Fallopian tube.
Impaired Glucose Tolerance and Bone Mineral Content in Overweight Latino Children With a Family History of Type 2 Diabetes
Authors: Afrooz Afghani, Martha L. Cruz, Michael I. Goran
Journal: Diabetes Care (2005)

OBJECTIVE—Research on the skeletal status of pre-diabetic (type 2 diabetic) children is warranted. We examined the hypothesis that bone mineral content (BMC) and bone mineral density (BMD) will be lower in children with impaired glucose tolerance (IGT) versus normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS—Total body BMC and BMD of 184 overweight Latino children (106 boys, 78 girls, 11.9 ± 1.7 years) with a family history of type 2 diabetes were measured using dual-energy X-ray absorptiometry. Glucose tolerance was assessed by 2-h glucose after an oral glucose tolerance test. Area under the insulin curve (AUC) assessed the cumulative insulin response to oral glucose. Acute insulin response to glucose (AIR) was determined by an intravenous glucose tolerance test. RESULTS—Partial correlations revealed an inverse relationship between BMC and AIR (r = −0.29, P = 0.00), AUC (r = −0.28, P = 0.00), fasting insulin (r = −0.16, P = 0.04), and 2-h insulin (r = −0.16, P = 0.04). There was no significant difference in BMC or BMD between children with IGT (n = 46) or NGT (n = 138). Stepwise multiple linear regression revealed that 89% of the variance in BMC is attributed to lean mass (87%), age (1%), and AIR (1%). BMD was explained by lean mass (69%), Tanner stage (3%), and AUC (2%). CONCLUSIONS—The findings of this study suggest that in overweight children, lean mass is the primary predictor of BMC and BMD, whereas age, Tanner stage, and the acute and cumulative insulin responses to oral glucose make subtle independent contributions to the total variances. In addition, poor glycemic control does not seem to be detrimental to bone mass of pre-diabetic children.
HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data
Authors: Angelo Di Leo, Christine Desmedt, John M S Bartlett, Fanny Piette, Bent Ejlertsen, Kathleen I Pritchard, Denis Larsimont, Christopher Poole, Jorma Isola, Helena Earl, Henning Mouridsen, Frances P O'Malley, Fatima Cardoso, Minna Tanner, Alison Munro, Chris J Twelves, Christos Sotiriou, Lois Shepherd, David Cameron, Martine J Piccart, Marc Buyse
Journal: The Lancet Oncology (2011)
Antibody to a 63 kilodalton insect protein in ankylosing spondylitis.
Authors: S R Brand, J Worthington, D P McIntosh, R M Bernstein
Journal: Annals of the Rheumatic Diseases (1992)

Ankylosing spondylitis (AS) is associated with antibodies to a heat shock puff on drosophila chromosomes. This observation was investigated by immunoblotting using extracts of the Schneider insect cell line and HeLa cells, before and after heat shock. An insect protein of 63 kilodaltons (but no equivalent human protein) was recognised by 21 (46%) of 46 serum samples from patients with AS, one of two patients with Reiter9s syndrome, four (7%) of 60 patients with systemic lupus erythematosus, and two (4%) of 50 control subjects, but not by serum samples from patients with rheumatoid arthritis (RA). Previous heat shock did not appear to affect the strength of reaction, but ML-30, a monoclonal antibody to the mycobacterial 65 kilodalton heat shock protein (hsp65), also recognised an insect protein of 63 kilodaltons by immunoblotting. Antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from patients with AS and RA. IgA binding to hsp65 was increased in 41% of AS and 19% of RA serum samples, but there was no correlation with detection of antibody to the insect 63 kilodalton protein.