tbuckley/cabot-search huggingface dataset:
Significance of Bladder Biopsies in Ta,T1 Bladder Tumors: A Report from the EORTC Genito-Urinary Tract Cancer Cooperative Group
Authors: Adrian van der Meijden, Wim Oosterlinck, Maurizio Brausi, Karl-Heinz Kurth, Richard Sylvester, Christine deBalincourt, and Members of the EORTC-GU Group Superficial Bladder Committee
Journal: European Urology (1999)
INTERACTIONS OF THE COMPLEMENT SYSTEM WITH ENDOTOXIC LIPOPOLYSACCHARIDE
Authors: R. Snyderman, H. Gewurz, S. E. Mergenhagen
Journal: The Journal of Experimental Medicine (1968)

Endotoxic lipopolysaccharide has recently been shown to fix large amounts of the complement components related to the biologic activities mediated by that system. The present study sought to determine whether the generation of chemotactic factor by endotoxin in serum was dependent upon complement system activation. Preheating serum, incubating at 0 degrees C, or incubating in the presence of EDTA, all prevented chemotactic factor generation as well as complement fixation by endotoxin. "Endotoxoids" deficient in complement-firing activity were also deficient in chemotactic factor generation. Chemotactic factor could not be generated by endotoxin in sera of mice congenitally deficient in the C'S component of complement, while chemotactic factor was generated by endotoxin in the sera of coisogenic mice with normal complement levels for that species. The chemotactic factor induced by endotoxin was heat stable and nondialyzable. Molecular sieve chromatography and sucrose density gradient ultracentrifugation demonstrated that the chemotactic factor was a relatively low molecular weight product (15,000-30,000) and as such different from previously scribed C' system-derived chemotactic factors. These experiments demonstrate that generation of chemotactic factor by endotoxin in serum is dependent upon C' system activation involving at least C'5. Furthermore, the relatively low molecular weight of this factor suggests that it might be derived from activation of a single complement component rather than from complexing of multiple complement components.
Localization of human platelet autoantigens to the cysteine-rich region of glycoprotein IIIa.
Authors: R Kekomaki, B Dawson, J McFarland, T J Kunicki
Journal: Journal of Clinical Investigation (1991)

The object of this study was to further localize autoantigenic structures on IIb-IIIa and, if possible, to precisely identify the epitopes recognized by human autoantibodies. In this paper, we identify a 50-kD chymotryptic fragment of IIIa that is recognized by a high percentage of human autoantibodies, typified by the prototype IgG autoantibody RA, which binds to IIIa on intact platelets as well as in an immunoblot assay under nonreduced conditions. Using an immunoblot assay, a carboxy-terminal region of this fragment (33 kD) that contains the cysteine-rich domains of IIIa was found to carry the epitope(s) recognized by the prototype autoantibody RA. The amino-terminal amino acid sequence of the reduced 33-kD fragment, the smallest fragment that retains the RA epitope, is XPSQQDEXSP, and that of the reduced 50-kD fragment is IVQVTFD. This indicates that the 33-kD fragment consists of approximately 175 amino acids beginning at residue 479 and extending at least through residues 636-654, while the 50-kD fragment spans the same region but begins at residue 427. It is apparent that the 33-kD fragment is generated from the 50-kD fragment by additional chymotryptic hydrolysis but remains associated because of the multiple disulfide bonds that are characteristic of this cysteine-rich domain. Sera from 48% of patients with chronic ITP and 2 of 8 patients with acute ITP contain antibodies that bind to the 50-kD fragment in an ELISA. Antibodies of the same specificity are also found in one-third of patients with either secondary immune thrombocytopenia or apparent non-immune thrombocytopenia. We conclude that the 50-kD cysteine-rich region of IIIa is a frequent target of autoantibodies in ITP, but that such antibodies may also be present in cases of thrombocytopenia that cannot be linked to an apparent autoimmune process.
Atrial Electrophysiology in Experimental Hyperthyroidism in Rabbits
Authors: MORTON F. ARNSDORF, RODERICK W. CHILDERS
Journal: Circulation Research (1970)

Male rabbits received l -thyroxine (250 µg/kg) subcutaneously for 7 days and exhibited marked tachycardia, elevation of protein-bound iodine levels and a 26% mean weight loss. Their hearts were isolated and perfused by the Langendorff technique. In 8 thyroid-treated rabbits the mean heart rate before they were killed and also after 30 minutes of perfusion was much higher than that of 10 controls; threshold in late diastole was lower, and the mean effective refractory period was shorter: 109 msec (95 to 116) as compared with 147 msec (130 to 170). The atrial multiple-response threshold was strikingly lower, and strength-interval curves were shifted to the left without overlap or change in contour. Atropine, 7 µg/liter, did not significantly affect these changes. Acute perfusion of four hearts with l -thyroxine (500 µg/liter) produced similar, but less consistent, results. Perfusion with either epinephrine or norepinephrine, regardless of concentration, could not reproduce the changes seen with thyroid treatment. It is concluded that thyroxine profoundly alters electrophysiologic variables of atrial tissue independently of the autonomic nervous system and that these changes are responsible for many cardiac effects of hyperthyroidism, including the enhanced susceptibility to atrial fibrillation in thyrotoxicosis.
Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats
Authors: Juan G. Abraldes, Aina Rodríguez-Vilarrupla, Mariona Graupera, Carmen Zafra, Héctor García-Calderó, Juan Carlos García-Pagán, Jaime Bosch
Journal: Journal of Hepatology (2007)
Tyrosinase mRNA in Blood of Patients With Melanoma Treated With Adjuvant Interferon
Authors: Begoña Mellado, Maria del Carmen Vela, Dolors Colomer, Lorena Gutierrez, Teresa Castel, Llorenç Quintó, Montserrat Fontanillas, Noemi Reguart, José M. Domingo-Domènech, Clara Montagut, Jordi Estapé, Pedro Gascón
Journal: Journal of Clinical Oncology (2002)

To evaluate the clinical significance of the detection of circulating melanoma cells in patients treated with adjuvant interferon and to determine their potential value as a marker of interferon response.We prospectively analyzed 616 peripheral-blood samples from 120 melanoma patients with stage IIA (n = 33), IIB (n = 22), III (n = 50), or IV (surgically resected) (n = 15) disease receiving adjuvant interferon alfa-2b therapy. Tyrosinase mRNA was assayed by reverse transcriptase polymerase chain reaction (RT-PCR) as a marker of circulating melanoma cells before the start of interferon and every 2 to 3 months thereafter.With a median follow-up time of 32.3 months (range, 7.1 to 77.5 months), 47 patients (39.8%) relapsed and 31 (26%) died. During adjuvant interferon treatment, 76 patients (64%) had undetected circulating melanoma cells and 44 patients (36%) had a positive RT-PCR result in at least one sample. Actuarial 5-year disease-free survival was 62% in patients with persistently negative RT-PCR during interferon treatment and 38% for patients with positive RT-PCR during interferon (P =.02). Actuarial 5-year overall survival was 75% and 50%, respectively (P =.03).Patients with melanoma and tyrosinase mRNA detected in the blood during adjuvant interferon therapy had a worse prognosis compared with patients with undetected tyrosinase mRNA during treatment. Further investigation into the detection of circulating melanoma cells as a surrogate marker of response to adjuvant interferon therapy is warranted.
Physical activity promotion and safety prevention: what is the relationship in different population groups?
Authors: E Diener-Martin, O Bruegger, BW Martin
Journal: British Journal of Sports Medicine (2011)

Background The bfu has the mandate to make sure that the aspects of injury prevention are taken into consideration in the process of promoting sports and physical activity for the sake of improving public health. Objective To determine to what extent the promotion of physical activity and sports can have a effect on the risk of incurring an injury at the population level. Methods Systematic review of pertinent literature and consultation proceedings involving national and international experts. Results There is evidence demonstrating that children who intensively engage in sports activities run a higher risk of incurring an injury, with some indication of a dose-effect relationship. Playing sports and doing strenuous physical activity are closely linked to a higher risk of incurring bone fractures as well as to a higher global injury risk. There is no correlation between non-sport related physical activity and global injury risk and that less intensive sports and physical activity can even help prevent accidents resulting in bone fractures. An increased level of sport and physical activity may be associated with more cases of sport and activity related injuries when considering the general population. People who do not do sport or physical activity on a regular basis are more likely to incur more severe injuries when engaging in such activity. Higher levels of physical activity are not necessarily related to an increased all-cause injury rate. There is a reduction in the risk of falls for those who do participate in physical activity programmes. Higher levels of physical activity can also be associated with a reduced risk of incurring osteoporotic fractures. Conclusion The bfu will participated in a study 2011 to determine for children and adults at working age which instructions and training programmes lead to a decrease in injury risk, in order to optimise sports and physical activity promotion programmes.
Some in-vitro comparisons of synovial cells dispersed by trypsin from rheumatoid and nonrheumatoid synovium.
Authors: B J Clarris, J R Fraser, J F Stanley
Journal: Annals of the Rheumatic Diseases (1981)

Life spans, growth rate, glucose utilisation, response to hydrocortisone, and intracellular activity of lysosomal N-acetyl-beta-glucosaminidase of rheumatoid synovial cells in culture were compared with these properties in nonrheumatoid synovial cells. Except for a small group of RA cells derived from tissue explants, the cells were all isolated by trypsinisation of synovial tissue, either within intact joints or after synovectomy. Cell lines were established by passaging with trypsin. In a study of 56 nonrheumatoid and 24 rheumatoid synovial lines isolated during a 7-year period the latter were found to have a shortened mean life expectancy in culture, though there was wide variation between individual lines. This is in agreement with reported findings from untrypsinised explant-derived synovial lines. However, in the present study mean multiplication rates were identical for nonrheumatoid and rheumatoid synovial cells, and on clear differences could be demonstrated for the other properties studied. No correlation could be found between the life spans of synovial cell lines and the age of the cell donors, whether from rheumatoid or nonrheumatoid sources. Rheumatoid synovial cells isolated from intact joints were notable for especially high proportions of macrophage-like cells and suppression of fibroblasts. In most cases cell lines could not be established from these rheumatoid primary cultures, and in others the lines were short-lived. Early association with relatively high proportions of macrophage-like cells in rheumatoid cultures might thus be important in influencing the establishment and behaviour of synovial cell lines.
Chylous Bronchial Casts After Fontan Operation
Authors: Maja Isabel Hug, Joerg Ersch, Marion Moenkhoff, René Burger, Sergio Fanconi, Urs Bauersfeld
Journal: Circulation (2001)

A 4-year old boy with D-transposition of the great arteries, pulmonary atresia with intact ventricular septum, and a hypoplastic left ventricle with mitral atresia underwent a Fontan operation.He had previously been treated with neonatal balloon atrial septostomy followed by a left modified Blalock-Taussig shunt and, at the age of 2 years, a Hemi-Fontan operation was performed.The Fontan operation was completed with an extracardiac conduit (Goretex) from the inferior vena cava to the superior vena cava.High central venous pressures and bilateral chylothoraces complicated the postoperative course.Despite 6 weeks of conservative treatment with fat-free nutrition and subsequent total parenteral nutrition, pleural fluid loss remained excessive, and a pleurodesis was performed bilaterally.A few days postoperatively, acute respiratory failure occurred due to bronchial casts.Cast analysis showed high triglyceride and protein concentrations (cast triglyceride, 0.96 mmol/L; cast protein, 66 g/L; serum triglyceride, 0.36 mmol/L; and serum protein, 47 g/L).Bronchoscopic attempts to remove the bronchial casts failed, and the child died of cardiorespiratory failure.At autopsy, the bronchial system was completely plugged by casts resembling bronchial tree anatomy (Figure 1).Thromboses obliterated the left innominate vein partially and reduced the lumen of the extracardiac conduit by 50%.These
Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes.
Authors: H Bouharoun-Tayoun, P Attanath, A Sabchareon, T Chongsuphajaisiddhi, P Druilhe
Journal: The Journal of Experimental Medicine (1990)

IgG extracted from the sera of African adults immune to malaria were injected intravenously into eight Plasmodium falciparum-infected nonimmune Thai patients. Clinical and parasitological improvement was reproducibly obtained in each case. After the disappearance of the transferred Ig, recrudescent parasites were equally susceptible to the same Ig preparation. High levels of antibodies to most parasite proteins were detected by Western blots in the receivers' sera (taken before transfer) as in the donors' Ig, thus indicating that the difference was qualitative rather than quantitative between donors and receivers. In vitro, the clinically effective Ig had no detectable inhibitory effect on either penetration or intra-erythrocytic development of the parasite. On the contrary, they sometimes increased parasite growth. In contrast, these IgG, as the receivers' Ig collected 4 d after transfer, but not those collected before transfer, proved able to exert an antibody-dependent cellular inhibitory (ADCI) effect in cooperation with normal blood monocytes. Results were consistent among the seven isolates studied in vitro, as with the recrudescent parasites. Thus, the results obtained in the ADCI assay correlate closely with clinical and parasitological observations.
Myelomonocytic leukaemia following cyclophosphamide therapy of rheumatoid disease.
Authors: R R Love, J M Sowa
Journal: Annals of the Rheumatic Diseases (1975)

A 69-year-old woman treated for 31 months with daily oral cyclophosphamide for refractory rheumatoid disease developed acute myelomonocytic leukemia 21/2 years after stopping the drug. The possibility of a casual association between the therapy and subsequent leukaemia is supported by the growing experience with cytotoxic agents.
Utilizing CD30 expression as a rational target for therapy of lymphoma
Authors: Won Seog Kim
Journal: Journal of Hematology & Oncology (2012)

Rituximab, identified through pivotal lymphoma research, was the first monoclonal antibody approved by the US FDA in 1997. Since the success of rituximab, monoclonal antibodies have been a major focus for development of targeted agents for lymphoma treatment. A major hurdle in the development of a new antibody is finding a new target antigen. CD30 is an attractive therapeutic target antigen, because it has been identified as a marker of Reed–Sternberg cells in Hodgkin lymphoma (HL) [1], it is known to be expressed on anaplastic large cell lymphoma (ALCL), some cases of mediastinal large cell lymphoma, primary effusion lymphoma and multiple myeloma. However, its expression on normal tissues is restricted to a small number of activated B- and T-lymphocytes [2]. Thus, based on its expression pattern, CD30 could be an ideal therapeutic target.
Determinants of community-acquired pneumonia in children and young adults in primary care
Authors: J. Teepe, L. Grigoryan, T. J. M. Verheij
Journal: European Respiratory Journal (2010)

Most studies on determinants of community-acquired pneumonia (CAP) in primary care have focused primarily on the elderly. Using a case–control study in four Dutch healthcare centres, determinants of CAP among children and young adults were identified. Cases included 156 young adults (aged 16–40 yrs) and 107 children (aged 0–15 yrs) diagnosed with CAP during 1999–2008. For each case, three controls were selected from the same age group. Separate logistic regression analyses were used to identify determinants in young adults and children. Lower age, asthma and previous upper respiratory tract infections (URTIs) were independently associated with CAP in children. Increasing age, asthma, three or more children at home, current smoking and three or more previous URTIs were independent determinants of CAP in young adults. The present study has three remarkable findings: 1) increasing age was an independent determinant of CAP in young adults; 2) having young children increased the risk of the development of CAP in young adults; and 3) the number of previous URTIs was independently associated with CAP in both children and young adults, possibly due to higher infection susceptibility. Further studies are required in order to better understand the aetiology of CAP and permit better diagnosis and treatment of this serious condition.
Objective cosmetic analyses after breast surgery with the breast analysing tool (BAT) correlates with subjective and objective scores: a new tool for prospective trials.
Authors: W Krois, O Riedl, P Dubsky, R Jakesz, M Gnant, T Wild, F Fitzal
Journal: Cancer Research (2009)

Abstract Abstract #5150 Objective: Objective cosmetic analyses are important to reproducibly evaluate cosmetic outcome after oncoplastic surgery, breast conserving surgery or new radiotherapy methods such as partial breast irradiation. We developed a new objective scoring software, the breast analysing tool (BAT), to measure cosmesis using a single frontal picture. Method: Images from 129 breast cancer patients after breast conserving therapy and radiotherapy were analysed with the software. Distances from the breast border to the nipple, from the Jugulum to the nipple and the breast circumference of one breast was subtracted from the other. The difference in pixels transferred to a breast symmetry index (BSI) by using a mathematic formula. This results in a BSI ranging between 0 (excellent cosmesis) and 11 (bad cosmesis). The results were correlated with the subjective Harris scale ranging from 1-4 (excellent, good, fair and poor cosmesis) and another objective tool, the breast cancer conserving treatment cosmetic result (bcct.core) software. Subjective analyses were done by students (n=4), surgeons (n=10) and experts in breast surgery (n=2) as well as by international experts using a Delphi procedure (n=13). Results: All subjective scores significantly (p&amp;lt;0.05) correlated with the BAT score with a Pearson correlation coefficient of 0.719 (students), 0.697 (surgeons), 0.760 (experts local) and 0.60 (experts international). There was also a significant correlation between the bcct.core and the BAT software with a correlation coefficient of 0.581.&amp;#x2028; &amp;#x2028; Conclusion: The BAT software is ready to be used for prospective and retrospective trials in local breast cancer therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5150.
Development of T Cells Redirected to Glypican-3 for the Treatment of Hepatocellular Carcinoma
Authors: Huiping Gao, Kesang Li, Hong Tu, Xiaorong Pan, Hua Jiang, Bizhi Shi, Juan Kong, Hongyang Wang, Shengli Yang, Jianren Gu, Zonghai Li
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The aim of our study is to elucidate whether T cells expressing GPC3-targeted chimeric antigen receptor (CAR) can efficiently eliminate GPC3-positive HCC cells and their potential in the treatment of HCC. Experimental Design: T cells expressing a first-generation and third-generation GPC3-targeted CAR were prepared using lentiviral vector transduction. The in vitro and in vivo cytotoxic activities of the genetically engineered CAR T cells were evaluated against various HCC cell lines. Results: GPC3-targeted CAR T cells could efficiently kill GPC3-positive HCC cells but not GPC3-negative cells in vitro. These cytotoxic activities seemed to be positively correlated with GPC3 expression levels in the target cells. In addition, T cells expressing the third-generation GPC3-targeted CAR could eradicate HCC xenografts with high level of GPC3 expression and efficiently suppress the growth of HCC xenografts with low GPC3 expression level in vivo. The survival of the mice bearing established orthotopic Huh-7 xenografts was significantly prolonged by the treatment with the third-generation GPC3-targeted CAR T cells. Conclusions: GPC3-targeted CAR T cells could potently eliminate GPC3-positive HCC cells, thereby providing a promising therapeutic intervention for GPC3-positive HCC. Clin Cancer Res; 20(24); 6418–28. ©2014 AACR.
Molecular Imaging of TGFβ-Induced Smad2/3 Phosphorylation Reveals a Role for Receptor Tyrosine Kinases in Modulating TGFβ Signaling
Authors: Shyam Nyati, Katrina Schinske, Dipankar Ray, Mukesh Nyati, Brian Dale Ross, Alnawaz Rehemtulla
Journal: Clinical Cancer Research (2011)

The dual modality of TGFβ, both as a potent tumor suppressor and a stimulator of tumor progression, invasion, and metastasis, make it a critical target for therapeutic intervention in human cancers. The ability to carry out real-time, noninvasive imaging of TGFβ-activated Smad signaling in live cells and animal models would significantly improve our understanding of the regulation of this unique signaling cascade. To advance these efforts, we developed a highly sensitive molecular imaging tool that repetitively, noninvasively, and dynamically reports on TGFBR1 kinase activity.The bioluminescent TGFβR1 reporter construct was developed using a split firefly luciferase gene containing a functional sensor of Smad2 phosphorylation, wherein inhibition of TGFβ receptor1 kinase activity leads to an increase in reporter signaling. The reporter was stably transfected into mammalian cells and used to image in vivo and in vitro bioluminescent activity as a surrogate for monitoring TGFBR1 kinase activity.The reporter was successfully used to monitor direct and indirect inhibition of TGFβ-induced Smad2 and SMAD3 phosphorylation in live cells and tumor xenografts and adapted for high-throughput screening, to identify a role for receptor tyrosine kinase inhibitors as modulators of TGFβ signaling.The reporter is a dynamic, noninvasive imaging modality for monitoring TGFβ-induced Smad2 signaling in live cells and tumor xenografts. It has immense potential for identifying novel effectors of R-Smad phosphorylation, for validating drug-target interaction, and for studying TGFβ signaling in different metastasis models.