tbuckley/cabot-search huggingface dataset:
Clinical Activity of Adjuvant Cytokine-Induced Killer Cell Immunotherapy in Patients with Post-Mastectomy Triple-Negative Breast Cancer
Authors: Ke Pan, Xun-Xing Guan, Yong-Qiang Li, Jing-Jing Zhao, Jian-Jun Li, Hui-Juan Qiu, De-Sheng Weng, Qi-Jing Wang, Qing Liu, Li-Xi Huang, Jia He, Shi-Ping Chen, Miao-La Ke, Yi-Xin Zeng, Jian-Chuan Xia
Journal: Clinical Cancer Research (2014)

Triple-negative breast cancer (TNBC) is a high risk form of this disease, even after surgery, due to the absence of targets for hormone treatment and anti-Her-2 therapy. Chemotherapy is the main therapeutic strategy for such patients with breast cancer, although the outcome is often unsatisfactory. Thus, the development of combination adjuvant therapies is essential for improved prognosis in patients with TNBC. In this study, we investigated the efficacy of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with post-mastectomy TNBC.From 2008 to 2012, 90 patients with post-mastectomy TNBC were included in this retrospective study: 45 cases received chemotherapy alone or with sequential radiotherapy; a further 45 cases received chemotherapy with/without radiotherapy and sequential CIK infusion.Survival analysis showed significantly higher disease-free survival (DFS) and overall survival (OS) rates in the CIK treatment group compared with the control group (P = 0.0382, P = 0.0046, respectively; log-rank test). Multivariate survival analysis showed that CIK adjuvant treatment was an independent prognostic factor for OS of patients with TNBC. In subgroup analyses, CIK adjuvant treatment significantly increased the DFS rate of patients with pathologic grade 3, and significantly increased the OS rate of patients in N1, N2, N3, IIB, III TNM (tumor-node-metastasis) stages, and with pathologic grade 3.These data indicate that adjuvant CIK treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with TNBC, particularly those with lymph node metastasis, advanced TNM stage, and poor pathologic grade. Clin Cancer Res; 20(11); 3003-11. ©2014 AACR.
In vitro synthesis of immunoglobulin by rheumatoid synovial membrane
Authors: J. Donald Smiley, Charlotte Sachs, Morris Ziff
Journal: Journal of Clinical Investigation (1968)

A technique for the in vitro culture of rheumatoid synovial tissue with 14C-amino acids and isolation and quantitation of the newly synthesized immunoglobulins has been developed. This technique has been used to compare immunoglobulin synthesis of 12 rheumatoid synovia with that of synovia from nonarthritic patients and with that of normal human lymph nodes and spleen. In addition, the spleen of a patient with Felty's syndrome has also been examined. Immunoglobulin synthesis in rheumatoid synovia has been shown to be quantitatively and qualitatively similar to that of normal human spleen and lymph nodes although somewhat less active than the Felty's syndrome spleen examined. 79% of the immunoglobulin produced in rheumatoid synovia was of the IgG type, whereas IgM comprised 10% and IgA, 11% of the total. Less than 10% of the IgM synthesized was found to be rheumatoid factor. A fraction containing approximately 90% of its radioactivity in the form of IgG has been obtained for further studies.
Weight loss and lumbosacral back pain in a 79-year-old Indian man
Authors: Masara Laginaf, James R Goodhand, Kezia Gaitskell, Katie Planche, Charles Murray
Journal: Gut (2012)

A 79-year-old retired Indian shopkeeper presented with a 7-month history of weight loss, anorexia, early satiety and lumbosacral back pain. He had type 2 diabetes mellitus complicated by nephropathy (baseline creatinine 92 μmol/l), bilateral cataracts, osteoporosis, vitamin B12 deficiency and a past history of pulmonary tuberculosis. Family history was unremarkable. He was an ex-smoker of 100 pack years, and did not drink alcohol. Regular medications included metformin, simvastatin, aspirin, alendronate and vitamin B12 injections. Physical examination revealed generalised muscle wasting, but no other stigmata of chronic disease.

Laboratory investigations showed a creatinine of 178 μmol/l (normal range 66–112) and a raised C-reactive protein of 61 mg/l (normal range 0–5). Complement 3 and 4 levels were normal; antineutrophil cytoplasmic antibody …
Identification of Inhibitors of ABCG2 by a Bioluminescence Imaging–Based High-Throughput Assay
Authors: Yimao Zhang, Youngjoo Byun, Yunzhao R. Ren, Jun O. Liu, John Laterra, Martin G. Pomper
Journal: Cancer Research (2009)

Abstract ABCG2 is a member of the ATP-binding cassette (ABC) family of transporters, the overexpression of which is associated with tumor resistance to a variety of chemotherapeutic agents. Accordingly, combining ABCG2 inhibitor(s) with chemotherapy has the potential to improve treatment outcome. To search for clinically useful ABCG2 inhibitors, a bioluminescence imaging (BLI)–based assay was developed to allow high-throughput compound screening. This assay exploits our finding that d-luciferin, the substrate of firefly luciferase (fLuc), is a specific substrate of ABCG2, and ABCG2 inhibitors block the export of d-luciferin and enhance bioluminescence signal by increasing intracellular d-luciferin concentrations. HEK293 cells, engineered to express ABCG2 and fLuc, were used to screen the Hopkins Drug Library that includes drugs approved by the Food and Drug Administration (FDA) as well as drug candidates that have entered phase II clinical trials. Forty-seven compounds showed BLI enhancement, a measure of anti-ABCG2 activity, of ≥5-fold, the majority of which were not previously known as ABCG2 inhibitors. The assay was validated by its identification of known ABCG2 inhibitors and by confirming previously unknown ABCG2 inhibitors using established in vitro assays (e.g., mitoxantrone resensitization and BODIPY-prazosin assays). Glafenine, a potent new inhibitor, also inhibited ABCG2 activity in vivo. The BLI-based assay is an efficient method to identify new inhibitors of ABCG2. As they were derived from a FDA-approved compound library, many of the inhibitors uncovered in this study are ready for clinical testing. [Cancer Res 2009;69(14):5867–75]
Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs
Authors: A Naing, H Veasey-Rodrigues, D S Hong, S Fu, G S Falchook, J J Wheler, A M Tsimberidou, S Wen, S N Fessahaye, E C Golden, J Aaron, M S Ewer, R Kurzrock
Journal: Annals of Oncology (2012)
Prevalence of generalised osteoarthritis in patients with advanced hip and knee osteoarthritis: The Ulm Osteoarthritis Study
Authors: K P Gunther, T Sturmer, S Sauerland, I Zeissig, Y Sun, S Kessler, H P Scharf, H Brenner, W Puhl
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVES</h3> Different prevalences of generalised osteoarthritis (GOA) in patients with knee and hip OA have been reported. The aim of this investigation was to evaluate radiographic and clinical patterns of disease in a hospital based population of patient subgroups with advanced hip and knee OA and to compare the prevalence of GOA in patients with hip or knee OA, taking potential confounding factors into account. <h3>METHODS</h3> 420 patients with hip OA and 389 patients with knee OA scheduled for unilateral total joint replacement in four hospitals underwent radiographic analysis of ipsilateral and contralateral hip or knee joint and both hands in addition to a standardised interview and clinical examination. According to the severity of radiographic changes in the contralateral joints (using Kellgren-Lawrence ⩾ grade 2 as case definition) participants were classified as having either unilateral or bilateral OA. If radiographic changes of two joint groups of the hands (first carpometacarpal joint and proximal/distal interphalangeal joints defined as two separate joint groups) were present, patients were categorised as having GOA. <h3>RESULTS</h3> Patients with hip OA were younger (mean age 60.4 years) and less likely to be female (52.4%) than patients with knee OA (66.3 years and 72.5% respectively). Intensity of pain and functional impairment at hospital admission was similar in both groups, while patients with knee OA had a longer symptom duration (median 10 years) compared with patients with hip OA (5 years). In 41.7% of patients with hip OA and 33.4% of patients with knee OA an underlying pathological condition could be observed in the replaced joint, which allowed a classification as secondary OA. Some 82.1% of patients with hip and 87.4% of patients with knee OA had radiographic changes in their contralateral joints (bilateral disease). The prevalence of GOA increased with age and was higher in female patients. GOA was observed more often in patients with knee OA than in patients with hip OA (34.9% versus 19.3%; OR=2.24; 95% CI: 1.56, 3.21). Adjustment for the different age and sex distribution in both patient groups, however, takes away most of the difference (OR=1.32; 95% CI: 0.89, 1.96). <h3>CONCLUSION</h3> The crude results confirm previous reports as well as the clinical impression of GOA being more prevalent in patients with advanced knee OA than in patients with advanced hip OA. However, these different patterns might be attributed to a large part to a different distribution of age and sex in these hospital based populations.
Addition of the Antioxidant Probucol to Angiotensin II Type I Receptor Antagonist Arrests Progressive Mesangioproliferative Glomerulonephritis in the Rat
Authors: Shuji Kondo, Maki Shimizu, Maki Urushihara, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki, Akira Nishiyama, Hiroshi Kawachi, Fujio Shimizu, Mark T. Quinn, David J. Lambeth, Shoji Kagami
Journal: Journal of the American Society of Nephrology (2006)

Angiotensin II (Ang II) and reactive oxidative species (ROS) that are produced by NADPH oxidase have been implicated in the progression of glomerulonephritis (GN). This study examined the effect of simultaneously interrupting Ang II and ROS with an Ang II receptor blocker (ARB), candesartan, and a free radical scavenger, probucol, in a model of progressive mesangioproliferative GN induced by the injection of anti-Thy-1 antibody into uninephrectomized rats. Nephritic rats were divided into four groups and given daily oral doses of the following: Vehicle, 1% probucol diet, 70 mg/L candesartan in drinking water, and probucol plus candesartan. These treatments lasted until day 56. Vehicle-treated nephritic rats developed progressively elevated proteinuria and glomerulosclerosis. Candesartan kept proteinuria significantly lower than vehicle or probucol. The addition of probucol to candesartan normalized urinary protein excretion. Increases in BP in nephritic rats were lowered by these treatments, except with probucol. It is interesting that both glomerular cell number and glomerulosclerosis were significantly decreased by candesartan and normalized by the addition of probucol. Immunohistochemical studies for TGF-beta1, collagen type I, and fibronectin revealed that the combined treatment abolished glomerular fibrotic findings compared with candesartan. In addition, glomerular expression of NADPH oxidase components and superoxide production suggested that the combined treatment completely eliminated NADPH oxidase-associated ROS production. In conclusion, our study provides the first evidence that the antioxidant probucol, when added to an Ang II receptor blockade, fully arrests proteinuria and disease progression in GN. Furthermore, the data suggest that NADPH oxidase-associated ROS production may play a pivotal role in the progression of GN. The combination of probucol and candesartan may represent a novel route of therapy for patients with progressive GN.
Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse.
Authors: R A Morawetz, L Gabriele, L V Rizzo, N Noben-Trauth, R Kühn, K Rajewsky, W Müller, T M Doherty, F Finkelman, R L Coffman, H C Morse
Journal: The Journal of Experimental Medicine (1996)

Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to IgE in the mouse. Here we report that IL-4-deficient (IL-4-/-) and wildtype mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4-/- mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4-/- mice and controls, but the levels of productive epsilon transcripts (p epsilon) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4-/- mice as compared with controls. Induction of g epsilon after anti-IgD treatment of IL-4-/- mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor alpha chain. Infection of IL-4-/- mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of g epsilon transcription and switch recombination to p epsilon.
Late vs Early Clamping of the Umbilical Cord in Full-term Neonates
Authors: Eileen K. Hutton, Eman S. Hassan
Journal: JAMA (2007)

With few exceptions, the umbilical cord of every newborn is clamped and cut at birth, yet the optimal timing for this intervention remains controversial.To compare the potential benefits and harms of late vs early cord clamping in term infants.Search of 6 electronic databases (on November 15, 2006, starting from the beginning of each): the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Neonatal Group trials register, the Cochrane library, MEDLINE, EMBASE, and CINHAL; hand search of secondary references in relevant studies; and contact of investigators about relevant published research.Controlled trials comparing late vs early cord clamping following birth in infants born at 37 or more weeks' gestation.Two reviewers independently assessed eligibility and quality of trials and extracted data for outcomes of interest: infant hematologic status; iron status; and risk of adverse events such as jaundice, polycythemia, and respiratory distress.The meta-analysis included 15 controlled trials (1912 newborns). Late cord clamping was delayed for at least 2 minutes (n = 1001 newborns), while early clamping in most trials (n = 911 newborns) was performed immediately after birth. Benefits over ages 2 to 6 months associated with late cord clamping include improved hematologic status measured as hematocrit (weighted mean difference [WMD], 3.70%; 95% confidence interval [CI], 2.00%-5.40%); iron status as measured by ferritin concentration (WMD, 17.89; 95% CI, 16.58-19.21) and stored iron (WMD, 19.90; 95% CI, 7.67-32.13); and a clinically important reduction in the risk of anemia (relative risk (RR), 0.53; 95% CI, 0.40-0.70). Neonates with late clamping were at increased risk of experiencing asymptomatic polycythemia (7 studies [403 neonates]: RR, 3.82; 95% CI, 1.11-13.21; 2 high-quality studies only [281 infants]: RR, 3.91; 95% CI, 1.00-15.36).Delaying clamping of the umbilical cord in full-term neonates for a minimum of 2 minutes following birth is beneficial to the newborn, extending into infancy. Although there was an increase in polycythemia among infants in whom cord clamping was delayed, this condition appeared to be benign.
COPD and osteoporosis: a lot of work to be done
Authors: S. Zeminian, M. Pattarello, F. Rubini
Journal: European Respiratory Journal (2008)

agree with this comment, and in our study we had excluded the patients with healed tuberculosis as described in the materials and methods section [1].The final comment from D. Aggarwal and P.R. Mohapatra is that the duration of treatment
Segmental pigmentation disorder
Authors: M. Hogeling, I.J. Frieden
Journal: British Journal of Dermatology (2010)

Journal Article Segmental pigmentation disorder Get access M. Hogeling, M. Hogeling Department of Dermatology, University of California, 1701 Divisadero St, 3rd Floor, Box 0316, San Francisco, CA 94115, U.S.A. Marcia Hogeling. E‐mail: hogelingm@yahoo.ca; friedeni@derm.ucsf.edu Search for other works by this author on: Oxford Academic Google Scholar I.J. Frieden I.J. Frieden Department of Dermatology, University of California, 1701 Divisadero St, 3rd Floor, Box 0316, San Francisco, CA 94115, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 6, 1 June 2010, Pages 1337–1341, https://doi.org/10.1111/j.1365-2133.2010.09702.x Published: 01 June 2010
Phylogenetic relationships of the pipid frogs Xenopus and Silurana: an integration of ribosomal DNA and morphology.
Authors: R O de Sá, D M Hillis
Journal: Molecular Biology and Evolution (1990)

Relationships of the pipid frog genus Silurana (= Xenopus tropicalis group of some authors) are of particular interest to developmental and molecular biologists because of the purported ancestral (i.e., unduplicated) karyotype of S. tropicalis relative to the genus Xenopus. Although most previous studies have assumed that Silurana is the sister group of Xenopus, recent morphological work suggests that Silurana is more closely related both to the South American genus Pipa and to the African genera Hymenochirus and Pseudhymenochirus than it is to Xenopus. We examined 1,486 bp of relatively variable regions of the ribosomal DNA array (including portions of the 18S and 28S genes, as well as part of an internal transcribed spacer) in Hymenochirus, Silurana, and Xenopus, as well as the outgroup genus Spea, in order to test the alternative hypotheses of relationships for Silurana. Maximum-parsimony analysis using bootstrapping and an analysis using Lake's method of invariants both significantly support the sister-group relationship between Xenopus and Silurana rather than the relationship suggested by morphology. Analysis of the combined morphological/molecular data matrix also significantly supports the Xenopus-Silurana relationship. Although our results are not inconsistent with the recognition of the genus Silurana to accommodate the species formerly called X. tropicalis and X. epitropicalis, the proposed relationships do not require the recognition of this genus in order to render Xenopus monophyletic.
Identification of novel methylation/expression markers and genes associated with breast cancer
Authors: Vladimir V. Strelnikov, Ekaterina B. Kuznetsova, Sergei S. Larin, Marina V. Nemtsova, Dmitri V. Zaletayev
Journal: Clinical Cancer Research (2006)

A96  Purpose: to identify cancer related genes undergoing altered epigenetic regulation in breast cancer; to evaluate methylation and expression alterations of the identified genes in breast cancer.Methods. We have elaborated a novel modification of arbitrary-primed methylation sensitive PCR to identify CpG islands differentially methylated in breast cancer and adjacent morphologically intact tissues. Genomic locations of the identified fragments were investigated by direct sequencing and BLAST search. Methylation frequencies in 108 breast cancer samples were evaluated by methylation sensitive PCR and direct sequencing of bisulphite-treated DNA. Fine methylation maps for the identified genes9 promoter CpG islands were constructed by means of direct bisulphite sequencing. Expression patterns were evaluated for each of the genes under study by real-time RT PCR.Results. CpG islands identified as differentially methylated in breast cancer and control samples in this study appeared to belong to SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, RPSA, CACNG4 and PSMF1 genes. The frequencies of abnormal methylation in breast cancer varied from 2% in RPSA to 38% in SEMA6B. Significant frequencies of abnormal methylation were detected for SEMA6B, BIN1, and LAMC3 (38%, 18%, and 8%, correspondingly). Methylation of the genes under study was not characteristic for morphologically intact breast tissues. Methylation mapping revealed nonrandom distribution of methylated cytosines across the CpG islands with certain regions within the same island being frequently and some rarely/never methylated in breast cancer. Abnotmal methylation was not necessarily restricted to the core regions of the CpG islands. Significant expression distortions were observed for all the genes under study with a pronounced shift towards underexpression. Downregulation of SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, RPSA, CACNG4 and PSMF1 in breast cancer was as frequent as 44% (SEMA6B) - 94% (LAMC3). Genes with higher methylation scores demonstrate more pronounced downregulation (by quantitative expression analysis, RT PCR).Conclusions. We have identified a number of candidate cancer related genes abnormal methylation of any of which has not been reported previously. Expression studies demonstrate their frequent downregulation in breast cancer. Further research will reveal their roles in carcinogenesis and may promote the development of novel cancer molecular markers.The study was partially supported by Applied Biosystems, USA.
Detecting patients at a high risk of developing chronic obstructive pulmonary disease in general practice: cross sectional case finding study
Authors: C P van Schayck
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To investigate the effectiveness of case finding of patients at risk of developing chronic obstructive pulmonary disease, whether the method is suitable for use in general practice, how patients should be selected, and the time required. <b>Design:</b> Cross sectional study. <b>Setting:</b> Two semirural general practices in the Netherlands. <b>Participants:</b> 651 smokers aged 35 to 70 years. <b>Main outcome measures:</b> Short standardised questionnaire on bronchial symptoms for current smokers, lung function with a spirometer, and the quality of the spirometric curve. <b>Results:</b> Of the 201 smokers not taking drugs for a pulmonary condition, 169 produced an acceptable curve (fulfilling American Thoracic Society criteria). Of these, 30 (18%, 95% confidence interval 12% to 24%) had a forced expiratory volume in one second (FEV<sub>1</sub>) &lt;80% of predicted. When smokers were preselected on the basis of chronic cough, the proportion with an FEV<sub>1</sub> &lt;80% of predicted increased to 27% (17 of 64; 12% to 38%). Chronic cough was a better predictor of airflow obstruction than other symptoms, such as wheeze and dyspnoea. The presence of two symptoms was a slightly better predictor than cough only (odds ratio 3.02 (1.37 to 6.64) <i>v</i> 2.50 (1.14 to 5.52)). Age was also a good predictor of obstruction; smokers over 60 with cough had a 48% chance of having an obstruction. The mean time needed for spirometry was four minutes. Detecting one smoker with an FEV<sub>1</sub> &lt;80% of predicted cost €5 to €10. <b>Conclusions:</b> Trained practice assistants could check all patients who smoke for chronic obstructive pulmonary disease at little cost to the practice. Cough and age are the most important predictors of the disease. By testing one smoker a day, an average practice could identify one patient at risk a week.