tbuckley/cabot-search huggingface dataset:
Ia-Restricted Interaction of Normal Lymphoid Cells and SJL Lymphoma (Reticulum Cell Sarcoma) Leading to Lymphokine Production. III. Relative Roles of Reticulum Cell Sarcoma and Normal Lymphoid Cells in Lymphokine Production&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Hayama, N M Ponzio, C Nagler, J Vilcek, R F Coico, G J Thorbecke
Journal: JNCI Journal of the National Cancer Institute (1984)

Production of interleukin 2 (IL-2) in mixed lymphocyte cultures of SJL/J lymph node (LN) and gamma-irradiated, syngeneic lymphoma cells of transplantable reticulum cell sarcoma (gamma-RCS) was abolished by pactamycin pretreatment of gamma-RCS. LN cells needed for this interaction were Lyt-2 T-cells, not adherent to Sephadex G-10. The effect of separation of T-cells and gamma-RCS after the first 24 hours of culture suggested that both components contributed to the IL-2 production. Exogenous IL-2, but not interleukin 1 (IL-1), restored the ability of pactamycin-treated gamma-RCS to induce syngeneic T-cell proliferation. The inability of T-cells from "nonresponder" F1 hybrids of SJL to proliferate to gamma-RCS was not corrected by addition of IL-1 or IL-2. Interferon (IFN) production also required the presence of untreated gamma-RCS and LN cells, but it was dependent on a Sephadex G-10 and plastic adherent cell in LN. IFN-free supernatant of LN cells plus gamma-RCS induced IFN production in fresh normal lymphoid cells, suggesting a possible indirect induction of this lymphokine. In addition, unirradiated RCS cells (la+ cells) produced immune IFN over a period of 3 weeks in vitro, after which the cells lost their viability. Prolonged IL-2 production was not observed in these cultures. The possible biological importance of the lymphokine production during the exaggerated syngeneic mixed lymphocyte reactions induced by RCS cells is discussed.
Protein Expression Profiles in Renal Cell Carcinoma: Staging, Prognosis, and Patient Selection for Clinical Trials
Authors: John S. Lam, Allan J. Pantuck, Arie S. Belldegrun, Robert A. Figlin
Journal: Clinical Cancer Research (2007)

Attempts to predict survival in patients with renal cell carcinoma (RCC) have traditionally relied on standard clinical variables, such as tumor-node-metastasis stage, histologic grade, and performance status. An accurate method for predicting patient survival is useful for patient counseling, planning follow-up, and selecting patients most likely to benefit from novel and established therapies. Furthermore, an improved prognostic system will allow for more accurate comparisons of clinical trials based on varying inclusion criteria. A large number of potential prognostic markers have recently been identified from methods based on gene arrays, which screen for differential expression of thousands of genes. The accepted method of clinical validation of novel markers is on formalin-fixed and paraffin-embedded specimens using immunohistochemistry. The development of tissue microarrays as a high-throughput technique has allowed for thousands of different cores of pathologic tissue to be assessed simultaneously in a timely and cost-efficient manner. This technology has enabled the analysis of protein expression profiles on specimens to determine their potential clinical significance and role in RCC biology. This article reviews the protein expression profiles in RCC and their association with pathobiology, prognosis, and response to treatment as well as their role in serving as potential molecular targets for therapy of RCC.
Facing up to surgical deaths
Authors: Marc R de Leval
Journal: BMJ (2004)

Each death should be subjected to forensic and statistical analysis 

This issue of the BMJ contains two articles on surgical mortality. The first considers the well rehearsed problem of statistical monitoring of surgical performance, whereas the second considers the less researched issue of the impact of surgical death on healthcare providers. Poloniecki et al apply retrospectively seven different statistical tests to compare with a benchmark the death rate in a transplantation programme that was closed because of concerns that the death rate was too high.1 They show that the point at which an alarm would have occurred had a prospective analysis been carried out varied with the choice of method and that the most scientifically appealing method (mortality chart adjusted for cumulative risks) would have detected only a decrease in the death rate early in the series. This paper is an invitation to reflect on the purpose and usefulness of statistical analysis to monitor performance in health care.

Medical audit was introduced by Florence Nightingale in the 19th century as a process of healthcare improvement. As time …
Soluble Tumor Necrosis Factor-α Receptors in Young Obese Subjects With Normal and Impaired Glucose Tolerance
Authors: Stella Dzienis-Straczkowska, Marek Straczkowski, Malgorzata Szelachowska, Agnieszka Stepien, Irina Kowalska, Ida Kinalska
Journal: Diabetes Care (2003)

Tumor necrosis factor-alpha (TNF-alpha) is a possible link between obesity and impaired glucose tolerance (IGT) and type 2 diabetes. Data about TNF-alpha and soluble forms of its receptors (sTNFR1 and sTNFR2) in IGT are controversial. The aim of the present study was to assess plasma TNF-alpha, sTNFR1, and sTNFR2 levels and to evaluate the relationships with insulin resistance in obese subjects with IGT.A total of 104 subjects participated in the present study: 30 obese subjects with IGT (obese-IGT), 32 obese subjects with normal glucose tolerance (obese-NGT), and 42 lean healthy control subjects (control-NGT). Anthropometry and blood biochemical parameters were measured and euglycemic-hyperinsulinemic clamp was performed.Obese-IGT subjects were more insulin resistant in comparison with obese-NGT and control-NGT groups; obese-NGT subjects were more insulin resistant than control-NGT. Plasma sTNFR1 and sTNFR2 were markedly higher in both groups of obese subjects in comparison with control-NGT and in the obese-IGT versus obese-NGT group. Plasma sTNFR1 and sTNFR2 were inversely related to insulin sensitivity. Both relationships remained significant after adjustment for age, BMI, waist girth, percent body fat, plasma glucose, insulin, nonesterified fatty acids, cholesterol, and triglycerides. Correlation between sTNFR2 and insulin sensitivity was also present in all the groups analyzed separately, but the correlation between sTNFR1 and insulin sensitivity was present only in the obese-NGT group.Our data suggest that TNF-alpha receptors are increased in obese-IGT subjects and are related to insulin resistance. These findings indicate that the TNF-alpha system might contribute to the development of insulin resistance in glucose-intolerant subjects.
Nucleotide-induced mucin release from primary hamster tracheal surface epithelial cells involves the P2u purinoceptor
Authors: KC Kim, HR Park, CY Shin, T Akiyama, KH Ko
Journal: European Respiratory Journal (1996)

Mucin release by airway surface epithelial cells is regulated by extracellular adenosine triphosphate (ATP) via a P2 purinoceptor-mediated mechanism. The objective of the present experiment was to examine the possible involvement of uridine triphosphate (UTP) in this purinergic signal transduction pathway. Using primary hamster tracheal surface epithelial cells, ATP and UTP were compared in their abilities: 1) to displace ATP gamma S35-binding to intact cells; 2) to accumulate inositol phosphates; and 3) to stimulate mucin release. Finally, the presence of a P2u receptor message was examined. Our results showed that: 1) UTP was much less effective than ATP in displacing ATP gamma S35-binding (median inhibitory concentrations (IC50S) 240 vs 2.9 microM); 2) UTP was more potent than ATP in accumulating inositol phosphates (100 vs 43% increase at 2mM); 3) UTP was equipotent with ATP in stimulating mucin release; 4) Northern blot analysis of messenger ribonucleic acids (mRNAs) with a mouse P2u receptor complementary deoxyribonucleic acid (cDNA) probe revealed a single specific band (2.8 kb), partial sequencing of which showed a great homology with those of human or mouse P2u receptors. We conclude that, although both ATP and UTP are equipotent in stimulating mucin release, their binding kinetics to the cell surface are quite different, suggesting the presence of a common binding domain which may be responsible for the mucin release by these nucleotides. We suggest that the P2u purinoceptor is likely to be responsible for mucin release by these nucleotides, probably via activation of phospholipase C.
Occult Tumor Burden Predicts Disease Recurrence in Lymph Node–Negative Colorectal Cancer
Authors: Terry Hyslop, David S. Weinberg, Stephanie Schulz, Alan Barkun, Scott A. Waldman
Journal: Clinical Cancer Research (2011)

Lymph node involvement by histopathology informs colorectal cancer prognosis, whereas recurrence in 25% of node-negative patients suggests the presence of occult metastasis. GUCY2C (guanylyl cyclase C) is a marker of colorectal cancer cells that identifies occult nodal metastases associated with recurrence risk. Here, we defined the association of occult tumor burden, quantified by GUCY2C reverse transcriptase-PCR (RT-PCR), with outcomes in colorectal cancer.Lymph nodes (range: 2-159) from 291 prospectively enrolled node-negative colorectal cancer patients were analyzed by histopathology and GUCY2C quantitative RT-PCR. Participants were followed for a median of 24 months (range: 2-63). Time to recurrence and disease-free survival served as primary and secondary outcomes, respectively. Association of outcomes with prognostic markers, including molecular tumor burden, was estimated by recursive partitioning and Cox models.In this cohort, 176 (60%) patients exhibited low tumor burden (Mol(Low)), and all but four remained free of disease [recurrence rate 2.3% (95% CI, 0.1-4.5%)]. Also, 90 (31%) patients exhibited intermediate tumor burden (Mol(Int)) and 30 [33.3% (23.7-44.1)] developed recurrent disease. Furthermore, 25 (9%) patients exhibited high tumor burden (Mol(High)) and 17 [68.0% (46.5-85.1)] developed recurrent disease (P < 0.001). Occult tumor burden was an independent marker of prognosis. Mol(Int) and Mol(High) patients exhibited a graded risk of earlier time to recurrence [Mol(Int), adjusted HR 25.52 (11.08-143.18); P < 0.001; Mol(High), 65.38 (39.01-676.94); P < 0.001] and reduced disease-free survival [Mol(Int), 9.77 (6.26-87.26); P < 0.001; Mol(High), 22.97 (21.59-316.16); P < 0.001].Molecular tumor burden in lymph nodes is independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer.
Microsatellite Variation and Evolutionary History of PCDHX/Y Gene Pair Within the Xq21.3/Yp11.2 Hominid-Specific Homology Block
Authors: Alexandra M. Lopes, Francesc Calafell, António Amorim
Journal: Molecular Biology and Evolution (2004)

To better understand the evolutionary dynamics of repetitive sequences in human sex chromosomes, we have analyzed seven new X/Y homologous microsatellites located within PCDHX/Y, one of the two recently described gene pairs in the Xq21.3/Yp11.2 hominid-specific homology block, in samples from Portugal and Mozambique. Sharp differences were observed on X/Y allele distributions, concerning both the presence of private alleles and a different modal repeat length for X-linked and Y-linked markers, and this difference was statistically significant. Higher diversity was found in X-linked microsatellites than in their Y chromosome counterparts; when comparing populations, Mozambicans showed more allele diversity for the X chromosome, but the contrary was true for the Y chromosome microsatellites. Evolutionary patterns, relying on intragenic PCDHX/Y SNPs, also revealed distinct scenarios for X and Y chromosomes. Greater microsatellite diversity was displayed by African X chromosomes within the most common haplotypes shared by both populations, whereas higher microsatellite diversity was found in Portugal for the ancestral Y chromosome haplotype. The most frequent PCDHY haplotype in Portuguese was the derived one, and it was not found in Mozambicans. TMRCA estimated by the rho parameter resulted in 13,700 years (7,500-20,000 years), which is consistent with a recent, post-Out-of-Africa origin for this haplotype. In conclusion, the newly described microsatellite loci generally displayed greater X-linked to Y-linked diversity and this pattern was also detected with slower evolving markers, with a remarkable differentiation between populations observed for Y chromosome haplotypes and, thus, greater divergence among Y chromosomes in human populations.
Diagnostic Performance of Nanoparticle-Enhanced Magnetic Resonance Imaging in the Diagnosis of Lymph Node Metastases in Patients With Endometrial and Cervical Cancer
Authors: Andrea G. Rockall, Syed A. Sohaib, Mukesh G. Harisinghani, Syed A. Babar, Naveena Singh, Arjun R. Jeyarajah, David H. Oram, Ian J. Jacobs, John H. Shepherd, Rodney H. Reznek
Journal: Journal of Clinical Oncology (2005)

Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria.Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients.Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25%). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29%*, 99%, 56%, and 96%, and by USPIO criteria (reader 1/reader 2) were 93%/82%* (*P = .008/.004), 97%/97%, 61%/59%, and 100%/99%, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27%*, 94%, 60%, and 79%, and by USPIO criteria (reader 1/reader 2) were 100%/91%* (*P = .031/.06), 94%/87%, 82%/71%, and 100%/96%, respectively. The kappa statistic was 0.93.Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning.
THE RELATIONSHIPS BETWEEN SERUM COMPLEMENT ACTIVITY AND THE DEVELOPMENT OF ALLERGIC LESIONS IN RABBITS
Authors: Marie Britt Rhyne, Frederick G. Germuth
Journal: The Journal of Experimental Medicine (1961)

Total serum hemolytic complement activity is consistently reduced in animals undergoing accelerated "serum sickness". The time of maximum reduction in complement titer invariably coincides with the time of complete antigen disappearance. This temporal relationship supports the belief that the reduction in complement titer is brought about by in vivo antigen-antibody combination. The intravenous administration of a single daily large dose of BGG-precipitated complexes produces a marked but temporary reduction in total complement hemolytic activity. On the other hand, multiple injections of soluble BGG immune complexes prepared in antigen excess failed to even temporarily alter complement titers. Animals undergoing the development of accelerated "serum sickness" treated by either type immune complex showed a significantly reduced incidence of arterial lesions. Apparently, this inhibiting effect on the development of arterial lesions was independent of variations in total complement hemolytic activity.
Prognostic Significance of Molecular Subtypes in Male Breast Cancer.
Authors: R. Foerster, F. Foerster, F. Foerster, V. Wulff, B. Schubotz, R. Lange, J. Habeck, D. Baaske, D. Baaske, W. Kuhn, C. Rudlowski
Journal: Cancer Research (2009)

Abstract INTRODUCTIONThe relatively unfavorable outcome in male breast cancer has been attributed to more advanced local tumor stage and high incidence of lymph node invasion at the time of diagnosis. This study aimed to classify the molecular subtypes of male breast cancers based on the expression profile of immunomarkers and to evaluate their association with clinicopathological features and patients outcome.METHODSTo define molecular subtypes a total of 174 cases of male breast carcinoma were examined retrospectively using immunostains for hormone receptors (HR) and cytokeratin 5/6 (CK5/6). Human epidermal growth factor receptor 2 (HER2) expression was evaluated by immunostaining and confirmed by fluorescent in situ hybridization. Tumor characteristics and overall survival (OS) data were available and correlated with protein expression and the molecular subtype.RESULTSThe luminal A subtype (HR+/HER2-) was the most common subtype in male breast cancer (82.8%; n=144) with a median patients OS of 122 month. Luminal B tumors (HR-/HER+) were found in 6.2% (n=11), basal-like (HR-/HER2-/CK5/6+) in 9.6% (n=17) and HER2+/HR- carcinomas in 1.1% (n=2). Basal like male breast carcinoma showed a statistically significant reduced overall survival (median: 51 month; p&amp;lt;0.01). Due to the low number of patients prognostic significance of HER2 positivity (luminal B and HER2+/HR-subtype) was not evaluable.CONCLUSIONSIn our study group, luminal A was the predominant subtype of male breast carcinoma and showed an excellent patients outcome. However, like in females tumors with a basal like subtype which were known to show minor chemotherapy response had a worse prognostic outcome. Therefore, new therapeutic options have to be defined. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2110.
Leukotrienes in Cardiovascular Diseases
Authors: GIANCARLO FOLCO, GIUSEPPE ROSSONI, CAROLA BUCCELLATI, FERRUCCIO BERTI, JACQUES MACLOUF, ANGELO SALA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Cysteinyl-leukotrienes (cys-LTs, LTC4, LTD4,and LTE4) are potent lipid mediators, resulting from the oxidative metabolism of arachidonic acid through the 5-lipoxygenase (5-LO) pathway. They are able to affect all major components of the cardiovascular system: they can constrict small and large vessels, modify cardiac and coronary functions, influence the microcirculation and contribute to the manifestations of ischaemia/reperfusion injury1,2. Furthermore cys-LTs are able to induce profound modification of vascular permeability, leading to oedema formation3.
A Randomized, Controlled Trial of Steroids and Cyclophosphamide in Adults with Nephrotic Syndrome Caused by Idiopathic Membranous Nephropathy
Authors: Vivekanand Jha, Anirban Ganguli, Tarun K. Saha, Harbir S. Kohli, Kamal Sud, Krishan L. Gupta, Kusum Joshi, Vinay Sakhuja
Journal: Journal of the American Society of Nephrology (2007)

Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Universal consensus regarding the need for and the modality of therapy has not been formed because of a lack of controlled trials of sufficient size, quality, and duration. This study compared the effect of a 6-mo course of alternating prednisolone and cyclophosphamide with supportive treatment in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine, development of ESRD, and quality of life in a randomized, controlled trial. Patients were followed up for 10 yr. Data were analyzed on an intention-to-treat basis. A total of 93 patients completed the study. Of the 47 patients who received the experimental protocol, 34 achieved remission (15 complete and 19 partial), compared with 16 (five complete, 11 partial) of 46 in the control group (P < 0.0001). The 10-yr dialysis-free survival was 89 and 65% (P = 0.016), and the likelihood of survival without death, dialysis, and doubling of serum creatinine were 79 and 44% (P = 0.0006) in the two groups. Treated patients exhibited significantly lower prevalence of edema, hypertension, hypoalbuminemia, hyperlipidemia that required therapy, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use, and better quality of life on follow-up. The incidence of infections was similar in the two groups. In conclusion, untreated IMN with nephrotic syndrome is associated with a high risk for deterioration of renal function. A 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion, arrests progression of renal insufficiency, and improves quality of life.
High-Risk Asthma Multidisciplinary Care Clinic Adherence Linked To Asthma Control Test (ACT) Score Improvement
Authors: Bradley A. Locke, Pippa Simpson, Tina Bromberger, Melodee Nugent, Sara A. Lowe, Juan Ruiz, Patricia Marik, Jacquelyn Smith, Joshua A. Steinberg, Dorothy S. Cheung
Journal: Journal of Allergy and Clinical Immunology (2014)
c-Met Overexpression Is a Prognostic Factor in Ovarian Cancer and an Effective Target for Inhibition of Peritoneal Dissemination and Invasion
Authors: Kenjiro Sawada, A. Reza Radjabi, Nariyoshi Shinomiya, Emily Kistner, Hilary Kenny, Amy R. Becker, Muge A. Turkyilmaz, Ravi Salgia, S. Diane Yamada, George F. Vande Woude, Maria S. Tretiakova, Ernst Lengyel
Journal: Cancer Research (2007)

Abstract The hepatocyte growth factor receptor c-Met is a receptor tyrosine kinase that plays an important role in tumor growth by activating mitogenic signaling pathways. The goal of this study was to evaluate the role of c-Met in the biology of ovarian cancer and to determine its potential as a therapeutic target. c-Met protein expression was detected by immunohistochemistry in 138 advanced-stage ovarian cancers using a tissue microarray annotated with disease-specific patient follow-up. Fifteen of 138 (11%) tissues had c-Met overexpression. Median survival for patients with high c-Met levels was 17 months versus 32 months (P = 0.001) for patients with low c-Met expression. Infection of SKOV-3ip1 cells with an adenovirus expressing a small interfering RNA (siRNA) against c-Met efficiently inhibited c-Met protein and mRNA expression as well as extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. It also inhibited adhesion to different extracellular matrix components, human primary mesothelial cells, and full-thickness human peritoneum and, in vivo, to mouse peritoneum. This was paralleled by a significant reduction in α5 and β1 integrin protein and mRNA expression as well as a reduction of urokinase and matrix metalloproteinase (MMP)-2/MMP-9 activity. In SKOV-3ip1 ovarian cancer xenografts, i.p. treatment with the c-Met siRNA significantly reduced tumor burden, ascites formation, protease activity, and the number of peritoneal implants but not tumor size or angiogenesis. These results suggest that c-Met overexpression is a prognostic factor in ovarian cancer and that targeting c-Met in vivo inhibits peritoneal dissemination and invasion through an α5β1 integrin-dependent mechanism. Therefore, c-Met should be explored further as a therapeutic target in ovarian cancer. [Cancer Res 2007;67(4):1670–9]