tbuckley/cabot-search huggingface dataset:
Antiangiogenesis Mediates Cisplatin-Induced Peripheral Neuropathy
Authors: Rudolf Kirchmair, Dirk H. Walter, Masaaki Ii, Kilian Rittig, Anne B. Tietz, Toshinori Murayama, Costanza Emanueli, Marcy Silver, Andrea Wecker, Carole Amant, Peter Schratzberger, Young-Sup Yoon, Alberto Weber, Eleftheria Panagiotou, Kenneth M. Rosen, Ferdinand H. Bahlmann, Lester S. Adelman, David H. Weinberg, Allan H. Ropper, Jeffrey M. Isner, Douglas W. Losordo
Journal: Circulation (2005)

Background— Toxic neuropathies induced by cisplatin and other chemotherapeutic agents are important clinical problems because of their high incidence, their lack of effective treatment, and the fact that neuropathy represents a dose-limiting factor for these therapies. The pathogenic basis for toxic neuropathies induced by chemotherapeutic agents has not been completely elucidated. Methods and Results— We investigated the hypothesis that experimental toxic neuropathy results from an antiangiogenic effect of these drugs, resulting in destruction of the vasa nervorum, and accordingly that the neuropathy could be prevented or reversed by locally administered VEGF gene transfer without augmenting tumor growth. In an animal model of cisplatin-induced neuropathy, nerve blood flow was markedly attenuated, and there was a profound reduction in the number of vasa nervorum associated with marked endothelial cell apoptosis, resulting in a severe peripheral neuropathy with focal axonal degeneration characteristic of ischemic neuropathy. After intramuscular gene transfer of naked plasmid DNA encoding VEGF-1 in animals with an established neuropathy, vascularity and blood flow returned to levels similar to those of control rats, peripheral nerve function was restored, and histological nerve architecture was normalized. Gene therapy administered in parallel with cisplatin chemotherapy completely attenuated endothelial cell apoptosis and inhibited destruction of nerve vasculature, deterioration of nerve function, and axonal degeneration. In a rat tumor model, VEGF gene transfer administered locally did not alter tumor growth or vascularity. Conclusions— These findings implicate microvascular damage as the basis for toxic neuropathy induced by cisplatin and suggest that local angiogenic gene therapy may constitute a novel prevention or treatment for this disorder without augmenting tumor growth or vascularization.
Association of a Functional Polymorphism in the Serotonin Transporter Gene With Abnormal Emotional Processing in Ecstasy Users
Authors: Jonathan P. Roiser, Lynnette J. Cook, Jason D. Cooper, David C. Rubinsztein, Barbara J. Sahakian
Journal: American Journal of Psychiatry (2005)

The long-term effects of the use of 3,4-methylenedioxymethamphetamine (MDMA, or Ecstasy) in humans are controversial and unclear. The authors' goal was to assess the contribution of a functional polymorphism in the gene encoding serotonin transporter to changes in emotional processing following chronic Ecstasy use.They investigated Beck Depression Inventory scores and performance on the Affective Go/No-Go test, a computerized neuropsychological test sensitive to emotional processing, in Ecstasy users and comparison subjects, stratifying the results by serotonin transporter genotype.Ecstasy use was associated with higher Beck Depression Inventory score and abnormalities in the Affective Go/No-Go test in individuals with the ss and ls genotype but not those with the ll genotype.Ecstasy users carrying the s allele, but not comparison subjects carrying the s allele, showed abnormal emotional processing. On the basis of a comparison with acute tryptophan depletion, the authors hypothesize that chronic Ecstasy use may cause long-term changes to the serotonin system, and that Ecstasy users carrying the s allele may be at particular risk for emotional dysfunction.
Study confirms tendency towards lower risk of myocardial infarction with second generation oral contraceptives in UK
Authors: P. O'Brien
Journal: BMJ (1999)

EDITOR—Lidegaard is mistaken in his commentary on the MICA study of oral contraceptives and myocardial infarction.1 Third generation oral contraceptives were, in fact, preferentially prescribed to women at lower risk of myocardial infarction. The odds ratios of third versus second generation pills increased rather than decreased when more potential confounders were entered into the logistic model.1 Similar preferential prescribing in favour of third generation contraceptives was found in the only empirical study of prescribing in the United Kingdom.2

The …
Predictors of sudden cardiac death after mustard or senning repair for transposition of the great arteries
Authors: Janneke A.E. Kammeraad, Carolien H.M. van Deurzen, Narayanswami Sreeram, Margreet Th.E. Bink-Boelkens, Jaap Ottenkamp, Willem A. Helbing, Jan Lam, Martha A. Sobotka-Plojhar, Otto Daniels, Seshadri Balaji
Journal: Journal of the American College of Cardiology (2004)
Interaction of Retroviral Tax Oncoproteins With Tristetraprolin and Regulation of Tumor Necrosis Factor- Expression
Authors: J.-C. Twizere, V. Kruys, L. Lefebvre, A. Vanderplasschen, D. Collete, C. Debacq, W. S. Lai, J.-C. Jauniaux, L. R. Bernstein, O. J. Semmes, A. Burny, P. J. Blackshear, R. Kettmann, L. Willems
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: The Tax oncoproteins are transcriptional regulators of viral expression involved in pathogenesis induced by complex leukemogenic retroviruses (or delta-retroviruses, i.e., primate T-cell leukemia viruses and bovine leukemia virus). To better understand the molecular pathways leading to cell transformation, we aimed to identify cellular proteins interacting with Tax. Methods: We used a yeast two-hybrid system to identify interacting cellular proteins. Interactions between Tax and candidate interacting cellular proteins were confirmed by glutathione S-transferase (GST) pulldown assays, co-immunoprecipitation, and confocal microscopy. Functional interactions between Tax and one interacting protein, tristetraprolin (TTP), were assessed by analyzing the expression of tumor necrosis factor-α (TNF-α), which is regulated by TTP, in mammalian cells (HeLa, D17, HEK 293, and RAW 264.7) transiently transfected with combinations of intact and mutant Tax and TTP. Results: We obtained seven interacting cellular proteins, of which one, TTP, was further characterized. Tax and TTP were found to interact specifically through their respective carboxyl-terminal domains. The proteins colocalized in the cytoplasm in a region surrounding the nucleus of HeLa cells. Furthermore, coexpression of Tax was associated with nuclear accumulation of TTP. TTP is an immediate-early protein that inhibits expression of TNF-α at the post-transcriptional level. Expression of Tax reverted this inhibition, both in transient transfection experiments and in stably transfected macrophage cell lines. Conclusion: Tax, through its interactions with the TTP repressor, indirectly increases TNF-α expression. This observation is of importance for the cell transformation process induced by leukemogenic retroviruses, because TNF-α overexpression plays a central role in pathogenesis.
FOREIGN BODIES IN THE INTESTINE
Authors: A. S. Hosford
Journal: BMJ (1912)

rPRIL 13, I9T2, only lhas to approach such cases with the above considera- tions in mind to discover some evidence of appendix irrita- tion in a large proportion.Finally, even in the absence of sucll evidence, the chances of failure to cure a case of threadworms, without removal of the appendix, should receive consideration, for it seems probable that the really obstinate cases may all be explained by the fact that there is a nursery beyond the reach of drugs passing througlh the intestine.Another case is doubtless an illustration of what is possibly a fairly common type.Twelve years ago a lady aged 26 complained that no one lhad been able to cnre her of threadworms, from which she had suffered since childlhood.At that time I had never met with an ilncurable case, and felt pretty confident of finally relieving hier.But I failed, and the affection continued intermiiittently until four years ago, when, visiting relations, she developed an attack of appendicitis, anid was operated on; and niow shie is free from the pest which troubled lher both phlysically and mentally for so many years.Thouiglh proof is wvanting, the explanation is fairly obvious.
Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction
Authors: S.Chiu Wong, Lynn A Sleeper, E.Scott Monrad, Mark A Menegus, Angela Palazzo, Vladimir Dzavik, Alice Jacobs, Xianjiao Jiang, Judith S Hochman
Journal: Journal of the American College of Cardiology (2001)
Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide
Authors: E. M. Fernandez, V. Valenti, C. Rockel, C. Hermann, B. Pot, I. G. Boneca, C. Grangette
Journal: Gut (2011)

<h3>Background and aims</h3> Inflammatory bowel disease (IBD) has been linked to a loss of tolerance towards the resident microflora. Therapeutic use of probiotics is known to be strain specific, but precise mechanisms remain unclear. The role of NOD2 signalling and the protective effect of <i>Lactobacillus</i> peptidoglycan (PGN) and derived muropeptides in experimental colitis were evaluated. <h3>Methods</h3> The anti-inflammatory capacity of lactobacilli and derived bacterial compounds was evaluated using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis model. The role of NOD2, MyD88 and interleukin 10 (IL-10) in this protection was studied using <i>Nod2</i><sup>−/−</sup>, <i>MyD88</i><sup>−/−</sup> and <i>Il10</i>-deficient mice, while induction of regulatory dendritic cells (DCs) was monitored through the expansion of CD103<sup>+</sup> DCs in mesenteric lymph nodes or after adoptive transfer of bone marrow-derived DCs. The development of regulatory T cells was investigated by following the expansion of CD4<sup>+</sup>FoxP3<sup>+</sup> cells. High-performance liquid chromatography and mass spectrometry were used to analyse the PGN structural differences. <h3>Results</h3> The protective capacity of strain <i>Lactobacillus salivarius</i> Ls33 was correlated with a local IL-10 production and was abolished in <i>Nod2</i>-deficient mice. PGN purified from Ls33 rescued mice from colitis in an IL-10-dependent manner and favoured the development of CD103<sup>+</sup> DCs and CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells. In vitro Ls33 PGN induced IL-10-producing DCs able to achieve in vivo protection after adoptive transfer in a NOD2-dependent way. This protection was also correlated with an upregulation of the indoleamine 2,3-dioxygenase immunosuppressive pathway. The protective capacity was not obtained with PGN purified from a non-anti-inflammatory strain. Structural analysis of PGNs highlighted in Ls33 the presence of an additional muropeptide, M-tri-Lys. The synthesised ligand protected mice from colitis in a NOD2-dependent but MyD88-independent manner. <h3>Conclusions</h3> The results indicated that PGN and derived muropeptides are active compounds in probiotic functionality and might represent a useful therapeutic strategy in IBD.
Immature Renal Dendritic Cells Recruit Regulatory CXCR6+ Invariant Natural Killer T Cells to Attenuate Crescentic GN
Authors: Jan-Hendrik Riedel, Hans-Joachim Paust, Jan-Eric Turner, André P. Tittel, Christian Krebs, Erik Disteldorf, Claudia Wegscheid, Gisa Tiegs, Joachim Velden, Hans-Willi Mittrücker, Natalio Garbi, Rolf A.K. Stahl, Oliver M. Steinmetz, Christian Kurts, Ulf Panzer
Journal: Journal of the American Society of Nephrology (2012)

Immature renal dendritic cells (DCs) are protective early in murine crescentic GN, but the mechanisms underlying this protection are unknown. Here, depletion of DCs reduced the recruitment of invariant natural killer T (iNKT) cells, which attenuate GN, into the kidney in the early stage of experimental crescentic GN. More than 90% of renal iNKT cells expressed the chemokine receptor CXCR6, and renal DCs produced high amounts of the cognate ligand CXCL16 early after induction of nephritis, suggesting that renal DC-derived CXCL16 might attract protective CXCR6(+) iNKT cells. Consistent with this finding, CXCR6-deficient mice exhibited less iNKT cell recruitment and developed nephritis that was more severe, similar to the aggravated nephritis observed in mice depleted of immature DCs. Finally, adoptive transfer of CXCR6-competent NKT cells ameliorated nephritis. Taken together, these results suggest an immunoprotective mechanism involving immature DCs, CXCL16, CXCR6, and regulatory iNKT cells, which might stimulate the development of new therapeutic strategies for GN.
Hemoglobin Targets for the Anemia of Chronic Kidney Disease
Authors: Giovanni F.M. Strippoli, Jonathan C. Craig, Carlo Manno, Francesco P. Schena
Journal: Journal of the American Society of Nephrology (2004)

Anemia affects almost all patients with chronic kidney disease (CKD), reduces quality of life, and is a risk factor for early death. Higher hemoglobin (Hb) targets have been widely advocated because of data from observational studies showing that higher Hb is associated with improved survival and quality of life, but higher Hb targets may cause access thrombosis and hypertension and are costly. This study aimed to evaluate the benefits and harms of different Hb targets in CKD on the basis of randomized trial evidence. A comprehensive search of the Cochrane Trials Registry, Medline, Embase, and reference lists was performed. Two independent reviewers assessed studies for inclusion criteria and extracted data on all-cause mortality, cardiovascular disease, strokes, hypertension, seizures, hyperkalemia, access thrombosis, and quality of life. Analysis was by a random-effects model, and results are expressed as relative risk (RR) or weighted mean difference with 95% confidence intervals (CI). Nineteen relevant trials were identified. Twelve trials (638 patients) compared use of erythropoietin versus no erythropoietin treatment, and seven trials (2058 patients) compared higher versus lower Hb targets. Compared with Hb values of >130 g/L or more in the CKD population with cardiovascular disease, Hb values of <120 g/L were associated with lower all-cause mortality (RR, 0.84; 95% CI, 0.71 to 1.00). Hb values of 100 g/L or less reduced the risk of hypertension (RR, 0.50; 95% CI, 0.33 to 0.76) but increased the risk of seizures (RR, 5.25; 95% CI, 1.13 to 24.34). From the available trial evidence, in CKD patients with cardiovascular disease, the benefits associated with higher Hb targets (reduced seizures) are outweighed by the harms (increased risk of hypertension and death). There is insufficient data to guide decisions in patients without cardiovascular disease or in the predialysis population.
Molecular Cloning of Translocation t(1;14)(q21;q32) Defines a Novel Gene (BCL9) at Chromosome 1q21
Authors: T.G. Willis, I.R. Zalcberg, L.J.A. Coignet, I. Wlodarska, M. Stul, D.M. Jadayel, C. Bastard, J.G. Treleaven, D. Catovsky, M.L.M. Silva, M.J.S. Dyer
Journal: Blood (1998)
Rosacea-like demodicidosis associated with acquired immunodeficiency syndrome
Authors: T. Jansen, U. Kastner, A. Kreuter, P. Altmeyer
Journal: British Journal of Dermatology (2001)

Journal Article Rosacea‐like demodicidosis associated with acquired immunodeficiency syndrome Get access T. Jansen, T. Jansen Department of Dermatology and Allergology, Ruhr‐University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany Search for other works by this author on: Oxford Academic Google Scholar U. Kastner, U. Kastner Department of Dermatology and Allergology, Ruhr‐University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany Search for other works by this author on: Oxford Academic Google Scholar A. Kreuter, A. Kreuter Department of Dermatology and Allergology, Ruhr‐University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany Search for other works by this author on: Oxford Academic Google Scholar P. Altmeyer P. Altmeyer Department of Dermatology and Allergology, Ruhr‐University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 1, 1 January 2001, Pages 139–142, https://doi.org/10.1046/j.1365-2133.2001.03794.x Published: 01 January 2001
Inhibition of the p38 Kinase Suppresses the Proliferation of Human ER-Negative Breast Cancer Cells
Authors: Lu Chen, Julie Ann Mayer, Tibor I. Krisko, Corey W. Speers, Tao Wang, Susan G. Hilsenbeck, Powel H. Brown
Journal: Cancer Research (2009)

p38 kinases are members of the mitogen-activated protein kinase family that transduce signals from various environmental stresses, growth factors, and steroid hormones. p38 is highly expressed in aggressive and invasive breast cancers. Increased levels of activated p38 are markers of poor prognosis. In this study, we tested the hypothesis that blockade of p38 signaling would inhibit breast cancer cell proliferation. We studied breast cancer cell proliferation and cell cycle regulation upon p38 blockade by using three independent approaches: dominant-negative (DN) constructs, small interfering RNA (siRNA), and small molecule inhibitors. p38alpha and p38delta are the most abundant isoforms expressed by all examined human breast tumors and breast cancer cell lines. Expression of a DN p38 inhibited both anchorage-dependent and -independent proliferation of MDA-MB-468 cells. Silencing of p38alpha, but not p38delta, using siRNA suppressed MDA-MB-468 cell proliferation. Pharmacologic inhibitors of p38 significantly inhibited the proliferation of p53 mutant and ER-negative breast cancer cells. Whereas p38 has previously been considered as a mediator of stress-induced apoptosis, we propose that p38 may have dual activities regulating survival and proliferation depending on the expression of p53. Our data suggest that p38 mediates the proliferation signal in breast cancer cells expressing mutant but not wild-type p53. Because most ER-negative breast tumors express mutant p53, our results provide the foundation for future development of p38 inhibitors to target p38 for the treatment of p53 mutant and ER-negative breast cancers.
Cystatin C and Subclinical Brain Infarction
Authors: Stephen L. Seliger, W.T. Longstreth, Ronit Katz, Teri Manolio, Linda F. Fried, Michael Shlipak, Catherine O. Stehman-Breen, Anne Newman, Mark Sarnak, Daniel L. Gillen, Anthony Bleyer, David S. Siscovick
Journal: Journal of the American Society of Nephrology (2005)

Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.
Detection of melanoma cells in sentinel lymph nodes, bone marrow and peripheral blood by a reverse transcription-polymerase chain reaction assay in patients with primary cutaneous melanoma: association with Breslow's tumour thickness
Authors: H-J. Blaheta, T. Paul, K. Sotlar, E. Maczey, B. Schittek, A. Paul, M. Moehrle, H. Breuninger, B. Bueltmann, G. Rassner, C. Garbe
Journal: British Journal of Dermatology (2001)

Background Tyrosinase reverse transcription–polymerase chain reaction (RT–PCR) has been shown to be highly sensitive in detecting tumour cells in melanoma patients. Objective To assess whether the detection of minimal residual disease by RT–PCR is improved by concomitant analysis of sentinel lymph nodes (SLNs), bone marrow (BM) and peripheral blood (PB) in patients with primary melanoma. Methods Thirty-five SLNs, 41 BM samples and 26 PB specimens from 26 patients with primary cutaneous melanoma (tumour thickness ≥ 0·75 mm) were examined by nested RT–PCR for tyrosinase and Melan-A. SLNs and BM samples were also analysed by histopathology. RT–PCR findings were related to tumour thickness of the primary melanoma. Results Overall, melanoma cells were detected by RT–PCR in 13 of 26 patients (50%). Seven patients had positive RT–PCR results in their SLNs (27%), including all patients (n = 4) with histologically positive SLNs, two patients had positive findings in their BM exclusively detected by RT–PCR (8%) and six patients in PB (23%). The presence of tumour cells detected by RT–PCR in SLNs was not related to the presence of melanoma cells in BM and/or PB. The incidence of RT–PCR-positive SLNs was significantly associated with greater tumour thickness (P = 0·004). Both patients with positive RT–PCR findings in their BM had a large tumour thickness (≥ 2 mm). No association between positive RT–PCR findings in PB and greater tumour thickness was observed. Conclusions RT–PCR-positive SLNs were strongly associated with greater tumour thickness, underlining the prognostic significance of SLN positivity. Similar to certain epithelial malignancies, molecular investigation of the BM might provide complementary prognostic information in the early stages of melanoma. In contrast, no association between positive RT–PCR results in PB and increasing tumour thickness was found, implying that RT–PCR findings in PB are of doubtful clinical relevance in primary melanoma.