tbuckley/cabot-search huggingface dataset:
A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas
Authors: Yin-Fai Lee, Megan John, Alison Falconer, Sandra Edwards, Jeremy Clark, Penny Flohr, Toby Roe, Rubin Wang, Janet Shipley, Robert J. Grimer, D. Chas Mangham, J. Meirion Thomas, Cyril Fisher, Ian Judson, Colin S. Cooper
Journal: Cancer Research (2004)

Abstract Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we have chosen leiomyosarcoma as a model for examining the relationship between gene expression profile and the development of metastasis in soft tissue sarcomas. Using cDNA microarray, we have identified a gene expression signature associated with metastasis in sarcoma that allowed prediction of the future development of metastases of primary tumors (Kaplan-Meier analysis P = 0.001). Our finding may aid the tailoring of therapy for individual sarcoma patients, where the aggressiveness of treatment is affected by the predicted outcome of disease.
INCREASED β-ENDORPHIN BUT NOT MET-ENKEPHALIN LEVELS IN HUMAN CEREBROSPINAL FLUID AFTER ACUPUNCTURE FOR RECURRENT PAIN
Authors: Vicky Clement-Jones, Susan Tomlin, LesleyH. Rees, Lorraine Mcloughlin, G.M. Besser, H.L. Wen
Journal: The Lancet (1980)
Combination Paclitaxel, Carboplatin, and Gemcitabine Is an Active Treatment for Advanced Urothelial Cancer
Authors: Maha Hussain, Ulka Vaishampayan, Wei Du, Bruce Redman, David C. Smith
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the efficacy and toxicity of the drug combination of carboplatin, paclitaxel, and gemcitabine in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: Patients eligible included those with advanced urothelial malignancy of any histology, no previous chemotherapy for metastatic disease, Southwest Oncology Group performance status of 2 or less, serum creatinine levels of 2 mg/dL or less, and adequate bone marrow and hepatic function. Treatment consisted of paclitaxel 200 mg/m 2 , carboplatin (target area under the curve = 5) on day 1, and gemcitabine 800 mg/m 2 on days 1 and 8, repeated every 21 days. RESULTS: Forty-nine patients (44 men and five women) were enrolled; the patients’ median age was 63 years, and their median creatinine clearance was 78 mL/min (range, 26 to 165 mL/min). Forty-three patients had transitional cell carcinoma, and six had squamous cell carcinoma or mixed histology. Ten patients had metastases to lymph nodes only, six had locally advanced disease, four had locally recurrent disease, 24 patients had visceral metastases, and five had soft tissue metastases. Twenty-one patients had disease in one site, 16 in two sites, and 12 in three sites. A total of 272 cycles were administered (median, six cycles; range, 1 to 15 cycles). Major toxicities were grade 3 and 4 neutropenia in 17 and 19 patients, respectively; grade 3 and 4 thrombocytopenia in 15 and six patients, respectively; grade 3 and 4 anemia in 10 and two patients, respectively; grade 3 neuropathy in four patients; and diarrhea in two patients. The incidence of febrile neutropenia was 1.4%; no patients died of drug toxicity. Forty-seven of the 49 patients were assessable for response. Fifteen (32%) patients experienced a complete response, and 17 (36%) patients experienced a partial response (32 of 47 patients, 68%; 95% confidence interval, 56.27 to 82.86). Responses were seen in all sites, including 15 (68%) of 22 patients with visceral metastases. The median survival was 14.7 months, with a 1-year survival of 59%. CONCLUSION: Combination paclitaxel, carboplatin, and gemcitabine is active; an encouraging number of patients with advanced urothelial carcinoma treated with this regimen experienced complete remission.
Evaluation of crew skin flora under conditions of a full quarantine lunar-exploration mission
Authors: CAROLYN CARMICHAEL, GERALD R. TAYLOR
Journal: British Journal of Dermatology (1977)

Crew-members of the Apollo 14 lunar exploration mission underwent a pre-flight seclusion designed to stabilize their health by freeing them from exposure to potentially infectious agents. After the flight, the crew-members were quarantined to protect the biosphere from possible lunar contamination. These isolations, along with the complete isolation of the spaceflight itself, provided the opportunity for a skin flora survey which included the sampling of seven sites at five different times. Quantification and identification of all aerobic and anaerobic bacteria from each site were performed. The results indicated that the pre-flight quarantine measures resulted in a decrease in total numbers of isolates as well as a decrease in the anaerobes. This was followed by a continued decrease throughout the flight with a return to the pre-flight norm within 16 days after the flight. The quantitative load of aerobic bacteria increased during the flight, due largely to an increase in coryneforms and micrococcaceae. The quantitative load of anaerobic bacteria decreased before and during the flight. No instance of microbial shock or intercrew transfer of micro-organisms was demonstrated. These findings indicate that alterations in the skin flora do not pose any unusual problem during short duration space flights. Further, there are no indications that problems will arise on longer missions.
Somatic <i>TP53</i> Mutations Are Relatively Rare among Adrenocortical Cancers with the Frequent 17p13 Loss of Heterozygosity
Authors: Rossella Libè, Lionel Groussin, Frédérique Tissier, Caroline Elie, Fernande René-Corail, Amato Fratticci, Eric Jullian, Paolo Beck-Peccoz, Xavier Bertagna, Christine Gicquel, Jérôme Bertherat
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Allelic losses [loss of heterozygosity (LOH)] at the 17p13 locus are frequent (85%) in adrenocortical cancers. The tumor suppressor gene TP53 is located at 17p13. The aim of the study was to determine the frequency of TP53 somatic inactivating mutations in adrenocortical tumors with 17p13 LOH and their clinico-biological correlations. Experimental Design: TP53 somatic mutations, intragenic LOH (VNTR1 marker), and p53 overexpression were studied in 36 adrenocortical tumors with 17p13 LOH determined by Southern blot. Results: TP53 mutations were detected in 33% of the tumors, and VNTR1 LOH was present in 44% of the cases and did not always correlate with the presence of a TP53 mutation. Only the TP53-mutant tumors exhibit a strong nuclear immunoreactivity. TP53-mutant tumors were significantly larger than wild-type TP53 tumors (median tumor weight: 640 versus 185 g; P = 0.02), were associated with a more advanced stage of tumor progression (MacFarlane stage IV; P = 0.01), and had a shorter disease-free survival (P = 0.03). Conclusions: The finding that only a minority of adrenocortical tumors with 17p13 LOH had either a VNTR1 LOH or a TP53 mutation indicates that TP53 might not be the only or major tumor suppressor gene at 17p13 involved in adrenocortical cancer progression. We suggest that a genetic instability of the 17p13 region, occurring early in adrenocortical cancer development, involves various genes located in this region. TP53 might be only one of them, and its alteration by the occurrence of inactivating mutation is associated with the development of more aggressive tumors.
Functional specialization in the lower and upper visual fields in humans: Its ecological origins and neurophysiological implications
Authors: Fred H. Previc
Journal: Behavioral and Brain Sciences (1990)

Abstract Functional specialization in the lower and upper visual fields in humans is analyzed in relation to the origins of the primate visual system. Processing differences between the vertical hemifields are related to the distinction between near (peripersonal) and far (extrapersonal) space, which are biased toward the lower and upper visual fields, respectively. Nonlinear/global processing is required in the lower visual field in order to pergeive the optically degraded and diplopic images in near vision, whereas objects in far vision are searched for and recognized primarily using linear/local perceptual mechanisms. The functional differences between near and far visual space are correlated with their disproportionate representations in the dorsal and ventral divisions of visual association cortex, respectively, and in the magnocellular and parvocellular pathways that project to them. Advances in far visual capabilities and forelimb manipulatory skills may have led to a significant enhancement of these functional specializations.
Multicenter Phase II Study of Erlotinib, an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
Authors: Denis Soulieres, Neil N. Senzer, Everett E. Vokes, Manuel Hidalgo, Sanjiv S. Agarwala, Lillian L. Siu
Journal: Journal of Clinical Oncology (2003)

To determine the efficacy and safety profiles of erlotinib in patients with advanced recurrent and/or metastatic squamous cell cancer of the head and neck (HNSCC).Patients with locally recurrent and/or metastatic HNSCC, regardless of their HER1/EGFR status, were treated with erlotinib at an initial dose of 150 mg daily. Dose reductions or escalations were allowed based on tolerability of erlotinib.One-hundred fifteen patients were enrolled onto this study. Forty-seven percent of patients received erlotinib at 150 mg daily throughout the entire study, 6% had dose escalations, and 46% required dose reductions and/or interruptions. Five patients achieved partial responses on study, for an overall objective response rate of 4.3% (95% CI, 1.4% to 9.9%). Disease stabilization was maintained in 44 patients (38.3%) for a median duration of 16.1 weeks. The median progression-free survival was 9.6 weeks (95% CI, 8.1 to 12.1 weeks), and the median overall survival was 6.0 months (95% CI, 4.8 to 7.0 months). Subgroup analyses revealed a significant difference in overall survival favoring patients who developed at least grade 2 skin rashes versus those who did not (P =.045), whereas no difference was detected based on HER1/EGFR expression. Rash and diarrhea were the most common drug-related toxicities, encountered in 79% and 37% of patients, respectively, though the severity was mild to moderate in most cases.Erlotinib was well tolerated in this heavily pretreated HNSCC population and produced prolonged disease stabilization; hence, further evaluation of its role in this tumor type is warranted.
The external world of gluten and autoimmunity
Authors: M LONDEI
Journal: Gut (2001)

See article on page 502 

This commentary is not about autoimmune diseases, and therefore I will not discuss why a significant proportion of individuals are prone to develop autoimmune diseases. Suffice to say that this failure to spare self might represent an advantage when fighting infections. In autoimmunity there is a clear genetic involvement with a strong association between these diseases and some HLA alleles,1but autoimmunity is not simply genetically controlled and environmental factors are essential. For example, in the syngenic NOD mice, the preferred animal model for type 1 diabetes, simple modifications in the “cleanness” of the housing conditions dramatically changes the incidence of the disease.2 More poignantly, in the context of a clinical setting, the concordance rate of autoimmune diseases in monozygous (genetically identical) twins is less than 50%.3 Hence environmental factor(s) are essential in induction of autoimmunity. Thus characterisation of “environmental” triggers and how they might promote autoimmunity is of paramount importance if we wish to understand, prevent, and eventually define strategies to treat these diseases. The gastrointestinal tract, with its vast surface of contact with the external world, represents the main door for the potential encounter of “environmental” triggers of autoimmunity.

To curb this risk, the gastrointestinal tract, as other mucosae, has devised means of inducing a protective response that however lacks the inflammatory flavour. In a simplistic way, antigens encountered on a mucosal surface trigger a Th2 (sometimes and depending on the authors Th3 or T regulatory) type of response instead of a proinflammatory Th1 …
The origins of inoculation
Authors: Arthur Boylston
Journal: Journal of the Royal Society of Medicine (2012)

Early in the 18 th century, variolation (referred to then as ‘inoculation’) was introduced to Britain and New England to protect people likely to be at risk of infection with smallpox. This triggered a number of important developments. Among them were early examples of what we refer to today as ‘evidence-based medicine’ – immunization, and quantitative measures of disease severity. Establishing the protective effects and subsequent spread of variolation paved the way for recognition that inoculation with cowpox (vaccination) also conferred protection. The definitive experiments that established that vaccination was protective showed that variolation did not ‘take’ following vaccination, thus confirming that immunity had been achieved. Vaccination led ultimately to the eradication of smallpox, one of the great achievements of medicine. Given the central role of variolation in these significant events, it is worth investigating where the practice originated.
Contribution of hMTH1 to the Maintenance of 8-Oxoguanine Levels in Lung DNA of Non-Small-Cell Lung Cancer Patients
Authors: E. Speina, K. D. Arczewska, D. Gackowski, M. Zielinska, A. Siomek, J. Kowalewski, R. Olinski, B. Tudek, J. T. Kusmierek
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: The level of 8-oxoguanine (8-oxoG), a general marker of oxidative DNA damage, in DNA is the result of both an equilibrium between the rates of its formation and removal from DNA by DNA repair enzymes and the removal of 8-oxodGTP from the cellular nucleotide pool by hydrolysis to 8-oxodGMP, preventing its incorporation into DNA. To determine the contribution of each component to the level of 8-oxoG in DNA, we compared 8-oxoG–excising activity (encoded by hOGG1), 8-oxodGTPase activity (encoded by hMTH1), and 8-oxoG levels in DNA from tumors and surrounding normal lung tissues from non–small-cell lung cancer patients. Methods : We measured the level of 8-oxoG in DNA of 47 patients by high-performance liquid chromatography/electrochemical detection (HPLC/ECD), hOGG1 activity in tissue extracts of 56 patients by the nicking assay using an oligodeoxynucleotide containing a single 8-oxoG, and hMTH1 activity in tissue extracts of 33 patients by HPLC/UV detection. All statistical tests were two-sided. Results : The 8-oxoG level was lower in tumor DNA than in DNA from normal lung tissue (geometric mean: 5.81 versus 10.18 8-oxoG/10 6 G, geometric mean of difference = 1.75; P <.001). The hOGG1 activity was also lower in tumor than in normal lung tissue (geometric mean: 8.76 versus 20.91 pmol/h/mg protein, geometric mean of difference = 2.39; P <.001), whereas the hMTH1 activity was higher in tumor than in normal lung tissue (geometric mean: 28.79 versus 8.94 nmol/h/mg protein, geometric mean of difference = 0.31; P <.001). The activity of hMTH1 was three orders of magnitude higher than that of hOGG1 (nanomoles versus picomoles per hour per milligram of protein, respectively). Conclusions : Several different components contribute to the maintenance of 8-oxoG levels in human DNA, with the greatest contributor being the removal of 8-oxodGTP from the cellular nucleotide pool by hMTH1.
Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120.
Authors: A Takeda, J E Robinson, D D Ho, C Debouck, N L Haigwood, F A Ennis
Journal: Journal of Clinical Investigation (1992)

There is increasing evidence that sera from HIV-1-infected individuals contain antibodies that enhance infection by HIV-1 in vitro. Previous work has demonstrated that complement receptors on T lymphoid cells and Fc receptors for IgG (Fc gamma R) on monocytic cells are required for enhanced infection by antibody-complexed HIV-1. Characterization of such infection-enhancing antibodies is essential because immunogenic epitopes which induce enhancing antibodies should be excluded from HIV-1 vaccines. This study was conducted to identify enhancing antibodies involved in Fc R-mediated enhancement of HIV-1 infection employing IgG human monoclonal antibodies (HMAbs) reactive against gp120 of HIV-1, which were produced by B cell lines derived from an HIV-1-infected individual. A potent neutralizing HMAb N70-1.5e did not enhance infection by HIV-1 (IIIB and MN strains), whereas HMAb N70-2.3a mediated enhancement of HIV-1 infection, but had little neutralizing activity. A competition radio immunoassay demonstrated that the two antibodies bind to distinct epitopes. These results indicated that enhancing and neutralizing antibodies can be induced by different epitopes on gp120, suggesting the potential for development of safe vaccines against HIV-1 by exclusion of immunogenic epitopes for enhancing antibodies. We made attempts to identify the epitope on gp120 that is recognized by the enhancing antibody N70-2.3a by using recombinant HIV-1 proteins and found that the antibody binds to a conformational site of nonvariable sequences in the carboxyl half (aa 272-509) of gp120.
Prevalence of Prediabetes and Diabetes and Metabolic Profile of Patients With Nonalcoholic Fatty Liver Disease (NAFLD)
Authors: Carolina Ortiz-Lopez, Romina Lomonaco, Beverly Orsak, Joan Finch, Zhi Chang, Valeria G. Kochunov, Jean Hardies, Kenneth Cusi
Journal: Diabetes Care (2012)

Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population.We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[(3)H]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIR(i)= endogenous glucose production × fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR(i)= fasting FFA × FPI).Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01-0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001).Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD.
Lung ultrasound in critically ill patients: comparison with bedside chest radiography
Authors: Nektaria Xirouchaki, Eleftherios Magkanas, Katerina Vaporidi, Eumorfia Kondili, Maria Plataki, Alexandros Patrianakos, Evaggelia Akoumianaki, Dimitrios Georgopoulos
Journal: Intensive Care Medicine (2011)
The effects of hydroxychloroquine on antiphospholipid antibody titres in SLE
Authors: A Broder, C Putterman
Journal: Annals of the Rheumatic Diseases (2010)

Purpose Treatment with hydroxychloroquine (HCQ) is associated with a decreased risk of thrombosis in APLS.In vitro, HCQ decreases the binding of aPL-beta2 glycoprotein I complexes to phospholipid bilayers and reduces aPL levels in clinical assays.The time-dependent effects of HCQ on aPL in SLE patients have not been studied extensively.We therefore investigated the association of changes in aPL titres over time with HCQ therapy.Method We identifi ed all SLE patients followed at a tertiary care centre with aPL or lupus anticoagulant (Lac), which had been checked at least twice between 2002 and 2009.At baseline, patients were defi ned as aPL/Lac-if they tested negative for both aPL and Lac, and as aPL/Lac+ if they tested positive for either aPL or Lac.We used the standard laboratory cut-offs for the above defi nitions.In the aPL/Lac+ group an 'event' was defi ned as aPL and/or Lac conversion from positive to negative.In the aPL/Lac-group an 'event' was defi ned as aPL or Lac conversion from negative to positive.'Time to event' was defi ned as the number of months from baseline to censoring or on August 17, 2023 by guest.
B7-H4–deficient mice display augmented neutrophil-mediated innate immunity
Authors: Gefeng Zhu, Mathew M. Augustine, Takeshi Azuma, Liqun Luo, Sheng Yao, Sudarshan Anand, A. Cecilia Rietz, Jiaqiang Huang, Haiying Xu, Andrew S. Flies, Sarah J. Flies, Koji Tamada, Marco Colonna, Jan M. A. van Deursen, Lieping Chen
Journal: Blood (2008)
The Cusum Plot: Its Utility in the Analysis of Clinical Data
Authors: Herbert Wohl
Journal: New England Journal of Medicine (1977)

Clinicians are constantly required to analyze clinical and laboratory data for trends. Is a patient's temperature really beginning to come down in response to antibiotics? Is the white-cell count or blood urea nitrogen really falling? These questions are particularly frustrating because these data often have a natural degree of scatter, which obscures early detection of trends. Discerning trends in reams of laboratory reports is extremely vexing. Flow sheets help, and plotting data on a graph helps more, although widely used only for vital signs. Other approaches are more powerful in the early detection of trends in data, and deserve recognition. . . .
Clinical profile of acute diarrhoea cases infected with the new epidemic strain of Vibrio cholerae O139: designation of the disease as cholera
Authors: S.K. Bhattacharya, M.K. Bhattacharya, G. Balakrish Nair, D. Dutta, A. Deb, T. Ramamurthy, Surabhi Garg, Pradip K. Saha, P. Dutta, A. Moitra, B.K. Mandal, Toshio Shimada, Yoshifumi Takeda, B.C. Deb
Journal: Journal of Infection (1993)