tbuckley/cabot-search huggingface dataset:
Treatment of orthotopic malignant peripheral nerve sheath tumors with oncolytic herpes simplex virus
Authors: Slawomir Antoszczyk, Melanie Spyra, Victor Felix Mautner, Andreas Kurtz, Anat O. Stemmer-Rachamimov, Robert L. Martuza, Samuel D. Rabkin
Journal: Neuro-Oncology (2014)

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive and often lethal sarcoma that frequently develops in patients with neurofibromatosis type 1 (NF1). We developed new preclinical MPNST models and tested the efficacy of oncolytic herpes simplex viruses (oHSVs), a promising cancer therapeutic that selectively replicates in and kills cancer cells.Mouse NF1(-) MPNST cell lines and human NF1(-) MPNST stemlike cells (MSLCs) were implanted into the sciatic nerves of immunocompetent and athymic mice, respectively. Tumor growth was followed by external measurement and sciatic nerve deficit using a hind-limb scoring system. Oncolytic HSV G47Δ as well as "armed" G47Δ expressing platelet factor 4 (PF4) or interleukin (IL)-12 were injected intratumorally into established sciatic nerve tumors.Mouse MPNST cell lines formed tumors with varying growth kinetics. A single intratumoral injection of G47Δ in sciatic nerve tumors derived from human S462 MSLCs in athymic mice or mouse M2 (37-3-18-4) cells in immunocompetent mice significantly inhibited tumor growth and prolonged survival. Local IL-12 expression significantly improved the efficacy of G47Δ in syngeneic mice, while PF4 expression prolonged survival. Injection of G47Δ directly into the sciatic nerve of athymic mice resulted in only mild symptoms that did not differ from phosphate buffered saline control.Two new orthotopic MPNST models are described, including in syngeneic mice, expanding the options for preclinical testing. Oncolytic HSV G47Δ exhibited robust efficacy in both immunodeficient and immunocompetent MPNST models while maintaining safety. Interleukin-12 expression improved efficacy. These studies support the clinical translation of G47Δ for patients with MPNST.
Genotype risk score of common susceptible variants for prediction of type 2 diabetes mellitus in Japanese: the Shimanami Health Promoting Program (J-SHIPP study)
Authors: Yasuharu Tabara, Haruhiko Osawa, Ryuichi Kawamoto, Hiroshi Onuma, Ikki Shimizu, Hideichi Makino, Katsuhiko Kohara, Tetsuro Miki
Journal: Metabolism (2011)
Should We Manage Patients With Non-ST Segment Elevation Myocardial Infarction With Renal Failure With an Invasive Strategy?
Authors: Christopher P. Cannon
Journal: Circulation (2009)

zummer and colleagues raise an important question: Should we manage patients presenting with non-STsegment elevation myocardial infarction (NSTEMI) with an early invasive strategy? 1 It makes good sense to do this.We know that patients with renal dysfunction are at high risk, 2 and the American College of Cardiology/American Heart Association and European Society of Cardiology guidelines both recommend an early invasive strategy for patients with unstable angina/NSTEMI who are high risk. 3,4Neither guideline, however, specifically notes that renal dysfunction should be a specific indication for an invasive strategy.
Short-Term Treatment-Related Symptoms and Quality of Life: Results From an International Randomized Phase III Study of Cisplatin With or Without Raltitrexed in Patients With Malignant Pleural Mesothelioma: An EORTC Lung-Cancer Group and National Cancer Institute, Canada, Intergroup Study
Authors: Andrew Bottomley, Rabab Gaafa, Christian Manegold, Sjaak Burgers, Corneel Coens, Catherine Legrand, Mark Vincent, Giuseppe Giaccone, Jan Van Meerbeeck
Journal: Journal of Clinical Oncology (2006)

For malignant pleural mesothelioma (MPM) patients with a poor prognosis, maintaining health-related quality of life (HRQOL) is important. This article compares the impact on HRQOL of first-line treatment with cisplatin versus raltitrexed and cisplatin.Patients with histologically-proven unresectable MPM, not pretreated with chemotherapy were randomly assigned to receive cisplatin 80 mg/m2 intravenously on day 1, with or without preceding infusion of raltitrexed 3 mg/m2. HRQOL was assessed with the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC Lung Cancer Module (QLQ-LC13) tools. Assessments were conducted at baseline, immediately before every treatment cycle, at the end of treatment, and every six weeks for 12 months.Two hundred fifty patients were randomly assigned, 80% were male with a median age of 58 years, WHO performance status 0, 1, and 2, in 25%, 62%, and 13% of cases. The clinical results found raltitrexed and cisplatin to be superior to cisplatin with regard to overall survival (P = .048). The global HRQOL scale was comparable at baseline on both treatment arms (P = .848); at no point was any significant difference apparent on this end point. Both treatments led to an improvement, over time, in dyspnoea. This effect is an important clinically meaningful reduction from baseline in the cisplatin/raltitrexed arm. However, the majority of scales of the EORTC QLQ-C30 or LC13 showed stabilization of HRQOL with few clinically significant differences between the treatment arms.This study provides important information about the HRQOL of chemotherapy-treated MPM patients.
High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma
Authors: M. C. Chamberlain, S. K. Johnston
Journal: Neuro-Oncology (2010)

We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS).Forty patients (25 men; 15 women), ages 18 -93 years (median 61.5), were treated.All patients received biweekly HD-MTX/rituximab (8 g/ m 2 /dose; 375 mg/m 2 /dose) for 4-6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m 2 /dose) for 4 cycles (maintenance).Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy.All patients were evaluable.A total of 303 cycles of HD-MTX (median 8 cycles; range 4-10) was administered.HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%).Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response.At the conclusion of maintenance therapy (6-10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response.Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5).Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months.Overall, PFS ranged from 2 to 80 months (median 21.0).HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months.
Model for Individualized Prediction of Breast Cancer Risk After a Benign Breast Biopsy
Authors: V. Shane Pankratz, Amy C. Degnim, Ryan D. Frank, Marlene H. Frost, Daniel W. Visscher, Robert A. Vierkant, Tina J. Hieken, Karthik Ghosh, Yaman Tarabishy, Celine M. Vachon, Derek C. Radisky, Lynn C. Hartmann
Journal: Journal of Clinical Oncology (2015)

Purpose Optimal early detection and prevention for breast cancer depend on accurate identification of women at increased risk. We present a risk prediction model that incorporates histologic features of biopsy tissues from women with benign breast disease (BBD) and compare its performance to the Breast Cancer Risk Assessment Tool (BCRAT). Methods We estimated the age-specific incidence of breast cancer and death from the Mayo BBD cohort and then combined these estimates with a relative risk model derived from 377 patient cases with breast cancer and 734 matched controls sampled from the Mayo BBD cohort to develop the BBD–to–breast cancer (BBD-BC) risk assessment tool. We validated the model using an independent set of 378 patient cases with breast cancer and 728 matched controls from the Mayo BBD cohort and compared the risk predictions from our model with those from the BCRAT. Results The BBD-BC model predicts the probability of breast cancer in women with BBD using tissue-based and other risk factors. The concordance statistic from the BBD-BC model was 0.665 in the model development series and 0.629 in the validation series; these values were higher than those from the BCRAT (0.567 and 0.472, respectively). The BCRAT significantly underpredicted breast cancer risk after benign biopsy (P = .004), whereas the BBD-BC predictions were appropriately calibrated to observed cancers (P = .247). Conclusion We developed a model using both demographic and histologic features to predict breast cancer risk in women with BBD. Our model more accurately classifies a woman's breast cancer risk after a benign biopsy than the BCRAT.
Vietnam Veterans' Risks for Fathering Babies With Birth Defects
Authors: J. David Erickson
Journal: JAMA (1984)

Vietnam veterans' risks for fathering babies with major structural birth defects were assessed using a case-control study. Information regarding military service in Vietnam was obtained from interviews with mothers and fathers of babies in case and control groups and from review of military records. Vietnam veterans, in general, did not have an increased risk of fathering babies with defects (all types combined; relative risk estimate, 0.97). Vietnam veterans who had greater estimated opportunities for Agent Orange exposure did not seem to be at greater risk for fathering babies with all types of defects combined. However, for a few specific types of defects the estimated risks were higher for subgroups of Vietnam veterans that may have had a greater likelihood of exposure to Agent Orange. These seemingly higher risks could be chance events, the result of some experience in the Vietnam service of the father, or the result of some other unidentified risk factor.
CpG Island Methylation Is Responsible for <b> <i>p14ARF</i> </b> Inactivation and Inversely Correlates with p53 Overexpression in Resected Non–Small Cell Lung Cancer
Authors: Han-Shui Hsu, Yu-Chien Wang, Ruo-Chia Tseng, Jer-Wei Chang, Jung-Ta Chen, Chuen-Ming Shih, Chih-Yi Chen, Yi-Ching Wang
Journal: Clinical Cancer Research (2004)

Abstract Purpose and Experimental Design: The molecular mechanisms by which the p14ARF gene is altered in non–small cell lung cancer (NSCLC) are complex and unclear. Using genetic and epigenetic analyses, we examined various molecular alterations including the loss of protein and mRNA expression, and 5′CpG hypermethylation, allelic imbalance, and mutation of the p14ARF gene in a series of 102 NSCLC samples, in parallel with clinicopathological and prognostic analyses. To clarify the biological significance of p14ARF alterations, its relationship with p16INK4a and p53 alterations was also examined. Results: We found that 34% of NSCLC patients had aberrant P14ARF protein expression, which was more frequent in adenocarcinomas (AD; 44%) than in squamous cell carcinomas (22%; P = 0.024). A high concordance was observed between alterations in protein and mRNA expression and 5′CpG hypermethylation (P ≤ 0.001). The p14ARF hypermethylation inversely correlated with P53 overexpression (P = 0.001). This mutually exclusive relationship for alteration between p14ARF and p53 was also supported by a worse prognosis of AD patients with positive P14ARF expression (P = 0.01) and of AD patients with P53 overexpression (P = 0.006). Our data also indicated that hemizygous/homozygous deletion and mutation in the p14ARF gene occurred at 26%, 9%, and 0%, respectively, of microdissected NSCLCs. Conclusions: Our data suggest that p14ARF 5′CpG hypermethylation is the predominant mechanism involved in the aberrant expression of the p14ARF gene. In addition, p14ARF 5′CpG hypermethylation occurs inversely to P53 overexpression.
Pharyngeal and Upper Esophageal Dysphagia
Authors: William B. Seaman
Journal: JAMA (1976)

"DYSPHAGIA" means difficulty in the transport of swallowed material from the mouth through the pharynx and esophagus into the stomach. True dysphagia does not imply pain but the awareness that something has lodged in the pharynx or esophagus, although this may be accompanied by some discomfort. Clinically, it may be acute or chronic and localized in the upper or lower esophagus. The patient can usually localize the site of obstruction with reasonable accuracy, although occasionally the sensation of dysphagia may be referred from the distal part of the esophagus to the region of the suprasternal notch or pharynx. If a balloon is distended in the distal part of the esophagus, induction of the sensation to the suprasternal notch occurs in about 10% of subjects. The type of food that causes the dysphagia may be a helpful clue to its origin. Bones from meat, fowl, or fish, or a large bolus
Pathogenic role of anti-β2-glycoprotein I antibodies on human placenta: functional effects related to implantation and roles of heparin
Authors: N. Di Simone, P.L. Meroni, M. D’Asta, F. Di Nicuolo, M.C. D’Alessio, A. Caruso
Journal: Human Reproduction Update (2006)

Most of the clinical manifestations of the antiphospholipid syndrome (APS) can be related to thrombotic events; however, placental thrombosis cannot explain all of the pregnancy complications that occur in women with this syndrome. In this regard, it has been hypothesized that antiphospholipid (aPL) antibodies can directly attack trophoblasts, but it is still unclear what pathogenetic mechanisms play a role and which aPL antibodies subpopulations are involved. Although it has been assumed that aPL antibodies are directed against anionic phospholipids (PLs), current advances in the field suggest that antibodies to PL-binding plasma protein such as β2-glycoprotein-I (β2-GPI) are the clinically relevant aPL antibodies. It appears that following the attachment of β2-GPI to PLs, both molecules undergo conformational changes that result in the exposure of cryptic epitopes within the structure of β2-GPI allowing the subsequent binding of antibodies. aPL antibodies detected by anti-β2-GPI assays are associated with fetal loss. However, there is still debate on how the antibodies might induce the obstetrical manifestations. The significantly improved outcome of pregnancies treated with heparin has stimulated interest in the drug’s mechanisms of action. Several mechanisms could explain its beneficial effects, because in addition to a direct effect of heparin on the coagulation cascade, it might protect pregnancies by reducing the binding of aPL antibodies, reducing inflammation, facilitating implantation and/or inhibiting complement activation. Further investigations are needed to better understand how aPL antibodies induce obstetric complications and to better clarify the functional role of heparin in the human placenta leading to more successful therapeutic options.
TINEA CAPITIS IN EAST LONDON AND ESSEX, 1944–1955.
Authors: CLARA M. WARREN
Journal: British Journal of Dermatology (1956)

Journal Article TINEA CAPITIS IN EAST LONDON AND ESSEX, 1944–1955. Get access CLARA M. WARREN, M.R.C.S., L.R.C.P. CLARA M. WARREN, M.R.C.S., L.R.C.P. Formerly Clinical Mycologist to the Skin Department, The London Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 7-8, 1 July 1956, Pages 264–267, https://doi.org/10.1111/j.1365-2133.1956.tb12814.x Published: 01 July 1956
Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer
Authors: M.A. Pantaleo, M. Nannini, A. Maleddu, S. Fanti, C. Nanni, S. Boschi, F. Lodi, G. Nicoletti, L. Landuzzi, P.L. Lollini, G. Biasco
Journal: Annals of Oncology (2008)
Effect of colloidal bismuth subcitrate on symptoms and gastric histology in non-ulcer dyspepsia. A double blind placebo controlled study.
Authors: J Y Kang, H H Tay, A Wee, R Guan, M V Math, I Yap
Journal: Gut (1990)

The aim of this study was to determine the effect of colloidal bismuth subcitrate (De Nol) on symptoms and gastric histology in patients with non-ulcer dyspepsia. In a single centre trial, patients with food related upper abdominal pain not caused by ulcer disease were randomised to receive one tablet of colloidal bismuth subcitrate or matching placebo four times daily for eight weeks. Seventy three patients were entered and 51 completed the trial: 28 patients in the colloidal bismuth subcitrate group and 23 in the placebo group. Overall there was no difference between the two groups in terms of symptom relief. Among patients with histological gastritis (n = 23), however, those who took colloidal bismuth subcitrate used fewer antacid tablets (for three of four fortnightly periods) and were more likely to become asymptomatic (eight of 11 v three of 12, p less than 0.05); their gastritis was more likely to resolve (five of 10 v 0 of 12, p less than 0.025) and their gastric biopsies more likely to become negative for Helicobacter like organisms (eight of nine v 0 of 12, p less than 0.001) when compared with patients taking placebo. In contrast, patients who did not have gastritis in their index biopsies (n = 28) fared similarly whether they received colloidal bismuth subcitrate or placebo. Our results indicate that the administration of colloidal bismuth subcitrate benefited non-ulcer dyspepsia patients with gastritis but had no effect on those without.
Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity
Authors: Troy Querec, Soumaya Bennouna, Sefik Alkan, Yasmina Laouar, Keith Gorden, Richard Flavell, Shizuo Akira, Rafi Ahmed, Bali Pulendran
Journal: The Journal of Experimental Medicine (2006)

The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in &amp;gt;400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-α. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.
Alcohol breath testing in patients with respiratory disease.
Authors: M J Morris
Journal: Thorax (1990)

Alcohol breath testing in patients with respiratory diseaseThe Road Safety Act 1967 introduced in Great Britain the concept of a statutory limit to the amount of alcohol legally permitted in a driver's body.Under this Act the maximum legal limit was set at 80 mg/100 ml in blood and 107 mg/ 100 ml in urine.The motorist was required to take a screening roadside breath test and if the result was positive the subject was arrested and taken to a police station for a blood or urine test.In 1974 the Blennerhasset Committee recommended that breath analysis should replace blood analysis, and evidential breath testing came into force in May 1983.At present the law concerning drink and motor vehicles is defined in the Road Traffic Act 1988, sections 4-11.'
Amelioration of ischemic acute renal failure by dietary fish oil administration in conscious dogs.
Authors: H H Neumayer, M Heinrich, M Schmissas, H Haller, K Wagner, F C Luft
Journal: Journal of the American Society of Nephrology (1992)

The hypothesis that dietary fish oil would protect dogs from ischemic acute renal failure was tested. Fish oil (eicosapentaenoic acid, 55 mg/kg per day, and docosahexaenoic acid, 40 mg/kg per day was given to eight instrumented, female, beagle dogs for 6 wk, while seven control dogs received vehicle. After 3 wk, unilateral nephrectomy was performed and a pneumatic cuff with flow probe was placed around the remaining renal artery of each dog. Three weeks thereafter, the cuff was inflated for 120 min. Renal function, RBF, and prostanoid excretion were measured 24 and 72 h after ischemia. In dogs receiving fish oil, blood pressure, GFR, RBF, renal vascular resistance (RVR), cholesterol, triglycerides, and prostanoid excretion were measured weekly for 6 wk. Further, cytosolic calcium was measured before and five times after fish oil. Blood pressure decreased, serum cholesterol and triglycerides decreased, and the cytosolic calcium within platelets decreased. The urinary excretion (expressed as picograms per milligram of creatinine) of the thromboxane (TX) metabolite TXB2 and the excretion of prostaglandin (PG)E2, as well as the excretion of the PGI2 metabolite 6-keto PGF1 alpha were decreased. GFR, RBF (Cl inulin and Cl para-aminohippuric acid), and RVR were not influenced by fish oil. Unilateral nephrectomy decreased GFR and RBF and increased RVR as expected, whereas it further decreased prostanoid excretion. Acute renal ischemia caused a significant, reversible decrease in GFR and urine volume in vehicle-treated animals, whereas no significant effect on renal function or urine volume was observed in animals pretreated with fish oil.(ABSTRACT TRUNCATED AT 250 WORDS)
Repeated Unidirectional Introgression of Nuclear and Mitochondrial DNA Between Four Congeneric Tanganyikan Cichlids
Authors: Bruno Nevado, Varvara Fazalova, Thierry Backeljau, Mark Hanssens, Erik Verheyen
Journal: Molecular Biology and Evolution (2011)

With an increasing number of reported cases of hybridization and introgression, interspecific gene flow between animals has recently become a widely accepted and broadly studied phenomenon. In this study, we examine patterns of hybridization and introgression in Ophthalmotilapia spp., a genus of cichlid fish from Lake Tanganyika, using mitochondrial and nuclear DNA from all four species in the genus and including specimens from over 800 km of shoreline. These four species have very different, partially overlapping distribution ranges, thus allowing us to study in detail patterns of gene flow between sympatric and allopatric populations of the different species. We show that a significant proportion of individuals of the lake-wide distributed O. nasuta carry mitochondrial and/or nuclear DNA typical of other Ophthalmotilapia species. Strikingly, all such individuals were found in populations living in sympatry with each of the other Ophthalmotilapia species, strongly suggesting that this pattern originated by repeated and independent episodes of genetic exchange in different parts of the lake, with unidirectional introgression occurring into O. nasuta. Our analysis rejects the hypotheses that unidirectional introgression is caused by natural selection favoring heterospecific DNA, by skewed abundances of Ophthalmotilapia species or by hybridization events occurring during a putative spatial expansion in O. nasuta. Instead, cytonuclear incompatibilities or asymmetric behavioral reproductive isolation seem to have driven repeated, unidirectional introgression of nuclear and mitochondrial DNA into O. nasuta in different parts of the lake.