tbuckley/cabot-search huggingface dataset:
Epidermal Growth Factor Receptor Signaling and the Invasive Phenotype of Ovarian Carcinoma Cells
Authors:  Alper O, E S Bergmann-Leitner, T A Bennett, N F Hacker, K Stromberg, W G Stetler-Stevenson
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Most (70%–100%) ovarian carcinomas express high levels of the epidermal growth factor receptor (EGFR). To examine the relationship between EGFR and the invasive phenotype, we assessed integrin expression, adhesion, matrix metalloproteinase (MMP) activity, and migration in ovarian cancer cells in which EGFR expression was modified. Methods: NIH:OVCAR-8 human ovarian carcinoma cells were transfected with an expression vector containing the human EGFR complementary DNA in an antisense orientation (EGFR-antisense cells) or the vector alone (vector control cells). We compared vector control and EGFR-antisense cells for cell morphology and adhesion by light microscopy, expression of α6- and α3-integrin subunits by flow cytometry, MMP and tissue inhibitor of MMP (TIMP) activity by zymography, and migration by a wound migration assay. In some experiments, EGFR kinase activity in parental cells was inhibited by treatment with PD153035. All statistical tests were two-sided. Results: EGFR-antisense cells were morphologically distinct from vector control cells and had a selective decrease in adhesion to laminin-1 that was not observed with vector control cells (P = .008) or on other extracellular matrix substrates. Compared with vector control cells, cell surface α6-integrin expression decreased by approximately 80% (difference = 78.7%; 95% confidence interval [CI] = 77.8% to 79.6), MMP-9 activity decreased by approximately 50%, and TIMP activity increased by approximately 50% in EGFR-antisense cells. Vector control cells were highly motile (5.51 arbitrary distance unit; 95% CI = 4.98 to 6.04), whereas the EGFR-antisense cells were not (0.99 arbitrary distance units; 95% CI = 0.38 to 1.60). The morphology and integrin profile of NIH:OVCAR-8 parental cells treated with PD153035 were similar to those of the EGFR-antisense cells. Conclusions: Reduced EGFR expression in ovarian carcinoma cells decreased their adhesion to laminin-1, expression of the α6-integrin subunit (a well-characterized laminin-1 receptor), and MMP-9 activity. These data support the hypothesis that EGFR overexpression in ovarian cancer cells results in multiple phenotypic changes that enhance the invasive phenotype.
Patient Online Self-Reporting of Toxicity Symptoms During Chemotherapy
Authors: Ethan Basch, David Artz, Dorothy Dulko, Kevin Scher, Paul Sabbatini, Martee Hensley, Nandita Mitra, John Speakman, Mary McCabe, Deborah Schrag
Journal: Journal of Clinical Oncology (2005)

Purpose Tracking symptoms related to treatment toxicity is standard practice in routine care and during clinical trials. Currently, clinicians collect symptom information via complex and often inefficient mechanisms, but there is growing interest in collecting outcome information directly from patients. Patients and Methods The National Cancer Institute Common Terminology Criteria for Adverse Events schema for seven common symptoms was adapted into a Web-based patient-reporting system, accessible from desktop computers in outpatient clinics and from home computers. Eighty patients with gynecologic malignancies beginning standard chemotherapy regimens were enrolled between April and September 2004. During an 8-week observation period, participants were encouraged to log in and report symptoms at each follow-up visit, or alternatively, to access the system from home. Results All patients completed an initial log in. At each subsequent appointment, most enrollees (80% to 85%) reported symptoms using the online system, with a mean of three follow-up visits per patient during the observation period (range, one to six). Sixty of 80 patients (75%) logged in at least once from home. Use was significantly associated with prior Internet experience. Forty-two severe toxicities (grade 3 to 4) entered from home prompted seven clinician interventions. Most patients (96%) found the system useful and would recommend it to others. Conclusion Patients are capable of reporting symptoms experienced during chemotherapy using a Web-based interface. Assessment in the clinical trial setting and comparison of direct patient- versus clinician-based approaches for reporting symptoms and their severity are warranted.
Adder bites in Britain.
Authors: H A Reid
Journal: BMJ (1976)

Ninety-five cases of adder bite that have occurred in Britain over the past 100 years are reviewed. Most bites occurred in men who foolishly picked up the adder. Three-quarters of the victims reached hospital within two hours of the bite. When venom is injected the early symptoms include local swelling and discoloration, vomiting, diarrhoea, and early collapse, which often resolves spontaneously. In severe poisoning persistent or recurrent shock is the main feature. Children recover quickly but adults may take weeks or months to recover, during which there may be considerable disability in the bitten limb. Deaths are rare: only 14 deaths from poisoning were recorded in the past 100 years. In England and Wales only one death from adder bite was recorded in 1950-72, but there were 61 deaths from bee or wasp stings. In most cases simple symptomatic treatment is enough, but all patients should be carefully monitored. With persistent or recurrent shock Zagreb antivenom is indicated; and it should also be considered in adults seen within two hours of the bite to minimise morbidity from local effects.
Telehealth Follow-up in Lieu of Postoperative Clinic Visit for Ambulatory Surgery
Authors: Kimberly Hwa, Sherry M. Wren
Journal: JAMA Surgery (2013)

Telehealth encounters can safely substitute for routine postoperative clinic visits in selected ambulatory surgical procedures.To examine whether an allied health professional telephone visit could safely substitute for an in-person clinic visit.Prospective case series during a 10-month study period from October 2011 to October 2012 (excluding July and August 2012).University-affiliated veterans hospital.Ambulatory surgery patients who underwent elective open hernia repair or laparoscopic cholecystectomy during the 10-month study period.Patients were called 2 weeks after surgery by a physician assistant and assessed using a scripted template. Assessment variables included overall health, pain, fever, incision appearance, activity level, and any patient concerns. If the telephone assessment was consistent with absence of infection and return to baseline activities, the patient was discharged from follow-up. Patients who preferred a clinic visit were seen accordingly.Percentage of patients who accepted telehealth follow-up and complications that presented in telehealth patients within 30 days of surgery.One hundred fifteen open herniorrhaphy and 26 laparoscopic cholecystectomy patients had attempted telehealth follow-up. Seventy-eight percent (110) of all patients were successfully contacted; of those, 70.8% (63) of hernia patients and 90.5% (19) of cholecystectomy patients accepted telehealth as the sole means of follow-up. Complications in the telehealth patients were zero for cholecystectomy and 4.8% (3) for herniorrhaphy. Nearly all patients expressed great satisfaction with the telephone follow-up method.Telehealth can be safely used in selected ambulatory patients as a substitute for the standard postoperative clinic visit with a high degree of patient satisfaction. Time and expense for travel (7-866 miles) were reduced and the freed clinic time was used to schedule new patients.
Autologous Hematopoietic Stem-Cell Transplantation for Children With Acute Myeloid Leukemia in First or Second Complete Remission: A Prognostic Factor Analysis
Authors: Kamar Godder, Mary Eapen, Joseph H. Laver, Mei-Jie Zhang, Bruce M. Camitta, Alan S. Wayne, Robert Peter Gale, John J. Doyle, Lolie C. Yu, Allen R. Chen, James H. Garvin, Eric S. Sandler, Andrew M. Yeager, John R. Edwards, Mary M. Horowitz
Journal: Journal of Clinical Oncology (2004)

To determine prognostic factors correlated with outcomes after autologous hematopoietic stem-cell transplantation (HSCT) in children with acute myeloid leukemia (AML).We studied 219 children who received autologous HSCT for AML in first complete remission (CR) and 73 children in second CR and who were reported to the Autologous Blood and Marrow Transplant Registry. Among 29 of 73 patients who underwent transplantation in second CR, duration of first CR was > or = 12 months.Three-year cumulative incidences of relapse were 37% (95% CI, 31% to 44%), 60% (95% CI, 41% to 74%), and 36% (95% CI, 20% to 53%) for children in first CR, second CR after a short (< 12 months) first CR, and second CR after a long (> or = 12 months) first CR, respectively. Corresponding 3-year probabilities of leukemia-free survival were 54% (95% CI, 47% to 60%), 23% (95% CI, 10% to 39%), and 60% (95% CI, 42% to 75%). In multivariate analyses, risks of relapse, mortality, and treatment failure (relapse or death, inverse of leukemia-free survival) were higher for patients in second CR after a short first CR than for the other two groups. Transplant-related mortality, treatment failure, and overall mortality rates were higher in older (> 10 years) children.Duration of first CR seems to be the most important determinant of outcome. Results in children who experience treatment failure with conventional chemotherapy support the use of autologous transplantation as salvage therapy if such patients achieve a subsequent CR.
The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial
Authors: Hideki Ishikawa, Michihiro Mutoh, Sadao Suzuki, Shinkan Tokudome, Yoshihisa Saida, Takashi Abe, Shozo Okamura, Masahiro Tajika, Takashi Joh, Shinji Tanaka, Shin-ei Kudo, Takahisa Matsuda, Masaki Iimuro, Tomomi Yukawa, Tetsuji Takayama, Yasushi Sato, Kyowon Lee, Shinji Kitamura, Motowo Mizuno, Yasushi Sano, Nobuhisa Gondo, Kenji Sugimoto, Masato Kusunoki, Chiho Goto, Nariaki Matsuura, Toshiyuki Sakai, Keiji Wakabayashi
Journal: Gut (2014)

Objective To evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy. Design A double-blinded, randomised, placebo-controlled multicentre clinical trial was conducted. Participants 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study (152 patients in the aspirin group and 159 patients in the placebo group). Enrolment began at the hospitals (n=19) in 2007 and was completed in 2009. Results The subjects treated with aspirin displayed reduced colorectal tumourigenesis and primary endpoints with an adjusted OR of 0.60 (95% CI 0.36 to 0.98) compared with the subjects in the placebo group. Subgroup analysis revealed that subjects who were non-smokers, defined as those who had smoked in the past or who had never smoked, had a marked reduction in the number of recurrent tumours in the aspirin-treated group. The adjusted OR for aspirin treatment in non-smokers was 0.37 (CI 0.21 to 0.68, p&lt;0.05). Interestingly, the use of aspirin in smokers resulted in an increased risk, with an OR of 3.44. In addition, no severe adverse effects were observed in either group. Conclusions Low-dose, enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population. The results are consistent with those obtained from other randomised controlled trials in Western countries. The clinical trial registry website and the clinical trial number http://www.umin.ac.jp (number UMIN000000697).
Hair analysis for drugs in child abuse
Authors: A. Boroda
Journal: Journal of the Royal Society of Medicine (2005)

Testing of blood and urine for drugs is limited by the narrow time scale in which substances and their metabolites can be detected. Hair analysis not only can detect substances taken a week to several months previously but also can be used to estimate the time of exposure. Hair analysis has been reported in a small number of cases of suspected child abuse.1-5
T helper subset development: roles of instruction, selection, and transcription
Authors: J. David Farrar, Helene Asnagli, Kenneth M. Murphy
Journal: Journal of Clinical Investigation (2002)

The past 15 years have seen the development of a field in immunology entirely devoted to understanding the divergence of CD4+ T cells into distinct cytokine-producing subsets. Generally speaking, the immune response to a pathogen can develop toward a more strongly cellular type (type 1), or toward a more allergic type of response (type 2). When well developed, these gear the immune response for the effective elimination of different types of pathogens, with a type 1 response being more effective against intracellular pathogens, for example Listeria monocytogenes or mycobacteria. Type 2 allergic responses, in contrast, favor the elimination of parasites such as helminths. The basis for this selective action resides in the cytokines made by the CD4+ T helper cell subsets in these responses. T helper type 1 (Th1) cells produce several characteristic cytokines, most notably IL-2 and IFN-γ, whereas Th2 cells produce a set of cytokines, most notably IL-4, IL-5, and IL-13. In turn, IL-2 and IFN-γ promote the development of strong cell-mediated immunity, whereas the type 2 cytokines promote allergic responses effective in eliminating parasites.

When confronted with a pathogen, it is important that the immune system activate the appropriate type of response. Fortunately, it has developed reliable mechanisms that help naive CD4 T cells in this choice. These mechanisms have been fairly well worked out at many levels over the last decade, and several thorough reviews have described recent findings regarding the signaling pathways and transcription factors that contribute to peripheral CD4+ Th development (1–3).

Despite the great progress in the molecular understanding of these processes, there are still issues in this area that are controversial and actively debated. Here, we will focus on some aspects that are unresolved within the various models of Th1 and Th2 development and will try to fit together some of the recent observations that have motivated these somewhat theoretical considerations. In particular, we will take this opportunity to focus on a difficult topic, that of whether Th1/Th2 development rests on selective or instructive mechanisms, a general issue that is also debated in regard to CD4/CD8 lineage commitment and is common to many developmental systems. Distinguishing between strictly selective and instructive models is difficult, as many experimental results can be compatible with both interpretations.
CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance
Authors: Maxime Hervé, Isabelle Isnardi, Yen-shing Ng, James B. Bussel, Hans D. Ochs, Charlotte Cunningham-Rundles, Eric Meffre
Journal: The Journal of Experimental Medicine (2007)

Hyper-IgM (HIGM) syndromes are primary immunodeficiencies characterized by defects of class switch recombination and somatic hypermutation. HIGM patients who carry mutations in the CD40-ligand (CD40L) gene expressed by CD4+ T cells suffer from recurrent infections and often develop autoimmune disorders. To investigate the impact of CD40L–CD40 interactions on human B cell tolerance, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from three CD40L-deficient patients. Antibody characteristics and reactivity from CD40L-deficient new emigrant B cells were similar to those from healthy donors, suggesting that CD40L–CD40 interactions do not regulate central B cell tolerance. In contrast, mature naive B cells from CD40L-deficient patients expressed a high proportion of autoreactive antibodies, including antinuclear antibodies. Thus, CD40L–CD40 interactions are essential for peripheral B cell tolerance. In addition, a patient with the bare lymphocyte syndrome who could not express MHC class II molecules failed to counterselect autoreactive mature naive B cells, suggesting that peripheral B cell tolerance also depends on major histocompatibility complex (MHC) class II–T cell receptor (TCR) interactions. The decreased frequency of MHC class II–restricted CD4+ regulatory T cells in CD40L-deficient patients suggests that these T cells may mediate peripheral B cell tolerance through CD40L–CD40 and MHC class II–TCR interactions.
LYMPHADENOPATHY-ASSOCIATED VIRUS TYPE 2 IN AIDS AND AIDS-RELATED COMPLEX
Authors: F. Brun-Vezinet, C. Katlama, D. Roulot, L. Lenoble, M. Alizon, J.J. Madjar, M.A. Rey, P.M. Girard, P. Yeni, F. Clavel, S. Gadelle, M. Harzic
Journal: The Lancet (1987)
Cyclin E1 Deregulation Occurs Early in Secretory Cell Transformation to Promote Formation of Fallopian Tube–Derived High-Grade Serous Ovarian Cancers
Authors: Alison M. Karst, Paul M. Jones, Natalie Vena, Azra H. Ligon, Joyce F. Liu, Michelle S. Hirsch, Dariush Etemadmoghadam, David D.L. Bowtell, Ronny Drapkin
Journal: Cancer Research (2013)

The fallopian tube is now generally considered the dominant site of origin for high-grade serous ovarian carcinoma. However, the molecular pathogenesis of fallopian tube-derived serous carcinomas is poorly understood and there are few experimental studies examining the transformation of human fallopian tube cells. Prompted by recent genomic analyses that identified cyclin E1 (CCNE1) gene amplification as a candidate oncogenic driver in high-grade serous ovarian carcinoma, we evaluated the functional role of cyclin E1 in serous carcinogenesis. Cyclin E1 was expressed in early- and late-stage human tumor samples. In primary human fallopian tube secretory epithelial cells, cyclin E1 expression imparted malignant characteristics to untransformed cells if p53 was compromised, promoting an accumulation of DNA damage and altered transcription of DNA damage response genes related to DNA replication stress. Together, our findings corroborate the hypothesis that cyclin E1 dysregulation acts to drive malignant transformation in fallopian tube secretory cells that are the site of origin of high-grade serous ovarian carcinomas.
T cell receptor V beta expression in human intestine: regional variation in postnatal intestine and biased usage in fetal gut.
Authors: R Thomas, G Schurmann, P Lionetti, S L Pender, T T MacDonald
Journal: Gut (1996)

A panel of T cell receptor V beta specific monoclonal antibodies was used to analyse V beta gene usage at different sites in human postnatal and fetal intestine. In normal small intestine, at a single site, different patients showed expansion of T cells expressing individual V beta s. Lamina propria and epithelial T cells from the same patient showed overlapping but not identical V beta dominance. V beta dominance was also shown in the T cells of the colonic lamina propria. Analysis of two separate regions of intestine from the same patient (5-100 cm apart) showed that T cells expressing a dominant V beta region were often present at both sites. In most patients, however, major biases in T cell V beta usage (two to 12-fold variation) were also apparent between the two sites. Analysis of V beta expression in human fetal intestine also showed considerable skewing, although the most common dominant V beta in postnatal intestine (V beta 22) was never predominant in fetal intestine. Patchy local variation in the expression of individual V beta s therefore occurs against a background of V beta dominance over large regions of the human gut. Furthermore the results from fetal gut show that factors other than luminal antigen control V beta expression in the gut.
Fluorescence Visualization in Oral Neoplasia: Shedding Light on an Old Problem
Authors: William H. Westra, David Sidransky
Journal: Clinical Cancer Research (2006)

In this issue of Clinical Cancer Research , Poh et al. ([1][1]) show the effectiveness of a simple handheld light (blue excitation light at 400-460 nm) to clarify the true extent of tumor spread and, in turn, guide complete removal of oral cancers in the operating room. Optical changes (specifically
Cortical Development in Typically Developing Children With Symptoms of Hyperactivity and Impulsivity: Support for a Dimensional View of Attention Deficit Hyperactivity Disorder
Authors: Philip Shaw, Mary Gilliam, Maria Liverpool, Catherine Weddle, Meaghan Malek, Wendy Sharp, Deanna Greenstein, Alan Evans, Judith Rapoport, Jay Giedd
Journal: American Journal of Psychiatry (2010)

Objective: There is considerable epidemiological and neuropsychological evidence that attention deficit hyperactivity disorder (ADHD) is best considered dimensionally, lying at the extreme end of a continuous distribution of symptoms and underlying cognitive impairments. The authors investigated whether cortical brain development in typically developing children with symptoms of hyperactivity and impulsivity resembles that found in the syndrome of ADHD. Specifically, they examined whether a slower rate of cortical thinning during late childhood and adolescence, which they previously found in ADHD, is also linked to the severity of symptoms of hyperactivity and impulsivity in typically developing children. Method: In a longitudinal analysis, a total of 193 typically developing children with 389 neuroanatomic magnetic resonance images and varying levels of symptoms of hyperactivity and impulsivity (measured with the Conners' Parent Rating Scale) were contrasted with 197 children with ADHD with 337 imaging scans. The relationship between the rates of regional cortical thinning and severity of symptoms of hyperactivity/impulsivity was determined. Results: Youth with higher levels of hyperactivity/impulsivity had a slower rate of cortical thinning, predominantly in prefrontal cortical regions, bilaterally in the middle frontal/premotor gyri, extending down the medial prefrontal wall to the anterior cingulate; the orbitofrontal cortex; and the right inferior frontal gyrus. For each increase of one point in the hyperactivity/impulsivity score, there was a decrease in the rate of regional cortical thinning of 0.0054 mm/year (SE=0.0019 mm/year). Children with ADHD had the slowest rate of cortical thinning. Conclusions: Slower cortical thinning during adolescence characterizes the presence of both the symptoms and syndrome of ADHD, providing neurobiological evidence for dimensionality of the disorder.