tbuckley/cabot-search huggingface dataset:
THE APPLICATION OF ULTRA-VIOLET LIGHT IN GENERAL PRACTICE
Authors: T. C. McKenzie
Journal: BMJ (1925)

sections this fibrosis was universal and no remains of carcinoma cells were to be found, but in the great majority of sections taken as long as one year after infiltration lighter staining areas were seen occupied by the debris of cells and representing the degenerated remains of columns of carcinoma.The stroma remained infiltrated with lymphocytes in the areas surrounding such masses of debris usually for several months.While these degenerative changes were well marked and easily observed, it was remarkable how fragments or debris of the carcinoma cells persisted even in cases showing cliniical cure.Clinical Changes.The clinical chaniges were usually well marked, and con- sisted of all degrees of improvement of the three main symptoms-haemorrlhage, pain, and discharge.Hacinorrhage was the symptom most completely controlled.Usually it ceased within the first ten days, and, in a case reacting satisfactorily, either did niot recur or only an occasional slight loss occurred.This often happened even when subsequent physical examination showed some persistence of ulceration which might bleed on manipulation.Ccssation of dischargc occurred in 18 cases, but in 6 others it was considerably diminished.It was usual for a patient to state that the bleeding had ceased and that she now had only a little discharge.Pain was affected variously.In about one-third of the cases it was entirely relieved, in another third partially relieved, and in the remaining third either unaffected or aggravated.It is probable that such aggravation is due to pelvic fibrosis compressing the nerves, in spite of the fact that the majority of such cases showed clinical improvement and increased mobility of the uterus.On local examnbation marked changes were found.Usually' by the end of the first month the ulcerated surface had cleared up considerably, and in another -month the improvement was such
Transcription Factor AP-2γ Is a Developmentally Regulated Marker of Testicular Carcinoma <b> <i>In situ</i> </b> and Germ Cell Tumors
Authors: Christina E. Hoei-Hansen, John E. Nielsen, Kristian Almstrup, Si Brask Sonne, Niels Graem, Niels E. Skakkebaek, Henrik Leffers, Ewa Rajpert-De Meyts
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Transcription factor activator protein-2γ (TFAP2C, AP-2γ) was reported previously in extraembryonic ectoderm and breast carcinomas but not in the testis. In our recent gene expression study we detected AP-2γ in carcinoma in situ testis (CIS, or intratubular germ cell neoplasia), precursor of testicular germ cell tumors. In this study we aimed to investigate the expression pattern of AP-2γ and to shed light on this factor in germ cell differentiation and the pathogenesis of germ cell neoplasia. Experimental Design: We analyzed expression pattern of AP-2γ at the RNA and protein level in normal human tissues and a panel of tumors and tumor-derived cell lines. In the gonads, we established the ontogeny of expression of AP-2γ in normal and dysgenetic samples. We also investigated the regulation of AP-2γ by steroids and retinoic acid. Results: We detected abundant AP-2γ in testicular CIS and in testicular germ cell tumors of young adults and confirmed differential expression of AP-2γ in somatic tumors. We found that AP-2γ expression was regulated by retinoic acid in an embryonal carcinoma cell line (NT2). The investigation of ontogeny of AP-2γ protein expression in fetal gonads revealed that it was confined to oogonia/gonocytes and was down-regulated with germ cell differentiation. In some prepubertal intersex cases, AP-2γ was detected outside of the normal window of expression, probably marking neoplastic transformation of germ cells. Conclusions: AP-2γ is developmentally regulated and associated with the undifferentiated phenotype in germ cells. This transcription factor may be involved in self-renewal and survival of immature germ cells and tissue-specific stem cells. AP-2γ is a novel marker of testicular CIS and CIS-derived tumors.
Food outlet visits, physical activity and body weight: variations by gender and race–ethnicity
Authors: L Frank, J Kerr, B Saelens, J Sallis, K Glanz, J Chapman
Journal: British Journal of Sports Medicine (2008)

Purpose: Recent evidence documents significant associations between community design, physical activity and obesity when adjusting for demographic covariates. Yet it is well understood that energy imbalance and weight gain are also a function of dietary patterns, and perhaps the degree of access to healthy food choices. Methods: The current study builds upon the Atlanta-based SMARTRAQ study of over 10 000 respondents and reports an integrated assessment of obesity impacts of physical activity and food outlet visitation. Respondents in the SMARTRAQ survey aged 25–65 provided BMI, self-reported physical activity levels (IPAQ), demographic factors, and where they went for food over a 2 day period. Results: The relative effect of physical activity, neighbourhood walkability, and food outlet visitation on BMI differed significantly across gender and ethnicity. BMI in females increased with fast food and decreased with grocery store visitation and physical activity, but not with walkability or walking. BMI in males was not related to where they went for food but decreased with walking and overall physical activity and with walkability. Fast food visitation was associated with increased BMI in white respondents and grocery store visitation with decreased BMI in black respondents. Meeting moderate activity guidelines was associated with lower BMI in both black and white respondents, yet walking was only significant in predicting reduced BMI in white respondents. Conclusion: Obesity influences of physical activity, walkability, and where people go for food differ significantly across gender and ethnicity and offer important policy implications and insights for future research.
Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle
Authors: Karim Hnia, Helene Tronchère, Kinga K. Tomczak, Leonela Amoasii, Patrick Schultz, Alan H. Beggs, Bernard Payrastre, Jean Louis Mandel, Jocelyn Laporte
Journal: Journal of Clinical Investigation (2010)

Muscle contraction relies on a highly organized intracellular network of membrane organelles and cytoskeleton proteins. Among the latter are the intermediate filaments (IFs), a large family of proteins mutated in more than 30 human diseases. For example, mutations in the DES gene, which encodes the IF desmin, lead to desmin-related myopathy and cardiomyopathy. Here, we demonstrate that myotubularin (MTM1), which is mutated in individuals with X-linked centronuclear myopathy (XLCNM; also known as myotubular myopathy), is a desmin-binding protein and provide evidence for direct regulation of desmin by MTM1 in vitro and in vivo. XLCNM-causing mutations in MTM1 disrupted the MTM1-desmin complex, resulting in abnormal IF assembly and architecture in muscle cells and both mouse and human skeletal muscles. Adeno-associated virus–mediated ectopic expression of WT MTM1 in Mtm1-KO muscle reestablished normal desmin expression and localization. In addition, decreased MTM1 expression and XLCNM-causing mutations induced abnormal mitochondrial positioning, shape, dynamics, and function. We therefore conclude that MTM1 is a major regulator of both the desmin cytoskeleton and mitochondria homeostasis, specifically in skeletal muscle. Defects in IF stabilization and mitochondrial dynamics appear as common physiopathological features of centronuclear myopathies and desmin-related myopathies.
Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies
Authors: Helena Ariño, Romana Höftberger, Nuria Gresa-Arribas, Eugenia Martínez-Hernández, Thaís Armangue, Michael C. Kruer, Javier Arpa, Julio Domingo, Bojan Rojc, Luis Bataller, Albert Saiz, Josep Dalmau, Francesc Graus
Journal: JAMA Neurology (2015)

Little is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment.To report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs.Retrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study.Analysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals.Eight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against γ-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff-person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor.Patients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.
Exosomes and Cancer: A Newly Described Pathway of Immune Suppression
Authors: Huang-Ge Zhang, William E. Grizzle
Journal: Clinical Cancer Research (2011)

Abstract Exosomes are small (30 to 100 nm) membrane-bound particles that are released from normal, diseased, and neoplastic cells and are present in blood and other bodily fluids. Exosomes contain a variety of molecules including signal peptides, mRNA, microRNA, and lipids. Exosomes can function to export from cells unneeded endogenous molecules and therapeutic drugs. When exosomes are taken up by specific cells, they may act locally to provide autocrine or paracrine signals or, at a distance, as a newly described nanoparticle-based endocrine system. Specifically, mRNA transferred to cells by exosomes can result in the production of new proteins. In cancer, signals via exosomes affect the immune system by inhibiting the functions of T cells and normal killer (NK) cells and by inhibiting the differentiation of precursors to mature antigen-presenting cells. Also, exosomes increase the number and/or activity of immune suppressor cells, including myeloid-derived suppressor cells, T-regulatory cells, and CD14+, HLA-DR−/low cells. The effects of exosomes on the development and progression of cancers, with an emphasis on suppression of immune surveillance, is described. Also discussed are potential uses of exosomes clinically, in the development of vaccines, in targeting tumors, and in diagnosis and/or early detection. Clin Cancer Res; 17(5); 959–64. ©2011 AACR.
Empagliflozin as Add-on to Metformin Plus Sulfonylurea in Patients With Type 2 Diabetes
Authors: Hans-Ulrich Häring, Ludwig Merker, Elke Seewaldt-Becker, Marc Weimer, Thomas Meinicke, Hans J. Woerle, Uli C. Broedl
Journal: Diabetes Care (2013)

To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes.
Research Recruitment Practices and Critically Ill Patients. A Multicenter, Cross-Sectional Study (The Consent Study)
Authors: Karen E. A. Burns, Celia Zubrinich, Wylie Tan, Stavroula Raptis, Wei Xiong, Orla Smith, Ellen McDonald, John C. Marshall, Raphael Saginur, Ron Heslegrave, Gordon Rubenfeld, Deborah J. Cook
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Limited cross-sectional data exist to characterize the challenges of enrolling critically ill patients into research studies.We aimed to describe recruitment practices, document factors that impact recruitment, and identify factors that may enhance future research feasibility.We conducted a prospective, observational study of all critically ill adults eligible to participate in research studies at 23 Canadian intensive care units. We characterized eligibility events into one of five consent outcomes, identified reasons why opportunities to recruit were missed or infeasible, and documented decision maker's rationale for providing or declining consent.Patients made decisions for themselves in 8.9% of encounters. In 452 eligibility events, consent was not required in 14 (3.1%), missed in 130 (28.8%), infeasible due to operational reasons in 129 (28.5%), obtained in 140 (31.0%), and declined in 39 (8.6%). More than half (57.3%) of all opportunities to recruit patients were missed or infeasible, largely because of research team workload, limited availability, narrow time windows for inclusion, difficulties in contacting families, nonexistent substitute decision makers (SDMs), physician refusals, and protocols prohibiting coenrollment. The rationale for providing consent differed between patients and SDMs. Greater research coordinator experience and site research volume and broader time windows for inclusion were significant predictors of fewer declined consents.A large gap exists between eligibility and the frequency with which consent encounters occur in intensive care unit research. Recruitment is susceptible to design and procedural inefficiencies that hinder recruitment and to personnel availability, given the need to interact with SDMs. Current enrollment practices may underrepresent potential study populations.
Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial
Authors: M Henderson, D Wight, G M Raab, C Abraham, A Parkes, S Scott, G Hart
Journal: BMJ (2006)

<b>Objective</b> To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS. <b>Design</b> Follow-up of cluster randomised trial 4.5 years after intervention. <b>Setting</b> NHS records of women who had attended 25 secondary schools in east Scotland. <b>Participants</b> 4196 women (99.5% of those eligible). <b>Intervention</b> SHARE programme (intervention group) <i>v</i> existing sex education (control group). <b>Main outcome measure</b> NHS recorded conceptions and terminations for the achieved sample linked at age 20. <b>Results</b> In an "intention to treat" analysis there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE <i>v</i> 274 control; difference 26, 95% confidence interval −33 to 86) and terminations per 1000 pupils (127 <i>v</i> 112; difference 15, −13 to 42) between ages 16 and 20. <b>Conclusions</b> This specially designed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers. <b>Trial registration</b>ISRCTN48719575.
Autism Spectrum Disorder and Particulate Matter Air Pollution before, during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort
Authors: Raanan Raz, Andrea L. Roberts, Kristen Lyall, Jaime E. Hart, Allan C. Just, Francine Laden, Marc G. Weisskopf
Journal: Environmental Health Perspectives (2014)

Autism spectrum disorder (ASD) is a developmental disorder with increasing prevalence worldwide, yet has unclear etiology.We explored the association between maternal exposure to particulate matter (PM) air pollution and odds of ASD in her child.We conducted a nested case-control study of participants in the Nurses' Health Study II (NHS II), a prospective cohort of 116,430 U.S. female nurses recruited in 1989, followed by biennial mailed questionnaires. Subjects were NHS II participants' children born 1990-2002 with ASD (n = 245), and children without ASD (n = 1,522) randomly selected using frequency matching for birth years. Diagnosis of ASD was based on maternal report, which was validated against the Autism Diagnostic Interview-Revised in a subset. Monthly averages of PM with diameters ≤ 2.5 μm (PM2.5) and 2.5-10 μm (PM10-2.5) were predicted from a spatiotemporal model for the continental United States and linked to residential addresses.PM2.5 exposure during pregnancy was associated with increased odds of ASD, with an adjusted odds ratio (OR) for ASD per interquartile range (IQR) higher PM2.5 (4.42 μg/m3) of 1.57 (95% CI: 1.22, 2.03) among women with the same address before and after pregnancy (160 cases, 986 controls). Associations with PM2.5 exposure 9 months before or after the pregnancy were weaker in independent models and null when all three time periods were included, whereas the association with the 9 months of pregnancy remained (OR = 1.63; 95% CI: 1.08, 2.47). The association between ASD and PM2.5 was stronger for exposure during the third trimester (OR = 1.42 per IQR increase in PM2.5; 95% CI: 1.09, 1.86) than during the first two trimesters (ORs = 1.06 and 1.00) when mutually adjusted. There was little association between PM10-2.5 and ASD.Higher maternal exposure to PM2.5 during pregnancy, particularly the third trimester, was associated with greater odds of a child having ASD.
Percutaneous Injuries During Surgical Procedures
Authors: J I Tokars, D M Bell, D H Culver, R Marcus, M H Mendelson, E P Sloan, B F Farber, D Fligner, M E Chamberland, P S McKibben
Journal: JAMA (1992)

<h3>Objective.</h3> —To study the numbers and circumstances of percutaneous injuries (eg, needle sticks, cuts) that occur during surgical procedures. Surgical personnel risk infection with blood-borne pathogens from percutaneous injuries; some injuries might also place patients at risk by exposing them to a health care worker's blood. <h3>Design.</h3> —Observers present at 1382 surgical procedures recorded information about the procedure, the personnel present, and percutaneous injuries that occurred. <h3>Setting.</h3> —Four US teaching hospitals during 1990. <h3>Participants.</h3> —Operating room personnel in five surgical specialties. <h3>Main Outcome Measures.</h3> —Numbers and circumstances of percutaneous injuries among surgical personnel and instances in which surgical instruments that had injured a worker recontacted the patient's surgical wound. <h3>Results.</h3> —Ninety-nine injuries occurred during 95 (6.9%) of the 1382 procedures. Seventy-six injuries (77%) were caused by suture needles and affected the nondominant hand (62 injuries [63%]), especially the distal forefinger. The risk of injury adjusted for confounding variables by logistic regression was higher during vaginal hysterectomy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.6 to 7.5) and lower during certain orthopedic procedures (OR, 0.2; CI, 0.1 to 0.7) than during 11 other types of procedures (reference group; OR, 1.0). Use of fingers rather than an instrument to hold the tissue being sutured was associated with 35 injuries (35%). Eighty-eight injuries (89%) were sustained by resident or attending surgeons; in 28 (32%) of the 88 injuries in surgeons, the sharp object that caused the injury recontacted the patient. <h3>Conclusion.</h3> —Percutaneous injuries occur regularly during surgery, placing surgical personnel and, to a lesser extent, patients at risk for infection with blood-borne pathogens. Many such injuries may be preventable with changes in devices, techniques, or protective equipment; all such measures require careful evaluation to determine their efficacy in reducing injury and their effect on patient care. (<i>JAMA</i>. 1992;267:2899-2904)
A CASE OF MYCOSIS FUNGOIDES
Authors: J. H. T. DAVIES
Journal: British Journal of Dermatology (1930)

Journal Article A CASE OF MYCOSIS FUNGOIDES Get access J. H. T. DAVIES, M.B., B.CH. J. H. T. DAVIES, M.B., B.CH. Dermatologist, Royal Sussex County Hospital, Brighton Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 42, Issue 7, 1 July 1930, Pages 324–326, https://doi.org/10.1111/j.1365-2133.1930.tb09423.x Published: 01 July 1930
Proliferation Potential-Related Protein, an Ideal Esophageal Cancer Antigen for Immunotherapy, Identified Using Complementary DNA Microarray Analysis
Authors: Yoshihiro Yoshitake, Tetsuya Nakatsura, Mikio Monji, Satoru Senju, Hidetake Matsuyoshi, Hirotake Tsukamoto, Seiji Hosaka, Hiroyuki Komori, Daiki Fukuma, Yoshiaki Ikuta, Toyomasa Katagiri, Yoichi Furukawa, Hiromi Ito, Masanori Shinohara, Yusuke Nakamura, Yasuharu Nishimura
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To establish effective antitumor immunotherapy for esophageal cancer, we tried to identify an useful target antigen of esophageal cancer. Experimental Design: We did cDNA microarray analysis to find a novel candidate antigen, proliferation potential-related protein (PP-RP). We examined cytotoxicity against tumor cells in vitro and in vivo of CTLs specific to PP-RP established from esophageal cancer patients. Results: In 26 esophageal cancer tissues, an average of relative ratio of the expression of the PP-RP mRNA in cancer cells versus adjacent normal esophageal tissues was 396.2. Immunohistochemical analysis revealed that, in 20 of the 22 esophageal cancer tissues, PP-RP protein was strongly expressed only in the cancer cells and not so in normal esophageal epithelial cells. PP-RP protein contains 10 epitopes recognized by HLA-A24–restricted CTLs. These CTLs, generated from HLA-A24–positive esophageal cancer patients, had cytotoxic activity against cancer cell lines positive for both PP-RP and HLA-A24. Furthermore, adoptive transfer of the PP-RP–specific CTL line inhibited the growth of a human esophageal cancer cell line engrafted in nude mice. Conclusions: The expression of PP-RP in esophageal cancer cells was significantly higher than in normal cells, and the CTLs recognizing PP-RP killed tumor cells in vitro and also showed tumor rejection effects in a xenograft model. Therefore, PP-RP may prove to be an ideal tumor antigen useful for diagnosis and immunotherapy for patients with esophageal cancer. cDNA microarray analysis is a useful method to identify ideal tumor-associated antigens.