tbuckley/cabot-search huggingface dataset:
Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries
Authors: B. J. McCarthy, S. Shibui, T. Kayama, E. Miyaoka, Y. Narita, M. Murakami, A. Matsuda, T. Matsuda, T. Sobue, B. E. Palis, T. A. Dolecek, C. Kruchko, H. H. Engelhard, J. L. Villano
Journal: Neuro-Oncology (2012)

Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004–2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004–2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984–2000) and (4) the US National Cancer Data Base (1990–2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.
Self-management education for patients with chronic obstructive pulmonary disease: a systematic review
Authors: E Monninkhof
Journal: Thorax (2003)

<b>Background:</b> The idea of self-management is to teach patients how to carry out the activities of daily living optimally in the face of their physiological impairment, and to prevent or decrease the severity of exacerbations by means of life style adaptation. In chronic obstructive pulmonary disease (COPD) the value of self-management education is not clear. This review was undertaken to clarify the effectiveness of self-management programmes in COPD. <b>Methods:</b> A search was made of the Cochrane Airways Group trial registers, Medline, reference lists, and abstracts of medical conferences for controlled trials of self-management education in patients with COPD. Two reviewers independently assessed each paper for methodological quality and extracted the data. <b>Results:</b> The reviewers included 12 articles describing eight randomised controlled trials and one controlled clinical trial in which self-management education was compared with usual care. The studies assessed a broad spectrum of outcome measures with different follow up times so meta-analysis could not be undertaken. Self-management education had no effect on hospital admissions, emergency room visits, days lost from work, and lung function. Inconclusive results were observed on health related quality of life, COPD symptoms, and use of healthcare facilities such as doctor and nurse visits. Self-management education reduced the need for rescue medication and led to increased use of courses of oral steroids and antibiotics for respiratory symptoms. <b>Conclusions:</b> Insufficient data were obtained to make recommendations because of the wide variation in outcome measures used and other limitations to generalisations in the current published literature. Further research in this area is needed.
Subpopulations of Normal and Leukemic Human Thymocytes: An Analysis With the Use of Monoclonal Antibodies<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: K F Bradstock, G Janossy, G Pizzolo, A V Hoffbrand, A McMichael, J R Pilch, C Milstein, P Beverley, F J Bollum
Journal: JNCI Journal of the National Cancer Institute (1980)

Combinations of antibodies to membrane antigens and to terminal deoxynucleotidyl transferase (TdT) were used to study human thymocyte and bone marrow sUbpopulations and leukemia cells. Cortical thymocytes were TdT+ and expressed Tcell antigens (HuTLA+), a thymocyte-specific antigen (HTA-1+), and a leukocyte antigen (HLe-I++) but lacked detectable HLAA, B,C and la (HLA-D) antigens. In contrast. medullary thymocytes were TdT-, HuTLA+, HTA-1-, HLe-I++. A small subpopulation of larger, probably immature, thymocytes were strongly TdT+, HuTLA+, la-, HTA-1-, HLe-I±. Many blast cells from cases of thymic acute lymphoblastic leukemia (Thy-ALL) showed the phenotype of this small subset, and only a proportion of Thy-ALL blast cells exhibited HTA-1 and HLe-l antigens as strongly as was observed on normal cortical thymocytes. In contrast, TdT+ cells observed in normal juvenile bone marrow were HuTLA-, HTA-1-. HLA+, la+. This phenotype corresponded to the phenotype of the common form of ALL (non-T, non-B) and indicated that further studies are necessary to analyze the differentiation of bone marrow precursors to thymic cells.
Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation
Authors: Robert M. Harmon, Cory L. Simpson, Jodi L. Johnson, Jennifer L. Koetsier, Adi D. Dubash, Nicole A. Najor, Ofer Sarig, Eli Sprecher, Kathleen J. Green
Journal: Journal of Clinical Investigation (2013)

Genetic disorders of the Ras/MAPK pathway, termed RASopathies, produce numerous abnormalities, including cutaneous keratodermas. The desmosomal cadherin, desmoglein-1 (DSG1), promotes keratinocyte differentiation by attenuating MAPK/ERK signaling and is linked to striate palmoplantar keratoderma (SPPK). This raises the possibility that cutaneous defects associated with SPPK and RASopathies share certain molecular faults. To identify intermediates responsible for executing the inhibition of ERK by DSG1, we conducted a yeast 2-hybrid screen. The screen revealed that Erbin (also known as ERBB2IP), a known ERK regulator, binds DSG1. Erbin silencing disrupted keratinocyte differentiation in culture, mimicking aspects of DSG1 deficiency. Furthermore, ERK inhibition and the induction of differentiation markers by DSG1 required both Erbin and DSG1 domains that participate in binding Erbin. Erbin blocks ERK signaling by interacting with and disrupting Ras-Raf scaffolds mediated by SHOC2, a protein genetically linked to the RASopathy, Noonan-like syndrome with loose anagen hair (NS/LAH). DSG1 overexpression enhanced this inhibitory function, increasing Erbin-SHOC2 interactions and decreasing Ras-SHOC2 interactions. Conversely, analysis of epidermis from DSG1-deficient patients with SPPK demonstrated increased Ras-SHOC2 colocalization and decreased Erbin-SHOC2 colocalization, offering a possible explanation for the observed epidermal defects. These findings suggest a mechanism by which DSG1 and Erbin cooperate to repress MAPK signaling and promote keratinocyte differentiation.
A Broad Spectrum Secreted Chemokine Binding Protein Encoded by a Herpesvirus
Authors: Christopher M. Parry, J. Pedro Simas, Vincent P. Smith, C. Andrew Stewart, Anthony C. Minson, Stacey Efstathiou, Antonio Alcami
Journal: The Journal of Experimental Medicine (2000)

Chemokines are a family of small proteins that interact with seven-transmembrane domain receptors and modulate the migration of immune cells into sites of inflammation and infection. The murine gammaherpesvirus 68 M3 gene encodes a secreted 44-kD protein with no sequence similarity to known chemokine receptors. We show that M3 binds a broad range of chemokines, including CC, CXC, C, and CX3C chemokines, but does not bind human B cell–specific nor mouse neutrophil–specific CXC chemokines. This herpesvirus chemokine binding protein (hvCKBP) blocks the interaction of chemokines with high-affinity cellular receptors and inhibits chemokine-induced elevation of intracellular calcium levels. hvCKBP is the first soluble chemokine receptor identified in herpesviruses; it represents a novel protein structure with the ability to bind all subfamilies of chemokines in solution and has potential therapeutic applications.
Risk Factors for Diabetes in Familial Partial Lipodystrophy, Dunnigan Variety
Authors: Wasim A. Haque, Elif Arioglu Oral, Kelly Dietz, Anne M. Bowcock, Anil K. Agarwal, Abhimanyu Garg
Journal: Diabetes Care (2003)

Familial partial lipodystrophy, Dunnigan variety (FPLD), is an autosomal dominant disorder due to missense mutations in the lamin A/C (LMNA) gene encoding nuclear lamina proteins. It is characterized by loss of subcutaneous fat from the extremities and trunk and accumulation of fat in the head and neck region beginning at puberty. Patients with FPLD are predisposed to metabolic complications of insulin resistance such as diabetes. We sought to identify risk factors for diabetes in patients with FPLD.A cross-sectional study comparing clinical, biochemical, and anthropometric variables and LMNA genotypes in FPLD patients with and without diabetes.We studied 52 women and 24 men with FPLD from 18 different families. Twenty-eight women (54%) but only four men (17%) had diabetes (P < 0.001); therefore further comparisons were mostly limited to women. Compared with women without diabetes, those with diabetes had higher BMI (median values 23 vs. 24 kg/m(2), respectively; P = 0.03), increased chin skinfold thickness (10 vs. 20 mm; P = 0.001), lower rates of nulliparity (60% vs. 28%; P = 0.04), and higher levels of fasting serum triglycerides (2.4 vs. 3.5 mmol/l; P < 0.001) but similar serum leptin levels (3.4 vs. 3.6 ng/ml; P = 0.9). The prevalence of diabetes was not related to age, menopausal status, family history of type 2 diabetes in unaffected relatives, or LMNA genotype.We conclude that increased adiposity as reflected by excess subcutaneous fat accumulation in the chin region and parity may predispose women with FPLD to develop diabetes.
H<scp>OW</scp>H<scp>OST</scp>-M<scp>ICROBIAL</scp>I<scp>NTERACTIONS</scp>S<scp>HAPE THE</scp>N<scp>UTRIENT</scp>E<scp>NVIRONMENT OF THE</scp>M<scp>AMMALIAN</scp>I<scp>NTESTINE</scp>
Authors: Lora V. Hooper, Tore Midtvedt, Jeffrey I. Gordon
Journal: Annual Review of Nutrition (2002)

▪ Abstract Humans and other mammals are colonized by a vast, complex, and dynamic consortium of microorganisms. One evolutionary driving force for maintaining this metabolically active microbial society is to salvage energy from nutrients, particularly carbohydrates, that are otherwise nondigestible by the host. Much of our understanding of the molecular mechanisms by which members of the intestinal microbiota degrade complex polysaccharides comes from studies of Bacteroides thetaiotaomicron, a prominent and genetically manipulatable component of the normal human and mouse gut. Colonization of germ-free mice with B. thetaiotaomicron has shown how this anaerobe modifies many aspects of intestinal cellular differentiation/gene expression to benefit both host and microbe. These and other studies underscore the importance of understanding precisely how nutrient metabolism serves to establish and sustain symbiotic relationships between mammals and their bacterial partners.
Chalcone Synthase Gene Lineage Diversification Confirms Allopolyploid Evolutionary Relationships of European Rostrate Violets
Authors: K. van den Hof, R. G. van den Berg, B. Gravendeel
Journal: Molecular Biology and Evolution (2008)

Phylogenetic relationships among and within the subsections of the genus Viola are still far from resolved. We present the first organismal phylogeny of predominantly western European species of subsection Rostratae based on the plastid trnS–trnG intron and intergenic spacer and the nuclear low-copy gene chalcone synthase (CHS) sequences. CHS is a key enzyme in the synthesis of flavonoids, which are important for flower pigmentation. Genes encoding for CHS are members of a multigene family. In Viola, 3 different CHS copies are present. CHS gene lineages obtained confirmed earlier hypotheses about reticulate relationships between species of Viola subsection Rostratae based on karyotype data. Comparison of the CHS gene lineage tree and the plastid species phylogeny of Viola reconstructed in this study indicates that the different CHS copies present in Viola are the products of both recent and more ancient duplications.
Cross-sectional analysis of the dermoscopic patterns and structures of melanocytic naevi on the back and legs of adolescents
Authors: M. Fonseca, M.A. Marchetti, E. Chung, S.W. Dusza, M.E. Burnett, A.A. Marghoob, A.C. Geller, M. Bishop, A. Scope, A.C. Halpern
Journal: British Journal of Dermatology (2015)

Junctional (flat) naevi predominate on the extremities, whereas dermal (raised) naevi are found primarily on the head, neck and trunk. Few studies have investigated the anatomical site prevalence of melanocytic naevi categorized using dermoscopy.To identify the prevalence of dermoscopic patterns and structures of naevi from the back and legs of adolescents.Dermoscopic images of acquired melanocytic naevi were obtained from the back and legs of students from a population-based cohort in Framingham, Massachusetts. Naevi were classified into reticular, globular, homogeneous or complex dermoscopic patterns. Multinomial logistic regression modelling assessed the associations between dermoscopic pattern and anatomical location.In total 509 participants (mean age 14 years) contributed 2320 back naevi and 637 leg naevi. Compared with homogeneous naevi, globular and complex naevi were more commonly observed on the back than the legs [odds ratio (OR) 29·39, 95% confidence interval (CI) 9·53-90·65, P < 0·001 and OR 6·8, 95% CI 2·7-17·14, P < 0·001, respectively], whereas reticular lesions were less likely to be observed on the back than on the legs (OR 0·67, 95% CI 0·54-0·84, P = 0·001). Naevi containing any globules were more prevalent on the back than on the legs (25% vs. 3·6%, P < 0·001). Naevi containing any network were more prevalent on the legs than on the back (56% vs. 40·6%, P < 0·001).These findings add to a robust body of literature suggesting that dermoscopically defined globular and reticular naevi represent biologically distinct naevus subsets that differ in histopathological growth pattern, age- and anatomical-site-related prevalence, molecular phenotype and aetiological pathways.
GP88 (PCDGF, granulin-epithelin precursor) and chemoresistance in breast cancer
Authors: Ginette Serrero, Jiangping Dong, Leslie Jones, Joseph Corvera, Randall Barton, Binbin Yue
Journal: Clinical Cancer Research (2006)

B37  Chemotherapy is widely used for the treatment of advanced stage breast cancer. However, after prolonged chemotherapy, breast cancer often progresses to a chemo-insensitive state. Constitutive overexpression of autocrine growth and survival factor is one possible mechanism of chemo resistance. PCDGF/GP88 (PC-Cell Derived Growth Factor, also known as progranulin or granulin-epithelin precursor) is an 88 kDa autocrine growth factor isolated in our laboratory and shown to play a critical role in breast tumorigenesis. GP88 is expressed in human breast tumors in a positive correlation with their tumorigenicity. In estrogen receptor positive (ER+) cells, GP88 expression is low and is stimulated by estradiol whereas it is constitutively overexpressed in ER negative cells. Inhibition of GP88 expression by antisense transfection in ER negative breast carcinoma leads to inhibition of breast tumor incidence and growth in nude mice. GP88 also increases survival, inhibits apoptosis, stimulates migration, matrix metallo-protease activities and angiogenesis. Pathological studies have shown that GP88 is expressed in 80% of human invasive ductal carcinomas and correlated with expression of markers of poor prognosis whereas normal tissues and benign breast lesions are negative. GP88 Overexpression in breast tumors conferred resistance to anti-estrogen therapy in ER+ breast cancer as well as doxorubicin, paclitaxel in ER- breast cancer and Herceptin in Her-2 overexpressing breast tumors, respectively. Conversely, chemoresistant breast tumors showed an increased in GP88 expression. Based on these data, we investigated whether inhibition of GP88 action in chemo resistant breast cancer cells would restore cellular responsiveness to the chemotherapy treatment. Anti-human GP88 neutralizing monoclonal antibodies were developed. Using paclitaxel resistant breast adenocarcinoma cells as model system, we show here that administration of a neutralizing anti GP88 monoclonal antibody inhibited cell proliferation in a time and dose dependent fashion. Additionally, treatment of the cells with anti-GP88 antibody restored the ability of paclitaxel to inhibit cell proliferation and stimulate apoptosis. In contrast, treatment of the cells with unrelated isotype specific antibody had no effect. Studies carried out with breast cancer cell lines resistant to other chemotherapy will also be performed. These results demonstrate the important role of GP88 expression in the development of chemoresistant breast cancer and suggest that GP88 is a suitable molecular therapeutic target for advanced breast cancer.
Topical application of delphinidin reduces psoriasiform lesions in the flaky skin mouse model by inducing epidermal differentiation and inhibiting inflammation
Authors: H.C. Pal, J.C. Chamcheu, V.M. Adhami, G.S. Wood, C.A. Elmets, H. Mukhtar, F. Afaq
Journal: British Journal of Dermatology (2014)

Journal Article Topical application of delphinidin reduces psoriasiform lesions in the flaky skin mouse model by inducing epidermal differentiation and inhibiting inflammation Get access H.C. Pal, H.C. Pal Department of Dermatology University of Alabama at Birmingham 1670 University Blvd Birmingham 35294 AL U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.C. Chamcheu, J.C. Chamcheu Department of Dermatology University of Wisconsin‐Madison 1300 University Avenue Madison 53706 WI U.S.A Search for other works by this author on: Oxford Academic Google Scholar V.M. Adhami, V.M. Adhami Department of Dermatology University of Wisconsin‐Madison 1300 University Avenue Madison 53706 WI U.S.A Search for other works by this author on: Oxford Academic Google Scholar G.S. Wood, G.S. Wood Department of Dermatology University of Wisconsin‐Madison 1300 University Avenue Madison 53706 WI U.S.A Search for other works by this author on: Oxford Academic Google Scholar C.A. Elmets, C.A. Elmets Department of Dermatology University of Alabama at Birmingham 1670 University Blvd Birmingham 35294 AL U.S.AComprehensive Cancer Center University of Alabama at Birmingham 1670 University Blvd Birmingham 35294 ALU.S.A Search for other works by this author on: Oxford Academic Google Scholar H. Mukhtar, H. Mukhtar Department of Dermatology University of Wisconsin‐Madison 1300 University Avenue Madison 53706 WI U.S.A Search for other works by this author on: Oxford Academic Google Scholar F. Afaq F. Afaq Department of Dermatology University of Alabama at Birmingham 1670 University Blvd Birmingham 35294 AL U.S.AComprehensive Cancer Center University of Alabama at Birmingham 1670 University Blvd Birmingham 35294 ALU.S.A Correspondence Farrukh Afaq. E‐mail: farrukhafaq@uabmc.edu and Hasan Mukhtar. E‐mail: hmukhtar@wisc.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 2, 1 February 2015, Pages 354–364, https://doi.org/10.1111/bjd.13513 Published: 01 February 2015
Cobalt chloride administration in athletes: a new perspective in blood doping?
Authors: G Lippi, M Franchini, G C Guidi
Journal: British Journal of Sports Medicine (2005)

Blood doping is an illegal and unfair way of enhancing athletic performance by increasing the oxygen carrying capacity of the blood. Currently used methods usually involve stimulation of erythropoiesis. Gene therapy targeting the hypoxia inducible factor pathway may be an attractive alternative to traditional blood doping techniques. Hypoxia activates a large number of genes with essential roles in cell and tissue adaptation to low oxygen. Cobalt chloride is a well established chemical inducer of hypoxia-like responses such as erythropoiesis. Cobalt supplementation is not banned and therefore would not be detected by current anti-doping testing. Although there is as yet no direct or anecdotal evidence of cobalt chloride administration to athletes, its use should be warned against as being not only unfair but potentially dangerous.
Randomized, Placebo-Controlled Phase III Study of Docetaxel Plus Carboplatin With Celecoxib and Cyclooxygenase-2 Expression As a Biomarker for Patients With Advanced Non–Small-Cell Lung Cancer: The NVALT-4 Study
Authors: Harry J.M. Groen, Hannie Sietsma, Andrew Vincent, Monique M.H. Hochstenbag, John W.G. van Putten, Anke van den Berg, Otilia Dalesio, Bonne Biesma, Hans J.M. Smit, Ariën Termeer, T. Jeroen N. Hiltermann, Ben E.E.M. van den Borne, Franz M.N.H. Schramel
Journal: Journal of Clinical Oncology (2011)

Purpose Cyclooxygenase-2 (COX-2) protein expression in patients with non–small-cell lung cancer (NSCLC) may be not only a prognostic marker but also predictive for COX-2 inhibition. We hypothesized that COX-2 expression is associated with shorter survival and that celecoxib, being a potent COX-2 inhibitor, increases tumor response and survival. Patients and Methods A phase III study was performed in patients with stage IIIb/IV NSCLC who had pathologic confirmation, no prior chemotherapy, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Treatment consisted of docetaxel and carboplatin every 3 weeks for five cycles. Patients were randomly assigned to receive celecoxib 400 mg or placebo twice daily. COX-2 expression on tumor cells was detected by immunohistochemistry. Primary end point was overall survival (OS). Results From July 2003 to December 2007, 561 patients were randomly assigned. Toxicity was mild, and no increase in cardiovascular events was observed. Tumor response was 38% in the celecoxib arm and 30% in the placebo arm (P = .08). Median progression-free survival was 4.5 months (95% CI, 4.0 to 4.8) for the celecoxib arm and 4.0 months (95% CI, 3.6 to 4.9) for the placebo arm (hazard ratio [HR], 0.8; 95% CI, 0.6 to 1.1; P = .25). Median OS was 8.2 months (95% CI, 7.5 to 8.8) for both treatment arms (HR, 0.9; 95% CI, 0.6 to 1.2; P = .32). COX-2 expression did not independently predict survival. Benefit from celecoxib, restricted to patients with low COX-2 expression, was not significant when adjusted for prognostic factors. Conclusion In advanced NSCLC, celecoxib does not improve survival. In this study, COX-2 expression was not a prognostic biomarker and had no predictive value when celecoxib was added to chemotherapy.