tbuckley/cabot-search huggingface dataset:
Association Between Parental History of Type 2 Diabetes and Glycemic Control in Urban African Americans
Authors: Lucy Gong, Wen Hong Linda Kao, Frederick L. Brancati, Marian Batts-Turner, Tiffany L. Gary
Journal: Diabetes Care (2008)

The purpose of this study was to examine the association between parental history of type 2 diabetes and glycemic control among diabetic urban African Americans.
Limitations of Angiography in the Assessment of Plaque Distribution in Coronary Artery Disease
Authors: Gary S. Mintz, Jeffrey J. Popma, Augusto D. Pichard, Kenneth M. Kent, Lowell F. Satler, Ya Chien Chuang, Robert A. DeFalco, Martin B. Leon
Journal: Circulation (1996)

Background Plaque distribution (eccentricity) may be a determinant of the success of transcatheter therapy, and certain devices may be better suited to treating severely eccentric lesions than others. However, no study has compared methods for assessing plaque distribution or systematically studied the validity of the angiographic assessment of plaque distribution. Methods and Results We studied 1446 native vessel target lesions in 1349 patients by intravascular ultrasound and coronary angiography. Angiographic and intravascular ultrasound criteria for lesion eccentricity were compared. Angiography showed that 795 of 1446 (55.0%) of target lesions were eccentric. When intravascular ultrasound was used, only 219 lesions (15.1%) had an arc of normal arterial wall within the lesion (equivalent to the pathological definition of lesion eccentricity). When an eccentricity index of ≥3.0 was used, intravascular ultrasound classified 659 lesions (45.6%) as eccentric. The concordance rates of classification were only 47.7% (versus lesions containing an arc of normal arterial wall) and 53.8% (versus lesions with an ultrasound eccentricity index of ≥3.0). More eccentric lesions had larger lumen cross-sectional areas, smaller plaque plus media and external elastic membrane cross-sectional areas, and smaller arcs of calcium, suggesting that they may represent less advanced atherosclerotic disease. Conclusions There was significant discordance between angiography and ultrasound in assessing plaque distribution. Angiography appeared to detect lesion eccentricity more often than intravascular ultrasound. Furthermore, markedly eccentric lesions, in which there is an arc of normal vessel wall, were uncommon.
Concurrent loss of <i>Ezh2</i> and <i>Tet2</i> cooperates in the pathogenesis of myelodysplastic disorders
Authors: Tomoya Muto, Goro Sashida, Motohiko Oshima, George R. Wendt, Makiko Mochizuki-Kashio, Yasunobu Nagata, Masashi Sanada, Satoru Miyagi, Atsunori Saraya, Asuka Kamio, Genta Nagae, Chiaki Nakaseko, Koutaro Yokote, Kazuya Shimoda, Haruhiko Koseki, Yutaka Suzuki, Sumio Sugano, Hiroyuki Aburatani, Seishi Ogawa, Atsushi Iwama
Journal: The Journal of Experimental Medicine (2013)

Polycomb group (PcG) proteins are essential regulators of hematopoietic stem cells. Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). In our patient cohort, EZH2 mutations were also found and often coincided with tet methylcytosine dioxygenase 2 (TET2) mutations. Consistent with these findings, deletion of Ezh2 alone was enough to induce MDS/MPN-like diseases in mice. Furthermore, concurrent depletion of Ezh2 and Tet2 established more advanced myelodysplasia and markedly accelerated the development of myelodysplastic disorders including both MDS and MDS/MPN. Comprehensive genome-wide analyses in hematopoietic progenitor cells revealed that upon deletion of Ezh2, key developmental regulator genes were kept transcriptionally repressed, suggesting compensation by Ezh1, whereas a cohort of oncogenic direct and indirect polycomb targets became derepressed. Our findings provide the first evidence of the tumor suppressor function of EZH2 in myeloid malignancies and highlight the cooperative effect of concurrent gene mutations in the pathogenesis of myelodysplastic disorders.
A Role for Dipeptidyl Peptidase IV in Suppressing the Malignant Phenotype of Melanocytic Cells
Authors: Umadevi V. Wesley, Anthony P. Albino, Shakuntala Tiwari, Alan N. Houghton
Journal: The Journal of Experimental Medicine (1999)

Dipeptidyl peptidase IV (DPPIV) is a cell surface peptidase expressed by normal melanocytes, epithelial cells, and other cells. Malignant cells, including melanomas and carcinomas, frequently lose or alter DPPIV cell surface expression. Loss of DPPIV expression occurs during melanoma progression at a stage where transformed melanocytes become independent of exogenous growth factors for survival. Tetracycline-inducible expression vectors were constructed to express DPPIV in human melanoma cells. Reexpressing DPPIV in melanoma cells at or below levels expressed by normal melanocytes induced a profound change in phenotype that was characteristic of normal melanocytes. DPPIV expression led to a loss of tumorigenicity, anchorage-independent growth, a reversal in a block in differentiation, and an acquired dependence on exogenous growth factors for cell survival. Suppression of tumorigenicity and reversal of a block in differentiation were dependent on serine protease activity, assessed using mutant DPPIV molecules containing serine→alanine substitutions. Surprisingly, dependence on exogenous growth factors was not dependent on serine protease activity. Reexpression of either wild-type or mutant DPPIV rescued expression of a second putative cell surface serine peptidase, fibroblast activation protein α, which can form a heterodimer with DPPIV. This observation suggests that rescue of fibroblast activation protein α may play a role in regulating growth of melanocytic cells. These results support the view that downregulation of DPPIV is an important early event in the pathogenesis of melanoma.
FAULTY FOOD FACTORS AND ATONIC CONSTIPATION
Authors: FRANCIS LOWELL BURNETT
Journal: JAMA (1924)

<h3>THE ESSENTIALS OF NOURISHMENT</h3> The complete and proper nourishment of the body is gradually assuming a more and more important aspect. The change has taken place, in part on account of the defects and deficient conditions found in the apparently healthy, in part because of the many and varied conditions of disease produced in animals with incomplete and badly proportioned foods; and, finally, through the improvement made in the well being of children and adults by dietary treatment. When the accessory food factors (vitamins) or the substances essential for nourishment have to be taken into account on the one hand, and the faulty food factors, or the refinement, proportion and abnormal ingredients of the diet have to be considered on the other, the requirements of the ingested material or the alimentary mixture for complete and proper nourishment are somewhat exacting. But this is natural and proper in considering the nutritive
The influence of recombination on the population structure and evolution of the human pathogen Neisseria meningitidis
Authors: E. C. Holmes, R. Urwin, M. C. Maiden
Journal: Molecular Biology and Evolution (1999)

The extent to which recombination disrupts the bifurcating treelike phylogeny and clonal structure imposed by binary fission on bacterial populations remains contentious. Here, we address this question with a study of nucleotide sequence data from 107 isolates of the human pathogen Neisseria meningitidis. Gene fragments from 12 house-keeping loci distributed around the meningococcal chromosome were analyzed, showing that (1) identical alleles are disseminated among genetically diverse isolates, with no evidence for linkage disequilibrium; (2) different loci give distinct and incongruent phylogenetic trees; and (3) allele sequences are incompatible with a bifurcating treelike phylogeny at all loci. These observations are consistent with the hypothesis that meningococcal populations comprise organisms assembled from a common gene pool, with alleles and allele fragments spreading independently, together with the occasional importation of genetic material from other species. Further, they support the view that recombination is an important genetic mechanism in the generation new meningococcal clones and alleles. Consequently, for anything other than the short-term evolution of this species, a bifurcating treelike phylogeny is not an appropriate model.
A plant-derived glucocorticoid receptor modulator attenuates inflammation without provoking ligand-induced resistance
Authors: V Gossye, D Elewaut, K Van Beneden, P Dewint, G Haegeman, K De Bosscher
Journal: Annals of the Rheumatic Diseases (2009)

Background: Acquired resistance to glucocorticoids constitutes a major clinical challenge, often overlooked in the search for improved alternatives to classic steroids. We sought to unravel how two glucocorticoid receptor-activating compounds, dexamethasone and Compound A, influence glucocorticoid receptor levels and how this can be correlated to their gene regulatory potential. Methods: Compound A and dexamethasone were applied in a short-term and long-term treatment protocol. By quantitative PCR analysis in fibroblast-like synoviocytes (FLS) the gene regulatory potential of both compounds in the two experimental conditions was analysed. A parallel Western blot assay revealed the glucocorticoid receptor protein levels in both conditions (ex vivo). In addition, this study examined the effect of systemic administration of dexamethasone and Compound A, in concentrations effective to inhibit collagen-induced arthritis, in DBA/1 mice on glucocorticoid receptor levels (in vivo). Results: Compound A does not induce a homologous downregulation of glucocorticoid receptor in vivo and ex vivo, thereby retaining its anti-inflammatory effects after prolonged treatment in FLS. This is in sharp contrast to dexamethasone, showing a direct link between prolonged dexamethasone treatment, decreasing glucocorticoid receptor levels, and the abolishment of inflammatory gene repression in FLS. It was also observed that the acquired low receptor levels after prolonged dexamethasone treatment are still sufficient to sustain the transactivation of endogenous glucocorticoid-responsive element-driven genes in FLS, a mechanism partly held accountable for the metabolic side-effects. Conclusion: Compound A is less likely to evoke therapy resistance, as it does not lead to homologous glucocorticoid receptor downregulation, which is in contrast to classic glucocorticoids.
Evaluation of the allergenicity of tropical pollen and airborne spores in Singapore
Authors: F. T. Chew, S. H. Lim, H. S. Shang, M. D. Siti Dahlia, D. Y. T. Goh, B. W. Lee, H. T. W. Tan, T. K. Tan
Journal: Allergy (2000)

Sensitization to pollen and spores of the Southeast Asian tropical region is not well documented. This study evaluated the allergenicity of the tropical airspora in Singapore.On the basis of the results of an aerobiologic survey of the airspora profile of Singapore, crude extracts of 23 main spore (fungal and fern) and pollen types were prepared. A total of 231 patients with asthma and/or allergic rhinitis and 76 healthy controls were evaluated by skin prick test (SPT). Total and specific IgE levels were also quantified by the fluorescence allergosorbent test (FAST).All 23 allergenic extracts tested elicited positive SPT responses. Among the patients with atopic diseases, extracts of oil-palm pollen (Elaeis guineensis) were observed to have the highest frequency of positive reactions (40%), followed by extracts of resam-fern spores (Dicranopteris linearis) (34%) and sea-teak pollen (Podocarpus polystachyus) (33.8%). Fungal spores with the highest SPT responses were Curvularia spp. (26-32%) and Drechslera-like spores (31%). Positive responses to these extracts correlated with total serum IgE levels of the subjects and were significantly associated with the presence of atopic disease.We have documented sensitization to tropical pollen and spores in our population. Its association with atopy suggests that it has a role in allergic diseases in the tropics.
Robert Edgar Hope-Simpson
Authors: D. Pereira Gray
Journal: BMJ (2003)

General practitioner who showed that shingles was caused by reactivation of the chickenpox virus Edgar Hope Simpson was one of the outstanding general practitioner researchers of the 20th century.In addition to working full time in family practice he charted precisely the pattern of the common diseases that he saw clinically.In 1940 his wife gave him Wensleydale general practitioner William Pickles' then new book Epidemiology in Country Practice.Hope-Simpson modelled his approach on this, and he exchanged visits with Pickles.Eventually he surpassed even Pickles' work.The bulk of his interest was in infectious diseases.He was self taught and without any formal epidemiological or research training, but he learnt fast.He established a small epidemiological research unit around his practice in 1946 and chaired a Medical Research Council committee.He started to write papers, particularly on chickenpox and herpes zoster, in the 1940s and 1950s, which were published in the Lancet and the BMJ, and he produced a series of publications of which many professors would be proud.Chickenpox and shingles were known to be related, but how?Experts at the time were suggesting that two different viruses existed.Hope-Simpson increasingly believed there was only one, but how to prove it?In the end, he took his small team of research colleagues to the Island of Yell in the Shetlands in 1953 and literally followed up every known case in a much closed community.He was empowered by local islanders' memories for occurrences and dates.By 1962, new microbiological techniques enabled him to prove his point.Only a great intellect could have conceived this possibility-that, remarkably, a virus could commonly lie dormant in the human body, for years, indeed decades, and then reappear in another form.Only an
Psoriasis clinical registries, genetics, and genomics
Authors: J. T Elder
Journal: Annals of the Rheumatic Diseases (2005)

Genetics and genomics are being widely applied in an effort to unlock the secrets of psoriasis. At the same time, an explosion of exciting new biological therapies has brought large numbers of patients into clinical trials. Opportunities exist for synergism between therapeutic trials and genetic/genomic studies of psoriasis (and psoriatic arthritis). This article reviews existing clinical registries of psoriasis, with an emphasis on genetic studies; compares and contrasts the types of information necessary for genetic, genomic, and clinical registries; and considers the impact of patient privacy on the use of registries for both clinical and genetic studies.
Candidate Targets of Balancing Selection in the Genome of Staphylococcus aureus
Authors: J. C. Thomas, P. A. Godfrey, M. Feldgarden, D. A. Robinson
Journal: Molecular Biology and Evolution (2011)

Signatures of balancing selection can highlight polymorphisms and functions that are important to the long-term fitness of a species. We performed a first genome-wide scan for balancing selection in a bacterial species, Staphylococcus aureus, which is a common cause of serious antimicrobial-resistant infections of humans. Using a sliding window approach, the genomes of 16 strains of S. aureus, including 5 new genome sequences presented here, and 1 outgroup strain of S. epidermidis were scanned for signatures of balancing selection. A total of 195 short windows were investigated based on their extreme values of both Tajima's D (>2.03) and π/K ratios (>0.12) relative to the rest of the genome. To test the unusualness of these windows, an Approximate Bayesian Computation framework was used to select a null demographic model that better accounted for the observed data than did the standard neutral model. A total of 186 windows were demonstrated to be unusual under the null model and, thus, represented candidate loci under balancing selection. These 186 candidate windows were located within 99 candidate genes that were spread across 62 different loci. Nearly all the signal (97.2%) was located within coding sequences; balancing selection on gene regulation apparently occurs through the targeting of global regulators such as agr and gra/aps. The agr locus had some of the strongest signatures of balancing selection, which provides new insight into the causes of diversity at this locus. The list of candidate genes included multiple virulence-associated genes and was significantly enriched for functions in amino acid and inorganic ion transport and metabolism and in defense mechanisms against innate immunity and antimicrobials, highlighting these particular functions as important to the fitness of this pathogen.
C-C chemokine receptor 6–regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE
Authors: Andrea Reboldi, Caroline Coisne, Dirk Baumjohann, Federica Benvenuto, Denise Bottinelli, Sergio Lira, Antonio Uccelli, Antonio Lanzavecchia, Britta Engelhardt, Federica Sallusto
Journal: Nature Immunology (2009)
Randomized Controlled Trial Comparing Oral Doxifluridine Plus Oral Cyclophosphamide With Doxifluridine Alone in Women With Node-Positive Breast Cancer After Primary Surgery
Authors: Takeshi Tominaga, Hiroki Koyama, Tetsuya Toge, Shigeto Miura, Keizo Sugimachi, Susumu Yamaguchi, Koichi Hirata, Yasumasa Monden, Yasuo Nomura, Masakazu Toi, Izo Kimijima, Shinzaburo Noguchi, Hiroshi Sonoo, Kazuaki Asaishi, Tadashi Ikeda, Tadaoki Morimoto, Jun Ota, Yasuo Ohashi, Osahiko Abe
Journal: Journal of Clinical Oncology (2003)

Purpose: We compared the therapeutic usefulness of doxifluridine (5′-DFUR) alone and a combination of 5′-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. Patients and Methods: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5′-DFUR alone or 5′-DFUR plus CPM. All patients initially received 5′-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5′-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5′-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5′-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. Results: Of the 1,088 eligible women, 546 were assigned to receive 5′-DFUR alone and 542 were assigned to receive 5′-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5′-DFUR plus CPM than in those who received 5′-DFUR alone (log-rank test, P = .021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5′-DFUR group and 32.3% of patients (175 of 542) in the 5′-DFUR plus CPM group (χ 2 test, P &lt; .001). Conclusion: Combination therapy with 5′-DFUR plus CPM is more effective in preventing recurrence than 5′-DFUR alone.
Effects of Antipsychotic Treatment on Emotion Perception Deficits in First-Episode Schizophrenia
Authors: Ellen S. Herbener, S. Kristian Hill, Robert W. Marvin, John A. Sweeney
Journal: American Journal of Psychiatry (2005)

The authors evaluated emotion perception in acutely ill patients experiencing a first episode of schizophrenia. They also investigated the effects of antipsychotic medication on emotion perception.Tests of the ability to perceive and discriminate emotional expressions from the Penn Computerized Neuropsychological Battery were given to 13 patients experiencing their first episode of schizophrenia. Patients were also assessed with the Positive and Negative Syndrome Scale. The patients were tested while they were unmedicated and again following clinical stabilization. Healthy individuals were evaluated over a similar time interval.Patients with first-episode schizophrenia demonstrated impairments in emotion perception before treatment and no significant improvement after treatment. Emotion perception deficits were correlated with negative symptoms after clinical stabilization.Deficits in emotion perception are present at illness onset in schizophrenia and show minimal response to effective antipsychotic treatment.
Cryptic Speciation and Recombination in the Fungus Paracoccidioides brasiliensis as Revealed by Gene Genealogies
Authors: Daniel R. Matute, Juan G. McEwen, Rosana Puccia, Beatriz A. Montes, Gioconda San-Blas, Eduardo Bagagli, Jason T. Rauscher, Angela Restrepo, Favia Morais, Gustavo Niño-Vega, John W. Taylor
Journal: Molecular Biology and Evolution (2005)

Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, a disease confined to Latin America and of marked importance in the endemic areas due to its frequency and severity. This species is considered to be clonal according to mycological criteria and has been shown to vary in virulence. To characterize natural genetic variation and reproductive mode in this fungus, we analyzed P. brasiliensis phylogenetically in search of cryptic species and possible recombination using concordance and nondiscordance of gene genealogies with respect to phylogenies of eight regions in five nuclear loci. Our data indicate that this fungus consists of at least three distinct, previously unrecognized species: S1 (species 1 with 38 isolates), PS2 (phylogenetic species 2 with six isolates), and PS3 (phylogenetic species 3 with 21 isolates). Genealogies of four of the regions studied strongly supported the PS2 clade, composed of five Brazilian and one Venezuelan isolate. The second clade, PS3, composed solely of 21 Colombian isolates, was strongly supported by the α-tubulin genealogy. The remaining 38 individuals formed S1. Two of the three lineages of P. brasiliensis, S1 and PS2, are sympatric across their range, suggesting barriers to gene flow other than geographic isolation. Our study provides the first evidence for possible sexual reproduction in P. brasiliensis S1, but does not rule it out in the other two species.
The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced colorectal carcinoma: Results of a phase III trial
Authors: M M Borner, M Castiglione, M Bacchi, W Weber, R Herrmann, M F Fey, O Pagani, S Leyvraz, R Morant, B Pestalozzi, S Hanselmann, A Goldhirsch
Journal: Annals of Oncology (1998)
HLA–DRB1–Associated Rheumatoid Arthritis Risk at Multiple Levels in African Americans: Hierarchical Classification Systems, Amino Acid Positions, and Residues
Authors: Richard J. Reynolds, Altan F. Ahmed, Maria I. Danila, Laura B. Hughes, Peter K. Gregersen, Soumya Raychaudhuri, Robert M. Plenge, S. Louis Bridges
Journal: Arthritis & Rheumatology (2014)

To evaluate HLA-DRB1 genetic risk of rheumatoid arthritis (RA) in African Americans by 3 validated allele classification systems and by amino acid position and residue, and to compare genetic risk between African American and European ancestries.