tbuckley/cabot-search huggingface dataset:
Effectiveness of two year balance training programme on prevention of fall induced injuries in at risk women aged 75-85 living in community: Ossébo randomised controlled trial
Authors: Fabienne El-Khoury, Bernard Cassou, Aurélien Latouche, Philippe Aegerter, Marie-Aline Charles, Patricia Dargent-Molina
Journal: BMJ (2015)

<b>Objective</b> To assess the effectiveness of a two year exercise programme of progressive balance retraining in reducing injurious falls among women aged 75-85 at increased risk of falls and injuries and living in the community. <b>Design</b> Pragmatic multicentre, two arm, parallel group, randomised controlled trial. <b>Setting</b> 20 study sites in 16 medium to large cities throughout France. <b>Participants</b> 706 women aged 75-85, living in their own home, and with diminished balance and gait capacities, randomly allocated to the experimental intervention group (exercise programme, n=352) or the control group (no intervention, n=354). <b>Intervention</b> Weekly supervised group sessions of progressive balance training offered in community based premises for two years, supplemented by individually prescribed home exercises. <b>Outcome measures</b> A geriatrician blinded to group assignment classified falls into one of three categories (no consequence, moderate, severe) based on physical damage and medical care. The primary outcome was the rate of injurious falls (moderate and severe). The two groups were compared for rates of injurious falls with a "shared frailty" model. Other outcomes included the rates of all falls, physical functional capacities (balance and motor function test results), fear of falling (FES-I), physical activity level, and perceived health related quality of life (SF-36). Analysis was by intention to treat. <b>Results</b> There were 305 injurious falls in the intervention group and 397 in the control group (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). The difference in severe injuries (68 in intervention group <i>v</i> 87 in control group) was of the same order of magnitude (0.83, 0.60 to 1.16). At two years, women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group. Among women who started the intervention (n=294), the median number of group sessions attended was 53 (interquartile range 16-71). Five injurious falls related to the intervention were recorded. <b>Conclusion</b> A two year progressive balance retraining programme combining weekly group and individual sessions was effective in reducing injurious falls and in improving measured and perceived physical function in women aged 75-85 at risk of falling. <b>Trial registration</b> ClinicalTrials.gov (NCT00545350).
Treatment of Acromegaly with the Growth Hormone–Receptor Antagonist Pegvisomant
Authors: Peter J. Trainer, William M. Drake, Laurence Katznelson, Pamela U. Freda, Vivien Herman-Bonert, A.J. van der Lely, Eleni V. Dimaraki, Paul M. Stewart, Keith E. Friend, Mary Lee Vance, G. Michael Besser, Michael O. Thorner, Craig Parkinson, Anne Klibanski, Jeffrey S. Powell, Ariel L. Barkan, Michael C. Sheppard, Mario Maldonado, D. Roderick Rose, David R. Clemmons, Gudmundur Johannsson, Bengt-Åke Bengt-Åke Bengtsson, Stavros Stavrou, David L. Kleinberg, David M. Cook, Lawrence S. Phillips, Martin Bidlingmaier, Christian J. Strasburger, Suzanne Hackett, Kenneth Zib, William F. Bennett, Robert J. Davis, John A. Scarlett
Journal: New England Journal of Medicine (2000)

Patients with acromegaly are treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone–receptor antagonist that blocks the action of growth hormone.
Current concepts in preimplantation genetic diagnosis (PGD): a molecular biologist's view
Authors: K. Sermon
Journal: Human Reproduction Update (2002)

The first clinically applied preimplantation genetic diagnosis (PGD) was reported more than a decade ago and since then PGD has known an exponential growth. This first report described the use of PCR to sex embryos from couples at risk for X-linked diseases. Not surprisingly, in the first years, the development of PCR-based tests led to PGD for well-known monogenic diseases such as cystic fibrosis and thalassaemia. When fluorescent in-situ hybridization (FISH) was introduced it quickly replaced PCR-based methods, which had led to misdiagnoses, for sexing of embryos. FISH was also quickly introduced for aneuploidy screening, which has as its main aim the improvement of IVF results in patients with poor reproductive outcome, and later for PGD in translocation carriers. In this review, PGD for patients with a pre-existing genetic risk will be discussed, i.e. the monogenic diseases and the translocations, as well as different biopsy methods and promising new developments.
Disruption of Cooperation Between Ras and MycN in Human Neuroblastoma Cells Promotes Growth Arrest
Authors: Shira Yaari, Jasmine Jacob-Hirsch, Ninette Amariglio, Ronit Haklai, Gideon Rechavi, Yoel Kloog
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Our aim was to examine whether active Ras and MycN cooperation contributes to the malignant phenotype of human neuroblastoma with amplified MycN gene, an aggressive incurable tumor. Experimental Design: Human neuroblastoma LAN-1 cells, in which the MycN gene is amplified, were used to examine the impact of the Ras inhibitor farnesylthiosalicylic acid on cell growth, on the levels Ras and MycN proteins, and on profiles of gene expression. Results: We show that LAN-1 cells express relatively large amounts of MycN and active Ras-GTP. Inhibition of active Ras by farnesylthiosalicylic acid led to attenuation of the Raf-MEK-ERK and phosphoinositide 3-kinase-Akt-glycogen synthase-3 (GSK-3) pathways, to reduction in cyclin D1, phospho-retinoblastoma, and E2F, and to increase in the cyclin-dependent kinase inhibitor p27 and in retinoblastoma-binding protein-1, an inhibitor of E2F transcriptional activity. Ras inhibition by farnesylthiosalicylic acid or by a dominant-negative Ras also led to complete disappearance of MycN protein from the nuclei of LAN-1 cells. This was a result of blocking of Akt inactivation of GSK-3, leading to GSK-3-dependent phosphorylation with consequent proteosomal degradation of MycN. Loss of active Ras and of MycN in LAN-1 cells was manifested in profiles of gene expression that could be expected from the loss of MycN transcriptional activity and of Ras signaling. These changes explain the farnesylthiosalicylic acid–induced inhibition of LAN-1 cell growth. Conclusions: Active Ras is needed to block MycN degradation, promoting cooperative Ras- and MycN-dependent cell cycle progression in LAN-1 cells. Ras inhibitors are therefore likely candidates for the treatment of advanced neuroblastoma characterized by high expression of MycN.
A Cross-Study Comparison of Gene Expression Studies for the Molecular Classification of Lung Cancer
Authors: Giovanni Parmigiani, Elizabeth S. Garrett-Mayer, Ramaswamy Anbazhagan, Edward Gabrielson
Journal: Clinical Cancer Research (2004)

Recent studies sought to refine lung cancer classification using gene expression microarrays. We evaluate the extent to which these studies agree and whether results can be integrated.We developed a practical analysis plan for cross-study comparison, validation, and integration of cancer molecular classification studies using public data. We evaluated genes for cross-platform consistency of expression patterns, using integrative correlations, which quantify cross-study reproducibility without relying on direct assimilation of expression measurements across platforms. We then compared associations of gene expression levels to differential diagnosis of squamous cell carcinoma versus adenocarcinoma via reproducibility of the gene-specific t statistics and to survival via reproducibility of Cox coefficients.Integrative correlation analysis revealed a large proportion of genes in which the patterns agreed across studies more than would be expected by chance. Correlation of t statistics for diagnosis of squamous cell carcinoma versus adenocarcinoma is high (0.85) and increases (0.925) when using only the most consistent genes identified by integrative correlation. Correlations of Cox coefficients ranged from 0.13 to 0.31 (0.33-0.49 with genes selected for consistency). Although we find genes that are significant in multiple studies but show discordant effects, their number is approximately that expected by chance. We report genes that are reproducible by integrative analysis, significant in all studies, and concordant in effect.Cross-study comparison revealed significant, albeit incomplete, agreement of gene expression patterns related to lung cancer biology and identified genes that reproducibly predict outcomes. This analysis approach is broadly applicable to cross-study comparisons of gene expression profiling projects.
Incidence of Osteoporosis in Elderly Whites and Elderly Negroes
Authors: Marc Moldawer
Journal: JAMA (1965)

X-ray examinations were made of the spines of 100 Negroes over 65 years of age. None had had back pain or injury or a metabolic disorder associated with osteoporosis. There was no history of prolonged bed rest or premature menopause. Twelve subjects showed compression fractures due to osteoporosis, in comparison with an incidence of 24% in two series of white patients. Review of 222 hip fractures in a homogeneous economic and geographic population revealed the prevalence to be 5.6 times greater in the white than in the Negro men, and 3 times greater in the white than in the Negro women. Despite differences in socioeconomic and geographic factors in the three series, the study, together with the hip-fracture data, suggests that osteoporosis is less prevalent in Negroes than in whites.
Novel methods of enhanced endoscopic imaging
Authors: J Van Dam
Journal: Gut (2003)

Endoscopy has become an essential part of the practice of gastroenterology. Techniques exploiting previously unused properties of light have demonstrated the potential to enhance the ability to make clinical diagnoses without removing tissue as has been standard practice for decades. The term used for many of these techniques is "optical biopsy" and, although not yet widely available, enthusiasm for such techniques has grown as has research in their potential clinical utility.
Mathematical Modeling of Tumor Cell Proliferation Kinetics and Label Retention in a Mouse Model of Lung Cancer
Authors: Yanyan Zheng, Helen Moore, Alexandra Piryatinska, Trinidad Solis, E. Alejandro Sweet-Cordero
Journal: Cancer Research (2013)

Abstract Slowly cycling tumor cells that may be present in human tumors may evade cytotoxic therapies, which tend to be more efficient at destroying cells with faster growth rates. However, the proportion and growth rate of slowly cycling tumor cells is often unknown in preclinical model systems used for drug discovery. Here, we report a quantitative approach to quantitate slowly cycling malignant cells in solid tumors, using a well-established mouse model of Kras-induced lung cancer (KrasG12D/+). 5-Bromo-2-deoxyuridine (BrdUrd) was administered to tumor-bearing mice, and samples were collected at defined times during pulse and chase phases. Mathematical and statistical modeling of the label-retention data during the chase phase supported the existence of a slowly cycling label-retaining population in this tumor model and permitted the estimation of its proportion and proliferation rate within a tumor. The doubling time of the slowly cycling population was estimated at approximately 5.7 weeks, and this population represented approximately 31% of the total tumor cells in this model system. The mathematical modeling techniques implemented here may be useful in other tumor models where direct observation of cell-cycle kinetics is difficult and may help evaluate tumor cell subpopulations with distinct cell-cycling rates. Cancer Res; 73(12); 3525–33. ©2013 AACR.
Imaging of basal cell carcinoma by high-definition optical coherence tomography: histomorphological correlation. A pilot study
Authors: M.A.L.M. Boone, S. Norrenberg, G.B.E. Jemec, V. Del Marmol
Journal: British Journal of Dermatology (2012)

With the continued development of noninvasive therapies for basal cell carcinoma (BCC) such as photodynamic therapy and immune therapies, noninvasive diagnosis and monitoring become increasingly relevant. High-definition optical coherence tomography (HD-OCT) is a high-resolution imaging tool, with micrometre resolution in both transversal and axial directions, enabling visualization of individual cells up to a depth of around 570 μm, and filling the imaging gap between conventional optical coherence tomography (OCT) and reflectance confocal microscopy (RCM).We sought to determine the feasibility of detecting BCC by this technique using criteria defined for RCM and conventional OCT and compared with histology.In this pilot study skin lesions of 21 patients with a histologically proven BCC were imaged by HD-OCT just before excision and images analysed qualitatively.Features for four different BCC subtypes were described in both transverse and axial directions. In general, these features were subepidermal or intradermal aggregations of cells. These islands or trabeculae were surrounded by a less refractile border corresponding with palisading and peritumoral mucin production. There was a pronounced architectural disarray of the epidermis. A variably refractile stroma together with abundant dilated peritumoral blood vessels was present. These features were comparable with histological features for each patient.Using features already suggested by RCM and conventional OCT, the study implies that HD-OCT facilitates in vivo diagnosis of BCC and allows the distinction between different BCC subtypes for increased clinical utility.
Self-reported Sleep and β-Amyloid Deposition in Community-Dwelling Older Adults
Authors: Adam P. Spira, Alyssa A. Gamaldo, Yang An, Mark N. Wu, Eleanor M. Simonsick, Murat Bilgel, Yun Zhou, Dean F. Wong, Luigi Ferrucci, Susan M. Resnick
Journal: JAMA Neurology (2013)

<h3>Importance</h3> Older adults commonly report disturbed sleep, and recent studies in humans and animals suggest links between sleep and Alzheimer disease biomarkers. Studies are needed that evaluate whether sleep variables are associated with neuroimaging evidence of β-amyloid (Aβ) deposition. <h3>Objective</h3> To determine the association between self-reported sleep variables and Aβ deposition in community-dwelling older adults. <h3>Design, Setting, and Participants</h3> Cross-sectional study of 70 adults (mean age, 76 [range, 53-91] years) from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging, a normative aging study. <h3>Exposure</h3> Self-reported sleep variables. <h3>Main Outcomes and Measures</h3> β-Amyloid burden, measured by carbon 11–labeled Pittsburgh compound B positron emission tomography distribution volume ratios (DVRs). <h3>Results</h3> After adjustment for potential confounders, reports of shorter sleep duration were associated with greater Aβ burden, measured by mean cortical DVR (B = 0.08 [95% CI, 0.03-0.14];<i>P</i> = .005) and precuneus DVR (B = 0.11 [0.03-0.18];<i>P</i> = .007). Reports of lower sleep quality were associated with greater Aβ burden measured by precuneus DVR (B = 0.08 [0.01-0.15];<i>P</i> = .03). <h3>Conclusions and Relevance</h3> Among community-dwelling older adults, reports of shorter sleep duration and poorer sleep quality are associated with greater Aβ burden. Additional studies with objective sleep measures are needed to determine whether sleep disturbance causes or accelerates Alzheimer disease.
DRUG USE-RATE IN A STATE HOSPITAL
Authors: J. R. WHITTIER, C. D. KORENYI, O. DIAMOND, P. J. TOMLINSON, H. A. LABURT
Journal: American Journal of Psychiatry (1959)

Use-rates for 9 tranquilizing and 3 stimulant drugs or drug-combinations were recorded in a state hospital population over a 4 year period, ending December 31, 1958. Data were plotted graphically, and userates were observed in descending order for chlorpromazine, promazine, reserpine, proclorpromazine, meprobamate, triflupromazine, mepazine, mepazine plus chlorpromazine, reserpine plus chlorpromazine, benzedrine, methylphenidate, and iproniazid. By the end of the observation period, 61% of the total hospital population, (21% of the male, and 40% of the female populations) were receiving one or more of the drugs. Of the total, male, and female populations on drugs, 34%, 11%, and 23% respectively were receiving chlorpromazine.
DAPT Enhances the Apoptosis of Human Tongue Carcinoma Cells
Authors: Brian E Grottkau, Xi‐rui Chen, Claudia C Friedrich, Xing‐mei Yang, Wei Jing, Yao Wu, Xiao‐xiao Cai, Yu‐rong Liu, Yuan‐ding Huang, Yun‐feng Lin
Journal: International Journal of Oral Science (2009)

To investigate the effect of DAPT (γ‐secretase inhibitor) on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of tongue carcinoma. Human tongue carcinoma Tca8113 cells were cultured with DAPT. Cell growth was determined using Indigotic Reduction method. The cell cycle and apoptosis were analyzed by flow cytometry. Real‐time PCR and Immuno‐Fluorescence (IF) were employed to determine the intracellular expression levels. DAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0–G1 cell cycle arrest and apoptosis. The mRNA levels of Hairy/Enhancer of Split‐1 (Hes‐1), a target of Notch activation, were reduced by DAPT in a dose‐dependent manner. Coincident with this observation, DAPT induced a dose‐dependent promotion of constitutive Caspase‐3 in Tca8113 cells. DAPT may have a therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in tumor inhibition may arise partly via the modulation of Notch‐1 and Caspase‐3.
Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling
Authors: D. Agrawal
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify markers. Methods: Total RNA from human colon tumors (n = 60) of multiple stages (adenomas; cancers with modified Astler Collier stages B, C, and D; and liver metastases) were pooled within stages and compared with pooled normal mucosal specimens (n = 10) by using oligonucleotide expression arrays. Genes that showed consistent increases or decreases in their expression through tumor progression were identified. Northern blot analysis was used to validate the findings. All statistical tests were two-sided. Results: More than 300 candidate tumor markers and more than 100 markers of tumor progression were identified. Northern analysis of 11 candidate tumor markers confirmed the gene expression changes. The gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in conjunction with tumor progression. Its potential as a progression marker was validated (Spearman's ρ = 0.903; P<.001) with northern blot analysis using RNA from an independent set of 10 normal and 43 tumor samples representing all stages. Moreover, a statistically significant correlation between osteopontin protein expression and advancing tumor stage was identified with the use of 303 additional specimens (human cancer = 185, adenomas = 67, and normal mucosal specimens = 51) (Spearman's ρ = 0.667; P<.001). Conclusions: Sample pooling can be a powerful, cost-effective, and rapid means of identifying the most common changes in a gene expression profile. We identified osteopontin as a clinically useful marker of tumor progression by use of gene expression profiling on pooled samples.
Relation of Familial Schizophrenia to Negative Symptoms But Not to the Deficit Syndrome
Authors: D Malaspina, R R Goetz, S Yale, A Berman, J H Friedman, F Tremeau, D Printz, X Amador, J Johnson, A Brown, J M Gorman
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Although a family history of schizophrenia has been associated with negative symptoms, family history is inconsistently related to the presence of the deficit syndrome.METHOD: The authors assessed family history and the deficit syndrome in 99 patients with DSM-III-R-diagnosed schizophrenia who were assessed during clinical treatment. Of these 99 patients, 45 were assessed both while antipsychotic free and during antipsychotic treatment to index their treatment response.RESULTS: Patients with (N=39) and without (N=60) a family history of schizophrenia had similar proportions of the deficit syndrome. Yet family history and deficit syndrome categorizations identified a group with greater negative symptoms on the Positive and Negative Syndrome Scale. Those with a family history had greater emotional withdrawal, poor rapport, and lack of spontaneity. Groups with and without the deficit syndrome similarly differed in these symptoms but also in affective blunting, motor retardation, and passive or apathetic social withdrawal. The study involving antipsychotic-free and antipsychotic treatment phases showed main medication effects explaining positive, psychopathology, depression, and activation symptoms but not negative symptoms. Only patients without a family history had improved negative symptoms with antipsychotic treatment.CONCLUSIONS: Patients with a family history of schizophrenia had greater and more treatment-resistant negative symptoms than those without a family history. They were not more likely to have the deficit syndrome. The group with a family history had more pathology only in negative symptoms related to psychosocial function. The stable negative symptoms specifically related to the genetic vulnerability to inherit schizophrenia might be those associated with psychosocial functioning.
Major Histocompatibility Complex Class I Allele-specific Cooperative and Competitive Interactions between Immune Evasion Proteins of Cytomegalovirus
Authors: Markus Wagner, Anja Gutermann, Jürgen Podlech, Matthias J. Reddehase, Ulrich H. Koszinowski
Journal: The Journal of Experimental Medicine (2002)

Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses with deletions of the three genes in all seven possible combinations. Surface expression of a set of MHC class I molecules specified by haplotypes H-2d (Kd, Dd, and Ld) and H-2b (Kb and Db) was the parameter for evaluation of the interference with class I trafficking. The data show the following: first, there exists no additional MCMV gene of major influence on MHC class I surface expression; second, the strength of the inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third, the immunoevasins act not only synergistically but can, in certain combinations, interact antagonistically. In essence, this work highlights the importance of studying the immunosubversive mechanisms of cytomegaloviruses in the context of gene expression during the viral replicative cycle in infected cells.