tbuckley/cabot-search huggingface dataset:
Can we clinically diagnose dementia with Lewy bodies yet?
Authors: Yue Huang, Glenda Halliday
Journal: Translational Neurodegeneration (2013)

Dementia with Lewy Bodies (DLB) was initially identified and confirmed primarily by pathology, but is soon to be incorporated into the Diagnostic and Statistical Manual criteria as a clinical disease entity. Despite these advances over more than 20 years, current data suggest that the sensitivity of accurate clinical diagnosis of DLB is still very low, although there is mounting evidence that supportive features may increase diagnostic accuracy. Although DLB remains easy to identify pathologically with different cellular pathologies differentiating it from other dementia syndromes, pathological identification using only Lewy body pathology has been shown to be inaccurate due to overlap with patients without dementia symptoms. A number of studies now suggest that a combination of cellular pathologies, which include α-synuclein and β-amyloid deposition as well as dopamine denervation, assist with differentiating this dementia syndrome from others. The clinical and pathological overlap with the tauopathy of Alzheimer's disease still remains to be clarified. To determine more robust and independent clinicopathological correlates from Alzheimer's disease, longitudinal prospective studies, using specific clinical batteries on dementia patients reaching the proposed criteria for DLB, with post-mortem assessment of the multiple pathologies associated with dementia, are required. Identifying genetic causes for DLB is another approach to investigate the pathogenesis of DLB. However this approach has been hindered to date by difficulties with identifying DLB clinically. The use of novel techniques is likely to advance knowledge on the pathogenesis of DLB and assist with redefining clinical and pathologic diagnostic criteria. To achieve the goal of more accurate clinical diagnosis of DLB, breakthroughs are necessary on the pathogenesis of DLB.
Nitric Oxide Modulates the Expression of Monocyte Chemoattractant Protein 1 in Cultured Human Endothelial Cells
Authors: Andreas M. Zeiher, Beate Fisslthaler, Beate Schray-Utz, Rudi Busse
Journal: Circulation Research (1995)

The recruitment of monocytes into the arterial wall is one of the earliest events in the pathogenesis of atherosclerosis. Since monocyte chemoattractant protein 1 (MCP-1) plays a key role in the subendothelial recruitment of monocytes, we tested whether nitric oxide (NO) modulates the expression of MCP-1 in cultured human endothelial cells. Inhibition of basal NO production by NG-nitro-L-arginine (L-NAG) upregulates endothelial MCP-1 mRNA expression (250 +/- 20%) and protein secretion. Exogenous addition of NO dose-dependently decreased MCP-1 mRNA expression and secretion. Changes in MCP-1 mRNA expression and protein secretion were paralleled by corresponding changes in chemotactic activity of cell-conditioned media for monocytes. An MCP-1 antibody reduced monocyte chemotactic activity by 85% and completely abolished the increased monocyte chemotactic activity induced by the inhibition of NO production. Elevation of endothelial cGMP levels had no significant effect on MCP-1 mRNA expression. Inhibition of basal endothelial NO production by L-NAG increased binding activity of a nuclear factor kappa B (NF-kappa B)-like transcriptional regulatory factor, whereas exogenous addition of NO decreased NF-kappa B-like binding activity during stimulation with tumor necrosis factor-alpha. Thus, NO modulates MCP-1 expression and monocyte chemotactic activity secreted by human umbilical vein endothelial cells (HUVECs) in culture. The activation of NF-kappa B-like transcriptional regulatory proteins by inhibition of NO suggests a molecular link between an oxidant-sensitive transcriptional regulatory mechanism and NO synthesis in HUVECs.
Controlled longitudinal study of bone mass accrual in children and adolescents with cystic fibrosis
Authors: H M Buntain
Journal: Thorax (2005)

A study was undertaken to observe the gains in bone mass in children and adolescents with cystic fibrosis (CF) over 24 months and to examine the relationship between areal bone mineral density (aBMD) and associated clinical parameters including physical activity, nutrition, and 25-hydroxyvitamin D (25OHD).Areal BMD of the total body (TB), lumbar spine (LS), and total femoral neck (FNt) were repeatedly measured in 85 subjects aged 5-18 years with CF and 100 age and sex matched controls over 2 years. At each visit anthropometric variables, nutritional parameters, pubertal status, disease severity, physical activity, dietary calcium, caloric intake, and serum 25OHD were assessed and related to aBMD.After adjusting for age, sex, and height Z-score, gains in LS aBMD in children (5-10 years) and TB and FNt aBMD in adolescents (11-18 years) with CF were significantly less than in controls. Lean tissue mass was significantly associated with TB and LS aBMD gains in children and adolescents and explained a significant proportion of the aBMD deficit observed. Lung function parameters were significantly associated with aBMD gains in adolescents with CF.Inadequate bone mass accrual during childhood and adolescence contributes to the low bone mass observed in adults with CF. Accounting for the height discrepancy which is frequently observed in those with CF, in addition to age and sex, is important when assessing low bone mass in children and adolescents with CF. To optimise an individual's potential to acquire maximal bone mass, it is necessary to maximise nutritional status and limit the progression of chronic suppurative lung disease.
Comparative Effectiveness of Prostate Cancer Treatments: Evaluating Statistical Adjustments for Confounding in Observational Data
Authors: J. Hadley, K. R. Yabroff, M. J. Barrett, D. F. Penson, C. S. Saigal, A. L. Potosky
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundUsing observational data to assess the relative effectiveness of alternative cancer treatments is limited by patient selection into treatment, which often biases interpretation of outcomes. We evaluated methods for addressing confounding in treatment and survival of patients with early-stage prostate cancer in observational data and compared findings with those from a benchmark randomized clinical trial.
WP1066, a Novel JAK2 Inhibitor, Suppresses Proliferation and Induces Apoptosis in Erythroid Human Cells Carrying the JAK2 V617F Mutation
Authors: Srdan Verstovsek, Taghi Manshouri, Alfonso Quintás-Cardama, David Harris, Jorge Cortes, Francis J. Giles, Hagop Kantarjian, Waldemar Priebe, Zeev Estrov
Journal: Clinical Cancer Research (2008)

The discovery of an activating somatic mutation in codon 617 of the gene encoding the Janus kinase (JAK)-2 (JAK2 V617F) in patients with myeloproliferative disorders has opened new avenues for the development of targeted therapies for these malignancies. However, no effective JAK2 inhibitors are currently available for clinical use.We investigated the activity of (E)-3(6-bromopyridin-2-yl)-2-cyano-N-(S0-1phenylethyl)acrylamide (WP1066), a novel analogue of the JAK2 inhibitor AG490, in JAK2 V617F-positive erythroleukemia HEL cells and in blood cells from patients with polycythemia vera.We found that WP1066 significantly inhibited JAK2 and its downstream signal transducer and activator of transcription-3, signal transducer and activator of transcription-5, and extracellular signal-regulated kinase-1/2 pathways in a dose- and time-dependent manner. As a result, WP1066 concentrations in the low micromolar range induced time- and dose-dependent antiproliferative and proapoptotic effects in HEL cells. As expected, WP1066 inhibited the proliferation of peripheral blood hematopoietic progenitors of patients with polycythemia vera carrying the JAK2 V617F mutation in a dose-dependent manner.Our data suggest that WP1066 is active both in vitro and ex vivo and should be further developed for the treatment of neoplasms expressing the JAK2 V617F mutation.
β-Blockade Therapy in the Perioperative Period
Authors: L. D. Britt
Journal: JAMA Surgery (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression.
Authors: S A Abdulkadir, S Krishna, D Thanos, T Maniatis, J L Strominger, S J Ono
Journal: The Journal of Experimental Medicine (1995)

The class II major histocompatibility complex gene HLA-DRA is expressed in B cells, activated T lymphocytes, and in antigen-presenting cells. In addition, HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma (IFN-gamma). Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines, and that the high mobility group protein (HMG) I/Y binds to multiple sites within the DRA promoter, including the Oct-2A binding site. Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression, and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter. Thus, Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells. By contrast, Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells, but antisense HMG I/Y dramatically decreases the level of induction. We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression, and that HMG I/Y may be important for B cell-specific expression, and is essential for IFN-gamma induction.
Phase I Study of a Novel Capecitabine Schedule Based on the Norton-Simon Mathematical Model in Patients With Metastatic Breast Cancer
Authors: Tiffany A. Traina, Maria Theodoulou, Kimberly Feigin, Sujata Patil, K. Lee Tan, Charles Edwards, Ute Dugan, Larry Norton, Clifford Hudis
Journal: Journal of Clinical Oncology (2008)

This study was conducted to determine, in patients with advanced-stage breast cancer, the maximum tolerated dose (MTD) of capecitabine administered orally for 7 days followed by a 7-day rest (7/7), a schedule based on a mathematical method for the optimization of anticancer drug scheduling.Eligible patients had measurable, metastatic breast cancer. There was no limit to number of prior treatments. A standard, three-patients-per-cohort dose-escalation scheme used flat-dose capecitabine beginning at 1,500 mg orally twice daily (bid) on a 7/7 schedule. Each cohort was monitored for 28 days before escalation to the next cohort to assess for delayed toxicity. Response was evaluated radiographically every 12 weeks; toxicity was assessed every 2 weeks.Twenty-one patients were treated on study. The most frequently reported treatment-related grade 2/3 adverse events were hand-foot syndrome (29%), leukopenia/neutropenia (24%), and fatigue (19%). Grade 3 toxicity was transient and easily managed. Three patients experienced grade 3 hand-foot syndrome; one of these patients had grade 3 diarrhea. There were no grade 4 events. The MTD of capecitabine 7/7 is 2,000 mg twice daily.As predicted by mathematical modeling, capecitabine dosing for 7 days followed by a 7-day rest is well tolerated. Efficacy of this schedule is being determined in a phase II clinical trial in patients with advanced breast cancer.
Peripubertal Suicide Attempts in Offspring of Suicide Attempters With Siblings Concordant for Suicidal Behavior
Authors: David A. Brent, Maria Oquendo, Boris Birmaher, Laurence Greenhill, David Kolko, Barbara Stanley, Jamie Zelazny, Beth Brodsky, Sekip Firinciogullari, Steven P. Ellis, J. John Mann
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors sought to determine 1) whether the risk for familial transmission of suicidal behavior is greater with increased family loading for suicide attempts, and 2) whether the transmission of suicidal behavior is mediated by impulsive aggression. METHOD: A reanalysis of a high-risk study compared the offspring of three mood disorder proband groups: suicide attempters with a sibling who also attempted suicide (N=19), suicide attempters whose siblings never made a suicide attempt (N=73), and nonsuicidal probands whose siblings also never engaged in suicidal behavior (N=73). Probands and offspring were assessed with respect to psychopathology, suicide attempt history, impulsive aggression, and exposure to familial adversity. RESULTS: Offspring of suicide attempters with siblings concordant for suicidal behavior showed a higher risk of suicide attempt than did offspring of nonsuicidal probands and had an earlier age at onset of suicidal behavior than offspring of suicide attempters with siblings discordant for suicidal behavior. Probands from sibling pairs concordant for suicidal behavior and their offspring reported greater lifetime impulsive aggression compared with each of the other two proband/offspring groups. In the offspring, impulsive aggression was the most powerful predictor of early age at first suicide attempt. CONCLUSIONS: Familial loading for suicide attempts may affect rates of transmission as well as age at onset of suicidal behavior, and its effect may be mediated by the familial transmission of impulsive aggression.
Associations of Gestational Diabetes, Existing Diabetes, and Glycosuria With Offspring Obesity and Cardiometabolic Outcomes
Authors: Sumaiya Patel, Abigail Fraser, George Davey Smith, Robert S. Lindsay, Naveed Sattar, Scott M. Nelson, Debbie A. Lawlor
Journal: Diabetes Care (2011)

To assess associations of gestational diabetes, existing diabetes, and glycosuria with adiposity and cardiometabolic risk factors in offspring at adolescence.Multivariable regression analyses were conducted in a prospective pregnancy cohort (n = 2,563-4,198 for different outcomes). Obstetric data were abstracted from clinical records. Offspring outcomes were assessed at mean age 15.5 years. Compared with those lost to follow-up, participants included in the analysis were of higher socioeconomic position. Outcomes included BMI, waist circumference, fat mass determined by dual-energy X-ray absorptiometry scan, systolic and diastolic blood pressure (sBP and dBP, respectively), fasting glucose, insulin, lipids, and C-reactive protein (CRP).Maternal existing diabetes, gestational diabetes, and glycosuria were associated with higher offspring BMI and fat mass (z scores); however, this effect was attenuated in the confounder-adjusted model, and the CIs included the null value. Existing diabetes and gestational diabetes were associated with higher offspring fasting glucose levels (0.24 mmol/L [95% CI 0.03-0.45] and 0.20 mmol/L [0.02-0.39], respectively). Glycosuria was associated with higher fasting insulin (adjusted ratio of geometric means 1.12 [1.01-1.25]), but there were no clear associations of existing or gestational diabetes with offspring fasting insulin. There was little evidence of an association of maternal diabetes or glycosuria with offspring dBP, sBP, lipids, or CRP.Maternal pregnancy glycosuria, gestational diabetes, and existing diabetes show some associations with higher offspring fasting glucose and insulin assessed in adolescence but are not clearly associated with a wider range of cardiometabolic risk factors.
Evolution of Protein Phosphorylation for Distinct Functional Modules in Vertebrate Genomes
Authors: Z. Wang, G. Ding, L. Geistlinger, H. Li, L. Liu, R. Zeng, Y. Tateno, Y. Li
Journal: Molecular Biology and Evolution (2010)

Recent publications have revealed that the evolution of phosphosites is influenced by the local protein structures and whether the phosphosites have characterized functions or not. With knowledge of the wide functional range of phosphorylation, we attempted to clarify whether the evolutionary conservation of phosphosites is different among distinct functional modules. We grouped the phosphosites in the human genome into the modules according to the functional categories of KEGG (Kyoto Encyclopedia of Genes and Genomes) and investigated their evolutionary conservation in vertebrate genomes from mouse to zebrafish. We have found that the phosphosites in the vertebrate-specific functional modules (VFMs), such as cellular signaling processes and responses to stimuli, are evolutionarily more conserved than those in the basic functional modules (BFMs), such as metabolic and genetic processes. The phosphosites in the VFMs are also significantly more conserved than their flanking regions, whereas those in the BFMs are not. These results hold for both serine/threonine and tyrosine residues, although the fraction of phosphorylated tyrosine residues is increased in the VFMs. Moreover, the difference in the evolutionary conservation of the phosphosites between the VFMs and BFMs could not be explained by the difference in the local protein structures. There is also a higher fraction of phosphosites with known functions in the VFMs than BFMs. Based on these findings, we have concluded that protein phosphorylation may play more dominant roles for the VFMs than BFMs during the vertebrate evolution. As phosphorylation is a quite rapid biological reaction, the VFMs that quickly respond to outer stimuli and inner signals might heavily depend on this regulatory mechanism. Our results imply that phosphorylation may have an essential role in the evolution of vertebrates.
DISINFECTION OF CLOUDS OF MENINGOPNEUMONITIS AND PSITTACOSIS VIRUSES WITH TRIETHYLENE GLYCOL VAPOR
Authors: Theodor Rosebury, Gordon Meiklejohn, Lawrence C. Kingsland, Martin H. Boldt
Journal: The Journal of Experimental Medicine (1947)

1. Triethylene glycol in excess of saturation, introduced as a vapor into a cloud chamber in which a dynamic cloud of either meningopneumonitis virus or psittacosis virus was developed simultaneously with, or in most instances subsequently to, the glycol cloud, induced distinct reduction in concentration of air-home virus, as measured both by cloud sampling in capillary impingers and by exposure of mice to the cloud. The relative humidity in the chamber was held between 35 and about 60 per cent. 2. Reduction of virus concentration in samplers, in glycol runs as compared with controls, ranged from 0 to 93 per cent (average, 62 per cent). 3. Reduction of infective response in mice, based on counts of focal lesions on lung surfaces, ranged from 55 to 98 per cent (average 73 per cent).
Predictive validity of health-related fitness in youth: a systematic review
Authors: J R Ruiz, J Castro-Pinero, E G Artero, F B Ortega, M Sjostrom, J Suni, M J Castillo
Journal: British Journal of Sports Medicine (2009)

The objective of the present systematic review was to investigate whether physical fitness in childhood and adolescence is a predictor of cardiovascular disease (CVD) risk factors, events and syndromes, quality of life and low back pain later in life. Physical fitness-related components were: cardiorespiratory fitness, musculoskeletal fitness, motor fitness and body composition. Adiposity was considered as both exposure and outcome. The results of 42 studies reporting the predictive validity of health-related physical fitness for CVD risk factors, events and syndromes as well as the results of five studies reporting the predictive validity of physical fitness for low back pain in children and adolescents were summarised. Strong evidence was found indicating that higher levels of cardiorespiratory fitness in childhood and adolescence are associated with a healthier cardiovascular profile later in life. Muscular strength improvements from childhood to adolescence are negatively associated with changes in overall adiposity. A healthier body composition in childhood and adolescence is associated with a healthier cardiovascular profile later in life and with a lower risk of death. The evidence was moderate for the association between changes in cardiorespiratory fitness and CVD risk factors, and between cardiorespiratory fitness and the risk of developing the metabolic syndrome and arterial stiffness. Moderate evidence on the lack of a relationship between body composition and low back pain was found. Due to a limited number of studies, inconclusive evidence emerged for a relationship between muscular strength or motor fitness and CVD risk factors, and between flexibility and low back pain.
A generous birthday present to the NHS
Authors: R. Klein
Journal: BMJ (1998)

News p 231 

New Labour has paid its tribute to the one symbol of Old Labour's achievements that has stood the test of time. The British government's 50th birthday present to the National Health Service has, at £21bn over the next three years, turned out to be even more generous than expected. It implies an annual growth of 4.7% in the NHS's budget, well above the rate conventionally assumed to be necessary to accommodate demographic pressures and technological change.1 Whatever the doubts about the precise significance of the figures announced by the chancellor of the exchequer, and whatever the reservations about how the money is to be spent, this represents morale boosting reassurance that the government's commitment to the NHS is more than rhetorical.

The planned 4.7% growth rate in real terms depends on one key assumption. This is that the rise in the costs of the inputs to the NHS—in particular, salaries—will not exceed 2.5% a year. This is unrealistic. The …