tbuckley/cabot-search huggingface dataset:
The Mental Activity and eXercise (MAX) Trial
Authors: Deborah E. Barnes, Wendy Santos-Modesitt, Gina Poelke, Arthur F. Kramer, Cynthia Castro, Laura E. Middleton, Kristine Yaffe
Journal: JAMA Internal Medicine (2013)

The prevalence of cognitive impairment and dementia are projected to rise dramatically during the next 40 years, and strategies for maintaining cognitive function with age are critically needed. Physical or mental activity alone result in relatively small, domain-specific improvements in cognitive function in older adults; combined interventions may have more global effects.To examine the combined effects of physical plus mental activity on cognitive function in older adults.Randomized controlled trial with a factorial design.San Francisco, California.A total of 126 inactive, community-residing older adults with cognitive complaints.All participants engaged in home-based mental activity (1 h/d, 3 d/wk) plus class-based physical activity (1 h/d, 3 d/wk) for 12 weeks and were randomized to either mental activity intervention (MA-I; intensive computer) or mental activity control (MA-C; educational DVDs) plus exercise intervention (EX-I; aerobic) or exercise control (EX-C; stretching and toning); a 2 × 2 factorial design was used so that there were 4 groups: MA-I/EX-I, MA-I/EX-C, MA-C/EX-1, and MA-C/EX-C.Global cognitive change based on a comprehensive neuropsychological test battery.Participants had a mean age of 73.4 years; 62.7% were women, and 34.9% were Hispanic or nonwhite. There were no significant differences between the groups at baseline. Global cognitive scores improved significantly over time (mean, 0.16 SD; P < .001) but did not differ between groups in the comparison between MA-I and MA-C (ignoring exercise, P = .17), the comparison between EX-I and EX-C (ignoring mental activity, P = .74), or across all 4 randomization groups (P = .26).In inactive older adults with cognitive complaints, 12 weeks of physical plus mental activity was associated with significant improvements in global cognitive function with no evidence of difference between intervention and active control groups. These findings may reflect practice effects or may suggest that the amount of activity is more important than the type in this subject population.clinicaltrials.gov Identifier: NCT00522899.
Clonal Evolution Enhances Leukemia-Propagating Cell Frequency in T Cell Acute Lymphoblastic Leukemia through Akt/mTORC1 Pathway Activation
Authors: Jessica S. Blackburn, Sali Liu, Jayme L. Wilder, Kimberly P. Dobrinski, Riadh Lobbardi, Finola E. Moore, Sarah A. Martinez, Eleanor Y. Chen, Charles Lee, David M. Langenau
Journal: Cancer Cell (2014)
Increased apoptosis induction in hepatocellular carcinoma by a novel tumor-targeted TRAIL fusion protein combined with bortezomib
Authors: Kristin Wahl, Martin Siegemund, Frank Lehner, Florian Vondran, Andreas Nüssler, Florian Länger, Till Krech, Roland Kontermann, Michael P. Manns, Klaus Schulze-Osthoff, Klaus Pfizenmaier, Heike Bantel
Journal: Hepatology (2012)

As the result of an increasing incidence and a prevalent therapy resistance of hepatocellular carcinoma (HCC), there is a strong need for novel strategies to enhance treatment responses in HCC. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising anticancer drug because it can selectively induce apoptosis in cancer cells, but not in healthy cells. Nevertheless, most tumor cells show TRAIL resistance, emphasizing the requirement for apoptosis-sensitizing agents and TRAIL molecules with improved tumor specificity. In this study, we employed a recombinant TRAIL molecule, in which three TRAIL protomers were expressed as a single polypeptide chain (scTRAIL), and a novel TRAIL variant, in which scTRAIL was additionally fused to an antibody fragment recognizing epidermal growth factor receptor (EGFR) to improve its HCC-targeting properties. We analyzed the proapoptotic effects of both TRAIL versions in combination with the proteasome inhibitor bortezomib (BZB) in hepatoma cells and primary human hepatocytes as well as in intact explants from HCC and healthy liver tissue. We demonstrate that EGFR-targeted TRAIL in combination with BZB induced significantly higher caspase activation and cell death in hepatoma cells, but not in primary hepatocytes. Importantly, when incubated with fresh liver explants, the combination of EGFR-targeted TRAIL and BZB displayed selective cytotoxicity for HCC, but not for tumor-free liver tissue, which could even be verified in liver explants from the same individuals. Unlike nontargeted TRAIL, EGFR-targeted TRAIL combined with BZB exerted no toxicity in liver tissues from nonalcoholic fatty liver disease patients.EGFR-targeted TRAIL reveals increased antitumor activity toward HCC without inducing toxicity to tumor-free liver tissue and might therefore represent a promising novel strategy for HCC treatment.
Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis and bronchiolitis obliterans
Authors: Tadeusz Chorzelskia†, Takashi Hashimotoc, Barbara Maciejewskab, Masayuki Amagaid, Grant J. Anhalte, Stefania Jablonskaa
Journal: Journal of the American Academy of Dermatology (1999)
Lipid loop instigates arthritis
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Lipid loop instigates arthritisArthritic joints are chock-full of activated immune cells.These cells produce chemotactic proteins that lure other cells into the joint, setting up a vicious cycle of inflammation.But what instigates this cycle in the first place?A study by Kim et al. (page 829) puts much of the blame on neutrophils.Neutrophils-granular cells that are among the immune system's earliest responders during infection and injury-are required for the development of joint inflammation during autoantibody-induced arthritis in mice.But the signals that trigger this joint invasion had not been identified.Kim and colleagues now identify a chemotactic lipid called leukotriene B 4 (LTB 4 ) as the instigating signal.In the absence of the receptor for LTB 4 (called BLT1), neutrophils failed to invade the joints, and mice did not develop arthritis.This effect was reversed when wild-type neutrophils were transferred into the deficient mice.Consistent with these data, a study by Chen et al. (page 837) shows that LTB 4 is essential for disease induction in the same model.Once in the joint, the neutrophils triggered the production of chemokines that attracted other cells-including more neutrophils-to the area.BLT1 expression was mandatory only for the initial vanguard of neutrophils that infiltrated the joint; it was dispensable for those that followed-presumably because other neutrophil-attracting chemokines were produced.According to Chen et al., neutrophils were also the primary producers of LTB 4 .But what entices the first neutrophils to enter the joint and, once there, what signals cause them to produce LTB 4 are still unknown.
Impaired myogenesis in the quadriceps muscle of cachectic COPD patients
Authors: Carme Casadevall, Sergi Pascual, Simón García, Pilar Ausín, Xavier Trepat, Esther Barreiro, Joaquim Gea
Journal: European Respiratory Journal (2014)

Although muscle mass loss is frequently observed in COPD patients, its etiology remains to be fully elucidated. Preliminary reports have suggested that there is a defect in the number or function of satellite cells resulting in an inefficient myonuclear turnover, which would involve a decrease in protein synthesis in the corresponding cytosolic domains. Aim: To test this hypothesis we have studied the myogenic process in the quadriceps muscle of cachectic COPD patients. Methods: Muscle biopsies from 15 cachectic and 15 non-cachectic severe COPD patients and 10 healthy subjects were obtained. Fibers and satellite cells were evaluated using immunohistochemistry and morphometric techniques, whereas the expression of the main myogenic factors was studied by real-time PCR. In addition, myocytes obtained from biopsies were cultured and their proliferation and differentiation phases were also analyzed. Main Results: The quadriceps of cachectic COPD patients showed smaller fibers and only slight signs of muscle injury. Surprisingly, the number of satellite cells was increased in this population, despite that muscles showed a concomitant downregulation of the late-stages markers of myogenesis. Proliferation and differentiation of myocytes in primary cultures did not show differences between cachectic patients and controls. Conclusions: Our results suggest that in cachectic COPD patients, the “in vivo” myogenic process is defective, and such impairment seems to be the result of the interaction of local factors with myogenic events in those patients.

Funded by SAF 2011-26908, FIS 11/02029 & 12/02534, SEPAR 761, FUCAP 2009 and CIBERES.
Longitudinal study of grass pollen exposure, symptoms, and exhaled nitric oxide in childhood seasonal allergic asthma
Authors: G Roberts
Journal: Thorax (2004)

Exhaled nitric oxide (NO) has been proposed as a marker of airway eosinophilic inflammation in asthma. There is currently a paucity of longitudinal data relating it to allergen exposure and asthma symptoms.Forty four children (6-16 years) with seasonal allergic asthma were sequentially followed before and during the grass pollen season. Asthma symptoms, lung function, NO levels, and pollen counts were recorded. The relationship between exhaled NO and both the pollen levels and asthma control were assessed longitudinally, comparing a subject's measurements with their previous ones.The median exhaled NO concentration was significantly increased during the pollen season (6.2 v 9.2 parts per billion (ppb), p<0.002; median change 2.9 ppb, 95% confidence interval 1.5 to 5.4). Exhaled NO was best associated with the mean pollen count in the week before measurement. It was also significantly associated with asthma control.The results suggest that, within a longitudinal model, the exhaled NO concentration is related to preceding allergen exposure and asthma control. It may be clinically more useful to compare exhaled NO values with a subject's previous values than to compare them with a population based normal range.
Delayed mouth-caecum transit of a lactulose labelled liquid test meal in patients with steatorrhoea caused by partially treated coeliac disease.
Authors: R C Spiller, Y C Lee, C Edge, D N Ralphs, J S Stewart, S R Bloom, D B Silk
Journal: Gut (1987)

Mouth-caecum transit time (M-CTT) of a lactulose labelled liquid test meal has been measured in 27 coeliac patients and 10 healthy controls using the breath hydrogen technique. Although all patients were urged to maintain a gluten free diet, not all did, and there was, therefore, a wide range in the severity of fat malabsorption within the patient group. Gastric emptying of a 113Indium DTPA-labelled liquid test meal was also assessed in separate studies on six healthy controls and 11 of the coeliac patients. Fasting breath hydrogen concentrations and the response to lactulose, as assessed both by the rate of rise, and the peak breath hydrogen concentration reached, showed no difference between coeliacs and controls, regardless of the presence or absence of steatorrhoea. Mouth-caecum transit time in the 16 coeliac patients with steatorrhea (faecal fat greater than 7 g/24 h) was, however, significantly prolonged being 158 +/- 18 minutes (mean +/- SEM), compared with 70 +/- 9 minutes for the controls (p less than 0.02), and 83 +/- 15 minutes for the 11 coeliacs without steatorrhoea (p less than 0.002). Mouth-caecum transit time in the coeliac patients was linearly related to the 24 hour faecal fat excretion, r = 0.55, n = 27, p less than 0.01. Slow mouth-caecum transit in the coeliacs with steatorrhoea was not caused by delayed gastric emptying as the t1/2 for coeliacs with steatorrhoea was within the normal range. Coeliacs with delayed mouth-caecum transit had impaired insulin release but the postprandial profiles of the other peptides measured (cholecystokinin, GIP, secretin, motilin, neurotensin, enteroglucagon, and peptide YY) were all within the normal range in this group of partially treated coeliac patients.
Raynaud's Disease and Nifedipine
Authors: E. Harris Pierce, Robert Dellavalle, James Wielenga
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 January 1983Raynaud's Disease and NifedipineE. HARRIS PIERCE, M.D., M.S., ROBERT DELLAVALLE, PHARM. D., JAMES WIELENGA, PHARM. D.E. HARRIS PIERCE, M.D., M.S., ROBERT DELLAVALLE, PHARM. D., JAMES WIELENGA, PHARM. D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-1-111_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Until recently, no therapeutic regimen for Raynaud's disease has provided consistent results without significant side effects (1). Two recent reports seem to indicate a role for calcium-channel blocking agents in the treatment of this disorder(2, 3). We report the successful use of nifedipine in a patient with Raynaud's disease not responsive to conventional therapy.A 64-year-old white woman had a 7-year history of bilateral numbness, coldness, and blanching of the distal ends of her index and middle fingers. At the time of diagnosis, no precipitating cause could be identified. Consequently, she was diagnosed as having Raynaud's disease....References1. HALPERIN J and COFFMAN J. Pathophysiology of Raynaud's disease. Arch Intern Med. 1979;139:89-92. CrossrefMedlineGoogle Scholar2. KAHAN A, WEBER S, AMOR B, SOPORTA L, HODARA M, and DEGEORGES M. Nifedipine and Raynaud's phenomenon [Letter]. Ann Intern Med. 1981;94:546. LinkGoogle Scholar3. VAYSSAIRAT M, CAPRON L, FIESSINGER J, MATHIEU J, and HOUSSET E. Calcium channel blockers and Raynaud's disease [Letter]. Ann Intern Med. 1981;95:243. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: E. HARRIS PIERCE, M.D., M.S.; ROBERT DELLAVALLE, PHARM. D.; JAMES WIELENGA, PHARM. D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInfluence of vasospasm on visual functionThe treatment of Raynaud's phenomenonVibration syndrome in industry: Dermatological viewpointPromising Uses of Calcium-Channel Blocking AgentsNifedipine: Two New Uses 1 January 1983Volume 98, Issue 1Page: 111-111 ePublished: 1 December 2008 Issue Published: 1 January 1983 PDF downloadLoading ...
A Randomized Trial of a Consultation Service to Reduce Falls in Nursing Homes
Authors: Wayne A. Ray
Journal: JAMA (1997)

Falls are a major health problem in nursing homes, but no interventions have been shown to prevent falls in nursing home residents.To evaluate an intervention program designed to prevent falls and associated injuries in high-risk nursing home residents.Randomized controlled trial.Seven pairs of middle Tennessee nursing homes with 1 facility in each pair randomly assigned to the intervention. Facilities had 482 (261 control, 221 intervention) residents who qualified for the study because they had high risk of falls and a potential safety problem that could be addressed by the intervention.Comprehensive structured individual assessment with specific safety recommendations that targeted suboptimal practices for environmental and personal safety, wheelchair use, psychotropic drug use, and transferring and ambulation. Facility staff were encouraged to implement the individual recommendations and to improve overall facility safety.The mean proportion of recurrent fallers and incidence rate of injurious falls in the facility in the year following the intervention.The mean proportion of recurrent fallers in intervention facilities (43.8%) was 19.1% (95% confidence interval, 2.4%-35.8%) lower than that in control facilities (54.1%, P=.03). Intervention facilities had a nonsignificant trend toward a lower mean rate of injurious falls (13.7 vs 19.9 per 100 person-years, reduction of 31.2%, P=.22). Subgroup analyses suggested greatest benefits for residents for whom the recommended interventions were carried out or who had 3 or more falls in the preceding year.The high rate of falls and related injuries in nursing homes should not be viewed as inevitable, but as outcomes that can be substantially improved through structured safety programs.
Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial
Authors: J. Lin, N. R. Cook, C. Albert, E. Zaharris, J. M. Gaziano, M. Van Denburgh, J. E. Buring, J. E. Manson
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundObservational studies suggested that a diet high in fruits and vegetables, both of which are rich with antioxidants, may prevent cancer development. However, findings from randomized trials of the association between antioxidant use and cancer risk have been mostly negative.
BiDil for Heart Failure in Black Patients: The U.S. Food and Drug Administration Perspective
Authors: Robert Temple, Norman L. Stockbridge
Journal: Annals of Internal Medicine (2007)

Critics of the U.S. Food and Drug Administration (FDA) approval of the fixed combination of hydralazine hydrochloride, 37.5 mg, and isosorbide dinitrate, 20 mg, for treating heart failure in black patients have suggested that data were insufficient to distinguish treatment effects in black and white people; that distinctions based on race, rather than pathophysiology, were scientifically unreasonable; and that a "race-based" approval could be a commercial ploy to avoid a more expensive and prolonged full evaluation of a drug. The criticisms acknowledge that data supporting the approval came from a well-designed clinical trial in which self-identified black patients with heart failure who took hydralazine hydrochloride–isosorbide dinitrate with standard therapy experienced a statistically significant 43% (95% CI, 11% to 63%) reduction in mortality compared with those who took only the standard therapy. The criticisms do not always recognize that the decision to conduct the trial in only black patients reflected careful analyses of 2 previous trials in racially mixed patient populations that compared hydralazine hydrochloride–isosorbide dinitrate with placebo or with enalapril. Both trials showed little or no overall effect of hydralazine hydrochloride–isosorbide dinitrate in the mostly white patient population but hinted at a substantial effect in subsets of black patients. Perhaps most critically, the criticisms do not appreciate the urgency of strong scientific evidence of a substantial survival benefit in black patients. A serious attempt to avoid race-based approval by mandating study of a mixed population to identify a possible white patient–responder subset, particularly without a plausible hypothesis as to what that subset might be, would have required years of work, many thousands of patients, and wholly unreasonable delay in approval of a treatment whose effectiveness had been well-documented in the group for which it was intended.
Evolution of nucleic acids coding for ribonucleases: the mRNA sequence of mouse pancreatic ribonuclease.
Authors: C Schüller, H M Nijssen, R Kok, J J Beintema
Journal: Molecular Biology and Evolution (1990)

The cDNA of mouse pancreatic mRNA has been cloned. After the library was screened with a rat ribonuclease cDNA probe, the positive clones were isolated and sequenced. There were no differences from the previously determined protein sequence. The mRNA codes for a preribonuclease of 149 amino acid residues including a signal peptide of 25 amino acids. The 3' noncoding region has a length of 260 bp, and the total mRNA length is approximately 940 bp. Comparison with the rat pancreatic ribonuclease sequence showed a high rate of nucleotide substitution. Within the coding region, nonsynonymous and synonymous substitution rates are 4.3 X 10(-9) and 15 X 10(-9) nucleotide substitutions/site/year, respectively. The latter value is one of the highest rates observed in the molecular evolution of mammalian nuclear genes. In the signal sequences the synonymous substitution rate is much lower and about the same as the nonsynonymous rate. Signal sequences of other mouse and rat proteins also exhibit little difference between synonymous and nonsynonymous rates. The sequences of rat and mouse pancreatic ribonuclease messengers were compared with those of bovine pancreatic, seminal, and brain ribonuclease. While the 3' noncoding regions of rat and mouse are very similar, as are those of the three bovine messengers, there is no significant similarity between both rodent and the three bovine messengers for the greater part of these regions. There is a duplication of approximately 50 nucleotides in the 3' noncoding region of the bovine messengers, with a region rich in A and C in between. The presence of this structural feature may be correlated with recent gene duplications that have occurred in the bovine genome.
Leptin promotes a proinflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes
Authors: D. Törőcsik, D. Kovács, E. Camera, M. Lovászi, K. Cseri, G.G. Nagy, R. Molinaro, R. Rühl, G. Tax, K. Szabó, M. Picardo, L. Kemény, C.C. Zouboulis, É. Remenyik
Journal: British Journal of Dermatology (2014)

Leptin, the adipocyte-secreted hormone that regulates weight, is known to link lipid metabolism with inflammation in various cell types. However, its role in human sebocytes has not yet been investigated.The purpose of this study was to investigate the effects of leptin in human sebaceous gland biology.Expression of the long form of the leptin receptor (Ob-Rb) was detected by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunochemistry. Lipid analysis was by high-performance thin-layer chromatography, gas chromatography-mass spectrometry and time-of-flight mass spectrometer mass detection. Lipid bodies were visualized by BODIPY staining using fluorescent microscopy and measured by flow cytometry. Interleukin (IL)-6 and IL-8 mRNA levels were assessed by real-time qRT-PCR and their release was evaluated by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 and 5-lipooxygenase (LOX) protein expression and phosphorylation of p65 and signal transducer and activator of transcription (STAT)-3 were determined by Western blot analysis.Expression of Ob-Rb was detected in human sebaceous glands and in cultured human SZ95 sebocytes. The treatment of SZ95 sebocytes with leptin led to enlarged intracellular lipid bodies, increased ratios of unsaturated/saturated fatty acids and decreased vitamin E levels. Further supporting a proinflammatory role, leptin induced COX-2 and 5-LOX expression in SZ95 sebocytes and augmented the production of IL-6 and IL-8 cytokines. On leptin treatment, the STAT-3 and nuclear factor-κB pathways were activated, indicating that these known leptin signalling pathways are active in human sebocytes.Our findings suggest that leptin signalling may be involved in the proinflammatory regulation of sebaceous lipid metabolism and the induction of inflammatory enzymes and cytokines.