tbuckley/cabot-search huggingface dataset:
Glycogen Storage Disease Type III (Glycogen Debranching Enzyme Deficiency): Correlation of Biochemical Defects with Myopathy and Cardiomyopathy
Authors: R A Coleman, H S Winter, B Wolf, J M Gilchrist, Y T Chen
Journal: Annals of Internal Medicine (1992)

Objective: To determine whether a specific subtype of glycogen storage disease type III is associated with myopathy and cardiomyopathy. Design: Case series. Setting: Three referral medical centers. Patients: All patients with glycogen storage disease type III who were followed in 1990 and for whom both immunoblot analysis and clinical data were available. Main Outcome Measures: Evaluation for myopathy and cardiomyopathy included determinations of serum creatine kinase activity; muscle strength testing; ischemic exercise testing; nerve conduction studies; and electromyographic, electrocardiographic, and echocardiographic studies. Results: Three patients with deficient debranching enzyme activity and deficient immunoreactive material in liver but normal debranching enzyme activity in muscle (glycogen storage disease IIIb) had no clinical evidence of myopathy or cardiomyopathy. Serum creatine kinase activity, muscle strength, ischemic exercise testing, electrocardiograms, and echocardiograms were normal in these patients. These studies and electromyograms were abnormal in seven patients with total debranching enzyme deficiency and an absence of immunoreactive material in both liver and muscle (glycogen storage disease IIIa) and in three patients who had debranching enzyme transferase deficiency but normal glucosidase activity in both liver and muscle (glycogen storage disease IIId). All 10 of these patients had progressive myopathy, and 6 had progressive cardiomyopathy. Conclusion: Clinical features of glycogen storage disease type III correlate with the particular biochemical defect seen with the disorder. Assessments of debranching enzyme or debranching enzyme transferase activity in muscle can be used to predict whether patients with glycogen storage disease type III will develop myopathy and cardiomyopathy.
Ectopic Runx2 Expression in Mammary Epithelial Cells Disrupts Formation of Normal Acini Structure: Implications for Breast Cancer Progression
Authors: Jitesh Pratap, Karen M. Imbalzano, Jean M. Underwood, Nathalie Cohet, Karthiga Gokul, Jacqueline Akech, Andre J. van Wijnen, Janet L. Stein, Anthony N. Imbalzano, Jeffrey A. Nickerson, Jane B. Lian, Gary S. Stein
Journal: Cancer Research (2009)

The transcription factor Runx2 is highly expressed in breast cancer cells compared with mammary epithelial cells and contributes to metastasis. Here we directly show that Runx2 expression promotes a tumor cell phenotype of mammary acini in three-dimensional culture. Human mammary epithelial cells (MCF-10A) form polarized, growth-arrested, acini-like structures with glandular architecture. The ectopic expression of Runx2 disrupts acini formation, and electron microscopic ultrastructural analysis revealed the absence of lumens. Characterization of the disrupted acini structures showed increased cell proliferation (Ki-67 positive cells), decreased apoptosis (Bcl-2 induction), and loss of basement membrane formation (absence of beta(4) integrin expression). In complementary experiments, inhibition of Runx2 function in metastatic MDA-MB-231 breast cancer cells by stable expression of either short hairpin RNA-Runx2 or a mutant Runx2 deficient in subnuclear targeting resulted in reversion of acini to more normal structures and reduced tumor growth in vivo. These novel findings provide direct mechanistic evidence for the biological activity of Runx2, dependent on its subnuclear localization, in promoting early events of breast cancer progression and suggest a molecular therapeutic target.
Performance of mechanical ventilators at the patient's home: a multicentre quality control study
Authors: R Farre
Journal: Thorax (2006)

<b>Background:</b> Quality control procedures vary considerably among the providers of equipment for home mechanical ventilation (HMV). <b>Methods:</b> A multicentre quality control survey of HMV was performed at the home of 300 patients included in the HMV programmes of four hospitals in Barcelona. It consisted of three steps: (1) the prescribed ventilation settings, the actual settings in the ventilator control panel, and the actual performance of the ventilator measured at home were compared; (2) the different ventilator alarms were tested; and (3) the effect of differences between the prescribed settings and the actual performance of the ventilator on non-programmed readmissions of the patient was determined. <b>Results:</b> Considerable differences were found between actual, set, and prescribed values of ventilator variables; these differences were similar in volume and pressure preset ventilators. The percentage of patients with a discrepancy between the prescribed and actual measured main ventilator variable (minute ventilation or inspiratory pressure) of more than 20% and 30% was 13% and 4%, respectively. The number of ventilators with built in alarms for power off, disconnection, or obstruction was 225, 280 and 157, respectively. These alarms did not work in two (0.9%), 52 (18.6%) and eight (5.1%) ventilators, respectively. The number of non-programmed hospital readmissions in the year before the study did not correlate with the index of ventilator error. <b>Conclusions:</b> This study illustrates the current limitations of the quality control of HMV and suggests that improvements should be made to ensure adequate ventilator settings and correct ventilator performance and ventilator alarm operation.
Pharmacogenetic analyses of hematotoxicity in advanced gastric cancer patients receiving biweekly fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: E. Goekkurt, S.-E. Al-Batran, U. Mogck, C. Pauligk, J.T. Hartmann, M. Kramer, E. Jaeger, G. Ehninger, J. Stoehlmacher
Journal: Annals of Oncology (2008)
Air pollution and multiple acute respiratory outcomes
Authors: Annunziata Faustini, Massimo Stafoggia, Paola Colais, Giovanna Berti, Luigi Bisanti, Ennio Cadum, Achille Cernigliaro, Sandra Mallone, Corrado Scarnato, Francesco Forastiere
Journal: European Respiratory Journal (2013)

Short-term effects of air pollutants on respiratory mortality and morbidity have been consistently reported but usually studied separately. To more completely assess air pollution effects, we studied hospitalisations for respiratory diseases together with out-of-hospital respiratory deaths. A time-stratified case-crossover study was carried out in six Italian cities from 2001 to 2005. Daily particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10)) and nitrogen dioxide (NO2) associations with hospitalisations for respiratory diseases (n = 100 690), chronic obstructive pulmonary disease (COPD) (n = 38 577), lower respiratory tract infections (LRTI) among COPD patients (n = 9886) and out-of-hospital respiratory deaths (n = 5490) were estimated for residents aged ≥35 years. For an increase of 10 μg·m(-3) in PM10, we found an immediate 0.59% (lag 0-1 days) increase in hospitalisations for respiratory diseases and a 0.67% increase for COPD; the 1.91% increase in LRTI hospitalisations lasted longer (lag 0-3 days) and the 3.95% increase in respiratory mortality lasted 6 days. Effects of NO2 were stronger and lasted longer (lag 0-5 days). Age, sex and previous ischaemic heart disease acted as effect modifiers for different outcomes. Analysing multiple rather than single respiratory events shows stronger air pollution effects. The temporal relationship between the pollutant increases and hospitalisations or mortality for respiratory diseases differs.
Effect of changing dietary sodium on the airway response to histamine.
Authors: P G Burney, J E Neild, C H Twort, S Chinn, T D Jones, W D Mitchell, C Bateman, I R Cameron
Journal: Thorax (1989)

The airway response to histamine has been shown to be related to the 24 hour urinary excretion of sodium. To assess whether this relation is likely to represent a direct causal association a randomised double blind crossover trial of slow sodium (80 mmol/day) was compared with placebo in 36 subjects having a low sodium diet. The dose of histamine causing a 20% fall in FEV1 (PD20) was 1.51 doubling doses lower when the men were taking sodium than when they were taking placebo (p less than 0.05). On the basis of PD10 values, the difference in men was 1.66 doubling doses of histamine (p less than 0.05). There was no corresponding effect in women. Regressing PD10 against urinary excretion of electrolytes with data from the two occasions during the trial and the measurements made before the trial showed a significant association with sodium excretion after allowance had been made for any effect associated with potassium or creatinine excretion, the latter being a marker of the completeness of the urine collection. Again there was no corresponding effect among women. These findings are compatible with the differences in regional mortality data for England and Wales, which show a relation between asthma mortality and regional per person purchases of table salt for men but not for women.
ALKBH3 Contributes to Survival and Angiogenesis of Human Urothelial Carcinoma Cells through NADPH Oxidase and Tweak/Fn14/VEGF Signals
Authors: Keiji Shimada, Tomomi Fujii, Kazutake Tsujikawa, Satoshi Anai, Kiyohide Fujimoto, Noboru Konishi
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The role and function of a novel human AlkB homologue, ALKBH3, in human urothelial carcinoma development were examined. Experimental design: Biologic roles of ALKBH3 were examined by gene silencing analysis using in vitro and in vivo siRNA transfection. Immunohistochemical analyses of ALKBH3 and the related molecules using human bladder cancer samples were conducted to estimate the association with clinicopathologic or prognostic parameters. Results: ALKBH3 knockdown induced cell cycle arrest at the G1 phase through downregulation of NAD(P)H oxidase-2 (NOX-2)–mediated generation of reactive oxygen species (ROS). ALKBH3 knockdown reduced VEGF expression by reducing expression of tumor necrosis factor-like weak inducer of apoptosis (Tweak) and its receptor, fibroblast growth factor-inducible 14 (Fn14). Silencing of ALKBH3 or Tweak significantly suppressed invasion and angiogenesis of urothelial carcinoma in vivo as assessed both by a chorioallantoic membrane assay and in an orthotopic mouse model. Interestingly, not only urothelial carcinoma cells but also vascular endothelial cells within cancer foci expressed Fn14, which was strongly reduced by ALKBH3 and Tweak knockdown in vivo, suggesting that ALKBH3-dependent expression of Tweak stabilizes Fn14. Immunohistochemical examination showed high expression of ALKBH3, Tweak, and Fn14 in urothelial carcinoma, especially in high-grade, superficially, and deeply invasive carcinomas; moreover, Fn14-positive vessel counts within cancer foci were increased in invasive phenotypes. Conclusions: ALKBH3 contributes to development of urothelial carcinomas by accelerating their survival, angiogenesis, and invasion through NOX-2-ROS and Tweak/Fn14-VEGF signals. Clin Cancer Res; 18(19); 5247–55. ©2012 AACR.
Evolution of satellite DNAs from the genus Palorus--experimental evidence for the "library" hypothesis
Authors: N Mestrović, M Plohl, B Mravinac, D Ugarković
Journal: Molecular Biology and Evolution (1998)

Satellite DNA profiles have been characterized in the congeneric species Palorus ratzeburgii, Palorus subdepressus, Palorus genalis, and Palorus ficicola (Coleoptera, Insecta), each of which contains a single, A + T-rich satellite DNA comprising a considerable portion of the genome (20%-40%). These satellites exhibit insignificant mutual sequence similarity. Using PCR assay, it has been shown that all four sequences are present in each of the tested Palorus species: one of them is amplified into a high copy number or a major satellite, while the three others are in the form of low-copy-number repeats estimated to make up approximately 0.05% of the genome. Each of the four satellites is interspecifically high conserved concerning the sequence, monomer length, and tandem repeat organization. Major, as well as low-copy-number, satellites are colocalized in the regions of pericentromeric heterochromatin on all chromosomes of the complement. The low-copy-number satellites are dispersed between the large arrays of the major satellite over the whole heterochromatic block. Our results explain satellite DNA evolution, confirming the hypothesis that related species share a "library" of conserved satellite sequences, some of which could be amplified into a major satellite. Due to the evolutionary dynamics of satellite DNAs, the content of the "library" is variable; the elimination of some sequences parallels the creation of the new ones. Quantitative changes in satellite DNAs, induced by occasional amplification of satellite repeat from the "library", could possibly occur in the course of the speciation process, thus forming a species-specific profile of satellite DNAs.
A prospective controlled study comparing brush and bile exfoliative cytology for diagnosing bile duct strictures.
Authors: T Kurzawinski, A Deery, J Dooley, R Dick, K Hobbs, B Davidson
Journal: Gut (1992)

Imaging of biliary strictures may suggest malignancy but cytology can provide a tissue diagnosis. The aim of this study is to compare the diagnostic value of brush cytology and bile cytology. Thirty two patients (20 males, 12 females, median age 66 years, range 31-84) with biliary strictures at endoscopic retrograde cholangio pancreatography (24) or percutaneous transhepatic cholangiography (8) had bile cytology and brush cytology. Brushings were taken using a modified Geenan cytology brush (6 Fr gauge, Wilson Cook) passed alongside a guide wire placed through the stricture. Bile was aspirated after insertion of an internal/external catheter or an endoprosthesis. Bile and brushings were examined by one experienced cytologist (AD) and was reported as positive or negative for malignant cells. Twenty nine patients had malignant strictures. Sixteen were confirmed by histology and 13 had malignancy suggested by clinical follow up. Three patients had resection of histologically benign strictures. The overall sensitivity of brush cytology (17 of 29 positive, 59%) was significantly greater than bile cytology (seven of 29 positive, 24%) (p < 0.01) as was the diagnostic accuracy (63 v 31%, p < 0.01). None of the patients had positive bile cytology with negative brush cytology. There were no procedure related complications and the average sampling time once the guide wire had been inserted was less than five minutes. It is concluded that brush cytology is more sensitive than bile cytology and with the technique described is safe and rapid.
Reduced Reperfusion–Induced Ins(1,4,5)P <sub>3</sub> Generation and Arrhythmias in Hearts Expressing Constitutively Active α <sub>1B</sub> -Adrenergic Receptors
Authors: Sharon N. Harrison, Dominic J. Autelitano, Bing Hui Wang, Carmelo Milano, Xiao-Jun Du, Elizabeth A. Woodcock
Journal: Circulation Research (1998)

Abstract —Reperfusion of globally ischemic rat hearts causes the generation of inositol(1,4,5) tris phosphate [Ins(1,4,5)P 3 ] and the initiation of arrhythmias. These responses are mediated by α 1 -adrenergic receptors (ARs), but the subtype of receptor involved has not been identified. Under normoxic conditions, hearts from transgenic animals expressing constitutively active α 1B -ARs in heart (α 1B -constitutively active mutant [CAM]) showed higher [ 3 H] inositol phosphate responses to norepinephrine (2.3-fold) than hearts from nontransgenic animals (α 1B -WT) (1.6-fold). α 1B -WT hearts responded to 2 minutes of reperfusion after 20 minutes of global ischemia by generation of Ins(1,4,5)P 3 (5301±1310 to 11 413±1597 CPM/g tissue; mean±SEM; n=6; P &lt;0.01 in [ 3 H] labeling studies and 3.8±0.2 to 6.3±0.6 nmol/g by mass analysis, n=6; P &lt;0.05). In contrast to findings in normoxia, hearts from α 1B -CAM animals showed no Ins(1,4,5)P 3 response in early reperfusion. In parallel studies, α 1B -WT hearts developed ventricular tachycardia and ventricular premature beats (VPB) during 5 minutes of reperfusion after 20 minutes of ischemia. The incidence of these arrhythmias was reduced in the α 1B -CAM hearts (95% to 62% for VPB and 47% to 12% for ventricular tachycardia; both P &lt;0.05). The resistance of the α 1B -CAM hearts was not due to α 1B -AR–mediated preconditioning, as the Ins(1,4,5)P 3 response to thrombin receptor activation during reperfusion was not different between the 2 groups. To investigate the possibility of reduced α 1A -receptor activity in the α 1B -CAM hearts, expression of the mRNA for α 1A - and α 1B -receptors was measured. α 1B -WT hearts contained mRNA for both receptor subtypes, but the levels of α 1B -receptor mRNA were 5-fold higher than α 1A -receptor mRNA. α 1B -CAM hearts contained very high levels of α 1B -receptor mRNA (26-fold increase), but the expression of mRNA for the α 1A -receptors (0.141±0.035 amol/μg RNA; mean±SEM; n=6) was reduced by 50% relative to α 1B -WT controls (0.276±0.046 amol/μg RNA; n=6; P &lt;0.01). The reduction in arrhythmogenic and Ins(1,4,5)P 3 responses in α 1B -CAM hearts provides evidence that these response are not mediated by α 1B -receptors.
Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist
Authors: Hal E. Broxmeyer, Christie M. Orschell, D. Wade Clapp, Giao Hangoc, Scott Cooper, P. Artur Plett, W. Conrad Liles, Xiaxin Li, Barbara Graham-Evans, Timothy B. Campbell, Gary Calandra, Gary Bridger, David C. Dale, Edward F. Srour
Journal: The Journal of Experimental Medicine (2005)

Improving approaches for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is clinically important because increased numbers of these cells are needed for enhanced transplantation. Chemokine stromal cell derived factor-1 (also known as CXCL12) is believed to be involved in retention of HSCs and HPCs in bone marrow. AMD3100, a selective antagonist of CXCL12 that binds to its receptor, CXCR4, was evaluated in murine and human systems for mobilizing capacity, alone and in combination with granulocyte colony-stimulating factor (G-CSF). AMD3100 induced rapid mobilization of mouse and human HPCs and synergistically augmented G-CSF-induced mobilization of HPCs. AMD3100 also mobilized murine long-term repopulating (LTR) cells that engrafted primary and secondary lethally-irradiated mice, and human CD34(+) cells that can repopulate nonobese diabetic-severe combined immunodeficiency (SCID) mice. AMD3100 synergized with G-CSF to mobilize murine LTR cells and human SCID repopulating cells (SRCs). Human CD34(+) cells isolated after treatment with G-CSF plus AMD3100 expressed a phenotype that was characteristic of highly engrafting mouse HSCs. Synergy of AMD3100 and G-CSF in mobilization was due to enhanced numbers and perhaps other characteristics of the mobilized cells. These results support the hypothesis that the CXCL12-CXCR4 axis is involved in marrow retention of HSCs and HPCs, and demonstrate the clinical potential of AMD3100 for HSC mobilization.
The Preservative Agency of Lowered Vitality
Authors: J. M. Fothergill
Journal: BMJ (1871)

Substance produced by the mere small addition of some one element; and all that we can say is, that the molecular rearrangement brings about a physical transformation.Chemical science is, in fact, a mere record of what is observed ; it does not explain the essential character of the phenomena.Much more is this the case when we have to deal with the processes which underlie life.If we attempt to investigate vital action, we are overwhelmed by the difficulties of the problem.CLINICAL RECORDS.
Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis
Authors: Wei Zhao, Merina Varghese, Shrishailam Yemul, Yong Pan, Alice Cheng, Paul Marano, Sadiq Hassan, Prashant Vempati, Fei Chen, Xianjuan Qian, Giulio M Pasinetti
Journal: Molecular Neurodegeneration (2011)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of mitochondrial biogenesis and oxidative metabolism.In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α). Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord.Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy.
Do Urbanicity and Familial Liability Coparticipate in Causing Psychosis?
Authors: Jim van Os, Manon Hanssen, Maarten Bak, Rob V Bijl, Wilma Vollebergh
Journal: American Journal of Psychiatry (2003)

The urban environment and familial liability are risk factors for psychotic illness, but it is not known whether a biological synergism exists between these two proxy causes.The amount of biological synergism between familial liability (defined as a family history of delusions and/or hallucinations necessitating psychiatric treatment) and a five-level rating of population density of place of residence was estimated from the additive statistical interaction in a general population risk set of 5,550 individuals.Both the level of urbanicity (adjusted summary odds ratio=1.57, 95% CI=1.30-1.89) and familial liability (adjusted odds ratio=4.59, 95% CI=2.41-8.74) increased the risk for psychotic disorder, independently of each other. However, the effect of urbanicity on the additive scale was much larger for individuals with evidence of familial liability (risk difference=2.58%) than in those without familial liability (risk difference=0.40%). An estimated 60%-70% of the individuals exposed to both urbanicity and familial liability had developed psychotic disorder because of the synergistic action of the two proxy causes.Given that familial clustering of psychosis is thought to reflect the effect of shared genes, the findings support a mechanism of gene-environment interaction in the causation of psychosis.