tbuckley/cabot-search huggingface dataset:
Subcutaneous Use of a Fast-Acting Insulin Analog
Authors: Thais Della Manna, Leandra Steinmetz, Paula R. Campos, Sylvia C.L. Farhat, Cláudio Schvartsman, Hilton Kuperman, Nuvarte Setian, Durval Damiani
Journal: Diabetes Care (2005)

OBJECTIVE—To look for technical simplification and economic efficiency in the treatment of pediatric diabetic ketoacidosis (DKA) with subcutaneous use of the fast-acting insulin analog (lispro) and compare its use with regular intravenous insulin treatment. RESEARCH DESIGN AND METHODS—In this controlled clinical trial from June 2001 to June 2003, we randomized 60 episodes of DKA with a blood glucose level ≥16.6 mmol/l (300 mg/dl), venous pH &amp;lt;7.3 and/or bicarbonate &amp;lt;15 mmol/l, or ketonuria greater than ++. Of the 60 episodes, 30 were treated with subcutaneous lispro (0.15 units/kg) given every 2 h (lispro group) and the other 30 cases received continuous intravenous regular insulin (0.1 unit · kg−1 · h−1; CIRI group). Volume deficit was repaired with 10-ml/kg aliquots of 0.9% sodium chloride. Laboratory monitoring included hourly bedside capillary glucose, venous blood gas, β-hydroxybutyrate, and electrolytes. Plasma blood glucose levels were measured on admission, 2 h after admission, when capillary blood glucose reached ≤13.8 mmol/l (250 mg/dl), and 6, 12, and 24 h thereafter. RESULTS—Capillary glucose levels decreased by 2.9 and 2.6 mmol · l−1 · h−1 in the lispro and CIRI groups, respectively, but blood glucose fluctuated at different time intervals. In the CIRI group, metabolic acidosis and ketosis resolved in the first 6-h period after capillary glucose reached 13.8 mmol/l, whereas in the lispro group, they resolved in the next 6-h interval; however, both groups met DKA recovery criteria without complications. CONCLUSIONS—DKA treatment with a subcutaneous fast-acting insulin analog represents a cost-effective and technically simplified procedure that precludes intensive care unit admission.
A Genetic Approach to Visualization of Multisynaptic Neural Pathways Using Plant Lectin Transgene
Authors: Yoshihiro Yoshihara, Takeo Mizuno, Masakiyo Nakahira, Miwa Kawasaki, Yasuyoshi Watanabe, Hiroyuki Kagamiyama, Kou-ichi Jishage, Otoya Ueda, Hiroshi Suzuki, Katsuhiko Tabuchi, Kazunobu Sawamoto, Hideyuki Okano, Tetsuo Noda, Kensaku Mori
Journal: Neuron (1999)
Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study
Authors: Kristin J. Redmond, E. Mark Mahone, Stephanie Terezakis, Omar Ishaq, Eric Ford, Todd McNutt, Lawrence Kleinberg, Kenneth J. Cohen, Moody Wharam, Alena Horska
Journal: Neuro-Oncology (2013)

Neurocognitive toxicity from radiation therapy (RT) for brain tumors may be related to damage to neural progenitor cells that reside in the subventricular zone and hippocampus. This prospective study examines the relationship between RT dose to neural progenitor cell niches, temporal lobes, and cerebrum and neurocognitive dysfunction following cranial irradiation. Standardized assessments of motor speed/dexterity, verbal memory, visual perception, vocabulary, and visuospatial working memory were conducted in 19 pediatric patients receiving cranial RT and 55 controls at baseline and 6, 15, and 27 months following completion of RT. Prescription doses ranged from 12 Gy to 59.4 Gy. Linear mixed effects regression model analyses were used to examine the relationships among neuropsychological performance, age, and radiation dose to the subventricular zone, hippocampus, temporal lobes, and cerebrum. Performance on all neuropsychological tests, except vocabulary, was significantly reduced in patients relative to controls, particularly among younger children. Performance on motor speed/dexterity decreased with increasing dose to hippocampus (P < .05) and temporal lobes (P < .035). There was also a significant relationship between (i) reduced performance on verbal learning and increasing dose to the cerebrum (P = .022) and (ii) reduced performance on visual perception and increasing dose to the left temporal lobe (P = .038). There was no association between radiation dose to evaluated structures and performance on vocabulary or visuospatial working memory. These prospective data demonstrate a significant association between increasing RT dose to hippocampus and temporal lobes and decline in neurocognitive skills following cranial irradiation. These findings have important implications for trials, including RTOG 0933 (hippocampal-sparing whole brain radiation therapy for brain metastases).
Exposure to thoracic dust, airway symptoms and lung function in cement production workers
Authors: K-C. Nordby, A.K.M. Fell, H. Notø, W. Eduard, M. Skogstad, Y. Thomassen, A. Bergamaschi, J. Kongerud, H. Kjuus
Journal: European Respiratory Journal (2011)

Cement dust exposure has previously been associated with airway symptoms and ventilatory impairment. The aim of the present study was to examine lung function and airway symptoms among employees in different jobs and at different levels of exposure to thoracic dust in the cement production industry. At the start of a 4-yr prospective cohort study in 2007, exposure to cement dust, symptoms and lung function were recorded cross-sectionally in 4,265 employees in 24 European cement plants. Bronchial exposure was assessed by 2,670 full-shift dust samples with cyclones collecting the thoracic aerosol fraction. A job exposure matrix was constructed by grouping dust concentrations according to job type and plant. Elevated odds ratios for symptoms and airflow limitation (range 1.2–2.6 in the highest quartile), but not for chronic bronchitis, were found in the higher quartiles of exposure compared with the lowest quartile. Forced expiratory volume in 1 s (FEV 1 ) showed an exposure–response relationship with a 270-mL deficit of FEV 1 (95% CI 190–300 mL) in the highest compared with the lowest exposure level. The results support the hypothesis that exposure to dust in cement production may lead to respiratory symptoms and airway obstruction.
Interior-branch and bootstrap tests of phylogenetic trees.
Authors: T Sitnikova, A Rzhetsky, M Nei
Journal: Molecular Biology and Evolution (1995)

We have compared statistical properties of the interior-branch and bootstrap tests of phylogenetic trees when the neighbor-joining tree-building method is used. For each interior branch of a predetermined topology, the interior-branch and bootstrap tests provide the confidence values, PC and PB, respectively, that indicate the extent of statistical support of the sequence cluster generated by the branch. In phylogenetic analysis these two values are often interpreted in the same way, and if PC and PB are high (say, > or = 0.95), the sequence cluster is regarded as reliable. We have shown that PC is in fact the complement of the P-value used in the standard statistical test, but PB is not. Actually, the bootstrap test usually underestimates the extent of statistical support of species clusters. The relationship between the confidence values obtained by the two tests varies with both the topology and expected branch lengths of the true (model) tree. The most conspicuous difference between PC and PB is observed when the true tree is starlike, and there is a tendency for the difference to increase as the number of sequences in the tree increases. The reason for this is that the bootstrap test tends to become progressively more conservative as the number of sequences in the tree increases. Unlike the bootstrap, the interior-branch test has the same statistical properties irrespective of the number of sequences used when a predetermined tree is considered. Therefore, the interior-branch test appears to be preferable to the bootstrap test as long as unbiased estimators of evolutionary distances are used. However, when the interior-branch is applied to a tree estimated from a given data set, PC may give an overestimate of statistical confidence. For this case, we developed a method for computing a modified version (P'C) of the PC value and showed that this P'C tends to give a conservative estimate of statistical confidence, though it is not as conservative as PB. In this paper we have introduced a model in which evolutionary distances between sequences follow a multivariate normal distribution. This model allowed us to study the relationships between the two tests analytically.
Type 2 Diabetes as a “Coronary Heart Disease Equivalent”
Authors: Auni Juutilainen, Seppo Lehto, Tapani Rönnemaa, Kalevi Pyörälä, Markku Laakso
Journal: Diabetes Care (2005)

OBJECTIVE—The purpose of this study was to investigate the hypothesis that coronary heart disease (CHD) mortality in diabetic subjects without prior evidence of CHD is equal to that in nondiabetic subjects with prior myocardial infarction or any prior evidence of CHD. RESEARCH DESIGN AND METHODS—During an 18-year follow-up total, cardiovascular disease (CVD) and CHD deaths were registered in a Finnish population-based study of 1,373 nondiabetic and 1,059 diabetic subjects. RESULTS—Adjusted multivariate Cox hazard models indicated that diabetic subjects without prior myocardial infarction, compared with nondiabetic subjects with prior myocardial infarction, had a hazard ratio (HR) of 0.9 (95% CI 0.6–1.5) for the risk of CHD death. The corresponding HR was 0.9 (0.5–1.4) in men and 1.9 (0.6 –6.1) in women. Diabetic subjects without any prior evidence of CHD (myocardial infarction or ischemic electrocardiogram [ECG] changes or angina pectoris), compared with nondiabetic subjects with prior evidence of CHD, had an HR of 1.9 (1.4–2.6) for CHD death (men 1.5 [1.0–2.2]; women 3.5 [1.8–6.8]). The results for CVD and total mortality were quite similar to those for CHD mortality. CONCLUSIONS—Diabetes without prior myocardial infarction and prior myocardial infarction without diabetes indicate similar risk for CHD death in men and women. However, diabetes without any prior evidence of CHD (myocardial infarction or angina pectoris or ischemic ECG changes) indicates a higher risk than prior evidence of CHD in nondiabetic subjects, especially in women.
Comparison of potency of inhaled beclomethasone and budesonide in New Zealand: retrospective study of computerised general practice records
Authors: B D Pethica, A Penrose, D MacKenzie, J Hall, R Beasley, M Tilyard
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective</b> To determine whether inhaled budesonide and beclomethasone are equipotent in the treatment of asthma in primary care. <b>Design</b> Retrospective study of computerised clinical records from 28 general practices in New Zealand. <b>Subjects</b> 5930 patients who received 16 725 prescriptions for inhaled budesonide or beclomethasone from 1 July 1994 to 30 June 1995. <b>Setting</b> General practices on the database of the Royal New Zealand College of General Practitioners Research Unit. Linked information from secondary care was available for a subset of the practices. <b>Main outcome measure</b> Mean prescribed daily inhaled corticosteroid dose. <b>Results</b> The daily prescribed dose was higher for patients receiving inhaled budesonide (mean 979 μg) than beclomethasone (mean 635 μg), a difference of 344 μg (95% confidence interval 313 to 376 μg). This difference was consistent in all age bands and with different types of inhalation device. Evidence of systematic prescribing of higher doses of budesonide to patients with more severe asthma was not found. <b>Conclusions</b> In primary care in New Zealand evidence suggests that budesonide is less potent than beclomethasone. Consideration of validated, established, and other possible markers of asthma severity did not support confounding by severity as a reason for the higher prescribed doses of budesonide. Pending further epidemiological evaluation, international asthma guidelines may need to be modified on the equivalence of inhaled corticosteroid doses. Furthermore, the comparative potency of newly developed inhaled steroids in clinical trials will need to be confirmed in appropriately designed epidemiological studies based in general practice. <h3>Key messages</h3> Important limitations of the randomised clinical trials comparing beclomethasone and budesonide have usually resulted in failure to detect differences in potency In this study using a computerised database in primary care inhaled budesonide had about two thirds of the potency of inhaled beclomethasone Asthma treatment guidelines may need to be modified concerning the dose equivalence of inhaled corticosteroids The relative potency of newly developed inhaled corticosteroids needs to be assessed in primary care
Activated Signal Transducer and Activator of Transcription (STAT) 3
Authors: Debra L. Silver, Honami Naora, Jinsong Liu, Wenjun Cheng, Denise J. Montell
Journal: Cancer Research (2004)

Abstract Constitutive activation of the Janus-activated kinase/signal transducer and activator of transcription (STAT) pathway promotes the proliferation and survival of cancer cells in culture and is associated with various cancers, including those of the ovary. We found that constitutively activated STAT3 levels correlated with aggressive clinical behavior of ovarian carcinoma specimens. Furthermore, inhibition of STAT3 reduced the motility of ovarian cancer cells in vitro. Surprisingly, we found that activated STAT3 localized not only to nuclei but also to focal adhesions in these cells. Activated STAT3 coimmunoprecipitated with phosphorylated paxillin and focal adhesion kinase and required paxillin and Src for its localization to focal adhesions. These results suggest that Janus-activated kinase/STAT signaling may contribute to ovarian cancer cell invasiveness.
Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-l-lysine
Authors: Luigi Fiume, Giuseppina Di Stefano, Corrado Busi, Alessandro Mattioli, Gian Battista Gervasi, Marco Bertini, Carlo Bartoli, Robeta Catalani, Giulio Caccia, Claudio Farina, Adriano Fissi, Osvaldo Pieroni, Robert Giuseppetti, Emilio D'Ugo, Maria Rapicetta
Journal: Journal of Hepatology (1997)
Increased Mutagen Sensitivity and DNA Damage in Pulmonary Arterial Hypertension
Authors: Chiara Federici, Kylie M. Drake, Christina M. Rigelsky, Lauren N. McNelly, Sirena L. Meade, Suzy A. A. Comhair, Serpil C. Erzurum, Micheala A. Aldred
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Pulmonary arterial hypertension (PAH) is a serious lung condition characterized by vascular remodeling in the precapillary pulmonary arterioles. We and others have demonstrated chromosomal abnormalities and increased DNA damage in PAH lung vascular cells, but their timing and role in disease pathogenesis is unknown.Objectives: We hypothesized that if DNA damage predates PAH, it might be an intrinsic cell property that is present outside the diseased lung.Methods: We measured DNA damage, mutagen sensitivity, and reactive oxygen species (ROS) in lung and blood cells from patients with Group 1 PAH, their relatives, and unrelated control subjects.Measurements and Main Results: Baseline DNA damage was significantly elevated in PAH, both in pulmonary artery endothelial cells (P < 0.05) and peripheral blood mononuclear cells (PBMC) (P < 0.001). Remarkably, PBMC from unaffected relatives showed similar increases, indicating this is not related to PAH treatments. ROS levels were also higher (P < 0.01). DNA damage correlated with ROS production and was suppressed by antioxidants (P < 0.001). PBMC from patients and relatives also showed markedly increased sensitivity to two chemotherapeutic drugs, bleomycin and etoposide (P < 0.001). Results were consistent across idiopathic, heritable, and associated PAH groups.Conclusions: Levels of baseline and mutagen-induced DNA damage are intrinsically higher in PAH cells. Similar results in PBMC from unaffected relatives suggest this may be a genetically determined trait that predates disease onset and may act as a risk factor contributing to lung vascular remodeling following endothelial cell injury. Further studies are required to fully characterize mutagen sensitivity, which could have important implications for clinical management.
Genomewide Single Nucleotide Polymorphism Microarray Mapping in Basal Cell Carcinomas Unveils Uniparental Disomy as a Key Somatic Event
Authors: Muy-Teck Teh, Diana Blaydon, Tracy Chaplin, Nicola J. Foot, Spyros Skoulakis, Manoj Raghavan, Catherine A. Harwood, Charlotte M. Proby, Michael P. Philpott, Bryan D. Young, David P. Kelsell
Journal: Cancer Research (2005)

Abstract Basal cell carcinoma is the most common human cancer with increasing incidence reported worldwide. Despite the aberrant signaling role of the Hedgehog pathway, little is known about the genetic mechanisms underlying basal cell carcinomas. Towards a better understanding of global genetic events, we have employed the Affymetrix Mapping 10K single nucleotide polymorphism (SNP) microarray technique for “fingerprinting” genomewide allelic imbalance in 14 basal cell carcinoma–blood pair samples. This rapid high-resolution SNP genotyping technique has revealed a somatic recombination event–uniparental disomy, leading to a loss of heterozygosity (LOH), as a key alternative genetic mechanism to allelic imbalances in basal cell carcinomas. A highly conserved LOH region at 9q21-q31 was found in 13 of 14 (93%) basal cell carcinomas. Further statistical and fluorescence in situ hybridization analyses confirmed that the 9q LOH was a result of uniparental disomy in 5 of 13 (38%) basal cell carcinomas. De novo mutations in the Patched 1 gene (PTCH) were found in 9 of 13 (69%) basal cell carcinomas with 9q LOH. A second important locus, containing LOH at 6q23-q27 was found in 5 of 14 (36%) basal cell carcinomas, suggesting that the presence of an additional putative tumor suppressor gene may be contributing to basal cell carcinoma development. This study shows that the rate of 9q LOH in basal cell carcinomas has been previously underestimated. Furthermore, we provide the first evidence that uniparental disomy due to somatic recombination constitutes one of the mechanisms of LOH in basal cell carcinoma tumorigenesis.
Myc interacts with Max and Miz1 to repress C/EBPδ promoter activity and gene expression
Authors: Junling Si, Xueyan Yu, Yingjie Zhang, James W. DeWille
Journal: Molecular Cancer (2010)

"Loss of function" alterations in CCAAT/Enhancer Binding Proteindelta (C/EBPdelta) have been reported in a number of human cancers including breast, prostate and cervical cancer, hepatocellular carcinoma and acute myeloid leukemia. C/EBPdelta gene transcription is induced during cellular quiescence and repressed during active cell cycle progression. C/EBPdelta exhibits tumor suppressor gene properties including reduced expression in cancer cell lines and tumors and promoter methylation silencing. We previously reported that C/EBPdelta expression is inversely correlated with c-Myc (Myc) expression. Aberrant Myc expression is common in cancer and transcriptional repression is a major mechanism of Myc oncogenesis. A number of tumor suppressor genes are targets of Myc transcriptional repression including C/EBPalpha, p15INK4, p21CIP1, p27KIP1 and p57KIP2. This study investigated the mechanisms underlying Myc repression of C/EBPdelta expression.Myc represses C/EBPdelta promoter activity in nontransformed mammary epithelial cells in a dose-dependent manner that requires Myc Box II, Basic Region and HLH/LZ domains. Chromatin Immunoprecipitation (ChIP) assays demonstrate that Myc, Miz1 and Max are associated with the C/EBPdelta promoter in proliferating cells, when C/EBPdelta expression is repressed. EMSAs demonstrate that Miz1 binds to a 30 bp region (-100 to -70) of the C/EBPdelta promoter which contains a putative transcription initiator (Inr) element. Miz1 functions exclusively as a repressor of C/EBPdelta promoter activity. Miz1 siRNA expression or expression of a Miz1 binding deficient Myc (MycV394D) construct reduces Myc repression of C/EBPdelta promoter activity. Max siRNA expression, or expression of a Myc construct lacking the HLH/LZ (Max interacting) region, also reduces Myc repression of C/EBPdelta promoter activity. Miz1 and Max siRNA treatments attenuate Myc repression of endogenous C/EBPdelta expression. Myc Box II interacting proteins RuvBl1 (Pontin, TIP49) and RuvBl2 (Reptin, TIP48) enhances Myc repression of C/EBPdelta promoter activity.Myc represses C/EBPdelta expression by associating with the C/EBPdelta proximal promoter as a transient component of a repressive complex that includes Max and Miz1. RuvBl1 and RuvBl2 enhance Myc repression of C/EBPdelta promoter activity. These results identify protein interactions that mediate Myc repression of C/EBPdelta, and possibly other tumor suppressor genes, and suggest new therapeutic targets to block Myc transcriptional repression and oncogenic function.
Effect of in vitro gastric and duodenal digestion on the allergenicity of grape lipid transfer protein
Authors: Emilia Vassilopoulou, Neil Rigby, F. Javier Moreno, Laurian Zuidmeer, Jaap Akkerdaas, Ioannis Tassios, Nikos G. Papadopoulos, Photini Saxoni-Papageorgiou, Ronald van Ree, Clare Mills
Journal: Journal of Allergy and Clinical Immunology (2006)
The Long-Term Outcome of Patients with IgA Nephropathy Treated with Fish Oil in a Controlled Trial
Authors: JAMES V. DONADIO, JOSEPH P. GRANDE, ERIK J. BERGSTRALH, RICHARD A. DART, TIMOTHY S. LARSON, DOROTHY C. SPENCER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. It was reported previously that dietary fish oil supplementation retarded the progression of renal disease in patients with IgA nephropathy in a multicenter, placebo-controlled, randomized, 2-yr clinical trial. The aim of this study was to determine the long-term influence of fish oil treatment on renal progression in observations on the study cohort of 106 patients extending beyond the 2-yr trial. Renal function was assessed by serial serum creatinine and 24-h urine protein measurements. Vital, end-stage renal disease (ESRD), and BP status and treatment beyond completion of the 2-yr trial were determined. As in the trial, the primary end point was an increase of 50% or more in the serum creatinine, and the secondary end point was ESRD. After a mean follow-up of 6.4 yr, 46 patients—17 in the fish oil group versus 29 in the placebo group—reached the primary end point ( P = 0.002), and 27 patients—eight in the fish oil group versus 19 in the placebo group—developed ESRD ( P = 0.009). At the end of the 2-yr trial, 75 patients (45 fish oil, 30 placebo) remained at risk for the primary end point. This is also when the double-blind part of the trial ended, allowing physicians to stop supplements, switch original placebo-assigned patients to fish oil, and continue fish oil in original fish oil-assigned patients. A significantly greater number of nonsupplemented placebo patients developed the primary end point ( P = 0.02) and ESRD ( P = 0.003) compared with long-term supplemented fish oil patients. Conversely, more fish oil-supplemented patients had stable renal function than nonsupplemented patients ( P = 0.02). By intention, BP control, primarily treated with angiotensin-converting enzyme inhibition, was equal in the fish oil and placebo groups. Proteinuria was modestly reduced in both groups. It is concluded that early and prolonged treatment with fish oil slows renal progression for high-risk patients with IgA nephropathy.