tbuckley/cabot-search huggingface dataset:
Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes
Authors: Katharine C Pike, Hazel M Inskip, Sian Robinson, Jane S Lucas, Cyrus Cooper, Nicholas C Harvey, Keith M Godfrey, Graham Roberts
Journal: Thorax (2012)

<h3>Background</h3> Studies exploring the relationship between prenatal vitamin D exposure and childhood asthma have yielded conflicting results. Higher vitamin D intake during pregnancy has been shown to lower the risk of childhood wheeze, yet a study of maternal late-pregnancy serum 25-hydroxyvitamin D suggested higher serum concentrations may be associated with increased childhood asthma. <h3>Objective</h3> To assess the relationship between mothers9 serum 25-hydroxyvitamin D status and asthma and wheeze phenotypes in their children at age 6 years. Also to explore the relationship between maternal 25-hydroxyvitamin D status and objective measures of childhood atopy and lung function. <h3>Methods</h3> Serum 25-hydroxyvitamin D was measured at 34 weeks9 gestation in the mothers of 860 children born at term. Wheeze was classified as either transient or persistent/late using questionnaire data collated from 6, 12, 24 and 36 months and 6 years. At 6 years spirometry was performed and atopic status was determined by skin prick testing, exhaled nitric oxide was measured in 451 children and bronchial hyperresponsiveness in 216 children. <h3>Results</h3> There were no significant associations between maternal late-pregnancy 25-hydroxyvitamin D status and either asthma or wheeze at age 6 years. Maternal vitamin D status was not associated with transient or persistent/late wheeze; no significant association was found between persistent/late wheeze when subdivided according to atopic status. No associations were found with skin sensitisation or lung function. <h3>Conclusions</h3> This study provides no evidence that exposure to higher concentrations of 25-hydroxyvitamin D in maternal serum during late pregnancy increases the risk of childhood asthma, wheeze or atopy.
High magnification chromoscopic colonoscopy or high frequency 20 MHz mini probe endoscopic ultrasound staging for early colorectal neoplasia: a comparative prospective analysis
Authors: D P Hurlstone
Journal: Gut (2005)

Successful endoscopic management of early colorectal cancer using endoscopic mucosal resection requires the mandatory prediction of invasive depth and lymph node metastasis. Previous data using the Nagata crypt types Vn(B)/(C) as clinical indicators of T2/N+ disease have shown low specificity (50%) with a tendency to over stage lesions. New mini probe ultrasound "through the scope" imaging permits staging of lesions proximal to the rectum using direct endoscopic visualisation.To compare the staging accuracy of the Nagata crypt type V with mini probe high frequency 20 MHz endoscopic ultrasound.Sixty two patients with a Paris type II flat cancer were imaged using magnification colonoscopy followed by 20/12.5 MHz ultrasound in a "back to back" design. Crystal violet staining (0.05%) at 100x magnification permitted Nagata crypt criteria to be defined. Submucosal deep invasion (sm3+) was defined at ultrasound by the presence or absence of a disrupted third sonographic layer. Predicted T0/1:N0 lesions were resected using endoscopic mucosal resection with the remaining referred for surgery. Ultrasound and magnification staging were then compared with the resected histopathological specimens.One patient was excluded from the study due to poor bowel preparation. Fifty two lesions from 52 patients therefore met inclusion criteria (12 sm1/13 sm2/27 sm3+). Ultrasound (20 MHz) was significantly more accurate for invasive depth staging compared with Nagata stage (p<0.0001) (overall accuracy 93% and 59%, respectively). The sensitivity for lymph node metastasis detection using ultrasound and magnification was 80% and 31%, respectively (p<0.001). The negative predictive value of ultrasound for invasive depth was better than that observed using magnification (88%/47%, respectively). The prevalence of nodal disease overall was 19% (10/52), with 80% (8/10) node positive lesions occurring in the sm3+ lesion group.High frequency 20 MHz ultrasound is superior to magnification alone when differentiating T1/2 disease with a high positive predictive value for sm3 differentiation. Sm3+ invasion was associated with nodal metastasis.
A STUDY OF AN EXTREMELY PURE PREPARATION OF RICIN
Authors: Cyrus W. Field
Journal: The Journal of Experimental Medicine (1910)

1. By following the method of Osborne, Mendel and Harris, we can obtain an extremely potent toxin from the castor bean. 2. It would appear, as a result of testing this preparation at the end of two and a half years, that the agglutinating function and the toxic function are two distinct properties. 3. This result is also borne out by the behavior under the electric current; either we are dealing with two different substances or else with a single substance with two distinct toxiphore groups, one of which is stable and the other labile.
Decreased Nucleotide Excision Repair Activity and Alterations of Topoisomerase IIα Are Associated with the<b><i>in Vivo</i></b>Resistance of a P388 Leukemia Subline to F11782, a Novel Catalytic Inhibitor of Topoisomerases I and II
Authors: Anna Kruczynski, Jean-Marc Barret, Benoît van Hille, Nathalie Chansard, Jackie Astruc, Yoann Menon, Carole Duchier, Laurent Créancier, Bridget T. Hill
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of the study was to investigate the mechanisms associated with antitumor activity and resistance to F11782, a novel dual catalytic inhibitor of topoisomerases with DNA repair-inhibitory properties. Experimental Design: For that purpose, an F11782-resistant P388 leukemia subline (P388/F11782) has been developed in vivo and characterized. Results: Weekly subtherapeutic doses of F11782 (10 mg/kg) induced complete resistance to F11782 after 8 weekly passages. This resistant P388/F11782 subline retained some in vivo sensitivity to several DNA-topoisomerase II and/or I complex-stabilizing poisons and showed marked collateral sensitivity to cisplatin, topotecan, colchicine, and Vinca alkaloids, while proving completely cross-resistant only to merbarone and doxorubicin. Therefore, resistance to F11782 did not appear to be associated with a classic multidrug resistance profile, as further reflected by unaltered drug uptake and no overexpression of resistance-related proteins or modification of the glutathione-mediated detoxification process. In vivo resistance to F11782 was, however, associated with a marked reduction in topoisomerase IIα protein (87%) and mRNA (50%) levels, as well as a diminution of the catalytic activity of topoisomerase IIα. In contrast, only minor reductions in topoisomerases IIβ and I levels were recorded. However, of major interest, nucleotide excision repair activity was decreased 3-fold in these P388/F11782 cells and was more specifically associated with a decreased (67%) level of XPG (human xeroderma pigmentosum group G complementing protein), an endonuclease involved in this DNA repair system. Conclusions: These findings suggest that both topoisomerase IIα and XPG are major targets of F11782 in vivo and further demonstrate the original mechanism of action of this novel compound.
Bird Mitochondrial Gene Order: Insight from 3 Warbler Mitochondrial Genomes
Authors: Tiratha Raj Singh, Ophir Shneor, Dorothée Huchon
Journal: Molecular Biology and Evolution (2008)

Two main gene orders exist in birds: the ancestral gene order and the remnant control region (CR) 2 gene order. These gene orders differ by the presence of 1 or 2 copies of the CR, respectively. Among songbirds, Oscines were thought to follow the ancestral gene order, with the exception of the lyrebird and Phylloscopus warblers. Here, we determined the complete mitochondrial genome sequence of 3 non-Phylloscopus warblers species and found that the blackcap (Sylvia atricapilla) and the reed warbler (Acrocephalus scirpaceus) have 2 almost identical copies of the CR, whereas the eastern orphean warbler (Sylvia crassirostris) follows the remnant CR 2 gene order. Our results contradict previous studies suggesting that Acrocephalus and most sylvioid warblers exhibit the ancestral gene order. We were able to trace this contradiction to a misidentification of gene order from polymerase chain reaction length determination. We thus suggest that passerine gene order evolution needs to be revised.
Localisation in Spinal Disease: Illustrated by (1) A Case of "Atrophic Paralysis" in an Adult; (2) A Case of Central Myelitis: (3) A Case of Alcoholic Paraplegia
Authors: J. Russell
Journal: BMJ (1878)

fulness and tenderness in the left ham; and then the femoral vein in Scarpa's triangle was tender, prominent, and distinctly hard, and the change could be traced beyond Poupart's ligament.But there was very little cedema of the limb.He was kept at rest in bed.The mischief in the left limb gradually subsided; but, in the course of the third week, he complained of his right thigh, and the right femoral vein was found to be tender, swollen, and evidently plugged also, up to or even above Poupart's ligament ; but no further mischief could be discovered in that limb.During the next week, he frequently complained of headache and heat, and his appetite failed, but there was no rise of pulse or of temperature.He was in the hospital nine weeks, during which time this evidence of fresh mischief slowly passed away; and, when he was discharged, hardly any abnormal condition could be discovered, either in the popliteal space or in Scarpa's triangle.To what cause should the mischief be attributed in the following case ?A young woman, aged 20, rather stout but of delicate aspect,
Molecular mechanism of the schedule-dependent synergistic interaction in EGFR-mutant non-small cell lung cancer cell lines treated with paclitaxel and gefitinib
Authors: Hua Cheng, She-Juan An, Song Dong, Yi-Fang Zhang, Xu-Chao Zhang, Zhi-Hong Chen, None Jian-Su, Yi-Long Wu
Journal: Journal of Hematology & Oncology (2011)

Abstract Background Chemotherapy combined concurrently with TKIs produced a negative interaction and failed to improve survival when compared with chemotherapy or TKIs alone in the treatment of non-small cell lung cancer (NSCLC). The present study investigated the sequence-dependent interaction between paclitaxel and gefitinib and clarified the underlying mechanism. Methods The effects on cell proliferation, EGFR signaling pathway, and TGFα expression were evaluated in a panel of human NSCLC cell lines harboring EGFR mutations with three different combination sequences: sequential treatment with paclitaxel followed by gefitinib (T→G), sequential treatment with gefitinib followed by paclitaxel (G→T), or concomitant treatment (T + G). Results The sequence-dependent anti-proliferative effects differed between EGFR-TKI-sensitive and -resistant cell lines carrying EGFR mutations. A synergistic anti-proliferative activity was obtained with paclitaxel treatment followed by gefitinib in all cell lines, with mean CI values of 0.63 in Hcc827, 0.54 in PC-9, 0.81 in PC-9/GR, and 0.77 in H1650 cells for the T→G sequence. The mean CI values for the G→T sequence were 1.29 in Hcc827, 1.16 in PC-9, 1.52 in PC-9/GR, and 1.5 in H1650 cells. The mean CI values for T+G concomitant treatment were 0.88 in Hcc827, 0.91 in PC-9, 1.05 in PC-9/GR, and 1.18 in H1650 cells. Paclitaxel produced a dose-dependent increase in EGFR phosphorylation. Paclitaxel significantly increased EGFR phosphorylation compared with that in untreated controls (mean differences: +50% in Hcc827, + 56% in PC-9, + 39% in PC-9/GR, and + 69% in H1650 cells; p &lt; 0.05). The T→G sequence produced significantly greater inhibition of EGFR phosphorylation compared with the opposite sequence (mean differences: -58% in Hcc827, -38% in PC-9, -35% in PC-9/GR, and -30% in H1650 cells; p &lt; 0.05). Addition of a neutralizing anti-TGFα antibody abolished paclitaxel-induced activation of the EGFR pathway in PC-9 and H1650 cells. Sequence-dependent TGFα expression and release are responsible for the sequence-dependent EGFR pathway modulation. Conclusion The data suggest that the sequence of paclitaxel followed by gefitinib is an appropriate treatment combination for NSCLC cell lines harboring EGFR mutations. Our results provide molecular evidence to support clinical treatment strategies for patients with lung cancer.
Phosphoinositide 3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells
Authors: Keun Hwa Choi, Jong-Eun Kim, Nu Ry Song, Joe Eun Son, Mun Kyung Hwang, Sanguine Byun, Jong Hun Kim, Ki Won Lee, Hyong Joo Lee
Journal: Cardiovascular Research (2009)

Abnormal migration and proliferation of human aortic smooth muscle cells (HASMCs) to the intima causes intimal thickening of the aorta, which is strongly related to the development of atherosclerosis. Previous studies have suggested that red wine polyphenols, particularly resveratrol, have great protective effects against cardiovascular diseases. Here, we compared the anti-atherosclerotic effect of piceatannol, a metabolite of resveratrol, and its underlying mechanisms. We demonstrated that piceatannol inhibited platelet-derived growth factor (PDGF)-BB-induced cell migration using a modified Boyden chamber assay and wound healing assay. Western blot analysis showed that PDGF-BB-induced phosphorylation of Akt, p70S6K, and p38 was inhibited by piceatannol, but not resveratrol. In vitro and ex vivo phosphoinositide 3-kinase (PI3K) assays demonstrated that piceatannol suppressed PI3K activity more effectively than resveratrol. PDGF-BB-induced migration and proliferation of HASMCs were inhibited by treatment with a commercial PI3K inhibitor, LY294002. Both in vitro and ex vivo pull-down assays revealed that piceatannol directly binds with sepharose 4B-PI3K beads in an ATP-competitive manner. The results of the present study demonstrate that piceatannol directly binds with PI3K in an ATP-competitive manner and suppresses PI3K activity with anti-atherosclerotic effects.
R331W Missense Mutation of Oncogene <i>YAP1</i> Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability
Authors: Hsuan-Yu Chen, Sung-Liang Yu, Bing-Ching Ho, Kang-Yi Su, Yi-Chiung Hsu, Chi-Sheng Chang, Yu-Cheng Li, Shi-Yi Yang, Pin-Yen Hsu, Hao Ho, Ya-Hsuan Chang, Chih-Yi Chen, Hwai-I Yang, Chung-Ping Hsu, Tsung-Ying Yang, Kun-Chieh Chen, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Jiun-Yi Hsia, Cheng-Yen Chuang, Shinsheng Yuan, Mei-Hsuan Lee, Chia-Hsin Liu, Guan-I Wu, Chao A. Hsiung, Yuh-Min Chen, Chih-Liang Wang, Ming-Shyan Huang, Chong-Jen Yu, Kuan-Yu Chen, Ying-Huang Tsai, Wu-Chou Su, Huei-Wen Chen, Jeremy J.W. Chen, Chien-Jen Chen, Gee-Chen Chang, Pan-Chyr Yang, Ker-Chau Li
Journal: Journal of Clinical Oncology (2015)

Adenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential.Whole-genome sequencing was performed for a family with an unusually high density of lung adenocarcinoma with available DNA from the affected mother, four affected daughters, and one nonaffected son. Candidate risk alleles were confirmed by matrix-assisted laser desorption ionization time of flight mass spectroscopy. Validation was conducted in an external cohort of 1,135 participants without cancer and 1,312 patients with lung adenocarcinoma. Family follow-ups were performed by genotyping the relatives of the original proband and the relatives of the identified risk-allele carriers. Low-dose computed tomography scans of the chest were evaluated for lung abnormalities.YAP1 R331W missense mutation from the original family was identified and validated in the external controls and the cohort with lung adenocarcinoma. The YAP1 mutant-allele carrier frequency was 1.1% in patients with lung adenocarcinoma compared with 0.18% in controls (P = .0095), yielding an odds ratio (adjusted for age, sex, and smoking status) of 5.9. Among the relatives, YAP1-mutant carriers have overwhelmingly higher frequencies of developing lung adenocarcinoma or ground-glass opacity lung lesions than those who do not carry the mutation (10:0 v 1:7; P < .001). YAP1 mutation was shown to increase the colony formation ability and invasion potential of lung cancer cells.These results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management.
Increased growth rate of vestibular schwannoma after resection of contralateral tumor in neurofibromatosis type 2
Authors: Matthieu Peyre, Stephane Goutagny, Sandrine Imbeaud, Alexis Bozorg-Grayeli, Michele Felce, Olivier Sterkers, Michel Kalamarides
Journal: Neuro-Oncology (2011)

Surgical management of bilateral vestibular schwannomas (VS) in neurofibromatosis type 2 (NF2) is often difficult, especially when both tumors threaten the brainstem. When the largest tumor has been removed, the management of the contralateral VS may become puzzling. To give new insights into the growth pattern of these tumors and to determine the best time point for treatment (surgery or medical treatment), we studied radiological growth in 11 VS (11 patients with NF2) over a long period (mean duration, 7.6 years), before and after removal of the contralateral tumor while both were threatening the brainstem. We used a quantitative approach of the radiological velocity of diametric expansion (VDE) on consecutive magnetic resonance images. Before first surgery, growth patterns of both tumors were similar in 9 of 11 cases. After the first surgery, VDE of the remaining VS was significantly elevated, compared with the preoperative period (2.5 ± 2.2 vs 4.4 ± 3.4 mm/year; P = .01, by Wilcoxon test). Decrease in hearing function was associated with increased postoperative growth in 3 cases. Growth pattern of coexisting intracranial meningiomas was not modified by VS surgery on the first side. In conclusion, removal of a large VS in a patient with NF2 might induce an increase in the growth rate of the contralateral medium or large VS. This possibility should be integrated in NF2 patient management to adequately treat the second VS.
Does This Patient Have Posttraumatic Stress Disorder?
Authors: Michele R. Spoont, John W. Williams, Shannon Kehle-Forbes, Jason A. Nieuwsma, Monica C. Mann-Wrobel, Raz Gross
Journal: JAMA (2015)

Posttraumatic stress disorder (PTSD) is a relatively common mental health condition frequently seen, though often unrecognized, in primary care settings. Identifying and treating PTSD can greatly improve patient health and well-being.To systematically review the utility of self-report screening instruments for PTSD among primary care and high-risk populations.We searched MEDLINE and the National Center for PTSD's Published International Literature on Traumatic Stress (PILOTS) databases for articles published on screening instruments for PTSD published from January 1981 through March 2015. Study quality was rated using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria.Studies of screening instruments for PTSD evaluated using gold standard structured clinical diagnostic interviews that had interview samples of at least 50 individuals.We identified 2522 citations, retrieved 318 for further review, and retained 23 cohort studies that evaluated 15 screening instruments for PTSD. Of the 23 studies, 15 were conducted in primary care settings in the United States (n = 14,707 were screened, n = 5374 given diagnostic interview, n = 814 had PTSD) and 8 were conducted in community settings following probable trauma exposure (ie, natural disaster, terrorism, and military deployment; n = 5302 were screened, n = 4263 given diagnostic interview, n = 393 were known to have PTSD with an additional 50 inferred by rates reported by authors). Two screens, the Primary Care PTSD Screen (PC-PTSD) and the PTSD Checklist were the best performing instruments. The 4-item PC-PTSD has a positive likelihood ratio of 6.9 (95% CI, 5.5-8.8) and a negative likelihood ratio of 0.30 (95% CI, 0.21-0.44) using the same score indicating a positive screen as used by the Department of Veterans Affairs in all of its primary care clinics. The 17-item PTSD Checklist has a positive likelihood ratio of 5.2 (95% CI, 3.6-7.5) and a negative likelihood ratio of 0.33 (95% CI, 0.29-0.37) using scores of around 40 as indicating a positive screen. Using the same score employed by primary care clinics in the Department of Veterans Affairs to indicate a positive screen, the 4-item PC-PTSD has a sensitivity of 0.69 (95% CI, 0.55-0.81), a specificity of 0.92 (95% CI, 0.86-0.95), a positive likelihood ratio of 8.49 (95% CI, 5.56-12.96) and a negative likelihood ratio of 0.34 (95% CI, 0.22-0.48). For the 17-item PTSD Checklist, scores around 40 as indicating a positive screen, have a sensitivity of 0.70 (95% CI, 0.64-0.77), a specificity of 0.90 (95% CI, 0.84-0.93), a positive likelihood ratio of 6.8 (95% CI, 4.7-9.9) and a negative likelihood ratio of 0.33 (95% CI, 0.27-0.40).Two screening instruments, the PC-PTSD and the PTSD Checklist, show reasonable performance characteristics for use in primary care clinics or in community settings with high-risk populations. Both are easy to administer and interpret and can readily be incorporated into a busy practice setting.
Tuberculosis-specific T-cell response after recent treatment and remote cure
Authors: J.P. van Gemert, S.F.T. Thijsen, A.W.J. Bossink
Journal: European Respiratory Journal (2011)

the TB treatment centre was significant for young and older individuals (OR 0.81 (p,0.01) and OR 0.71 (p,0.001),respectively), indicating lower completion of treatment if the patient lived .7.3 km from the treatment centre.This research indicates that moves towards centralisation of TB services, such as implementation of the UK recommendations that clinicians see o10 TB patients per year [2], should be implemented alongside measures to ensure accessibility of services, targeted to individuals born outside the UK who live far from the treatment centres.