tbuckley/cabot-search huggingface dataset:
The MRC OX-44 antigen marks a functionally relevant subset among rat thymocytes.
Authors: D J Paterson, J R Green, W A Jefferies, M Puklavec, A F Williams
Journal: The Journal of Experimental Medicine (1987)

A monoclonal antibody called MRC OX-44 is described that labels all myeloid cells and peripheral lymphoid cells but only 12% of thymocytes. The OX-44+ thymic cells include most if not all cells found in the medulla but only a small fraction of the cortical cells. Together with CD4 and CD8 antigens, seven subsets of thymic cell were defined and it was notable that most CD4- CD8- cells were OX-44+ whereas almost all CD4+ CD8+ cells were OX-44-. In functional tests, the OX-44+ cells accounted for all proliferation by thymocytes when stimulated by allogeneic spleen cells or concanavalin A plus growth factors and OX-44- cells were completely negative in these assays. Also, in tests for thymopoiesis after intra-thymic injection of cells, all activity was OX-44+. It seems possible that the OX-44+ set may include all functionally relevant cells in the rat thymus.
Tracing the Origin of the Compensasome: Evolutionary History of DEAH Helicase and MYST Acetyltransferase Gene Families
Authors: R Sanjuán, I Marín
Journal: Molecular Biology and Evolution (2001)

Dosage compensation in Drosophila is mediated by a complex of proteins and RNAs called the "compensasome." Two of the genes that encode proteins of the complex, maleless (mle) and males-absent-on-the-first (mof), respectively, belong to the DEAH helicase and MYST acetyltransferase gene families. We performed comprehensive phylogenetic and structural analyses to determine the evolutionary histories of these two gene families and thus to better understand the origin of the compensasome. All of the members of the DEAH and MYST families of the completely sequenced Saccharomyces cerevisiae and Caenorhabditis elegans genomes, as well as those so far (June 2000) found in Drosophila melanogaster (for which the euchromatic part of the genome has also been fully sequenced) and Homo sapiens, were analyzed. We describe a total of 39 DEAH helicases in these four species. Almost all of them can be grouped in just three main branches. The first branch includes the yeast PRP2, PRP16, PRP22, and PRP43 splicing factors and their orthologs in animal species. Each PRP gene has a single ortholog in metazoans. The second branch includes just four genes, found in yeast (Ecm16) and Drosophila (kurz) and their orthologs in humans and Caenorhabditis. The third branch includes (1) a single yeast gene (YLR419w); (2) six Drosophila genes, including maleless and spindle-E/homeless; (3) four human genes, among them the ortholog of maleless, which encodes RNA helicase A; and (4) three C. elegans genes, including orthologs of maleless and spindle-E. Thus, this branch has largely expanded in metazoans. We also show that, for the whole DEAH family, only MLE and its metazoan orthologs have acquired new protein domains since the fungi/animals split. We found a total of 17 MYST family proteins in the four analyzed species. We determined putative orthologs of mof in both C. elegans and H. sapiens, and we show that the most likely ortholog in yeast is the Sas2 gene. Moreover, a paralog of mof exists in Drosophila. All of these results, together with those found for a third member of the compensasome, msl-3, suggest that this complex emerged after the fungi/animals split and that it may be present in mammalian species. Both gene duplication and the acquisition of new protein modules may have played important roles in the origin of the compensasome.
Caffeine levels following treatment of obstructive sleep apnoea
Authors: G V Robinson
Journal: Thorax (2003)

Randomised trials show that treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (CPAP) greatly improves sleepiness and also lowers diurnal systemic blood pressures (BP). Such patients consume more coffee than controls (presumably to combat their sleepiness) and might reduce their consumption following effective treatment, thus lowering BP by this mechanism rather than via a direct effect of alleviating OSA.Plasma caffeine levels before and after treatment with either therapeutic (n=52) or subtherapeutic (control, n=49) CPAP were measured in stored blood samples from a previous randomised controlled trial of CPAP for 4 weeks in patients with OSA.There was a small significant rise in caffeine levels when the two groups were analysed as a whole (p=0.02), but not individually. Despite the fall in sleepiness measured objectively in the therapeutic CPAP group, there was no difference in absolute (or change in) caffeine levels between the two groups (mean (SE) micro mol/l; therapeutic CPAP 9.2 (1.2), 10.2 (1.0), subtherapeutic 6.7 (0.9), 8.6 (0.9) before and after treatment, respectively).Reduced coffee consumption is unlikely to be the explanation for the falls in BP following treatment of OSA.
A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation
Authors: Y. Suzaki, K. Hamada, T. Nomi, T. Ito, M. Sho, Y. Kai, Y. Nakajima, H. Kimura
Journal: European Respiratory Journal (2007)

Asthma is associated with increased numbers of T-cells in the lung. CC chemokine receptor (CCR)5 and CXC chemokine receptor (CXCR)3 have been reported to play important roles in the lung T-cell homing pathway, and may be potential targets for asthma therapy. The aim of the present study was to investigate the role of CCR5 and CXCR3 in allergen-induced acute asthma and to determine whether a novel small-molecule compound, TAK-779, targeting CCR5 and CXCR3 can attenuate allergic airway responses. Mice were sensitised with ovalbumin (OVA). mRNA expression of chemokine receptors in the lung were measured after the challenge with either aerosolised phosphate-buffered saline or OVA. OVA-sensitised mice were also treated with TAK-779. Respiratory function was measured, bronchoalveolar lavage was performed, and blood and lung samples were obtained. OVA challenge increased CCR3, CCR5 and CXCR3 expression in the lung. Treatment with TAK-779 significantly attenuated altered respiratory function and pulmonary allergic inflammation. The beneficial effect was associated with reduced expression of CCR5 and CXCR3 in the lung. These data demonstrate that blockade of CC chemokine receptor 5 and CXC chemokine receptor 3 using TAK-779, a synthetic nonpeptide compound, can prevent the development of asthma features in a mouse model. Thus, CC chemokine receptor 5 and CXC chemokine receptor 3 may be potential targets for asthma therapy.
Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study
Authors: F. Roila, B. Ruggeri, E. Ballatori, S. Fatigoni, C. Caserta, L. Licitra, A. Mirabile, M.T. Ionta, B. Massidda, L. Cavanna, M.A. Palladino, A. Tocci, S. Fava, I. Colantonio, L. Angelelli, L. Ciuffreda, G. Fasola, F. Zerilli
Journal: Annals of Oncology (2015)
Syme's Operation Modified and Improved by Saving the Periosteum of the Os Calcis
Authors: J. Bell
Journal: BMJ (1875)

DiSEASES of the oEsophagus often prov:e somewhat difficult of investi- gation, and it is not likely that we shall ever succeed in bringing this tube within the range of vision, as we have brought the larynx, the inner eye, and even the cavity of the bladder.Diseases of the aesopha.gus, moreover, even when benignant in character, have a peculiar terror in the peril of starvation wvhich th'eatens the sufferer.Any help, then, which we can obtain either ikm our diagnosis or our treat.ment of disease in this part, should be carefully cherished; and for this reason I venture to bring berore you a means of diagnosis which, in my opinion, has been unduly neglected.The only means used in cases of alleged disease of the amsophagus are the catechising of.the
Micron-sized particle deposition in the developing rodent lung
Authors: Holger Schulz, Gunter Eder, Ines Bolle, Akira Tsuda, Stefan Karrasch
Journal: European Respiratory Journal (2011)

Background:  Little is known about the effects of postnatal developmental changes in lung architecture and breathing patterns on intrapulmonary particle deposition. We measured deposition on postnatal days (P) 7, 14, 21, 35 and 90 in WKY rats, whose lung development largely parallels that of humans.   Methods:  Intrapulmonary deposition of 2 μm sebacate particles was determined in anaesthetized, intubated, spontaneously breathing rats. Continuous measurement of aerosol concentration as a function of respired volume was accomplished by aerosol photometry (Karrasch et al. 2009). Respiratory parameters were determined by whole-body plethysmography.   Results:  Tidal volume increased more than 10-fold from P7 (0.19 mL) to P90 (2.1 mL) while respiratory rate declined from 182 to 113/min. Deposition per breath was lowest (9%) at P7 and P90 and markedly higher at P35 (almost 16%). Structural changes of the alveolar region include an increase in surface area from 744 cm 2  at P7 to 6536 cm 2  at P90 (Bolle et al. 2008). Consequently, particle deposition per unit time and surface area (D ST ) peaked at P35 and showed a minimum at P90 indicating that D ST  is always higher in the developing than in the adult lung. At an inhaled particle number concentration of 10E5/cm 3  an estimated 450, 690 and 290 particles are deposited per min*cm 2  at P7, P35 and P90, respectively.   Discussion:  Micron-sized particle deposition was dependent on the stage of postnatal lung development in rats. A maximum was observed during late alveolarisation (P35), which corresponds to human lungs of about 8 years of age. Children at this age may therefore be more susceptible to airborne environmental health hazards. Supported by NIH-Grant HL070542
Early functional rehabilitation or cast immobilisation for the postoperative management of acute Achilles tendon rupture? A systematic review and meta-analysis of randomised controlled trials
Authors: R McCormack, J Bovard
Journal: British Journal of Sports Medicine (2015)

Objective To determine which postoperative rehabilitation regime is superior following surgical repair of acute Achilles tendon rupture. The primary outcomes were patient safety and satisfaction. Design Intervention meta-analysis. Data sources The MEDLINE and CINAHL electronic databases were searched from their date of inception until June 2015 using keywords related to acute Achilles tendon rupture, surgical repair and rehabilitation. The electronic database search was supplemented with forward citation tracking using the Web of Science. Eligibility criteria Randomised controlled trials comparing clinical and/or patient-reported outcomes between patients receiving early functional postoperative ankle motion and weight bearing (bracing group), and traditional ankle immobilisation with a non-weight bearing rigid cast (cast group) were eligible for inclusion. Fourteen articles were identified as potentially eligible; 10 sufficient-quality randomised controlled trials involving 570 patients were included for meta-analysis. Main results A high proportion of patients were able to return to prior employment and sporting activity in both groups. Five of the six trials measuring the time interval showed a faster return to prior sporting level in the bracing group. Subjective patient outcomes were significantly better in the bracing group (for good and excellent results, p=0.01; OR, 3.13; 95% CI 1.30 to 7.53). There was no difference in major complications between the two groups (p=0.21; RD, −0.03; 95% CI −0.06 to 0.01). Dynamometry and anthropometry measurements favoured functional rehabilitation at 6–12 weeks postoperation; however, by 6 months postoperative, the differences were negligible. Conclusions Compared to traditional ankle immobilisation, with a non-weight bearing cast following surgical repair of acute Achilles tendon rupture, early dynamic functional rehabilitation is as safe with higher patient satisfaction.
A Phase I Study of Weekly R1507, A Human Monoclonal Antibody Insulin-like Growth Factor-I Receptor Antagonist, in Patients with Advanced Solid Tumors
Authors: Razelle Kurzrock, Amita Patnaik, Joseph Aisner, Terri Warren, Stephen Leong, Robert Benjamin, S. Gail Eckhardt, Joseph E. Eid, Gerard Greig, Kai Habben, Cinara D. McCarthy, Lia Gore
Journal: Clinical Cancer Research (2010)

A phase I study was conducted to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of R1507-a fully human IgG1 type monoclonal antibody directed against the human insulin-like growth factor-I receptor.Patients with advanced solid tumors were assigned to receive i.v. R1507 weekly (qW), starting with 1 mg/kg. Subsequent cohorts were dosed at 3 and then 9 mg/kg. An additional 12 patients received 9 mg/kg R1507 qW. Patients remained on the study until the development of a dose-limiting toxicity or progressive disease.In total, 37 patients were treated with R1507 qW. No dose-limiting toxicities were identified and the maximum tolerated dose was not reached. The pharmacokinetics of R1507 were characterized by a slow clearance and limited volume of distribution, with an estimated elimination half-life justifying weekly administration. Serum IGF-I ligand levels increased proportionally to dose during the first 72 hours in all cohorts. R1507 was well tolerated. Two patients diagnosed with Ewing's sarcoma had partial responses of 11.5 and >26 months (ongoing at time of submission); 13 patients had stable disease; and 16 had progressive disease as best response by the Response Evaluation Criteria in Solid Tumors.R1507 is well tolerated and shows antitumor activity in patients with solid neoplasms, in particular Ewing's sarcoma. The recommended dose for the weekly schedule is 9 mg/kg qW.
Secondary Leukemia Associated With a Conventional Dose of Etoposide: Review of Serial Germ Cell Tumor Protocols
Authors: C. R. Nichols, E. S. Breeden, P. J. Loehrer, S. D. Williams, L. H. Einhorn
Journal: JNCI Journal of the National Cancer Institute (1993)

Background: Case reports have suggested that treatment with high-dose etoposide can result in development of a unique secondary leukemia. Purpose: This study was designed to estimate the risk of developing leukemia for patients receiving conventional doses of etoposide along with cisplatin and bleornycin. Methods: We reviewed the records at Indiana University of all untreated patients entering clinical trials using etoposide at conventional doses (cumulative dose, 2000 mg/rn2 or less) for germ cell cancer between 1982 and 1991. The records of all patients who received a chemotherapy regimen containing etoposide, ifosfamide, or cisplatin after failing to respond to primary chemotherapy were also reviewed. Results: Between 1982 and 1991, 538 patients entered serial clinical trials with planned cumulative etoposide doses of 1500–2000 mg/rn2 in combination with cisplatin plus either ifosfamide or bleomycin. Of these 538 patients, 348 received an etoposide combination as initial chemotherapy and 190 received etoposide as part of salvage treatment. To date, 315 patients are alive, with median follow-up of 4.9 years, and 337 patients have had follow-up beyond 2 years. Two patients (0.37%) developed leukemia. One developed acute undifferentiated leukemia with a t(4;11) (q21;q23) cytogenetic abnormality 2.0 years after starting etoposide-based therapy, and one developed acute myelomonoblastic leukemia with no chromosome abnormalities 2.3 years after beginning chemotherapy. During this period, several hundred patients were treated with etoposide-based chemotherapy and did not enter clinical trials. Three of these patients are known to have developed hematologic abnormalities, including one patient with acute monoblastic leukemia with a t(11;19)(q13;p13) abnormality. Conclusions: Secondary leukemia after treatment with a conventional dose of etoposide does occur, but the low incidence does not alter the risk-to-benefit ratio of etoposide-based chemotherapy in germ cell cancer. Implications: The reports of leukemia associated with high doses of etoposide emphasize the need for diligent follow-up of patients and make careful risk-to- benefit analysis imperative. [J NatI Cancer Inst 85:36–40, 1993]
Hematology research output from Chinese authors and other countries: a 10-year survey of the literature
Authors: Lei Zhang, Xin Ye, Yi Sun, An-mei Deng, Bao-hua Qian
Journal: Journal of Hematology & Oncology (2015)

Hematologic disease affects people of all ages worldwide. In the past decade, researchers have made great progress in the field of hematology. In the present study we compared the hematology research output from China and other countries (USA, Germany, UK, Japan and South Korea) over the past 10 years and 5 years.The related articles were extracted based on the PubMed database. We recorded the number of publications, clinical trials, randomized controlled trials, meta-analyses, case reports, reviews, citations, impact factors, articles in the top 10 journals and most published journals to assess the quantity and quality of research output in each region.A total of 120,641 hematology-related articles were published from 2004 to 2013. The USA accounted for 27.13% (32,732/120,641) of the publications, followed by Germany (7,479/120,641; 6.20%), Japan (6,347/120,641; 5.26%), the UK (5,453/120,641; 4.52%), China (2,924/120,641; 2.42%) and South Korea (1,413/120,641; 1.17%). The ranking for cumulative impact factors was as follows: USA; Germany; UK; Japan; China and South Korea. The median impact factors in the UK, USA, and Germany were higher than Japan, South Korea, and China. Interestingly, the median impact factors in the three Asia countries were similar both in 2004-2013 and 2009-2013. The UK had the highest percentage of publications in the top 25% of journals, while China lagged behind and ranked last. When comparing the number of articles in the top 10 journals, the results were similar to the IF findings. Germany had the highest number of average citations, while China had the lowest number of average citation. The status of hematology research output from the 6 countries in 2009-2013 had little difference from 2004-2013.Thus, the USA has had a dominant role in hematologic research in the past 10 years. Overall, the quality of publications in European countries was better than Asia countries. Although China has made considerable progress in hematology research, the quality of research needs improvement.
Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans
Authors: Jaime Guevara-Aguirre, Priya Balasubramanian, Marco Guevara-Aguirre, Min Wei, Federica Madia, Chia-Wei Cheng, David Hwang, Alejandro Martin-Montalvo, Jannette Saavedra, Sue Ingles, Rafael de Cabo, Pinchas Cohen, Valter D. Longo
Journal: Science Translational Medicine (2011)

Mutations in growth signaling pathways extend life span, as well as protect against age-dependent DNA damage in yeast and decrease insulin resistance and cancer in mice. To test their effect in humans, we monitored for 22 years Ecuadorian individuals who carry mutations in the growth hormone receptor (GHR) gene that lead to severe GHR and IGF-1 (insulin-like growth factor-1) deficiencies. We combined this information with surveys to identify the cause and age of death for individuals in this community who died before this period. The individuals with GHR deficiency exhibited only one nonlethal malignancy and no cases of diabetes, in contrast to a prevalence of 17% for cancer and 5% for diabetes in control subjects. A possible explanation for the very low incidence of cancer was suggested by in vitro studies: Serum from subjects with GHR deficiency reduced DNA breaks but increased apoptosis in human mammary epithelial cells treated with hydrogen peroxide. Serum from GHR-deficient subjects also caused reduced expression of RAS, PKA (protein kinase A), and TOR (target of rapamycin) and up-regulation of SOD2 (superoxide dismutase 2) in treated cells, changes that promote cellular protection and life-span extension in model organisms. We also observed reduced insulin concentrations (1.4 μU/ml versus 4.4 μU/ml in unaffected relatives) and a very low HOMA-IR (homeostatic model assessment-insulin resistance) index (0.34 versus 0.96 in unaffected relatives) in individuals with GHR deficiency, indicating higher insulin sensitivity, which could explain the absence of diabetes in these subjects. These results provide evidence for a role of evolutionarily conserved pathways in the control of aging and disease burden in humans.
Pseudomonas aeruginosa transmission is infrequent in New Zealand cystic fibrosis clinics
Authors: J. Schmid, L. J. Ling, J. L. S. Leung, N. Zhang, J. Kolbe, A. W. Wesley, G. D. Mills, P. J. Brown, D. T. Jones, R. T. R. Laing, P. K. Pattemore, D. R. Taylor, K. Grimwood
Journal: European Respiratory Journal (2008)

Pseudomonas aeruginosa is an important pathogen in cystic fibrosis (CF). Although most patients harbour unique P. aeruginosa isolates, some clinics report patients sharing common strains. The overall importance of person-to-person transmission in P. aeruginosa acquisition and whether routine patient segregation is necessary remains uncertain. The present authors therefore investigated the extent of P. aeruginosa transmission in New Zealand CF clinics. New Zealand’s seven major CF centres were assessed, combining epidemiological data with computer-assisted Sal I DNA fingerprinting of 496 isolates from 102 patients. One cluster of related isolates was significantly more prevalent in the largest clinic than expected by chance. The seven patients with isolates belonging to this cluster had more contact with each other than the remaining patients attending this centre. No other convincing evidence of transmission was found in any of the other smaller clinics. Three P. aeruginosa strains believed to be transmissible between patients in Australian and British CF clinics are present in New Zealand, but there was no definite evidence they had spread. Pseudomonas aeruginosa transmission is currently infrequent in New Zealand cystic fibrosis clinics. This situation could change rapidly and ongoing surveillance is required. The current results confirm that computer-assisted Sal I DNA fingerprinting is ideally suited for such surveillance.
Activation of Vitamin D Receptor Signaling Downregulates the Expression of Nuclear FOXM1 Protein and Suppresses Pancreatic Cancer Cell Stemness
Authors: Zhiwei Li, Zhiliang Jia, Yong Gao, Dacheng Xie, Daoyan Wei, Jiujie Cui, Lopa Mishra, Suyun Huang, Yanqiao Zhang, Keping Xie
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Dysregulated signaling of nuclear transcription factors vitamin D receptor (VDR) and Forkhead box M1 (FOXM1) plays important roles in transformation and tumorigenesis. In this study, we sought to determine whether VDR signaling causally affected FOXM1 signaling in and pathogenesis of pancreatic ductal adenocarcinoma (PDAC). Experimental Design: Genetic and pharmacologic approaches were used to manipulate VDR signaling. The impacts of altered VDR signaling on FOXM1 expression and function in PDAC cells were determined using molecular and biochemical methods, whereas those on PDAC cell biology and tumorigenicity were determined using in vitro and in vivo experimental systems. The clinical relevance of our findings was validated by analyzing human PDAC specimens. Results: There was a striking inverse correlation between reduced expression of VDR and increased expression of FOXM1 in human PDAC cells and tissues. Treatment of PDAC cells with 1,25-dihydroxyvitamin D3 (1,25D), its synthetic analogue EB1089 (EB), and VDR transgenics drastically inhibited FOXM1 signaling and markedly suppressed tumor stemness, growth, and metastasis. Mechanistically, 1,25D and EB repressed FOXM1 transcription and reduced the expression level of nuclear FOXM1 protein. Conclusion: Inactivation of Vitamin D/VDR signaling is a critical contributor to PDAC development and progression via elevated expression and function of FOXM1 and enhanced PDAC cell stemness, invasion, and metastasis. Clin Cancer Res; 21(4); 844–53. ©2014 AACR.