tbuckley/cabot-search huggingface dataset:
Impact of a Lung Transplantation Donor–Management Protocol on Lung Donation and Recipient Outcomes
Authors: Luis F. Angel, Deborah J. Levine, Marcos I. Restrepo, Scott Johnson, Edward Sako, Andrea Carpenter, John Calhoon, John E. Cornell, Sandra G. Adams, Gary B. Chisholm, Joe Nespral, Ann Roberson, Stephanie M. Levine
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: One of the limitations associated with lung transplantation is the lack of available organs.Objective: To determine whether a lung donor–management protocol could increase the number of lungs for transplantation without affecting the survival rates of the recipients.Methods: We implemented the San Antonio Lung Transplant protocol for managing potential lung donors according to modifications of standard criteria for donor selection and strategies for donor management. We then compared information gathered during a 4-yr period, during which the protocol was used with information gathered during a 4-yr period before protocol implementation. Primary outcome measures were the procurement rate of lungs and the 30-d and 1-yr survival rates of recipients.Main Results: We reviewed data from 711 potential lung donors. The mean rate of lung procurement was significantly higher (p < 0.0001) during the protocol period (25.5%) than during the pre-protocol period (11.5%), with an estimated risk ratio of 2.2 in favor of the protocol period. More patients received transplants during the protocol period (n = 121) than during the pre-protocol period (n = 53; p < 0.0001). Of 98 actual lung donors during the protocol period, 53 (54%) had initially been considered poor donors; these donors provided 64 (53%) of the 121 lung transplants. The type of donor was not associated with significant differences in recipients' 30-d and 1-yr survival rates or any clinical measures of adequate graft function.Conclusions: The protocol was associated with a significant increase in the number of lung donors and transplant procedures without compromising pulmonary function, length of stay, or survival of the recipients.
Cyclophosphamide, adriamycin and dexamethasone (CAD) is a highly effective therapy for patients with advanced multiple myeloma
Authors: H. Szelényi, E.D. Kreuser, U. Keilholz, H.D. Menssen, C. Keitel-Wittig, J. Siehl, W. Knauf, E. Thiel
Journal: Annals of Oncology (2001)
Complaints: consumerism leads to poor services
Authors: C K Connolly
Journal: BMJ (1993)

policy that aims to deliver infants weighing less than 1000 g in a larger unit.We accept that in utero transfer is vastly superior to postnatal transfer and aim to transfer infants of 27 weeks or less if possible.This policy enables us to maintain the skills necessary to deal with such infants in the short term if they are born locally or if the regional unit is full.The Audit Commission's statements on neonatal care are far too influenced by the vested interests of the larger units, to the detriment of neonates.
Questionnaire survey of post-traumatic stress disorder in doctors involved in the Omagh bombing
Authors: J. Firth-Cozens, S. J Midgley, C. Burges
Journal: BMJ (1999)

On 15 August 1998 a bomb exploded in the main street of Omagh.It killed 29 people, including nine children, and injured over 300.The local hospital, Tyrone County Hospital, took most casualties into its very small accident and emergency department, and others were sent to the Erne Hospital in Enniskillen, 40 miles away.A postal questionnaire study of the health of all staff of Sperrin Lakeland Health and Social Care Trust, which covers both hospitals, took place four months later, and analyses are continuing.This paper presents findings on the 41 doctors who replied in terms of their levels of post-traumatic stress disorder.
Homologs of Drosophila P Transposons Were Mobile in Zebrafish but Have Been Domesticated in a Common Ancestor of Chicken and Human
Authors: Sabine E. Hammer, Sabine Strehl, Sylvia Hagemann
Journal: Molecular Biology and Evolution (2004)

A substantial fraction of vertebrate and invertebrate genomes is composed of mobile elements and their derivatives. One of the most intensively studied transposon families, the P elements of Drosophila, was thought to exist exclusively in the genomes of dipteran insects. Based on the data provided by the human genome project, in 2001 our group has identified a P element–homologous sequence in the human genome. This P element–homologous human gene, named Phsa, is 19,533 nucleotides long, comprises six exons and five introns, and encodes a protein of still unknown function with a length of 903 amino acid residues. The N-terminal THAP domain of the putative Phsa protein shows similarities to the site-specific DNA-binding domain of the Drosophila P element transposase. In the present study, FISH analysis and the screening of a human lambda genomic library revealed a single copy of Phsa located on the long arm of chromosome 4, upstream of a gene coding for the hypothetical protein DKFZp686L1814. The same gene arrangement was found for the homologous gene Pgga in the genome of chicken, thus, displaying Pgga at orthologous position on the long arm of chromosome 4. The single-copy gene status and the absence of terminal inverted repeats and target-site duplications indicate that Phsa and Pgga constitute domesticated stationary sequences. In contrast, a considerable number of P-homologous sequences with terminal inverted repeats and intact target-site duplications could be identified in zebrafish, strongly indicating that Pdre elements were mobile within the zebrafish genome. Pdre elements are the first P-like transposons identified in a vertebrate species. With respect to Phsa, gene expression studies showed that Phsa is expressed in a broad range of human tissues, suggesting that the putative Phsa protein plays a not yet understood but essential role in a specific metabolic pathway. We demonstrate that P-homologous DNA sequences occur in the genomes of 21 analyzed vertebrates but only as rudiments in the rodents. Finally, the evolutionary history of P element–homologous vertebrate sequences is discussed in the context of the "molecular domestication" hypothesis versus the "source gene hypothesis."
<i>Cytokeratin-19</i> and <i>Mammaglobin</i> Gene Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients Enrolled in North Central Cancer Treatment Group Trials, N0234/336/436/437
Authors: Monica M. Reinholz, Kathleen A. Kitzmann, Kathleen Tenner, David Hillman, Amylou C. Dueck, Timothy J. Hobday, Donald W. Northfelt, Alvaro Moreno-Aspitia, Vivek Roy, Betsy LaPlant, Jake B. Allred, Philip J. Stella, Wilma L. Lingle, Edith A. Perez
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). Experimental Design: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan + cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched with CD45 depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized to β2-microglobulin and calibrated to healthy blood using the 2–ΔΔCq algorithm; positivity was defined as 2 or more. Results: CK19+mRNA cells were detected in 56% to 75% and MGB1+mRNA cells in 23% to 38% of 86 patients at baseline. CK19+mRNA cells were detected in 30% to 67% and MGB1+mRNA cells in 14% to 64% of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). Conclusions: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients. Clin Cancer Res; 17(22); 7183–93. ©2011 AACR.
Treatment-related outcome of oropharyngeal cancer patients differentiated by HPV dictated risk profile: a tertiary cancer centre series analysis
Authors: P Bossi, E Orlandi, R Miceli, F Perrone, M Guzzo, L Mariani, R Granata, L Locati, C Fallai, B Cortelazzi, S Pilotti, G Scaramellini, A Gloghini, L Licitra
Journal: Annals of Oncology (2014)

BackgroundTo date, no treatment modality has been identified as more effective for oropharyngeal cancer (OPC), and no predictive factors are known to guide treatment decision for this disease. This retrospective study evaluates the differential effects of diverse treatment options for OPC according to patient risk profiles.Patients and methodsWe considered two series of locally advanced squamous cell OPC patients treated with either surgery followed by radiotherapy (surgical series) or chemoradiation (CRT) with/without induction docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy (CRT series). Smoking habits, tumor p16 expression/human papillomavirus (HPV) status and T and N stage were analyzed to stratify the patients according to Ang's risk profile (low, intermediate and high risk). Overall survival (OS) and disease-free survival were calculated with the Kaplan–Meier method.ResultsGlobally, 171 patients were considered, 56 in surgical and 115 in CRT series. Patients were stratified in low- (20% of surgical and CRT groups), intermediate- (23% and 41%) and high-risk (57% and 39%) groups. In the surgical series, 5-year OS was 54.5%, 46.9% and 40.0% in low, intermediate and high Ang's risk profiles, respectively, whereas in the CRT series those were 100%, 78.9% and 46.7%, respectively. In the multivariable analyses, adjusting for inhomogeneity between the treatment group, the CRT effect was significantly higher in the low- and intermediate-risk groups (P-value for the interaction treatment risk group = 0.034 in the OS analysis).ConclusionsIn this retrospective analysis, low- and intermediate-risk OPC patients had a better survival when treated with CRT compared with open surgery followed by radiation therapy. These data suggest that different treatment approaches might be essential in determining outcome results.
Patches of Disorganization in the Neocortex of Children with Autism
Authors: Rich Stoner, Maggie L. Chow, Maureen P. Boyle, Susan M. Sunkin, Peter R. Mouton, Subhojit Roy, Anthony Wynshaw-Boris, Sophia A. Colamarino, Ed S. Lein, Eric Courchesne
Journal: New England Journal of Medicine (2014)

Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development.To systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type-specific molecular markers to phenotype cortical microstructure. We assayed markers for neurons and glia, along with genes that have been implicated in the risk of autism, in prefrontal, temporal, and occipital neocortical tissue from postmortem samples obtained from children with autism and unaffected children between the ages of 2 and 15 years.We observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches.In this small, explorative study, we found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. (Funded by the Simons Foundation and others.).
Anti-Inflammatory and Proresolving Lipid Mediators
Authors: Charles N. Serhan, Stephanie Yacoubian, Rong Yang
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that nonsteroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held as a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution and that possess potent anti-inflammatory and proresolving actions. A lipid-mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates, which also contain lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. Given their potent bioactions, these new chemical mediator families were termed resolvins and protectins. Here, we review the recent advances in our understanding of the biosynthesis and stereospecific actions of these new proresolving mediators, which have also proven to be organ protective and antifibrotic.
Marie Unna hereditary hypotrichosis: Identification of a U2HR mutation in the family from the original 1925 report
Authors: Silke Redler, Roland Kruse, Sibylle Eigelshoven, Sandra Hanneken, Melanie Refke, Yaran Wen, Xue Zhang, Sven Cichon, Regina C. Betz, Markus M. Nöthen
Journal: Journal of the American Academy of Dermatology (2010)
Sustained phenotypic correction of canine hemophilia A using an adeno-associated viral vector
Authors: Ciaran D. Scallan, David Lillicrap, Haiyan Jiang, Xiaobing Qian, Susannah L. Patarroyo-White, Amy E. Parker, Tongyao Liu, Joseph Vargas, Dea Nagy, Sharon K. Powell, J. Fraser Wright, Patricia V. Turner, Shawn J. Tinlin, Sandra E. Webster, Alan McClelland, Linda B. Couto
Journal: Blood (2003)
Effectiveness of mobile phone messaging in prevention of type 2 diabetes by lifestyle modification in men in India: a prospective, parallel-group, randomised controlled trial
Authors: Ambady Ramachandran, Chamukuttan Snehalatha, Jagannathan Ram, Sundaram Selvam, Mary Simon, Arun Nanditha, Ananth Samith Shetty, Ian F Godsland, Nish Chaturvedi, Azeem Majeed, Nick Oliver, Christofer Toumazou, K George Alberti, Desmond G Johnston
Journal: The Lancet Diabetes & Endocrinology (2013)
Medication Treatment of Different Types of Alcoholism
Authors: Bankole A. Johnson
Journal: American Journal of Psychiatry (2010)

Alcoholism remains a serious cause of morbidity and mortality despite progress through neurobiological research in identifying new pharmacological strategies for its treatment. Drugs that affect neural pathways that modulate the activity of the cortico-mesolimbic dopamine system have been shown to alter drinking behavior, presumably because this dopaminergic system is closely associated with rewarding behavior. Ondansetron, naltrexone, topiramate, and baclofen are examples. Subtyping alcoholism in adults into an early-onset type, with chronic symptoms and a strong biological predisposition to the disease, and a late-onset type, typically brought on by psychosocial triggers and associated with mood symptoms, may help in the selection of optimal therapy. Emerging adults with binge drinking patterns also might be aided by selective treatments. Although preliminary work on the pharmacogenetics of alcoholism and its treatment has been promising, the assignment to treatment still depends on clinical assessment. Brief behavioral interventions that encourage the patient to set goals for a reduction in heavy drinking or abstinence also are part of optimal therapy.
Human intestinal M cells exhibit enterocyte-like intermediate filaments
Authors: T Kucharzik, N Lügering, K W Schmid, M A Schmidt, R Stoll, W Domschke
Journal: Gut (1998)

Background —The derivation and ultrastructural composition of M cells covering the lymphoid follicles of Peyer’s patches is still unknown. Results from different animal models have shown that there are species specific differences in the composition of intermediate filaments between M cells and neighbouring enterocytes. Little is known, however, about intermediate filaments of human M cells. Aims —To compare components of the cytoskeleton of human M cells with those of adjacent absorptive enterocytes. Methods —The expression and localisation of different cytokeratins, vimentin, and desmin in M cells was determined on follicle associated epithelia of human appendix using immunohistochemistry and immunogold electron microscopy. Results —Cytokeratins specific for human intestinal epithelial cells such as cytokeratins 8, 18, 19, and 20 were expressed in both absorptive enterocytes and M cells with no differences in intensity and cellular distribution between both cell types. Vimentin and desmin, tissue specific markers of either mesenchymal or myogenic cells, as well as other cytokeratins were not detectable in enterocytes or M cells. Conclusion —This is the first study on the structure of intermediate filaments in human intestinal M cells. Our results show that in contrast to several animal models, human M cells apparently do not differ from adjacent enterocytes in the composition of their intermediate filament cytoskeleton. The presence of enterocyte like cytokeratins and the absence of other cytokeratins as well as of vimentin and desmin supports the hypothesis of an epithelial origin of human intestinal M cells and suggests that M cells may derive from differentiated enterocytes.
Endometriosis: a dysfunction and disease of the archimetra
Authors: G Leyendecker
Journal: Human Reproduction Update (1998)

Endometriosis is considered primarily a disease of the endometrial-subendometrial unit or archimetra. The clinical picture of endometriosis characterises this disease as a hyperactivation of genuine archimetrial functions such as proliferation, inflammatory defence and peristalsis. While the aetiology of the disease remains to be elucidated, a key event appears to consist in the local production of extraovarian oestrogen by a pathological expression of the P450 aromatase. The starting event may consist in a hyperactivity of the endometrial inflammatory defence, a hyperactivity of the endometrial oxytocin/oxytocin receptor system or in the pathological expression of the P450 aromatase system itself. Regardless of which of these levels the starting event is localized in, they influence each other on both the level of the archimetra and the endometriotic lesions. Locally elevated oestrogen levels inevitably up-regulate the endometrial oxytocin mRNA and increased levels of oxytocin result in uterine hyper-peristalsis, increased transtubal seeding of endometrial tissue fragments and finally subfertility and infertility by impairment of the uterine mechanism of rapid and sustained sperm transport. Locally increased levels of oestrogen lead, on both the level of the endometrial-subendometrial unit and the endometriotic lesion, to processes of hyperproliferation. These processes result, on the level of the uterus, in an infiltrative growth of elements of the archimetra into the neometra and, on the level of the endometriotic lesion, in infiltrative endometriosis. There is circumstantial evidence that trauma might be an important initial event that induces the specific biochemical and cellular responses of the archimetra. This model is able to explain both the pleiomorphic appearance of endometriosis and the, up until now, enigmatic infertility associated with mild and moderate endometriosis.
Neoplasms in Rats Protected Against Lethal Doses of Irradiation by Parabiosis or &lt;italic&gt;Para&lt;/italic&gt;-Aminopropriophenone
Authors: G BRECHER, E P CRONKITE, J H PEERS
Journal: JNCI Journal of the National Cancer Institute (1953)

Neoplasms in Rats Protected Against Lethal Doses of Irradiation by Parabiosis or Para-Aminopropriophenone G. Brecher, M. D., G. Brecher, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar E. P. Cronkite, M. D., E. P. Cronkite, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar James H. Peers, M. D. James H. Peers, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 1, August 1953, Pages 159–175, https://doi.org/10.1093/jnci/14.1.159 Published: 01 August 1953 Article history Received: 22 April 1953 Published: 01 August 1953
Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas
Authors: Tieneke B.M. Schaaij-Visser, A. Peggy Graveland, Sharon Gauci, Boudewijn J.M. Braakhuis, Marijke Buijze, Albert J.R. Heck, Dirk J. Kuik, Elisabeth Bloemena, C. René Leemans, Monique Slijper, Ruud H. Brakenhoff
Journal: Clinical Cancer Research (2009)

PURPOSE: The 5-year survival rates of head and neck squamous cell carcinomas (HNSCC) remain disappointing. HNSCCs develop in precursor fields of genetically altered cells that are often not completely resected when the tumor is excised, causing local relapse. These precursor fields are mostly recognized as dysplasia, but histologic grading cannot reliably predict malignant transformation. Our aim was to discover and validate protein biomarkers that can detect precursor fields and predict local relapse in HNSCC using immunostaining of surgical margins. EXPERIMENTAL DESIGN: We compared paired and genetically characterized normal, precursor, and tumor tissues of eight patients by proteome analysis to identify differentially expressed proteins. The prognostic value of candidate protein biomarkers was evaluated by immunohistochemical analysis of 222 surgical margins of 46 HNSCC patients who developed local relapse or remained disease free. Significant associations were determined by Kaplan-Meier survival analysis and Cox-proportional hazards models. RESULTS: Forty proteins showed significant differential expression (false discovery rate-corrected P < 0.05). Most discriminative markers suited for immunostaining were keratin 4 and cornulin. Low expression in the surgical margins of keratin 4 (hazard ratio, 3.8; P = 0.002), cornulin (hazard ratio, 2.7; P = 0.025), and their combination (hazard ratio, 8.8; P = 0.0005) showed a highly significant association with the development of local relapse. Dysplasia grading had no prognostic relevance. CONCLUSIONS: Immunohistochemical assessment of keratin 4 and cornulin expression in surgical margins of HNSCC patients outperforms histopathologic grading in predicting the risk for local relapse. These markers can be used to initiate more frequent and lifelong surveillance of patients at high risk of local relapse, and enable selection for adjuvant treatment or tertiary prevention trials. (Clin Cancer Res 2009;15(24):7666-75).