tbuckley/cabot-search huggingface dataset:
STUDIES UPON EXPERIMENTAL MEASLES
Authors: Charles W. Duval, Rigney D'Aunoy
Journal: The Journal of Experimental Medicine (1922)

An active transmissible virus exists in the blood of measles patients during the eruptive stage of the disease. This virus produces in rabbits after intravenous injection a specific reaction analogous in all essential features to that of the human infection. Following a definite incubation period of from 2 to 5 days the animals infected show pyrexial, leucocytic, and cutaneous alterations. Fully 90 per cent of such inoculated rabbits react in a remarkable manner. The earliest constant symptom of the infection is a rise in temperature, which on the average occurs 4 days after inoculation and most probably marks the end of the incubation period. Concomitantly with this temperature rise there is a diminution in the total number of circulating leucocytes. This decrease in the number of white blood elements may be relative or may appear in the form of a well defined leucopenia. The most striking objective signs are the coryza, conjunctival injection, enanthemata, and exanthemata. The mucous membrane lesions are similar in their physical appearance to the so called Koplik spots seen in man. They occur on the buccal side of the oral cavity ranging in number from two to eight discrete hemorrhagic areas with paler centers. They appear as a rule coincidently with the temperature rise or shortly thereafter. The exanthematous lesions though occurring only in about 40 per cent of the infected animals complete the clinical syndrome in this particular experimental host. The rash may appear as early as the 3rd and as late as the 7th day after inoculation. In its early stage it is of the macular variety, appearing as a diffuse eruption which later develops into a more papular type of lesion. At this time the cutaneous manifestations appear as slightly raised, flattened, purplish red, discrete areas in the skin of the face, neck, chest, and abdomen. Repeated passage of the virus of measles through the rabbit seems to increase its virulence. A number of animals infected with such passage virus succumb in the fourth and subsequent generations, undoubtedly as the direct result of the action of the specific excitant, as in none of the animals was there cultural evidence of secondary intercurrent infection. In the animals dying presumably as a result of the specific virus grave nephritic changes were evident. It is a noteworthy fact that the pneumonia so common in fatal cases of human measles was not evident in any of the experimental animals. We believe this to be of considerable significance, especially in elucidating the direct etiological factor of the fatal pneumonias so often present in human measles cases. Apparently such infections in man can be explained purely on the basis of the destruction of normal defense barriers by the specific excitant of the infectious disease, and the lack of host resistance to the ordinary pyogenic microorganism.
Phenotype of atopic dermatitis subjects with a history of eczema herpeticum
Authors: Lisa A. Beck, Mark Boguniewicz, Tissa Hata, Lynda C. Schneider, Jon Hanifin, Rich Gallo, Amy S. Paller, Susi Lieff, Jamie Reese, Daniel Zaccaro, Henry Milgrom, Kathleen C. Barnes, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2009)
Sport related injuries attending the accident and emergency department.
Authors: R S Jones, T Taggart
Journal: British Journal of Sports Medicine (1994)

Of new patients attending our hospital, 7.1% had injured themselves playing sport. The majority had been playing football and had sustained a soft tissue injury. Many of the patients presented late, i.e. after 24 h or longer. These patients would be best dealt with in a sports clinic, staffed by personnel with an interest in this field.
<i>CYP2D6</i> Polymorphisms as Predictors of Outcome in Breast Cancer Patients Treated with Tamoxifen: Expanded Polymorphism Coverage Improves Risk Stratification
Authors: Werner Schroth, Ute Hamann, Peter A. Fasching, Silke Dauser, Stefan Winter, Michel Eichelbaum, Matthias Schwab, Hiltrud Brauch
Journal: Clinical Cancer Research (2010)

Abstract Purpose: This study aimed to validate matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS)/Taqman copy number assay (CNA) CYP2D6 genotyping by AmpliChip CYP450 Test for the prediction of tamoxifen metabolizer phenotypes in breast cancer, and to investigate the influence of CYP2D6 variant coverage on genotype-phenotype relationships and tamoxifen outcome. Experimental Design: Hormone receptor–positive postmenopausal breast cancer patients (n = 492) treated with adjuvant tamoxifen, previously analyzed by MALDI-TOF MS/CNA, were reanalyzed by AmpliChip CYP450 Test and validated by independent methods. Cox proportional hazard ratios (HR) were calculated for recurrence of poor (PM) relative to extensive metabolizer (EM) phenotypes with increasing numbers of CYP2D6 variants. Kaplan-Meier distributions were calculated for different phenotype classifications. Results: Concordance was 99.2% to 99.5% for CNA and 99.8% to 100% per CYP2D6 allele (*3, *4, *5, *9, *10, and *41). The prevalence of predicted phenotypes was 1.2% for ultrarapid metabolizer (UM), 37.2% for EM without variant, 43.5% for heterozygous EM, 9.7% for intermediate metabolizer (IM), and 8.3% for PM. Approximately, one third of patients were misclassified based on a *4 analysis only, but inclusion of all reduced-function alleles increased the PM-associated HR from 1.33 (P = 0.58) to 2.87 (P = 0.006). Kaplan-Meier analyses showed highest and lowest clinical benefit for UM and PM with respect to both the AmpliChip-based and a redefined phenotype assignment. The latter revealed significant allele–dose-dependent associations (P = 0.011) and largest effect size (HRPM_EM = 2.77; 95% confidence interval, 1.31-5.89). Conclusions: MALDI-TOF MS/CNA is suitable for accurate CYP2D6 genotyping. For tamoxifen pharmacogenetics, broad CYP2D6 allele coverage is recommended to reduce phenotype misclassification. Classification based on refined EM and reduced-function metabolizers is advisable. Clin Cancer Res; 16(17); 4468–77. ©2010 AACR.
Aberrations in the epidermal growth factor receptor gene in 958 patients with diverse advanced tumors: implications for therapy
Authors: J.J. Wheler, G.S. Falchook, A.M. Tsimberidou, D.S. Hong, A. Naing, S.A. Piha-Paul, S.S. Chen, S. Fu, B. Stephen, J.Y. Fok, F. Janku, R. Kurzrock
Journal: Annals of Oncology (2012)
Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study
Authors: M. Koopman, N.F. Antonini, J. Douma, J. Wals, A.H. Honkoop, F.L.G. Erdkamp, R.S. de Jong, C.J. Rodenburg, G. Vreugdenhil, J.M. Akkermans-Vogelaar, C.J.A. Punt
Journal: Annals of Oncology (2006)
Transient engraftment of syngeneic bone marrow after conditioning with high‐dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia
Authors: Kosei Matsue, Takeo Niki, Shintaro Shiobara, Mikio Ueda, Shigeki Ohtake, Takao Mori, Tamotsu Matsuda, Mine Harada
Journal: American Journal of Hematology (1990)

Abstract We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high‐dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non‐HLA antigens. This case report implies that graft failure in some cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.
Calculus Vesicae in a Hermaphrodite: Lithotomy: Recovery
Authors: M. D. Moriarty
Journal: BMJ (1879)

For the sake of those who may wish to see the data on which the figures given in the preceding tables are based, I append others, show- ing the population and number of deaths from phthisis for the whole colony, and for Melbourne separately, in i86i and I871.TABLE VII.-Deat/zs from Phlthisis.
Enhanced Cancer Radiotherapy through Immunosuppressive Stromal Cell Destruction in Tumors
Authors: Chao-Yi Wu, Li-Hua Yang, Huang-Yu Yang, Jayne Knoff, Shiwen Peng, Yi-Hsin Lin, Chenguang Wang, Ronald D. Alvarez, Sara I. Pai, Richard B.S. Roden, Chien-Fu Hung, T-C Wu
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Radiotherapy kills cancer cells by causing DNA damage, and stimulates a systemic antitumor immune response by releasing tumor antigen and endogenous adjuvant within the tumor microenvironment. However, radiotherapy also induces the recruitment of immunosuppressive myeloid cells, which can interfere with the antitumor immune responses elicited by apoptotic tumor cells. We hypothesized that local delivery of vaccine following radiotherapy will lead to the priming of antigen-specific CTL immune responses and render immunosuppressive myeloid cells susceptible to killing by the activated CTLs. Experimental Design: Using several antigenic systems, we tested whether intratumoral injection of antigenic peptide/protein in irradiated tumors would be able to prime CTLs as well as load myeloid cells with antigen, rendering them susceptible to antigen-specific CTL killing. Results: We show that by combining radiotherapy and targeted antigenic peptide delivery to the tumor, the adjuvant effect generated by radiotherapy itself was sufficient to elicit the priming and expansion of antigen-specific CTLs, through the type I IFN-dependent pathway, leading to synergistic therapeutic antitumor effects compared with either treatment alone. In addition, using two different types of transgenic mice, we demonstrated that CTL-mediated killing of stromal cells in tumors by our approach is important for tumor control. Finally, we confirmed the efficacy of this approach in our preclinical model using two clinically tested therapeutic human papilloma virus (HPV) vaccines. Conclusions: These data serve as an important foundation for the future clinical translation of radiotherapy combined with a clinically tested therapeutic HPV vaccine for the control of HPV-associated cancers. Clin Cancer Res; 20(3); 644–57. ©2013 AACR.
Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component.
Authors: P N Hawkins, M J Myers, A A Epenetos, D Caspi, M B Pepys
Journal: The Journal of Experimental Medicine (1988)

Highly specific, high-resolution scintigraphic images of amyloid-laden organs in mice with experimentally induced amyloid A protein (AA) amyloidosis were obtained after intravenous injection of 123I-labeled serum amyloid P component (SAP). Interestingly, a much higher proportion (up to 40%) of the injected dose of heterologous human SAP localized to amyloid and was retained there than was the case with isologous mouse SAP, indicating that human SAP binds more avidly to mouse AA fibrils than does mouse SAP. Specificity of SAP localization was established by the failure of the related proteins, human C-reactive protein and Limulus C-reactive protein, to deposit significantly in amyloid and by the absence of human SAP deposition in nonamyloidotic organs. However, only partial correlations were observed between the quantity of SAP localized and two independent estimates, histology and RIA for AA of the amount of amyloid in particular organs. It is not clear which of the three methods used reflects better the extent or clinical significance of the amyloid deposits but in vivo localization of radiolabeled SAP, detectable and quantifiable by gamma camera imaging, is apparently extremely sensitive. These findings establish the use of labeled SAP as a noninvasive in vivo diagnostic probe in experimental amyloidosis, potentially capable of revealing the natural history of the condition, and suggest that it may also be applicable generally as a specific targeting agent for diagnostic and even therapeutic purposes in clinical amyloidosis.
A method for bronchoscopic evaluation of salivary aspiration in a disabled child
Authors: N.J Zurick, A.J.W Henderson, S.C Langton-Hewer
Journal: European Respiratory Journal (2000)

Chronic aspiration is a cause of life-threatening respiratory complications and repeated hospital admissions, particularly in children with neurological disabilities. Determining the source of aspiration is important for optimizing treatment. This report describes a simple technique to demonstrate salivary aspiration during fibreoptic bronchoscopy. A child with a history of recurrent pneumonia was given methylene blue orally 2 h prior to fibreoptic bronchoscopy. Bronchoscopy was carried out through a laryngeal mask airway under inhalational anaesthesia. The stained saliva was seen to be pooling in the valleculae and then running down the trachea into the bronchi, confirming salivary aspiration.
Randomized Phase III Trial of Capecitabine Compared With Bevacizumab Plus Capecitabine in Patients With Previously Treated Metastatic Breast Cancer
Authors: Kathy D. Miller, Linnea I. Chap, Frankie A. Holmes, Melody A. Cobleigh, P. Kelly Marcom, Louis Fehrenbacher, Maura Dickler, Beth A. Overmoyer, James D. Reimann, Amy P. Sing, Virginia Langmuir, Hope S. Rugo
Journal: Journal of Clinical Oncology (2005)

This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility.From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer Treatment--Breast were comparable in both treatment groups.Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.
Molecular Phylogenies and Divergence Times of Sea Urchin Species of Strongylocentrotidae, Echinoida
Authors: Y.-H. Lee
Journal: Molecular Biology and Evolution (2003)

Sea urchins of the family Strongylocentrotidae have been important model systems in many fields of basic biology, yet knowledge of their evolutionary identities such as the phylogenetic relationships and divergence times remains limited. Here, I inferred molecular phylogenies of seven Strongylocentrotid species (Strongylocentrotus franciscanus, S. nudus, S. purpuratus, S. intermedius, S. droebachiensis, S. pallidus, and Hemicentrotus pulcherrimus) from the analyses of mitochondrial DNA sequences of 12SrDNA (349 nt), 12SrDNA-tRNA(gln) region (862 nt), and a combined sequence of cytochrome oxidase subunit I (COI, 1080 nt) and NADH dehydrogenase subunit I (NDI, 742 nt). The rate of sequence evolution and divergence times for each species were then estimated from the trees with reference to the time of separation between Strongylocentrotidae and Parechinidae, 35 to 50 MYA. The three trees agree well with each other, and the phylogeny is summarized by ((S. franciscanus, S. nudus), (H. pulcherrimus (S. purpuratus, S. intermedius (S. droebachiensis, S. pallidus)))). It is notable that the genus Strongylocentrotus consists of two distinct clades and that H. pulcherrimus branches off within Strongylocentrotus, implying assignment of a separate, monospecific genus to this species inappropriate. The rate of sequence evolution is calibrated to be 0.24%–0.34%/Myr in 12SrDNA, 0.25%–0.36%/Myr in 12SrDNA-tRNA(gln), and 0.65%–0.93%/Myr in COI-NDI combined sequences. S. purpuratus, in particular, shows the significantly higher rate of evolution in the 12SrDNA and 12SrDNA-tRNA(gln) regions compared to other species, suggesting careful use of its sequences in comparative studies. The two clades of Strongylocentrotidae seem to have split 13–19 MYA, and H. pulcherrimus branched off 7.2–14 MYA. In the former clade, S. franciscanus and S. nudus separated 5.7–8.1 MYA. In the latter clade, S. purpuratus, S. intermedius, and the clade of S. droebachiensis and S. pallidus diverged approximately 4.6–12 MYA, and the last two closest species separated 2.1–3.1 MYA.
Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis
Authors: C Rigamonti
Journal: Gut (2005)

<b>Backgrounds and aims:</b> To evaluate the prognosis of primary biliary cirrhosis (PBC) together with systemic sclerosis (SSc), as this is unknown. <b>Methods and results:</b> A PBC database of 580 patients identified 43 with PBC and SSc: two patients with PBC alone were matched to each PBC-SSc patient for serum bilirubin concentration at the initial visit. Forty (93%) patients had limited cutaneous SSc. At diagnosis of PBC, median values were: 49.7 years, bilirubin 17 μmol/l, and albumin 40.5 g/l. Liver diagnosis occurred a median 4.9 years after SSc in 24 (56%) patients. In matched patients, median values at diagnosis were: 53.2 years, bilirubin 12 μmol/l, and albumin 41 g/l. Median follow up was similar: 3.16 years (PBC-SSc) and 4.8 years (PBC alone). The risk of transplantation or death from diagnosis, adjusting for sex, age, log bilirubin, and alkaline phosphatase was significantly lower in PBC-SSc (hazard ratio 0.116, p = 0.01) due to less transplantation (hazard ratio 0.068, p = 0.006). The rate of bilirubin increase was less in PBC-SSc (p = 0.04). Overall survival was similar (hazard ratio 1.11, p = 0.948); there were nine deaths (21%) in PBC-SSc (six SSc related and two liver related) and nine (11%) in PBC alone (six liver related). <b>Conclusions:</b> Liver disease has a slower progression in PBC-SSc compared with matched patients with PBC alone.
PanIN-Specific Regulation of Wnt Signaling by HIF2α during Early Pancreatic Tumorigenesis
Authors: Angela Criscimanna, Li-Juan Duan, Julie A. Rhodes, Volker Fendrich, Emily Wickline, Douglas J. Hartman, Satdarshan P.S. Monga, Michael T. Lotze, George K. Gittes, Guo-Hua Fong, Farzad Esni
Journal: Cancer Research (2013)

Abstract Hypoxia promotes angiogenesis, proliferation, invasion, and metastasis of pancreatic cancer. Essentially, all studies of the hypoxia pathway in pancreatic cancer research to date have focused on fully malignant tumors or cancer cell lines, but the potential role of hypoxia inducible factors (HIF) in the progression of premalignant lesions has not been critically examined. Here, we show that HIF2α is expressed early in pancreatic lesions both in human and in a mouse model of pancreatic cancer. HIF2α is a potent oncogenic stimulus, but its role in Kras-induced pancreatic neoplasia has not been discerned. We used the Ptf1aCre transgene to activate KrasG12D and delete Hif2α solely within the pancreas. Surprisingly, loss of Hif2α in this model led to markedly higher, rather than reduced, number of low-grade pancreatic intraepithelial neoplasia (mPanIN) lesions. These lesions, however, failed to progress to high-grade mPanINs, and displayed exclusive loss of β-catenin and SMAD4. The relationship among HIF2α, β-catenin, and Smad4 was further confirmed in vitro, where silencing of Hif2α resulted in reduced β-catenin and Smad4 transcript levels. Thus, with oncogenic Ras expressed in the pancreas, HIF2α modulates Wnt-signaling during mPanIN progression by maintaining appropriate levels of both Smad4 and β-catenin. Cancer Res; 73(15); 4781–90. ©2013 AACR.
Identification of Transformation-Related Pathways in a Breast Epithelial Cell Model Using a Ribonomics Approach
Authors: Krystyna Mazan-Mamczarz, Patrick R. Hagner, Bojie Dai, William H. Wood, Yongqing Zhang, Kevin G. Becker, Zhenqui Liu, Ronald B. Gartenhaus
Journal: Cancer Research (2008)

Abstract The aberrant expression of many genes is a common feature in the malignant transformation of cells. In mammalian cells, posttranscriptional gene regulatory processes are emerging as critical determinants controlling gene expression both in physiologic and pathologic conditions. These regulatory mechanisms are directed primarily by the interaction of mRNAs with specific RNA-binding proteins (RBP). There is an emerging body of data demonstrating that two RBPs, AUF1 and HuR, can antagonistically affect the posttranscriptional fate of target mRNAs, as well as concurrently bind to common target transcripts. Employing MCT-1 oncogene-mediated transformation of immortalized breast epithelial MCF10A cells, we characterized the largely reciprocal association of these two RBPs with target mRNAs and their influence on protein expression vis-a-vis cellular transformation. Using a ribonomics approach, we identified mRNAs from cancer-related pathways whose association with AUF1 and/or HuR were altered when comparing immortalized with transformed MCF10A cells. Significantly, we were able to show that knockdown of HuR expression using RNA interference reduced anchorage-independent growth capacity in transformed MCF10A cells and decreased protein expression of a number of validated target genes. Our data show that the global alterations in binding of HuR and AUF1 with target transcripts have a critical role in posttranscriptional regulation of genes encoding proteins involved in breast epithelial cell transformation. These findings further support the feasibility of using a ribonomics approach for the identification of cancer-related pathways. [Cancer Res 2008;68(19):7730–5]
Human oocyte cryopreservation
Authors: Debra A. Gook, David H. Edgar
Journal: Human Reproduction Update (2007)

The clinical role of oocyte cryopreservation in assisted reproduction, as an adjunct to sperm and embryo cryopreservation, has been comparatively slow to evolve as a consequence of theoretical concerns related to efficacy and safety. Basic biological studies in the 1990's alleviated many of these concerns leading to more widespread adoption of the technology. While a number of babies were born from the approach validated in the 1990's, its perceived clinical inefficiency led to the search for improved methods. Introduction of elevated dehydrating sucrose concentrations during cryopreservation increased survival and fertilization rates, but there is no well-controlled evidence of improved clinical outcome. Similarly, the use of sodium-depleted cryopreservation media has not been demonstrated to increase clinical efficiency. More recently, and in the absence of basic biological studies addressing safety issues, the application of vitrification techniques to human oocytes has resulted in reports of a number of live births. The small number of babies born from clinical oocyte cryopreservation and the paucity of well-controlled studies currently preclude valid comparisons between approaches. Legal restrictions on the ability to select embryos from cryopreserved oocytes in Italy, where many of the available reports originate, also obscure attempts to assess oocyte cryopreservation objectively.