tbuckley/cabot-search huggingface dataset:
Abstract 3235: Validation of anti-human PD1 and PD-L1 antibodies in MiXeno mouse models
Authors: Juan Zhang, Meng Qiao, Lan Zhang, Qian Shi
Journal: Cancer Research (2015)

Abstract As evidenced by strong clinical data from antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death protein-1 (PD-1), and its ligand PD-L1, cancer immunotherapy is now a major breakthrough in cancer treatment. Meanwhile, new immunotherapeutic agents with various targets and mechanisms, as well as new drug combinations are under active preclinical development. However, reliable humanized animal models are of increasing importance as more programs are reaching the in vivo stage, where direct evaluation of therapeutics with anti-human targets are necessary. We have previously reported our efforts in generating mouse MiXeno models that harbor human immune cells by engrafting immuno-deficient mice with human PBMC (the MiXenoTM model) to evaluate anti-PD-L1 antibody. In the current study, we carried out extensive validation of these models in vivo by generating multiple cell line-derived MiXeno models and testing them with anti-human PD-1 or PD-L1 antibodies in different animal strains (NOD/SCID vs. NPG). Our studies demonstrated that MiXeno models can successfully reconstitute human T cells in mice to support the anti-tumor activity of the immuno-therapeutic agents. MiXeno model is simple and fast, and may become valuable tools for in vivo evaluation of immunotherapeutic agents. Citation Format: Juan Zhang, Meng Qiao, Lan Zhang, Qian Shi. Validation of anti-human PD1 and PD-L1 antibodies in MiXeno mouse models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3235. doi:10.1158/1538-7445.AM2015-3235
Evolution in Nervous Systems
Authors: E. A. Arbas, I. A. Meinertzhagen, S. R. Shaw
Journal: Annual Review of Neuroscience (1991)

Evolution is the unifying theme of biological thought. It is therefore surprising that until recently it has little shaped the ideas of those who have sought principles among the cells and circuits of nervous systems. After relegation to an historic approach for many decades, an evolutionary perspective in neuroscience has revived, armed now with evidence available from the identified-neuron approach (Bullock & Horridge 1965; Bullock 1974; Wiersma 1974; Hoyle 1983) and fortified by modern molecular developments. In this review we have concentrated mostly on the molec­ ular, cellular, and circuit level of analysis wherever there is an evolutionary dimension, compelled for want of space to neglect the extensive fields of comparative neurology and of behavior, except for a few cases for which correlated cell or molecular information was available. Of the several good reasons for renewed interest in the evolutionary background to neural operation, two may be singled out. First, understanding how nervous systems evolve may give critical insight into otherwise inexplicable details of their construction. Animals were not designed de novo by engineers, but sculpted through natural selection acting upon variations arising within their ontogenetic programs,
Mechanisms for anterior cruciate ligament injuries in badminton
Authors: Yuka Kimura, Yasuyuki Ishibashi, Eiichi Tsuda, Yuji Yamamoto, Harehiko Tsukada, Satoshi Toh
Journal: British Journal of Sports Medicine (2010)

A high incidence of anterior cruciate ligament (ACL) injuries related to sports activities has been reported; however, the injury situation of ACL injury in badminton has not been elucidated. This study investigated the mechanism of ACL injury in badminton using a questionnaire.Information on injury mechanism was gathered from interviews with six male and 15 female badminton players who received a non-contact ACL injury playing badminton and underwent ACL reconstruction.The most common injury mechanism (10 of 21 injuries) was single-leg landing after overhead stroke. Nine of 10 players had injured the knee opposite to the racket-hand side. The second most frequent injury mechanism (eight of 21 injuries) was plant-and-cut while side-stepping or backward stepping. All eight players injured the knee of the racket-hand side. Eleven injuries occurred in the rear court, and six of the 11 injuries occurred during single-leg landing after an overhead stroke.The knee opposite to the racket-hand side tended to sustain the ACL injuries during single-leg landing after a backhand overhead stroke, whereas the knee of the racket-hand side tended to be injured by plant-and-cut during side or backward stepping. These injury patterns appear to be due to specific movements during badminton.
Realist review to understand the efficacy of school feeding programmes
Authors: Trisha Greenhalgh, Elizabeth Kristjansson, Vivian Robinson
Journal: BMJ (2007)

A recent Cochrane review found that school feeding programmes significantly improve the growth and cognitive performance of disadvantaged children. <b>Trisha Greenhalgh,</b><b>Elizabeth Kristjansson, </b>and<b> Vivian Robinson</b> look more closely at the highly heterogeneous trials to see what works, for whom, and in what circumstances
Behavior Therapy for Families of Adolescents With Diabetes
Authors: Tim Wysocki, Peggy Greco, Michael A. Harris, Jeannie Bubb, Neil H. White
Journal: Diabetes Care (2001)

OBJECTIVE—This study reports 6- and 12-month follow-up for the families of adolescents with diabetes who participated in a trial of Behavioral–Family Systems Therapy (BFST). RESEARCH DESIGN AND METHODS—A total of 119 families of adolescents with type 1 diabetes were randomized to 3 months of treatment with either BFST, an education and support (ES) group, or current therapy (CT). Family relationships, adjustment to diabetes, treatment adherence, and diabetic control were assessed at baseline, after 3 months of treatment, and 6 and 12 months later. This report focuses on the latter two evaluations. RESULTS—Compared with CT and ES, BFST yielded lasting improvements in parent-adolescent relationships and diabetes-specific conflict. Delayed effects on treatment adherence emerged at 6- and 12-month follow-ups. There were no immediate or delayed effects on adolescents’ adjustment to diabetes or diabetic control. CONCLUSIONS—BFST yielded lasting improvement in parent-adolescent relationships and delayed improvement in treatment adherence, but it had no effect on adjustment to diabetes or diabetic control. A variety of adaptations to BFST could enhance its impact on diabetes outcomes.
Bacillus oleronius and Demodex mite infestation in patients with chronic blepharitis
Authors: A. Szkaradkiewicz, I. Chudzicka-Strugała, T.M. Karpiński, O. Goslińska-Pawłowska, T. Tułecka, W. Chudzicki, A.K. Szkaradkiewicz, R. Zaba
Journal: Clinical Microbiology and Infection (2011)
Application of Metabolomics to Diagnosis of Insulin Resistance
Authors: Michael V. Milburn, Kay A. Lawton
Journal: Annual Review of Medicine (2013)

Metabolomics, the global interrogation of the biochemical components in a biological sample, has become an important complement to genomics and proteomics to aid in the understanding of pathophysiology. Major advantages of metabolomics are the size of the metabolome relative to the genome or proteome and the fact that it provides a view of the existing biochemical phenotype. As such, metabolomics is fast becoming an important discovery tool for new diagnostic and prognostic biomarkers. Although many methods exist for performing metabolomics, relatively few have led to successful development of new diagnostic tests. This review will aid the reader in understanding various metabolomic methods and their applications, as well as some of their inherent advantages and disadvantages. In addition, we present one example of the application of metabolomics to the identification of new fasting blood biomarkers for the diagnosis and monitoring of insulin resistance.
Deficiency in p53 but not Retinoblastoma Induces the Transformation of Mesenchymal Stem Cells <i>In vitro</i> and Initiates Leiomyosarcoma <i>In vivo</i>
Authors: Ruth Rubio, Javier García-Castro, Iván Gutiérrez-Aranda, Jesús Paramio, Mirentxu Santos, Purificación Catalina, Paola E. Leone, Pablo Menendez, René Rodríguez
Journal: Cancer Research (2010)

Sarcomas have been modeled in mice by the expression of specific fusion genes in mesenchymal stem cells (MSC), supporting the concept that MSCs might be the target initiating cell in sarcoma. In this study, we evaluated the potential oncogenic effects of p53 and/or retinoblastoma (Rb) deficiency in MSC transformation and sarcomagenesis. We derived wild-type, p53(-/-), Rb(-/-), and p53(-/-)Rb(-/-) MSC cultures and fully characterized their in vitro growth properties and in vivo tumorigenesis capabilities. In contrast with wild-type MSCs, Rb(-/-), p53(-/-), and p53(-/-)Rb(-/-) MSCs underwent in vitro transformation and showed severe alterations in culture homeostasis. More importantly, p53(-/-) and p53(-/-)Rb(-/-) MSCs, but not Rb(-/-) MSCs, were capable of tumor development in vivo after injection into immunodeficient mice. p53(-/-) or p53(-/-)Rb(-/-) MSCs originated leiomyosarcoma-like tumors, linking this type of smooth muscle sarcoma to p53 deficiency in fat tissue-derived MSCs. Sca1+ and Sca1 low/- cell populations isolated from ex vivo-established, transformed MSC lines from p53(-/-)Rb(-/-) tumors showed identical sarcomagenesis potential, with 100% tumor penetrance and identical latency, tumor weight, and histologic profile. Our findings define the differential roles of p53 and Rb in MSC transformation and offer proof-of-principle that MSCs could provide useful tools to dissect the sarcoma pathogenesis.
Treatment of Former Smokers With 9-cis-Retinoic Acid Reverses Loss of Retinoic Acid Receptor- Expression in the Bronchial Epithelium: Results From a Randomized Placebo-Controlled Trial
Authors: J. M. Kurie, R. Lotan, J. J. Lee, J. S. Lee, R. C. Morice, D. D. Liu, X.-C. Xu, F. R. Khuri, J. Y. Ro, W. N. Hittelman, G. L. Walsh, J. A. Roth, J. D. Minna, W. K. Hong
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Loss of retinoic acid receptor beta (RAR-β) expression in the bronchial epithelium is considered a biomarker of preneoplasia. Retinoids can restore expression of this receptor and, presumably, halt the progression of carcinogenesis. This study was designed to investigate whether either of two retinoid-based regimens, 9-cis-retinoic acid (RA) or 13-cis-RA plus α-tocopherol (AT), could reverse RAR-β expression loss in former smokers after 3 months of treatment. Methods: Individuals (n = 226) who had smoked at least 20 pack-years and had ceased smoking for at least 12 months were randomly assigned to receive 3 months of daily oral 9-cis-RA (100 mg), 13-cis-RA (1 mg/kg) + AT (1200 IU), or placebo. Bronchoscopy and biopsy at six predetermined sites of the bronchial tree were performed before treatment and at 3 and 6 months thereafter. Specimens were evaluated for squamous metaplasia, dysplasia, and RAR-β expression. McNemar’s test was used to test changes in RAR-β expression and squamous metaplasia within each treatment group, and a generalized estimating equations model was applied to model the treatment effect, adjusting for covariates. All statistical tests were two-sided. Results: A total of 177 assessable subjects completed at least 3 months of therapy and underwent at least the baseline and 3-month bronchoscopic evaluations with biopsies. RAR-β was detected in 69.7% of all baseline biopsy samples, and metaplasia was evident in 6.9% of all baseline samples from 240 subjects. Restoration of RAR-β expression (P = .03) and reduction of metaplasia (P = .01) were found in the 9-cis-RA group. After adjustment for years of smoking, packs/day smoked, and metaplasia, treatment with 9-cis-RA, but not with 13-cis-RA + AT, led to a statistically significant increase in RAR-β expression compared with placebo (P = .03). Conclusion: 9-cis-RA treatment can restore RAR-β expression in the bronchial epithelium of former smokers, raising the possibility that this retinoid has potential chemopreventive properties in former smokers.
Circulating Tumor Cells: From Bench to Bedside
Authors: Marija Balic, Anthony Williams, Henry Lin, Ram Datar, Richard J. Cote
Journal: Annual Review of Medicine (2012)

Circulating tumor cells (CTCs) represent a surrogate biomarker of hematogenous metastases. In recent years, their detection has gained increasing interest. There is ample evidence regarding the ability to detect CTCs and their prognostic relevance, but their demonstrated predictive value in therapeutic response monitoring is clinically even more meaningful. Many clinical trials in the early and metastatic cancer setting now include CTCs as a monitoring parameter, and numerous translational studies attempting their molecular characterization are under way. There has been great progress in defining the clinical importance of CTCs, and it now seems likely that we may expect wider implementation of CTCs as a diagnostic oncology tool to monitor therapeutic response in real time. Novel technologies may further facilitate molecular characterization of CTCs and development of novel therapeutic targets, possibly leading to more powerful treatment strategies for cancer patients. As the detection and evaluation of CTCs are becoming an increasingly important diagnostic and prognostic tool, the goal of this review is to communicate the knowledge obtained through analysis of primary tumors and CTCs to oncologists and medical specialists in managing patients with cancer.
Pneumococcal septicaemia in a patient with systemic lupus erythematosus
Authors: A R Mackenzie, R B S Laing, A G MacDonald, C C Smith
Journal: Annals of the Rheumatic Diseases (1997)

Case reportA thirty eight year old woman with insulin dependent diabetes mellitus and systemic lupus erythematosus (SLE) was admitted with a two day history of fever, rigors, and diarrhoea.SLE was diagnosed at the age of 18 years when she presented with joint pain, a positive antinuclear antibody (ANA), and severe autoimmune thrombocytopenia, which was treated with corticosteroids.At no stage of her illness did she have evidence of renal, central nervous system, muscle or skin involvement.She had also suVered four miscarriages in association with anticardiolipin antibodies.There was no history of arterial or venous thrombosis and her disease had been inactive for a number of years.When reviewed as an outpatient, two months before admission, she was well with no clinical manifestations of SLE.ANA was positive (1:160), extractable nuclear antigen screen negative, C3 141g/l (88-201), C4 23.1g/l (16-47), DNA binding 3I U/l (0-7), anticardiolipin antibody was 30 gpl units (<10) and lupus anticoagulant test was not performed.Full blood count, including lymphocyte count and blood film, was entirely normal.She was not receiving immunosuppressive or corticosteroid therapy.On admission to the Infection Unit she was febrile at 40°C, with a tachycardia of 130/min, blood pressure 65/38 mm Hg, and tenderness over the frontal sinuses.There was no neck stiVness and she was lucid.She was receiving no immunosuppressive therapy and her only medication was regular subcutaneous insulin injections.Her initial investigations showed a white cell count 30.4 × 10 9 /l (neutrophils 28 × 10 9 /l, lymphocytes 1.8 × 10 9 /l), haemoglobin 104 g/l, platelets 247 × 10 9 /l.The blood film showed prominent Howell -Jolly bodies and giant platelets, consistent with hyposplenism.The XDPs (X fraction of the fibrinogen degradation products) were raised at >200 ng/ml (normal <200) but the clotting screen was normal implying low grade disseminated intravascular coagulation.Urine analysis, blood urea, and electrolytes were normal but the blood glucose was increased at 15.5 mmol/l.C reactive protein was < 1.0 g/l.Immunoglobulin concentration were IgG 11.0 g/l (8-14), IgA 1.1 g/l (0.9-3.5), and IgM 1.9 g/l (0.5-2.5).
Respiratory Arrest After Intrathecal Morphine
Authors: N. Katherine Babcock
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The article "Intrathecal Morphine for Intraoperative and Postoperative Analgesia" by Tung et al (1980;244:2637) suggested that subarachnoid narcotics may be used both in the surgical patient and in the terminal cancer patient with intractable pain. The report suggested that intrathecal morphine has the potential to give long-term analgesia (up to 30 hours) at low dosages (as little as 1 mg) without cardiovascular or respiratory depression, even in the extremely debilitated patient. There have been recent reports of respiratory arrest several hours after small doses of intrathecally given narcotics. Davies et al<sup>1</sup>reported two cases of respiratory arrest ten hours after morphine administration. Glynn et al<sup>2</sup>reported two cases of respiratory depression six and 11 hours after subarachnoid narcotic administration. The respiratory depression was readily reversed by naloxone in these patients. The delayed onset of respiratory depression may be caused by the slow movement of the
Large Variations in Bacterial Ribosomal RNA Genes
Authors: K. Lim, Y. Furuta, I. Kobayashi
Journal: Molecular Biology and Evolution (2012)

Ribosomal RNA (rRNA) genes, essential to all forms of life, have been viewed as highly conserved and evolutionarily stable, partly because very little is known about their natural variations. Here, we explored large-scale variations of rRNA genes through bioinformatic analyses of available complete bacterial genomic sequences with an emphasis on formation mechanisms and biological significance. Interestingly, we found bacterial genomes in which no 16S rRNA genes harbor the conserved core of the anti-Shine-Dalgarno sequence (5'-CCTCC-3'). This loss was accompanied by elimination of Shine-Dalgarno-like sequences upstream of their protein-coding genes. Those genomes belong to 1 or 2 of the following categories: primary symbionts, hemotropic Mycoplasma, and Flavobacteria. We also found many rearranged rRNA genes and reconstructed their history. Conjecturing the underlying mechanisms, such as inversion, partial duplication, transposon insertion, deletion, and substitution, we were able to infer their biological significance, such as co-orientation of rRNA transcription and chromosomal replication, lateral transfer of rRNA gene segments, and spread of rRNA genes with an apparent structural defect through gene conversion. These results open the way to understanding dynamic evolutionary changes of rRNA genes and the translational machinery.
Pretreatment Prostate-Specific Antigen (PSA) Velocity and Doubling Time Are Associated With Outcome but Neither Improves Prediction of Outcome Beyond Pretreatment PSA Alone in Patients Treated With Radical Prostatectomy
Authors: Matthew Frank O'Brien, Angel M. Cronin, Paul A. Fearn, Brandon Smith, Jason Stasi, Bertrand Guillonneau, Peter T. Scardino, James A. Eastham, Andrew J. Vickers, Hans Lilja
Journal: Journal of Clinical Oncology (2009)

Controversy exists as to whether current pretreatment prostate-specific antigen (PSA) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer. We assessed whether pretreatment PSA velocity (PSAV) or doubling time (PSADT) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model.The cohort included 2,938 patients with two or more PSA values before radical prostatectomy. Biochemical recurrence (BCR) occurred in 384 patients, and metastases occurred in 63 patients. Median follow-up for patients without BCR was 2.1 years. We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis. Predictive accuracy was assessed using the concordance index.On univariate analysis, two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis (P < .05). One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone, and four PSAV definitions improved prediction of metastasis. However, the improvements in predictive accuracy were small, associated with wide CIs, and markedly reduced if additional predictors of stage and grade were included alongside PSA. Modeling with random variables suggests that similar results would be expected by chance. CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone.
Inhibitory Smads and TGF-β Signaling in Glomerular Cells
Authors: Mario Schiffer, Lena E. Schiffer, Arti Gupta, Andrey S. Shaw, Ian S.D. Roberts, Peter Mundel, Erwin P. Bo[Combining Diaeresis]ttinger
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-β, receptor tyrosine kinase (RTK), JAK/STAT, and NF-κB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGF-β signaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is upregulated in podocytes in all examined glomerular diseases (focal segmental glomerulosclerosis [FSGS], minimal-change disease [MCD], membranous nephropathy [MNP], lupus nephritis [LN], and diabetic nephropathy [DN]) with a statistically significant upregulation in "classical" podocyte-diseases such as FSGS and MCD. TGF-β induces Smad7 synthesis in cultured podocytes and Smad6 synthesis in cultured mesangial cells. Although Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-β signaling in podocytes, it inhibited only Smad3 but not Smad2 signaling in mesangial cells. In contrast, Smad6 had no effect on TGF-β/Smad signaling in podocytes and enhanced Smad3 signaling in mesangial cells. These data suggest that Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-β/Smad signaling in addition to its pro-apoptotic activity, whereas Smad6 has no role in TGF-β response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-β/Smad signaling. These data indicate an important role for Smad6 and Smad7 in glomerular cells in vivo that could be important for the cell homeostasis in physiologic and pathologic conditions.