tbuckley/cabot-search huggingface dataset:
Radiotherapy of Experimental Lung Tumors in the Presence and Absence of a Radioprotective Drug, S-2-(3-aminopropylamino)ethylphosphorothioic Acid (WR-2721)2
Authors: John M. Yuhas
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Radiotherapy of Experimental Lung Tumors in the Presence and Absence of a Radioprotective Drug, S-2-(3-aminopropylamino)ethylphosphorothioic Acid (WR-2721) Get access John M. Yuhas John M. Yuhas Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 1, January 1973, Pages 69–78, https://doi.org/10.1093/jnci/50.1.69 Published: 01 January 1973 Article history Received: 10 February 1972 Accepted: 08 August 1972 Revision received: 29 August 1972 Published: 01 January 1973
Strain DD, a New High Mammary Tumor Strain, and Comparison of DD With Strain C3H
Authors: W. E. Heston, George Vlahakis, Y. Tsu-Bura
Journal: JNCI Journal of the National Cancer Institute (1964)

Strain DD is a new high mammary tumor strain unrelated to other high mammary tumor strains in origin. It has the mammary tumor virus. Comparison is made between DD and our strain C3H which has the highest susceptibility to mammary tumors of any strain we know. The incidence of mammary tumors in DD is high, although not quite so high as in C3H, but, like in C3H, the incidence is high in virgin females as well as in breeders. Data presented show that strain C3HfB (C3H without the mammary tumor virus) continues to have a median incidence of mammary tumors in breeding females of a relatively old age, which we believe to be the result of high genetic susceptibility and hormonal stimulation from breeding in the absence of the mammary tumor virus. Reciprocal foster-nursing between DD and C3H and the use of fostered virgin C3HfB females for assay demonstrated that the mammary tumor virus of DD was weaker either qualitatively or quantitatively than that of C3H. There was no consistent evidence that the strains differed in their genetic susceptibility to the virus. The most interesting characteristic of females of DD is the progression and regression of some of their mammary tumors involving early plaque formation in relation to pregnancy, as described by others for strain RIII and RIII hybrids.
Generation of immunoglobulin heavy chain diversity subsequent to cell surface immunoglobulin expression in the avian bursa of Fabricius.
Authors: M J Ratcliffe
Journal: The Journal of Experimental Medicine (1989)

The avian bursa of Fabricius represents a site for the generation of antibody diversity. Transfer of neonatal bursal cells into cyclophosphamide-treated neonatal chickens results in reconstitution of recipient bursae with donor-derived bursal stem cells. These stem cells express cell surface IgM and, under conditions of limiting donor bursal stem cell numbers, each reconstituted bursal follicle is colonized by a single precursor cell. The expression of an Ig VH idiotype, CVH-1, was found to be heterogenous within such clonal follicles. The diversity generated within the bursa is subsequently found within the peripheral B cell compartment. Thus, the generation of functional Ig H chain diversity is shown to occur subsequent to Ig H chain rearrangement and expression.
Challenges for Biomedical Informatics and Pharmacogenomics
Authors: Russ B. Altman, Teri E. Klein
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Pharmacogenomics requires the integration and analysis of genomic, molecular, cellular, and clinical data, and it thus offers a remarkable set of challenges to biomedical informatics. These include infrastructural challenges such as the creation of data models and databases for storing these data, the integration of these data with external databases, the extraction of information from natural language text, and the protection of databases with sensitive information. There are also scientific challenges in creating tools to support gene expression analysis, three-dimensional structural analysis, and comparative genomic analysis. In this review, we summarize the current uses of informatics within pharmacogenomics and show how the technical challenges that remain for biomedical informatics are typical of those that will be confronted in the postgenomic era.
Non-cardiac, non-oesophageal chest pain: the relevance of psychological factors
Authors: K Y Ho, J Y Kang, B Yeo, W L Ng
Journal: Gut (1998)

Background —No cause has been determined for chest pain that is neither cardiac nor oesophageal in origin. Aims —To compare the prevalence of lifetime psychiatric disorders and current psychological distress in three consecutive series of patients with chronic chest or abdominal pain. Patients —Thirty nine patients with non-cardiac chest pain and no abnormality on oesophagogastroduodenoscopy, oesophageal manometry, and 24 hour pH monitoring; 22 patients with non-cardiac chest pain having endoscopic abnormality, oesophageal dysmotility, and/or pathological reflux; and 36 patients with biliary colic. Methods —The Diagnostic Interview Schedule and the 28 item General Health Questionnaire were administered to all patients. Results —Patients with non-cardiac chest pain and no upper gastrointestinal disease had a higher proportion of panic disorder (15%), obsessive-compulsive disorder (21%), and major depressive episodes (28%) than patients with gallstone disease (0%, p&lt;0.02; 3%, p&lt;0.02; and 8%, p&lt;0.05, respectively). In contrast, there were no differences between patients with non-cardiac chest pain and upper gastrointestinal disease and patients with gallstone disease in any of the DSM-111 defined lifetime psychiatric diagnoses. Using the General Health Questionnaire, 49% of patients with non-cardiac chest pain without upper gastrointestinal disease scored above the cut off point (that is, more than 4), which was considered indicative of non-psychotic psychiatric disturbance, whereas only 14% of patients with gallstones did so (p&lt;0.005). The proportions of such cases were however similar between patients with non-cardiac chest pain and upper gastrointestinal disease (27%) and patients with gallstones. Conclusions —Psychological factors may play a role in the pathogenesis of chest pain that is neither cardiac nor oesophagogastric in origin.
Wall shear stress in the human common carotid artery as function of age and gender
Authors: S.K. Samijo, J.M. Willigers, R. Barkhuysen, P.J.E.H.M. Kitslaar, R.S. Reneman, P.J. Brands, A.P.G. Hoeks
Journal: Cardiovascular Research (1998)

Objectives: It has been postulated that in the arterial system mean wall shear stress is maintained at a constant value. The present study was performed to investigate the level of wall shear stress in the common carotid artery (CCA) as function of age and possible interactions between diameter and storage capacity, defined as the absolute area change per heart beat, with mean wall shear stress. Methods: Wall shear stress (wall shear rate multiplied by whole blood viscosity) was assessed in the right CCA of 111 presumed healthy male (n=56) and female (n=55) volunteers, varying in age between 10 and 60 years. Wall shear rate was measured with a high resolution ultrasound system. Simultaneously, arterial diameter and storage capacity were determined. Whole blood viscosity was calculated from haematocrit, plasma viscosity and shear rate. Results: From the second to the sixth age decade peak wall shear stress was significantly higher in males than in females and decreased from 4.3 Pa to 2.6 Pa (r=−0.56, p<0.001) in males and from 3.3 Pa to 2.5 Pa (r=−0.54, p<0.001) in females. Mean wall shear stress tended to decrease from 1.5 Pa to 1.2 Pa (r=−0.26, p=0.057) in males and decreased significantly from 1.3 Pa to 1.1 Pa (r=−0.30, p=0.021) in females. No significant difference in mean wall shear stress was found between males and females in any age decade. The diameter of the CCA increased significantly in both males (r=0.26, p<0.05) and females (r=0.40, p<0.003). Storage capacity decreased significantly in both sexes (males: r=−0.63, p<0.001; females: r=−0.68, p<0.001). Conclusions: These observations suggest that the reduction in mean wall shear stress with age results from the concomitant increase in diameter in an attempt of the arterial system to limit the reduction in storage capacity of the arterial system with increasing age.
Minister admits to "dysfunctional" NHS care for child and adolescent mental health
Authors: A. O'Dowd
Journal: BMJ (2014)

The NHS is currently “dysfunctional” when it comes to caring properly for child and adolescent mental health needs, a government health minister has said. Norman Lamb, minister for care and support, told an evidence session of the parliamentary health committee that services had to improve and that a national review would begin soon, to gather an accurate picture of the scale of the problem among young people.

The committee, holding the final evidence session for its inquiry into child and adolescent mental health services (CAMHS), asked what the government was doing about current statistics on the prevalence of mental health problems, which were 10 years old and out of date. 

Lamb said, “It is horribly out of …
Dendritic Cells Transduced with SOCS1 Gene Exhibit Regulatory DC Properties and Prolong Allograft Survival
Authors: Hong Fu, Shaohua Song, Fang Liu, Zhijia Ni, Yi Tang, Xiaoyun Shen, Liang Xiao, Guoshan Ding, Quanxing Wang
Journal: Cellular and Molecular Immunology (2009)
Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer
Authors: Sruti Shiva, Michael N. Sack, James J. Greer, Mark Duranski, Lorna A. Ringwood, Lindsay Burwell, Xunde Wang, Peter H. MacArthur, Amir Shoja, Nalini Raghavachari, John W. Calvert, Paul S. Brookes, David J. Lefer, Mark T. Gladwin
Journal: The Journal of Experimental Medicine (2007)

Nitrite (NO2−) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the mechanism of nitrite-mediated cytoprotection is unknown, NO is a mediator of the ischemic preconditioning cell-survival program. Analogous to the temporally distinct acute and delayed ischemic preconditioning cytoprotective phenotypes, we report that both acute and delayed (24 h before ischemia) exposure to physiological concentrations of nitrite, given both systemically or orally, potently limits cardiac and hepatic reperfusion injury. This cytoprotection is associated with increases in mitochondrial oxidative phosphorylation. Remarkably, isolated mitochondria subjected to 30 min of anoxia followed by reoxygenation were directly protected by nitrite administered both in vitro during anoxia or in vivo 24 h before mitochondrial isolation. Mechanistically, nitrite dose-dependently modifies and inhibits complex I by posttranslational S-nitrosation; this dampens electron transfer and effectively reduces reperfusion reactive oxygen species generation and ameliorates oxidative inactivation of complexes II–IV and aconitase, thus preventing mitochondrial permeability transition pore opening and cytochrome c release. These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet.
Topical amitriptyline combined with topical ketamine for the management of recalcitrant localized pruritus: A retrospective pilot study
Authors: Timothy J. Poterucha, Sinead L. Murphy, Paola Sandroni, Richard H. Rho, Roger A. Warndahl, William T. Weiss, Mark D.P. Davis
Journal: Journal of the American Academy of Dermatology (2013)
A Monocyte Chemoattractant Protein-1 (MCP-1) Polymorphism And Outcome After Renal Transplantation
Authors: Bernd Kru[Combining Diaeresis]ger, Bernd Schro[Combining Diaeresis]ppel, Rami Ashkan, Brad Marder, Carl Zu[Combining Diaeresis]lke, Barbara Murphy, Bernhard K. Kra[Combining Diaeresis]mer, Michael Fischereder
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Among the factors modulating transplant rejection and cardiovascular disease, chemokines and their respective receptors deserve special attention. In this respect, increased expression of MCP-1 and the corresponding receptor CCR2 have been demonstrated in renal transplant rejection and coronary artery disease. The impact of the MCP-1–2518G and CCR2–64I genotypes on renal allograft function was investigated in 232 patients who underwent transplantation over an 11-yr period. Genomic DNA was genotyped using PCR with sequence-specific primers followed by restriction fragment length polymorphism analysis. Eighteen (7.8%) patients were homozygous for the MCP-1–2518G mutation. The G/G allele of MCP-1 -2518 behaved as a determinant for long-term allograft survival and resulted in reduction of the mean graft survival, as compared with the heterozygous (A/G) or wild-type (A/A) allele (67 ± 14 versus 95 ± 4 mo; Log rank P = 0.0052). The 64I mutation of CCR2 had no effect on kidney graft failure (93 ± 6 and 91 ± 5 mo, respectively; P = 0.81). None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups. In conjunction with these findings, peripheral blood mononuclear cells from kidney transplant recipients carrying the G-allele were characterized by a 2.5-fold higher MCP-1 secretion (P < 0.05). In conclusion, recipients of renal transplants homozygous for the –2518 G mutation of the MCP-1 gene are at risk for premature kidney graft failure. This variant of MCP-1 may be a future predictor for long-term kidney graft failure. E-mail: [email protected]
Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model
Authors: Xiu-Min Li, Teng-Fei Zhang, Chih-Kang Huang, Kamal Srivastava, Ariel A. Teper, Libang Zhang, Brian H. Schofield, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2001)
Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir
Authors: J. Gerardo García-Lerma, Ron A Otten, Shoukat H Qari, Eddie Jackson, Mian-er Cong, Silvina Masciotra, Wei Luo, Caryn Kim, Debra R Adams, Michael Monsour, Jonathan Lipscomb, Jeffrey A Johnson, David Delinsky, Raymond F Schinazi, Robert Janssen, Thomas M Folks, Walid Heneine
Journal: PLoS Medicine (2008)

In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.
Jekyll and Hyde: Two Faces of Cannabinoid Signaling in Male and Female Fertility
Authors: Haibin Wang, Sudhansu K. Dey, Mauro Maccarrone
Journal: Endocrine Reviews (2006)

Mammalian reproduction is a complicated process designed to diversify and strengthen the genetic complement of the offspring and to safeguard regulatory systems at various steps for propagating procreation. An emerging concept in mammalian reproduction is the role of endocannabinoids, a group of endogenously produced lipid mediators, that bind to and activate cannabinoid receptors. Although adverse effects of cannabinoids on fertility have been implicated for years, the mechanisms by which they exert these effects were not clearly understood. With the identification of cannabinoid receptors, endocannabinoid ligands, their key synthetic and hydrolytic pathways, and the generation of mouse models missing cannabinoid receptors, a wealth of information on the significance of cannabinoid/endocannabinoid signaling in spermatogenesis, fertilization, preimplantation embryo development, implantation, and postimplantation embryonic growth has been generated. This review focuses on various aspects of the endocannabinoid system in male and female fertility. It is hoped that a deeper insight would lead to potential clinical applications of the endocannabinoid signaling as a target for correcting infertility and improving reproductive health in humans.
Characteristic Elevation of Matrix Metalloproteinase Activity in Idiopathic Interstitial Pneumonias
Authors: MORITAKA SUGA, KAZUHIRO IYONAGA, TATSUYA OKAMOTO, YASUHIRO GUSHIMA, HISAKO MIYAKAWA, TAKAAKI AKAIKE, MASAYUKI ANDO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Destruction of subepithelial basement membrane is a key event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To evaluate the role of matrix metalloproteinases (MMPs) in parenchymal remodeling in idiopathic interstitial pneumonia (IIP), we studied MMP-2 and -9 activity, in bronchoalveolar lavage fluid (BALF) by zymography and the expression of MMP-2 and -9 and TIMP-2 in lung tissue by immunohistochemistry. BALF and lung tissues were collected from 26 patients with usual interstitial pneumonia (IPF-UIP), 11 with nonspecific interstitial pneumonia (NSIP), and 6 with bronchiolitis obliterans organizing pneumonia (BOOP). IPF-UIP cases showed predominant expression of MMP-9, whereas NSIP and BOOP cases showed predominant MMP-2 expression in BALF and in tissues. In BALF samples from rapidly progressive IPF-UIP cases, neutrophil-derived MMP-9 activity, as well as MMP-9 active form were characteristically detected. Furthermore, the MMP-9 activity correlated significantly with an increase of neutrophils in BALF, whereas the MMP-2 activity associated with NSIP and BOOP correlated with an increase of lymphocytes. These results indicate that MMP-9 in IPF-UIP and MMP-2 in NSIP and BOOP may contribute to pulmonary structural remodeling through type IV collagenolytic activity. The characteristic contributions of matrix-degrading proteins may relate to the distinct prognostic features of these diseases.
Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria
Authors: Wenyi Shen, Michael J. Clemente, Naoko Hosono, Kenichi Yoshida, Bartlomiej Przychodzen, Tetsuichi Yoshizato, Yuichi Shiraishi, Satoru Miyano, Seishi Ogawa, Jaroslaw P. Maciejewski, Hideki Makishima
Journal: Journal of Clinical Investigation (2014)

Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disease of hematopoietic stem cells that is associated with hemolysis, marrow failure, and thrombophilia. PNH has been considered a monogenic disease that results from somatic mutations in the gene encoding PIGA, which is required for biosynthesis of glycosylphosphatidylinisotol-anchored (GPI-anchored) proteins. The loss of certain GPI-anchored proteins is hypothesized to provide the mutant clone with an extrinsic growth advantage, but some features of PNH argue that there are intrinsic drivers of clonal expansion. Here, we performed whole-exome sequencing of paired PNH+ and PNH– fractions on samples taken from 12 patients as well as targeted deep sequencing of an additional 36 PNH patients. We identified additional somatic mutations that resulted in a complex hierarchical clonal architecture, similar to that observed in myeloid neoplasms. In addition to mutations in PIGA, mutations were found in genes known to be involved in myeloid neoplasm pathogenesis, including TET2, SUZ12, U2AF1, and JAK2. Clonal analysis indicated that these additional mutations arose either as a subclone within the PIGA-mutant population, or prior to PIGA mutation. Together, our data indicate that in addition to PIGA mutations, accessory genetic events are frequent in PNH, suggesting a stepwise clonal evolution derived from a singular stem cell clone.
Toxicities of Immunotherapy for the Practitioner
Authors: Jeffrey S. Weber, James C. Yang, Michael B. Atkins, Mary L. Disis
Journal: Journal of Clinical Oncology (2015)

The toxicities of immunotherapy for cancer are as diverse as the type of treatments that have been devised. These range from cytokine therapies that induce capillary leakage to vaccines associated with low levels of autoimmunity to cell therapies that can induce damaging cross-reactivity with normal tissue to checkpoint protein inhibitors that induce immune-related adverse events that are autoinflammatory in nature. The thread that ties these toxicities together is their mechanism-based immune nature and the T-cell-mediated adverse events seen. The basis for the majority of these adverse events is a hyperactivated T-cell response with reactivity directed against normal tissue, resulting in the generation of high levels of CD4 T-helper cell cytokines or increased migration of cytolytic CD8 T cells within normal tissues. The T-cell immune response is not tissue specific and may reflect a diffuse expansion of the T-cell repertoire that induces cross-reactivity with normal tissue, effectively breaking tolerance that is active with cytokines, vaccines, and checkpoint protein inhibitors and passive in the case of adoptive cell therapy. Cytokines seem to generate diffuse and nonspecific T-cell reactivity, whereas checkpoint protein inhibition, vaccines, and adoptive cell therapy seem to activate more specific T cells that interact directly with normal tissues, potentially causing specific organ damage. In this review, we summarize the toxicities that are unique to immunotherapies, emphasizing the need to familiarize the oncology practitioner with the spectrum of adverse events seen with newly approved and emerging modalities.
Double tracer gas single-breath washout: promising for clinics or just a toy for research?
Authors: Philipp Latzin, Bruce Thompson
Journal: European Respiratory Journal (2014)

Ventilation inhomogeneity reflects the efficiency of gas transport in both central, convection-dependent and peripheral, diffusion-dependent airways. In recent years, there has been a renaissance of studies using inert-gas washout to assess ventilation inhomogeneity. This trend is due to promising results of multiple-breath washout (MBW) tests in different populations with various lung diseases, such as cystic fibrosis [1] and asthma [2]. Even though the MBW is becoming more widely used and better standardised, the long duration of the test is a potential impediment in daily clinical practice and in patients with severe lung disease. One alternative is to study the ventilation distribution based on one single breath, by performing the so-called single-breath washout (SBW). The SBW test is not new, having been done for the first time more than 60 years ago, by using 100% oxygen to study the washout of the resident nitrogen (N2) [3], or by using a double tracer gas (DTG) mixture, such as helium (He) and sulfur hexafluoride (SF6) [4]. Usually the SBW test is done during a vital capacity manoeuvre (VC-SBW) and there is a recent European Respiratory Society/American Thoracic Society consensus statement on how to perform the VC-SBW test [5]. A clear disadvantage of the VC-SBW test is the dependence on the vital capacity manoeuvre. This is particularly a problem in children younger than 12 years and, in general, results might be influenced by restricted ability of patients performing the manoeuvre [5]. Furthermore, it has been shown that deep inspiration influences expiratory slopes [6 …
The Influence of Prior Abiraterone Treatment on the Clinical Activity of Docetaxel in Men with Metastatic Castration-resistant Prostate Cancer
Authors: Michael T. Schweizer, Xian C. Zhou, Hao Wang, Sunakshi Bassi, Michael A. Carducci, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: European Urology (2014)