tbuckley/cabot-search huggingface dataset:
New Drugs: Prescribing for infants and children
Authors: G W Rylance
Journal: BMJ (1988)

<b>1496</b> <h3><b>Objectives:</b></h3> A room size PET scanner with head tracking will enable investigation of the brain function of active human subjects in a natural setting. The geometric sensitivity of such a scanner at the center of the field of view (FOV) has been previously studied. The purpose of this work is to characterize the geometric sensitivity of a room PET scanner throughout the entire FOV. <h3><b>Methods:</b></h3> An analytic expression for spatial-dependent geometric sensitivity was derived for the case of a rectangular room with PET detectors along each of the walls. The detectors are at the same distance above the floor and their height is the same, thus forming an open box configuration. For a point source at an arbitrary location in the PET FOV the probability of escape of one or both annihilation photons through the top or bottom bounding planes of the PET detector box is modeled. The sensitivity expression has 12 terms and uses formulae for the solid angle of right square pyramids. The derived expression will apply to any open box arrangement of PET detectors. As an application, sensitivity maps were calculated for a square room with dimensions 3 m on a side, and for detectors with heights of 1 and 2 m. Representative linear profiles through the FOV were generated and compared. <h3><b>Results:</b></h3> Geometric sensitivities from the derived equation agree with values from limiting cases, such as for points on the central axis of the PET FOV. In horizontal slices parallel to the floor, sensitivity in central planes is peaked at the center of the FOV. In horizontal slices closer to the top and bottom of the detectors, sensitivity decreases near the center of the FOV and increases toward the walls of the room. In vertical slices parallel to the walls the sensitivity profiles have a triangular shape at the center of the FOV and approximate a triangular shape closer to the walls. This is similar to the triangular sensitivity profile along the central axis of a conventional cylindrical PET scanner. Geometric sensitivity increases with the height of the detectors, as expected, and the sensitivity maps show similar features for different detector heights. <h3><b>Conclusions:</b></h3> An analytic expression was developed for the 3D spatial-dependent geometric sensitivity of a rectangular room PET scanner. The formula will apply to any open box arrangement of PET detectors. Application of the expression provides insight into the sensitivity function of a room PET system and is useful in system design.
Sun shows how not to report a case of HIV
Authors: D. Kirkham
Journal: BMJ (2015)

Critics are investigating the possibility that the UK national newspaper the Sun infringed press regulations with a story on its Remembrance Day front page headlined “Hollywood HIV panic.”1

The tabloid newspaper reported that “Hollywood was gripped with fear last night after a womanising A-list actor was diagnosed with HIV” but that it was “choosing not to name” the actor. The story continued, “His lawyers are believed to be aware of the situation and preparing for a raft of potential legal claims from previous lovers.”

An immediate media backlash ensued, with …
Inhibition of phagocytic recognition of anti-D opsonized Rh D+ RBC by polymer-mediated immunocamouflage
Authors: Li Li, Ghislain T. Noumsi, Yin Yu Eunice Kwok, Joann M. Moulds, Mark D. Scott
Journal: American Journal of Hematology (2015)

The Rh D antigen posed both a significant clinical risk and inventory supply issue in transfusion medicine. The successful development of the immunocamouflaged RBC has the potential to address both the risk of acute anti-D transfusion reactions and to improve D- blood inventory in geographic locations where D- blood is rare (e.g., China). The immunocamouflage of RBC was mediated by the covalent grafting of methoxy(polyethylene glycol) to the cell membrane thereby obscuring the D protein from the immune system. To determine the potential efficacy of mPEG-D+ RBC in D- recipients, anti-D alloantibodies from previously alloimmunized individuals were utilized. The effects of polymer chain size (2-30 kDa) and grafting concentration (0-4 mM) on antibody binding and erythrophagocytosis were determined using the clinically validated monocyte monolayer assay (MMA) and flow cytometry. The immunocamouflage of D was polymer size and grafting concentration dependent as determined using human anti-D alloantibodies (both pooled [RhoGAM] and single donors). Importantly, the 20 kDa polymer provided excellent immunocamouflage of D and reached a clinically significant level of protection, as measured by the MMA, at grafting concentrations of ≥1.5 mM. These findings further support the potential use of immunocamouflaged RBC to reduce the risk of acute transfusion reactions following administration of D+ blood to D- recipients in situations where D- units are unavailable or supply is geographically constrained.
Vitamin D3 Receptors: Structure and Function in Transcription
Authors: J W Pike
Journal: Annual Review of Nutrition (1991)

PERSPECTIVES AND SUMMARY   190 VITAMIN D3 HORMONE  191 Metabolism to the Active Form .........   . ....   191 Biologic Actions. ...... . ....... ......... . .   . . . . ...... ..... ...... . . ... . . .. . . .... . . . . . ... 192 Transcriptional Mechanism of Action . . . . . . . . . . ....... . . . . .. . . . ...... . .   192 VITAMIN D3 RECEPTOR  193 Cellular Distribution. .       193 Biochemical Properties and Subcellular Distribution.. . .. . . . . . . . . . . . . . .. . . . . . . . . . . . . .... . . 194 Vitamin D3 Receptor Regulation.... . . . ........ . ..... .   .... ........ . . . . .... .. . . . ...... 196 MOLECULAR BIOLOGY OF THE VITAMIN D3 RECEPTOR   198 Recombinant Cloning of the Vitamin D3 Receptor .... .... . ...... . . ..... .. . .. . ....... ...... 198 Steroid, Thyroid, and Retinoid Receptor Supeifamily   200 Structural Organization of the Nuclear Receptors   ..... ....... . .. . . . .... . . . .. 200 Role of the Vitamin D3 Receptor in Transactivation . ........ . ...... . . . ..... . . ..... . . . . . .. 202 HUMAN SYNDROME OF HEREDITARY 1,25-DIHYDROXYVITAMIN D3 RESISTANCE  205 Vitamin DrResistant Fibroblast Model .... ......... .   . ........ .. . . . . . . ...... 205 Genetic Lesions in the Vitamin D3 Receptor Chromosomal Locus . ....... . . ...... . . . .. 206 Functional Activity of Receptors Derived from Patient Genotypes  208 CONCLUSIONS  208
Evaluation of zirconia–porcelain interface using X-ray diffraction
Authors: Tariq F Alghazzawi, Gregg M Janowski
Journal: International Journal of Oral Science (2015)

The aim of this study was to determine if accelerated aging of porcelain veneering had an effect on the surface properties specific to a tetragonal-to-monoclinic transformation (TMT) of zirconia restorations. Thirty-six zirconia samples were milled and sintered to simulate core fabrication followed by exposure to various combinations of surface treatments including as-received (control), hydrofluoric acid (HF), application of liner plus firings, application of porcelain by manual layering and pressing with firing, plus accelerated aging. The quantity of transformed tetragonal to monoclinic phases was analyzed utilized an X-ray diffractometer and one-way analysis of variance was used to analyze data. The control samples as provided from the dental laboratory after milling and sintering process had no TMT (Xm = 0). There was an effect on zirconia samples of HF application with TMT (Xm = 0.8%) and liner plus HF application with TMT (Xm = 8.7%). There was an effect of aging on zirconia samples (no veneering) with significant TMT (Xm = 70.25%). Both manual and pressing techniques of porcelain applications reduced the TMT (manual, Xm = 4.41%, pressing, Xm = 11.57%), although there was no statistical difference between them. It can be concluded that simulated applications of porcelain demonstrated the ability to protect zirconia from TMT after aging with no effect of a liner between different porcelain applications. The HF treatment also caused TMT. Porcelain veneers protect zirconia dental restorations on aging but how the porcelain is applied has little effect on zirconia stability. Porcelain is added to zirconia restorations principally for cosmetic reasons, however, it is prone to chipping. The phase transformation of zirconia from a tetragonal to a monoclinic crystal structure is believed to be a contributing factor to chipping. This transformation may be influenced by the preparation conditions of the restorations and aging within the oral environment. Using X-ray diffraction, Tariq Alghazzawi and Gregg Janowski at the University of Alabama at Birmingham, US, showed that porcelain protected zirconia samples from the structural transformation under accelerated aging conditions. There was no significant difference in the protection offered between manual layering and pressing methods of porcelain application.
A Distinct Mitochondrial Genome with DUI-Like Inheritance in the Ocean Quahog<i>Arctica islandica</i>
Authors: Cyril Dégletagne, Doris Abele, Christoph Held
Journal: Molecular Biology and Evolution (2015)

Mitochondrial DNA (mtDNA) is strictly maternally inherited in metazoans. The major exception to this rule has been found in many bivalve species which allow the presence of different sex-linked mtDNA molecules. This mechanism, named doubly uniparental inheritance (DUI), is characterized by the presence of two mtDNAs: The female mtDNA is found in somatic tissue and female gonads, whereas the male mtDNA is usually found in male gonads and sperm. In this study we highlight the existence of two divergent mitochondrial haplotypes with a low genetic difference around 6–8% in Arctica islandica, a long-lived clam belonging to the Arcticidae, a sister group to the Veneridae in which DUI has been found. Phylogenetic analysis on cytochrome b and 16S sequences from somatic and gonadic tissues of clams belonging to different populations reveals the presence of the "divergent" type in male gonads only and the "normal" type in somatic tissues and female gonads. This peculiar segregation of divergent mtDNA types speaks for the occurrence of the DUI mechanism in A. islandica. This example also highlights the difficulties to assess the presence of such particular mitochondrial inheritance system and underlines the possible misinterpretations in phylogeographic and phylogenetic studies of bivalve species linked to the presence of two poorly differentiated mitochondrial genomes.
T-Lymphocyte Recognition of Antigen in Association with Gene Products of the Major Histocompatibility Complex
Authors: Ronald H. Schwartz
Journal: Annual Review of Immunology (1985)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Reintroduction of a Homocysteine Level-Associated Allele into East Asians by Neanderthal Introgression
Authors: Ya Hu, Qiliang Ding, Yungang He, Shuhua Xu, Li Jin
Journal: Molecular Biology and Evolution (2015)

In this study, we present an analysis of Neanderthal introgression at the dipeptidase 1 gene, DPEP1. A Neanderthal origin for the putative introgressive haplotypes was demonstrated using an established three-step approach. This introgression was under positive natural selection, reached a frequency of >50%, and introduced a homocysteine level- and pigmentation-associated allele (rs460879-T) into East Asians. However, the same allele was also found in non-East Asians, but not from Neanderthal introgression. It is likely that rs460879-T was lost in East Asians and was reintroduced subsequently through Neanderthal introgression. Our findings suggest that Neanderthal introgression could reintroduce an important previously existing allele into populations where the allele had been lost. This study sheds new light on understanding the contribution of Neanderthal introgression to the adaptation of non-Africans.
Phase I trial of high-dose mitoxantrone plus cyclophosphamide and filgrastim in patients with advanced breast carcinoma.
Authors: J A Sparano, N Robert, P Silverman, H Lazarus, U Malik, U Venkatraj, C Sarta
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the maximum-tolerated dose (MTD) of mitoxantrone that could be safely used in combination with cyclophosphamide and filgrastim in patients with advanced breast carcinoma. PATIENTS AND METHODS Twenty-seven patients with metastatic (n = 24) or locally advanced (n = 3) breast carcinoma received escalating doses of mitoxantrone (16, 20, 24, 28, or 32 mg/m2) plus cyclophosphamide at one of three dose levels: group 1, 1,200 mg/m2; group 2, 2,400 mg/m2; and group 3,600 mg/m2. All patients also received filgrastim 5 micrograms/kg administered subcutaneously beginning on day 2 and continuing until the post-nadir absolute neutrophil count (ANC) was &gt; or = 10,000/microL. Treatment was repeated every 3 weeks if the ANC was &gt; or = 2,000/microL and platelet count &gt; or = 90,000/microL for a maximum of six cycles. Dose escalation occurred within each group if zero of three or one of four patients had dose-limiting toxicity during the first cycle. RESULTS The MTD of mitoxantrone was 24 mg/m2 in group 1, less than 16 mg/m2 in group 2, and 28 mg/m2 in group 3. Neutropenia was dose-limiting, and cumulative neutropenia and thrombocytopenia occurred with continued therapy. Nonhematologic toxicity consisted predominantly of nausea, vomiting, alopecia, and fatigue. Three patients (11%) had a &gt; or = 10% decrease in the left ventricular ejection fraction (LVEF), one patient (4%) had a decrease in the LVEF below normal, and none developed clinical congestive heart failure. Of patients with stage IV breast carcinoma who had not received prior chemotherapy for advanced disease, objective responses occurred in nine of 20 (45%), and the median response duration was 5 months. CONCLUSION In combination with 600 mg/m2 of cyclophosphamide and filgrastim, the MTD of mitoxantrone is 28 mg/m2, a dose that is approximately twofold to 2.8-fold higher than the conventional dose used without a hematopoietic growth factor.
Duration of tamoxifen therapy and occurrence of endometrial cancer.
Authors: P V Plourde, M Scott
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.8.2142 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7669113 Duration of tamoxifen therapy and occurrence of endometrial cancer. P V PlourdexP V PlourdeSearch for articles by this author , M ScottxM ScottSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.8.2142 PDF "Duration of tamoxifen therapy and occurrence of endometrial cancer.." Journal of Clinical Oncology, 13(8), p. 2142© 1995 by American Society of Clinical Oncology
Cardiac Complications of Cocaine Abuse
Authors: J M Isner, S K Chokshi
Journal: Annual Review of Medicine (1991)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis
Authors: Anaïs Briot, Mete Civelek, Atsuko Seki, Karen Hoi, Julia J. Mack, Stephen D. Lee, Jason Kim, Cynthia Hong, Jingjing Yu, Gregory A. Fishbein, Ladan Vakili, Alan M. Fogelman, Michael C. Fishbein, Aldons J. Lusis, Peter Tontonoz, Mohamad Navab, Judith A. Berliner, M. Luisa Iruela-Arispe
Journal: The Journal of Experimental Medicine (2015)

Although much progress has been made in identifying the mechanisms that trigger endothelial activation and inflammatory cell recruitment during atherosclerosis, less is known about the intrinsic pathways that counteract these events. Here we identified NOTCH1 as an antagonist of endothelial cell (EC) activation. NOTCH1 was constitutively expressed by adult arterial endothelium, but levels were significantly reduced by high-fat diet. Furthermore, treatment of human aortic ECs (HAECs) with inflammatory lipids (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [Ox-PAPC]) and proinflammatory cytokines (TNF and IL1β) decreased Notch1 expression and signaling in vitro through a mechanism that requires STAT3 activation. Reduction of NOTCH1 in HAECs by siRNA, in the absence of inflammatory lipids or cytokines, increased inflammatory molecules and binding of monocytes. Conversely, some of the effects mediated by Ox-PAPC were reversed by increased NOTCH1 signaling, suggesting a link between lipid-mediated inflammation and Notch1. Interestingly, reduction of NOTCH1 by Ox-PAPC in HAECs was associated with a genetic variant previously correlated to high-density lipoprotein in a human genome-wide association study. Finally, endothelial Notch1 heterozygous mice showed higher diet-induced atherosclerosis. Based on these findings, we propose that reduction of endothelial NOTCH1 is a predisposing factor in the onset of vascular inflammation and initiation of atherosclerosis.
Dietary Treatment of Inborn Errors of Metabolism
Authors: N A Holtzman
Journal: Annual Review of Medicine (1970)

Over the past fifteen years the rate of discovery of new inborn errors of metabolism has increased logarithmically. (1) Enzyme and transport defects lccount for the majority of these diseases and are potentially amenable to :iietary therapy (2). In the treatment of enzyme defects the diet can be lltered to reduce substrate or its precursors, add product or its derivatives, a.dd cofactor, or add a substance which will reduce excessive enzyme ac­ tivity. In transport defects, a mal absorbed nutrient can be restricted or an a.lternate, or derivative added which can be adequately absorbed. In this review, disorders which exemplify each of these modes of therapy are pre­ sented in sufficient detail to permit an appreciation of two problems: (a) management of the disease under discussion, and (b) evaluation of therapy of inborn errors in general. Brief mention is made of other disorders in which the same mode of dietary therapy has had some effect. Several reviews offer additional information on the treatment of inborn errors (3-11) and the text of Stanbury et al. (12) is a valuable source of information. Although the basic defect is often known, with few exceptions we remain ignorant of the processes which produce the clinical manifestations in the inborn errors. Frequently, the clinical manifestations and response to treat­ ment vary in patients with very similar chemical abnormalities. Either the basic defect differs between these patients or there are modifying genetic or environmental differences. This heterogeneity complicates the evaluation of therapy. An added problem is the possibility that therapy may reverse the chemical manifestations without producing a significant effect on the clinical picture. At the conclusion of this review some generalizations will be made concerning the types of inborn errors amenable to dietary treatment and the appropriate methods for the evaluation of such treatment.
Rapid Clearance of Necrolytic Migratory Erythema Following Intravenous Administration of Amino Acids
Authors: Elena Thomaidou, Avital Nahmias, Leon Gilead, Abraham Zlotogorski, Yuval Ramot
Journal: JAMA Dermatology (2015)

Rapid Clearance of Necrolytic Migratory Erythema Following Intravenous Administration of Amino AcidsNecrolytic migratory erythema (NME) is a rare paraneoplastic skin disorder, considered the hallmark clinical sign of glucagonoma syndrome.Its recognition allows for early diagnosis of the tumor, which might lead to a better prognosis. 1Additional mucocutaneous features can include angular stomatitis and glossitis. 2We present a case of NME that cleared rapidly following intravenous administration of amino acids.
Pathogenesis is multifactorial
Authors: R. Gniadecki
Journal: BMJ (1995)

PrimiparaDied who are at high risk of developing matemal tetanus.This is because women (especially teen- agers) with unwanted pregnancies often do not attend for antenatal care and may resort to unsafe abortion.On the basis of our personal experience we support the authors' proposal to include adolescent girls as a target for vaccination for tetanus toxoid.This strategy would substantially reduce the rates of maternal mortality in young women from maternal tetanus secondary to induced abortion.
Vitamin D and risk of cause specific death
Authors: Rajiv Chowdhury, Setor K Kunutsor, Anna Vitezova, Clare Oliver-Williams, Susmita Chowdhury, Jessica C Kiefte-de-Jong, Hassan Khan, Cristina P Baena, Dorairaj Prabhakaran, Moshe B Hoshen, Becca S Feldman, An Pan, Laura Johnson, Francesca Crowe, Frank B Hu, Oscar H Franco
Journal: BMJ (2014)
Direct Estimate of the Spontaneous Mutation Rate Uncovers the Effects of Drift and Recombination in the<i>Chlamydomonas reinhardtii</i>Plastid Genome
Authors: Rob W. Ness, Susanne A. Kraemer, Nick Colegrave, Peter D. Keightley
Journal: Molecular Biology and Evolution (2015)

Plastids perform crucial cellular functions, including photosynthesis, across a wide variety of eukaryotes. Since endosymbiosis, plastids have maintained independent genomes that now display a wide diversity of gene content, genome structure, gene regulation mechanisms, and transmission modes. The evolution of plastid genomes depends on an input of de novo mutation, but our knowledge of mutation in the plastid is limited to indirect inference from patterns of DNA divergence between species. Here, we use a mutation accumulation experiment, where selection acting on mutations is rendered ineffective, combined with whole-plastid genome sequencing to directly characterize de novo mutation in Chlamydomonas reinhardtii. We show that the mutation rates of the plastid and nuclear genomes are similar, but that the base spectra of mutations differ significantly. We integrate our measure of the mutation rate with a population genomic data set of 20 individuals, and show that the plastid genome is subject to substantially stronger genetic drift than the nuclear genome. We also show that high levels of linkage disequilibrium in the plastid genome are not due to restricted recombination, but are instead a consequence of increased genetic drift. One likely explanation for increased drift in the plastid genome is that there are stronger effects of genetic hitchhiking. The presence of recombination in the plastid is consistent with laboratory studies in C. reinhardtii and demonstrates that although the plastid genome is thought to be uniparentally inherited, it recombines in nature at a rate similar to the nuclear genome.
P-124 Clinical outcome and impact of lymph node level assessment in biliary tract cancers
Authors: J. Martinez-Galán, C. González-Rivas, V. Conde, J. Ruiz-Vozmediano, L. Castillo, L. Ochoa, V. Amezcua, J. García-García, J.A. Ortega, E. González-Flores, J.R. Delgado
Journal: Annals of Oncology (2015)