A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year ( with possible extension for responders). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months ( patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 mug of Seocalcitol. This is the first study showing activity, by reduction in tumour dimensions, of a differentiating agent in patients with an advanced bulky, solid tumour. Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies

High Affinity Antibodies to Plasmodium falciparum Merozoite Antigens Are Associated with Protection from Malaria

Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown. In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as k(d)) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up. This study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations

Ornamental plants: annual reports and research reviews, 2002

Ohio State University Extension Nursery, Landscape, and Turf Team directory: 2003 / Jack Kerrigan -- Floriculture Industry Roundtable of Ohio: 2003 / Charles Behnke -- Ohio State University Extension 2002 Buckeye Yard and Garden Line evaluation survey / Amy K. Stone and James A. Chatfield -- Weather, environmental, and cultural problems of ornamental plants in Ohio: 2002 / Pamela J. Bennett -- Infectious disease problems of ornamental plants in Ohio: 2002 / James A. Chatfield, Nancy A. Taylor, Erik A. Draper, and Joseph F. Boggs -- A biological calendar for predicting pest activity: six years of plant and insect phenology in Secrest Arboretum / Daniel A. Herms -- Biological suppression of foliar diseases of ornamental plants with composted manures, biosolids, and Trichoderma hamatum 382 / Harry A. J. Hoitink, Carol A. Musselman, Terry L. Moore, Leona E. Horst, Charles R. Krause, Randy A. Zondag, and Hannah Mathers -- Growth and water use by four leguminous tree species in containers on a gravel surface or embedded in mulch / Michael Knee, Daniel K. Struve, Michael H. Bridgewater, and Joseph W. Phillips -- The effects of sprayer configuration on efficacy for the control of scab on crabapple / Charles R. Krause, Richard C. Derksen, Leona E. Horst, Randall Zondag, Ross D. Brazee, Michael G. Klein, and Michael E. Reding -- Update on honeylocust knot / Pierluigi Bonello, Maria Bellizzi, and Harry A. J. Hoitink -- Control of phytophthora and other major diseases of Ericaceous plants / Harry A. J. Hoitink, Steven T. Nameth, and James C. Locke -- Is your landscape mulch going up in smoke? / Larry G. Steward, T. Davis Sydnor, and Bert Bishop -- IR-4 ornamental trials conducted by USDA-ARS in Ohio: 2002 / Betsy A. Anderson, Michael E. Reding, Michael G. Klein, and Charles R. Krause -- Research on black vine weevil and white grubs in ornamental nurseries-in Ohio by USDA-ARS / Michael E. Reding, Michael G. Klein, Ross D. Brazee, and Charles R. Krause -- Herbaceous ornamental field trial results in Clark County, Ohio – 2002 / Pamela J. Bennett -- Results of annual trial gardens at the Cincinnati Zoo and Botanical Garden for 2002 / Dave Dyke -- Ohio State University Learning Garden annual cultivar trials / Monica M. Kmetz-Gonzalez and Claudio C. Pasian -- A collection of crabapple knowledge from Secrest Arboretum: 1993-2002 / Erik A. Draper, James A. Chatfield, and Kenneth D. Cochran -- Key results of the 2001 Ohio Green Industry Survey / Gary Y. Gao, John J. Smith, James A. Chatfield, Joseph F. Boggs, Erik A. Draper, and Hannah Mathers -- The USDA/Agricultural Research Service research weather network in Lake County, Ohio - 2002 update / R. D. Brazee, R. C. Derksen, C. R. Krause, K. A. Williams, D. Lohnes, M. G. Klein, M. Reding, R. Lyons, W. Hendricks, R. Zondag, R. D. Fox, and D. Herms -- The OSU Chadwick Arboretum Learning Gardens / Dr. Steven Still and Annette Duetz -- Choosing soil testing labs / Gary Y, Gao, Maurice E. Watson, Joseph F. Boggs, and James A. Chatfield -- Top horticultural references for a green industry professional's library / Gary Y. Gao and Pamela J. Bennett -- The maples of Secrest Arboretum / Gary W. Graham, James A. Chatfield, and Kenneth D. Cochran -- Deck the halls with boughs from Ollie! / Kenneth D. Cochran and James A. Chatfiel

The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.National Human Genome Research Institute (U.S.) (Grant number 1U54HG004555-01)Wellcome Trust (London, England) (Grant number WT062023)Wellcome Trust (London, England) (Grant number WT077198

Globetrotting strangles: the unbridled national and international transmission of Streptococcus equi between horses.

The equine disease strangles, which is characterized by the formation of abscesses in the lymph nodes of the head and neck, is one of the most frequently diagnosed infectious diseases of horses around the world. The causal agent, Streptococcus equi subspecies equi, establishes a persistent infection in approximately 10 % of animals that recover from the acute disease. Such 'carrier' animals appear healthy and are rarely identified during routine veterinary examinations pre-purchase or transit, but can transmit S. equi to naïve animals initiating new episodes of disease. Here, we report the analysis and visualization of phylogenomic and epidemiological data for 670 isolates of S. equi recovered from 19 different countries using a new core-genome multilocus sequence typing (cgMLST) web bioresource. Genetic relationships among all 670 S. equi isolates were determined at high resolution, revealing national and international transmission events that drive this endemic disease in horse populations throughout the world. Our data argue for the recognition of the international importance of strangles by the Office International des Épizooties to highlight the health, welfare and economic cost of this disease. The Pathogenwatch cgMLST web bioresource described herein is available for tailored genomic analysis of populations of S. equi and its close relative S. equi subspecies zooepidemicus that are recovered from horses and other animals, including humans, throughout the world. This article contains data hosted by Microreact

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead