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At least 1,693 records · Page 94Linked to original sources
PubMed2006

Gene amplification and associated loss of 5' regulatory sequences of CoAA in human cancers.

CoAA is an RRM-containing transcriptional coactivator that stimulates transcriptional activation and regulates alternative splicing. We show that the CoAA gene is amplified at the chromosome 11q13 locus in a subset of primary human cancers including non-small cell lung carcinoma, squamous cell skin carcinoma and lymphoma. Analysis of 42 primary tumors suggests that CoAA amplifies independently from the CCND1 locus. Detailed mapping of three CoAA amplicons reveals that the amplified CoAA gene is consistently located at the 5' boundaries of the amplicons. The CoAA coding and basal promoter sequences are retained within the amplicons but upstream silencing sequences are lost. CoAA protein is overexpressed in tumors containing the amplified CoAA gene. RNA dot blot analysis of 100 cases of primary tumors suggests elevated CoAA mRNA expression. CoAA positively regulates its own basal promoter in transfection assays. Thus, gene amplification, loss of silencing sequence and positive feedback regulation may lead to drastic upregulation of CoAA protein. CoAA has transforming activities when tested in soft agar assays, and CoAA is homologous to oncoproteins EWS and TLS, which regulate alternative splicing. These data imply that CoAA may share a similar oncogenic mechanism with oncogene EWS and that CoAA deregulation may alter the alternative splicing of target genes.

Animals↗
PubMed1999

Student nurses' conceptions of internationalization: a phenomenographic study.

A phenomenographic approach was used when analysing and interpreting interviews with 25 student nurses in order to describe their conceptions of internationalization. The results are presented in five categories and various subcategories, forming an outcome space. The categories describe forms of understanding, or ways of thinking about internationalization, which, in relation to internationalization as a whole, were either atomistic or holistic in character. The data revealed that nursing students shared some aspects of meaning when thinking of internationalization. These aspects seemed to be understood in a similar way by all students, whereas, when students thought about internationalization as a whole, they assigned it different meanings. In two of the categories aspects of meaning were fragmentarily related to each other, and represented only one perspective. These two categories are to be compared to the other three categories which were more complex and holistic in character, since they contained more than one perspective as well as more aspects of meaning, and related in several different ways. From a pedagogical point of view, the findings point to the importance of teachers trying, in an active way, to confront students with as many existing variations of conceptualized wholes related to internationalization as possible, by using forms of understanding originating from a holistic approach.

Adult↗
PubMed1978

Silkmoth chorion proteins: sequence analysis of the products of a multigene family.

Five polypeptide components have been isolated from the eggshell (chorions) of a silkmoth. Two are homogeneous on sodium dodecyl sulfate and isoelectric focusing gels, and three contain predominantly two proteins each. Amino acid analyses show that all five components are similar to each other. These proteins have been sequenced from the amino terminus. Homogeneous components yielded single sequences; heterogeneous components yielded two residues at some positions, consistent with their containing two major electrophoretic components. Striking similarities are apparent among all these sequences. These similarities can be increased dramatically by separating each of the three protein mixtures into two sequences and introducing a small number of gaps or insertions. This is due in part to bringing into register a portion that contains short repeating subunits found in all sequences. All proteins are also characterized by a region of high cysteine content near the amino terminus followed by a longer low-cysteine region. The data suggest that these proteins share a common evolutionary origin and are encoded by a multigene family.

Amino Acid Sequence↗
PubMed1994

A mismatch recognition defect in colon carcinoma confers DNA microsatellite instability and a mutator phenotype.

We have analyzed spontaneous mutations in the adenine phosphoribosyltransferase gene of Chinese hamster clone B cells that exhibit a mutator phenotype because of defective mismatch binding. The mutator phenotype conferred increases in a limited number of mutational classes. The rates of transitions and most transversions were not significantly increased. The rates of A to T transversions and -2 frameshifts were strikingly elevated. These mutations were in repeated elements and 5 of 9 of the frameshifts were dinucleotide deletions in DNA sequences resembling microsatellites. The mismatch binding protein that is defective in the mutator line is a G-T mismatch recognition factor. Band-shift analysis indicated that the preferred substrate for the mismatch recognition protein is duplex DNA containing an extrahelical mono- or dinucleotide within repeated sequences. In agreement with a role in preventing minus frameshifts, a defective binding protein conferred an instability in clone B microsatellite DNA. A mismatch binding defect was also detected in Lo Vo, a human colorectal carcinoma cell line. Extracts of clone B or a second mismatch binding-deficient line, Raji-F12, did not complement Lo Vo extracts, indicating that these lines share a common defect. Our data provide a mechanistic explanation for the relation between defective mismatch recognition and the microsatellite instability of human colon cancer.

Adenine Phosphoribosyltransferase↗
PubMed1998

Cell division regulates the T cell cytokine repertoire, revealing a mechanism underlying immune class regulation.

Naive T lymphocytes have the potential to differentiate and produce a range of cytokines crucial for appropriate immune responses. How T lymphocytes vary their cytokine output during differentiation is unknown, although they are clearly influenced by the cytokines already present in the environment. Here we show that the number of divisions taken by the cells after activation is a critical element in T cell differentiation. Our experiments used the dye 5-(and 6-)carboxyfluorescein diacetate, succinimidyl ester to track cells in different divisions after activation by anti-CD3 in the presence of the differentiating cytokine interleukin (IL)-4. The patterns of acquisition or loss of secretion of IL-2, IL-3, IL-4, IL-5, IL-10, and interferon gamma all varied markedly with division number. These relationships were consistent regardless of the time-dependent variation in distribution of T cells among divisions. Thus, the observed combination of complex asynchronous T cell growth, overlaying a fixed probability of acquisition or loss of a cytokine at each division can explain why T cell differentiation displays the contradictory features of being both highly stochastic and highly controlled. Furthermore, these data reveal that T cells share a common regulatory strategy with B cells, whereby changes in the class of immune response are linked to the process of clonal expansion.

Animals↗
PubMed1996

Signal transduction by CD28 costimulatory receptor on T cells. B7-1 and B7-2 regulation of tyrosine kinase adaptor molecules.

This study compares the biochemical responses in T cells activated with the CD28 ligands B7-1 and B7-2. The patterns of tyrosine phosphorylation induced in T cells by these two CD28 ligands are identical, but clearly different from the tyrosine phosphorylation induced by the T cell receptor (TCR). The TCR regulates protein complexes mediated by the adapter Grb2 both in vivo and in vitro. In contrast, there is no apparent regulation of in vivo Grb2 complexes in response to B7-1 or B7-2. Rather, B7-1 and B7-2 both induce tyrosine phosphorylation of a different adaptor protein, p62. The regulation of p62 is a unique CD28 response that is not shared with the TCR. These data indicate that B7-1 and B7-2 induce identical tyrosine kinase signal transduction pathways. The data show also that the TCR and CD28 couple to different adapter proteins, which could explain the divergence of TCR and CD28 signal transduction pathways during T cell activation.

Adaptor Proteins, Signal Transducing↗
PubMed2004

HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains.

Huntingtin-interacting protein 1-related (HIP1r) is the only known mammalian relative of huntingtin-interacting protein 1 (HIP1), a protein that transforms fibroblasts via undefined mechanisms. Here we demonstrate that both HIP1r and HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains. In contrast to other ENTH domain-containing proteins, lipid binding is preferential to the 3-phosphate-containing inositol lipids, phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,5-bisphosphate. Furthermore, the HIP1r ENTH domain, like that of HIP1, is necessary for lipid binding, and expression of an ENTH domain-deletion mutant, HIP1r/deltaE, induces apoptosis. Consistent with the ability of HIP1r and HIP1 to affect cell survival, full-length HIP1 and HIP1r stabilize pools of growth factor receptors by prolonging their half-life following ligand-induced endocytosis. Although HIP1r and HIP1 display only a partially overlapping pattern of protein interactions, these data suggest that both proteins share a functional homology by binding 3-phosphorylated inositol lipids and stabilizing receptor tyrosine kinases in a fashion that may contribute to their ability to alter cell growth and survival.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Physical and functional interaction between Elongator and the chromatin-associated Kti12 protein.

Cells lacking KTI12 or Elongator (ELP) genes are insensitive to the toxin zymocin and also share more general phenotypes. Moreover, data from low stringency immunoprecipitation experiments suggest that Elongator and Kti12 may interact. However, the precise relationship between these factors has not been determined. Here we use a variety of approaches to investigate the possibility that Elongator and Kti12 functionally overlap. Native Kti12 purified to virtual homogeneity under stringent conditions is a single polypeptide, but depletion of Kti12 from a yeast extract results in co-depletion of Elongator, indicating that these factors do interact. Indeed, biochemical evidence suggests that Elongator and Kti12 form a fragile complex under physiological salt conditions. Purified Kti12 does not affect Elongator histone acetyltransferase activity in vitro. However, a variety of genetic experiments comparing the effects of mutation in ELP3 and KTI12 alone and in combination with other transcription factor mutations clearly demonstrate a significant functional overlap between Elongator and Kti12 in vivo. Intriguingly, chromatin immunoprecipitation experiments show that Kti12 is associated with chromatin throughout the genome, even in non-transcribed regions and in the absence of Elongator. Conversely, RNA-immunoprecipitation experiments indicate that Kti12 only plays a minor role for Elongator association with active genes. Together, these experiments indicate a close physical and functional relationship between Elongator and the highly conserved Kti12 protein.

Acetyltransferases↗
PubMed2003

Phenotypic and genotypic relationship between Campylobacter spp isolated from humans and chickens in Northern Ireland--a comparison of three phenotyping and two genotyping schemes.

Human campylobacteriosis is currently the most common cause of acute bacterial gastroenteritis on the island of Ireland, accounting for over 3,000 laboratory reports per year, where circa 2,000 reports originate from the Republic of Ireland and circa 1,000 reports from Northern Ireland. Elsewhere, consumption of contaminated poultry has been associated with the zoonotic transmission of disease, therefore it was the aim of this study to examine the phenotypic and genotypic relatedness of campylobacters isolated from chickens and humans locally. Sixty isolates were subtyped using phenotyping techniques (biotyping, phage-typing), as well as genotyping techniques (multilocus enzyme electrophoresis (MEE), ribotyping) and the data compared. The frequency of shared phenotypes and genotypes between poultry and humans varied depending on the typing technique employed ranging from 98.2% of human isolates sharing a similar resistotyping (MAST) disc type with poultry strains to 20% similarity with MEE typing. Overall, this small study is the first report on phenotypic and genotypic relatedness between human and poultry campylobacters in Northern Ireland, isolated under controlled conditions. The study demonstrated an association between chicken and human sub-species types, taken from a relatively contained epidemiological environment. Further work is required with larger numbers of isolates coupled with typing schemes, which are able to reliably cluster strains from chicken and humans, which share high degrees of clonality, before local poultry can be conclusively proven to be a significant source of human campylobacteriosis.

Animals↗
PubMed2006

Exploring the role of the mental health nurse in community mental health care for the aged.

There is currently considerable discussion about the impact of the aging population on the demand for health care services, however there is considerably less attention paid to the impact of mental health issues on the needs of the aged population. Nurses comprise the largest professional group within the mental health workforce in Australia. The availability of a high quality mental health nursing workforce will therefore be crucial to meeting the health needs of aging clients in the future, accompanied by an increased pressure to increase the proportion of care delivered in the community. There is however, a paucity of literature on the role and contribution of community mental health nurses specialising in the aged care field. The aim of this paper is to present the findings of a project designed to examine the role of mental health nursing within aged persons' community mental health teams in Victoria, Australia, with particular emphasis on the biopsychosocial interventions used. Fifteen participants from three community mental health services in Victoria participated in a focus group interview to share their insights and experiences. Data analysis revealed two main themes, the role of the nurse, and the specific functions of the nurse. This data is presented as a beginning contribution to the paucity of literature currently available in this important area.

Aged↗
PubMed1993

Changes in equipment sharing in injecting drug users in Sydney 1989-1990.

We investigated levels of equipment sharing in injecting drug users in Sydney, Australia, in two consecutive samples recruited in a non-treatment setting using similar methodology in 1989 (n = 1,245) and 1990 (n = 550). Comparison between the two waves of the study indicated that there were consistent and major reductions in percentage of time used equipment was re-used, and number of people from whom used equipment had been accepted. There was a corresponding significant and major increase in use of sterile injection equipment, obtained more frequently in the second sample from needle and syringe exchanges. The proportion of respondents reporting they had never shared equipment rose significantly. These data suggest that there is a continuing increase in the adoption of safer injecting practices and utilisation of needle and syringe exchanges over time in response to the threat of HIV transmission in injecting drug users.

Journal Article↗
PubMedDate not supplied

Does genetic variance for cognitive abilities account for genetic variance in educational achievement and occupational status? A study of twins reared apart and twins reared together.

Studies of brothers and twins have shown that about 50 per cent of the variance in educational achievement and 40 per cent of the variance in occupational status reflects between-family variance. About half of the between-family variance for educational achievement and even more for occupational status is due to genetic effects and the remainder is due to sharing the same environment. With data on 35 pairs of male twins reared apart and 56 pairs reared together we investigated the extent to which genetic variance in SES can be attributed to genetic variance for cognitive abilities. For both educational achievement and occupational status there was significant genetic variance both in common with and independent of genetic variance for cognitive abilities. Thus, there are genetic effects contributing to familial similarity for SES that are not the same as those of importance for cognitive abilities. Candidate traits that may account for this remaining genetic variance in SES are personality, interests, or talents not represented in standard cognitive tests.

Achievement↗
PubMed1993

Overlapping distribution of two glycosyltransferases in the Golgi apparatus of HeLa cells.

Thin, frozen sections of a HeLa cell line were double labeled with specific antibodies to localize the trans-Golgi enzyme, beta 1,4 galactosyltransferase (GalT) and the medial enzyme, N-acetylglucosaminyltransferase I (NAGT I). The latter was detected by generating a HeLa cell line stably expressing a myc-tagged version of the endogenous protein. GalT was found in the trans-cisterna and trans-Golgi network but, contrary to expectation, NAGT I was found both in the medial- and trans-cisternae, overlapping the distribution of GalT. About one third of the NAGT I and half of the GalT were found in the shared, trans-cisterna. These data show that the differences between cisternae are determined not by different sets of enzymes but by different mixtures.

Base Sequence↗
PubMed2000

Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q.

Pyoderma gangrenosum, cystic acne, and aseptic arthritis are clinically distinct disorders within the broad class of inflammatory diseases. Although this triad of symptoms is rarely observed in a single patient, a three-generation kindred with autosomal-dominant transmission of these three disorders has been reported as "PAPA syndrome" (MIM 604416). We report mapping of a disease locus for familial pyoderma gangrenosum-acne-arthritis to the long arm of chromosome 15 (maximum two-point LOD score, 5.83; recombination fraction [straight theta] 0 at locus D15S206). Under the assumption of complete penetrance, haplotype analysis of recombination events defined a disease interval of 10 cM, between D15S1023 and D15S979. Successful identification of a single disease locus for this syndrome suggests that these clinically distinct disorders may share a genetic etiology. These data further indicate the role of genes outside the major histocompatibility locus in inflammatory disease.

Acne Vulgaris↗
PubMed2001

Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis.

The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the transmission/disequilibrium test (chi2=138.3; P<.0001). We obtained significant evidence of linkage throughout the whole data set (mlod=4.09; 59.9% sharing). Surprisingly, similar sharing was also observed in 58 families in which both parents lacked the DRB1*15 allele (mlod=1.56; 62.7% sharing; P=.0081). Our findings suggest that the notion that HLA-DRB1*15 is the sole major-histocompatibility-complex determinant of susceptibility in northern-European populations with MS may be incorrect. It remains possible that the association of MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes.

Alleles↗
PubMed1999

Current activities at the Centers for Disease Control and Prevention's National Diabetes Laboratory.

In 1997, the Centers for Disease Control and Prevention established the National Diabetes Laboratory in order to help prevent and treat type 1 diabetes. This state-of-the-art laboratory collaborates with research scientists and key national and international organizations throughout the world to identify and study risk factors for type 1 diabetes by developing measurements for glycosylated proteins, developing and evaluating technology for measuring genetic risk factors for the disease, and working to standardize autoantibody measurements. Developing improved technologies for diagnosing and managing diabetes and developing reference materials for properly calibrating and standardizing blood glucose meters are also critical aspects of the laboratory's work. In addition, the laboratory provides quality storage for valuable collections of biologics and other materials and facilitates sharing of specimens, associated epidemiologic data, and test results. Working with our partners in diabetes research, we are improving the diagnosis, treatment, and prevention of type 1 diabetes.

Autoantibodies↗
PubMed2003

Knowledge acquisition, consistency checking and concurrency control for Gene Ontology (GO).

MOTIVATION: A critical element of the computational infrastructure required for functional genomics is a shared language for communicating biological data and knowledge. The Gene Ontology (GO; http://www.geneontology.org) provides a taxonomy of concepts and their attributes for annotating gene products. As GO increases in size, its ongoing construction and maintenance becomes more challenging. In this paper, we assess the applicability of a Knowledge Base Management System (KBMS), Protégé-2000, to the maintenance and development of GO. RESULTS: We transferred GO to Protégé-2000 in order to evaluate its suitability for GO. The graphical user interface supported browsing and editing of GO. Tools for consistency checking identified minor inconsistencies in GO and opportunities to reduce redundancy in its representation. The Protégé Axiom Language proved useful for checking ontological consistency. The PROMPT tool allowed us to track changes to GO. Using Protégé-2000, we tested our ability to make changes and extensions to GO to refine the semantics of attributes and classify more concepts. AVAILABILITY: Gene Ontology in Protégé-2000 and the associated code are located at http://smi.stanford.edu/projects/helix/gokbms/. Protégé-2000 is available from http://protege.stanford.edu.

Artificial Intelligence↗
PubMed1997

Epidemiology of an unusually prolonged outbreak of typhoid fever in Terrassa, Spain.

An unusually prolonged outbreak of typhoid fever, from 1988 to 1994, in Terrassa (Barcelona, Spain), was caused by a casual food handler who was a carrier. The pattern of this outbreak suggested intermittent low-level exposure to Salmonella typhi. We found 70 patients with S. typhi infections, 52 of whom were available for study. Medical records were reviewed and patients were interviewed with use of a standard questionnaire. Phage typing and pulsed-field gel electrophoresis (PFGE) for strain subtyping were used to confirm the epidemiological data. The 27 outbreak strains shared the same phage type and the same PFGE pattern. Four sporadic strains shared the same phage type as the outbreak strain. PFGE was found to be useful for differentiating strains for epidemiological purposes.

Adult↗