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At least 649 records · Page 36Linked to original sources
PubMed2003

Postradiotherapy surveillance practice for head and neck squamous cell carcinoma--too much for too little?

INTRODUCTION: Limited information is available regarding surveillance patterns after head and neck cancer radiotherapy. We cataloged follow-up for a specified patient cohort treated at three neighboring university, community, and Veterans Administration institutions. METHODS: One hundred fifteen patients were treated with curative intent between 1994-1998 with definitive or postoperative radiotherapy for newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. One hundred patients had continuous follow-up at their treating institution and were included for analysis. Median follow-up until disease recurrence or censorship was 28.5 months. RESULTS: Median follow-up frequency was 5.7 visits/year and was highly variable. Although visit frequency correlated with disease stage and the presence of high-risk disease features, this association was lost when patients with early recurrences were removed from analysis. Procedure and test utilization closely mirrored visit frequency, resulting in a wide range of estimated yearly charges (0-15,668 dollars/year; median, 1,772 dollars/year). Actuarial 3-year overall survival for the study group was 71%. Eighty-six percent (19 of 22) of potentially salvageable locoregional failures were discovered secondary to symptomatic complaint rather than by test results. Disease failure, whether detected by symptom or testing, predicted for poor survival (22% at 24 months after recurrence). CONCLUSIONS: Postradiotherapy surveillance for head and neck cancer is inconsistently pursued. A proven correlation between intensive follow-up and improved patient survival is lacking. Surveillance directed by patient symptoms should be investigated as an alternative approach.

Adult↗
PubMed2003

RettBASE: The IRSA MECP2 variation database-a new mutation database in evolution.

Rett syndrome (RTT) is a neurodevelopmental disorder affecting primarily females, with an incidence of around 1 in 15,000 females. In 1999, mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) were first reported in RTT subjects, and since that time there have been a number of publications describing cohorts of patients and their mutations. In addition, MECP2 mutations have been reported in patients who do not fit the diagnostic criteria for Rett syndrome. We have developed a new locus-specific database, RettBASE (http://mecp2.chw.edu.au/), loosely based on the PAHdb website. The aim is to obtain data relating to all known instances of MECP2 variations, including published ta and data directly submitted by one of various means (either by using an online submission form, or by sending the same form in Adobe portable document format (pdf) or Microsoft Word format by email or fax to the database curators). The database has a range of query capabilities, allowing for simple or complex interrogation of the database. To address the issue of patient confidentiality, we have incorporated an Excel spreadsheet algorithm that allows the generation of a unique number based on the subject's name and date of birth. We believe this database will prove to be a useful resource, allowing the development of accurate prevalence data for disease-causing mutations, providing a catalog of polymorphisms, and potentially allowing more accurate phenotype-genotype correlations to be drawn.

Chromosomal Proteins, Non-Histone↗
PubMed2001

ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC half-transporter (ALDP) involved in the import of very long-chain fatty acids (VLCFA) into the peroxisome. The disease is characterized by a striking and unpredictable variation in phenotypic expression. Phenotypes include the rapidly progressive childhood cerebral form (CCALD), the milder adult form, adrenomyeloneuropathy (AMN), and variants without neurologic involvement. There is no apparent correlation between genotype and phenotype. In males, unambiguous diagnosis can be achieved by demonstration of elevated levels of VLCFA in plasma. In 15 to 20% of obligate heterozygotes, however, test results are false-negative. Therefore, mutation analysis is the only reliable method for the identification of heterozygotes. Since most X-ALD kindreds have a unique mutation, a great number of mutations have been identified in the ABCD1 gene in the last seven years. In order to catalog and facilitate the analysis of these mutations, we have established a mutation database for X-ALD ( http://www.x-ald.nl). In this review we report a detailed analysis of all 406 X-ALD mutations currently included in the database. Also, we present 47 novel mutations. In addition, we review the various X-ALD phenotypes, the different diagnostic tools, and the need for extended family screening for the identification of new patients.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed2005

eOPA1: an online database for OPA1 mutations.

Autosomal dominant optic atrophy (ADOA), also known as Kjer disease, is characterized by moderate to severe loss of visual acuity with an insidious onset in early childhood, blue-yellow dyschromatopsia, and central scotoma. An optic atrophy gene, called OPA1, has been identified in most cases of the disease. A total of 83 OPA1 mutations, often family-specific, have been reported so far, and the observations support the hypothesis that haploinsufficiency and the functional loss of a single allele may lead to ADOA. We have developed a new locus-specific database (LSDB), eOPA1 (http://lbbma.univ-angers.fr/eOPA1/) aimed at collecting published and unpublished sequence variations in OPA1. The database has been designed to incorporate new submissions rapidly and will provide a secured online catalog of OPA1 mutations and nonpathogenic sequence variants (NPSVs). The LSDB should prove useful for molecular diagnosis, large-scale mutation statistics, and the determination of original genotype-phenotype correlations in studies on ADOA.

Base Sequence↗
PubMed1983

Translational products of mRNAs coding for non-epidermal cytokeratins.

Total RNA and poly(A)+ RNA were isolated from tissues and cultured cells of various mammalian species (bovine muzzle epidermis and bladder urothelium; rat hepatoma cells; human cell lines HeLa, MCF-7 and A-431) and examined by translation in vitro using the reticulocyte lysate system. Polypeptides were separated and identified by two-dimensional electrophoresis and cytokeratins were selectively enriched from the translation assays by co-polymerization with added heterologous cytokeratins. In all three species, non-epidermal cytokeratins A, D and mol. wt. 40,000 (corresponding to numbers 8, 18 and 19 of the human cytokeratin catalog of Moll et al., 1982) were identified as translation products capable of co-polymerization with epidermal keratins. Several other basic and other acidic cytokeratins were also identified as translational products. In addition, two unidentified polypeptides (mol. wt. 52,000 and 43,000) which were minor polypeptides in cytoskeletons and translation assays were found to be specifically enriched in co-polymers with bovine epidermal keratins. The results indicate that many, perhaps all, non-epidermal cytokeratins characteristic of simple epithelia are genuine products of translation and that their diversity is not due to post-translational modification or processing. These findings, taken together with observations of in vitro translation of epidermal mRNAs, suggest that the diversity of cell type-specific expression of the different members of the cytokeratin polypeptide family is largely due to the cell type-specific synthesis of diverse mRNAs.

Animals↗
PubMed1986

Higher order structure in ribosomal RNA.

The only reliable general method currently available for determining precise higher order structure in the large ribosomal RNAs is comparative sequence analysis. The method is here applied to reveal 'tertiary' structure in the 16S-like rRNAs, i.e. structure more complex than simple double-helical, secondary structure. From a list of computer-generated potential higher order interactions within 16S rRNA one such interaction considered likely was selected for experimental test. The putative interaction involves a Watson-Crick one to one correspondence between positions 570 and 866 in the molecule (E. coli numbering). Using existing oligonucleotide catalog information several organisms were selected whose 16S rRNA sequences might test the proposed co-variation. In all of the (phylogenetically independent) cases selected, full sequence evidence confirms the predicted one to one (Watson-Crick) correspondence. An interaction between positions 570 and 866 is, therefore, considered proven phylogenetically.

Base Sequence↗
PubMed1989

DNA-directed oligomerization of the monomeric Ner repressor from the Mu-like bacteriophage D108.

We have purified the 8.6 kd ner gene product (a lambda Cro-like protein which negatively regulates transcription from two divergent and overlapping promoters) from the Mu-like transposable bacteriophage D108. Chemical and enzymatic protection experiments show the D108 ner-operator to contain two perfect 11 bp (5'-CCG-TGAGCTAC-3') inverted repeats separated by an 8 bp AT-rich region. Ner makes base-specific contacts in the major groove spanning the 11 bp repeats and also interacts with regions flanking these sites such that its operator comprises five turns of the DNA helix. Furthermore, gel filtration chromatography and dimethyl suberimidate crosslinking experiments indicate that D108 Ner (at concentrations exceeding 5 microM) is a monomer in solution, yet crosslinks as a dimer when bound to its operator site. As a small (73 amino acids) monomeric protein, Ner does not display strong homology with any known DNA-binding proteins. By virtue of the interactions with its operator it appears to bind DNA in a markedly different manner from other known prokaryotic repressors thus adding to the growing catalog of protein motifs used for specific binding to DNA.

Bacteriophage mu↗
PubMed1979

An X-ray microanalysis survey of the concentration of elements in the cytoplasm of different mammalian cell types.

Electron probe energy dispersive X-ray microanalysis was performed on freeze-dried tissue sections. The dry weight concentration of elements (mmole/kg dry weight) was measured in the cytoplasm of several cell types from adult mice and rats. This comparative investigation showed: (1) That the energy dispersive X-ray spectrum of element concentration from the cytoplasm of a specific cell type allows one to distinguish this specific cell type from other cell types with considerable accuracy. (2) That there is a relationship between the concentration of the various elements and the ultrastructural features of the cytoplasmic regions being analyzed. For example, areas rich in ribosomes are also rich in P, K and Mg. (3) These data support the idea that K is directly involved in the control of protein synthesis. The catalog of element concentrations in the cytoplasm of 13 cell types from both mice and rats should be of value to others who seek to answer various questions about these cell types.

Animals↗
PubMed1986

Effects of retinoids on human bronchial epithelial cells: differential regulation of hyaluronate synthesis and keratin protein synthesis.

Respiratory tract epithelia are one type of tissue targeted by vitamin A. In this study the effects of vitamin A and its analogs (retinoids) on human bronchial epithelial (HBE) cells have been investigated in a serum-free hormone-supplemented medium. This serum-free medium, which was developed for the long-term cultivation of protease-dissociated HBE cells, consists of Ham's F12 nutrient medium supplemented with insulin, transferrin, epidermal growth factor, hydrocortisone, cholera toxin, and bovine hypothalamus extract. Under these in vitro conditions, retinoids specifically stimulate the synthesis and secretion of hyaluronate (HA) and alter the pattern of synthesis of keratin proteins. In regard to HA, the degree of stimulation ranges from two-fold to ten-fold and is concentration dependent. In regard to keratin proteins, the most prominent effects of retinoids are inhibition of synthesis of the 48 kd and 50 kd keratin proteins (corresponding to cytokeratins 16 and 14, respectively, in the catalog of human cytokeratins; Moll et al., 1982) and stimulation of synthesis of the 40 kd and 52-54 kd proteins. The data indicate that retinoid effects on HA and keratin protein synthesis occur at different levels. The stimulation of HA synthesis occurs immediately after the addition of retinoid and cannot be prevented by pretreatment with actinomycin D, whereas the alterations in the pattern of keratin protein synthesis appear later and are inhibited by treatment with actinomycin D at or before the administration of retinoid. This study demonstrates that HBE cultures maintained in the serum-free condition can serve as an in vitro model to elucidate the mechanisms of retinoid actions.

Bronchi↗
PubMed1988

A quantitative study of command elements for abdominal positioning behavior in the crayfish Procambarus clarkii.

We develop a statistical method to estimate the total number of command elements devoted to abdominal positioning behavior in crayfish. We assumed that all command elements can be identified, that each identified cell is equivalent to a tagged individual in a population, and that the cells were sampled randomly. Samples of 29, 30, 20, and 35 cells from abdominal ganglia A3, A4, A5, and A6, respectively, were taken from our catalog. We characterized each cell using several morphological and physiological criteria, determined how many times each identified cell was present in the sample, and estimated the total number of command elements using both a maximum likelihood method and a modification of the Lincoln index. The larger the proportion of identified cells seen only once in the sample, the more identified cells there were that were unrepresented in the sample. We estimate there are approximately 34, 60, 86, and 98 command elements in ganglia A3, A4, A5, and A6, respectively. Using a slightly different data set we show that the motor output of unipolar cells is more often stronger in the direction of the cell's axonal projection. In bipolar command elements, the output strength was uncorrelated with the relative sizes of the two projecting axons. No two cells in our sample were completely identical, and this morphological variability sometimes made it difficult to determine whether or not two cells obtained from different individuals were the same identified cell. We discuss why caution should be exercised in studies requiring precision in cell identification.

Animals↗
PubMed2008

Maternal control of pattern formation in Xenopus laevis.

We review the essential role of maternal factors in pattern formation for Xenopus laevis, focusing on VegT, Vg1, and Wnt11. Results from loss of function experiments demonstrate a clear requirement for these genes in germ layer specification, dorsal-ventral axis formation, and convergence extension. We also discuss these genes in the broader context of metazoan development, exploring whether and how their functions in the X. laevis model organism may or may not be conserved in other species. Wnt11 signaling in particular provides a classic example where understanding context in development is crucial to understanding function. Genomic sequencing, gene expression, and functional screening data that are becoming available in more species are providing invaluable aid to decoding and modeling signaling pathways. More work is needed to develop a comprehensive catalog of the Wnt signaling, T-box, and TGF-beta genes in metazoans both near and far in evolutionary distance. We finally discuss some specific experimental and modeling efforts that will be needed to understand the behavior of these signaling networks in vivo so that we can interpret these critical pathways in an evolutionary framework.

Animals↗
PubMed1998

Profile of human macrophage transcripts: insights into macrophage biology and identification of novel chemokines.

High throughput partial sequencing of randomly selected cDNA clones has proven to be a powerful tool for examining the relative abundance of mRNAs and for the identification of novel gene products. Because of the important role played by macrophages in immune and inflammatory responses, we sequenced over 3000 randomly selected cDNA clones from a human macrophage library. These sequences represent a molecular inventory of mRNAs from macrophages and provide a catalog of highly expressed transcripts. Two of the most abundant clones encode recently identified CC chemokines. Macrophage-derived chemokine (MDC) plays a complex role in immunoregulation and is a potent chemoattractant for dendritic cells, T cells, and natural killer cells. The chemokine receptor CCR4 binds MDC with high affinity and also responds by calcium flux and chemotaxis. CCR4 has been shown to be expressed by Th2 type T cells. Recent studies also implicate MDC as a major component of the host defense against human immunodeficiency virus.

Base Sequence↗
PubMed1993

Position paper: imaging methods for primary renal tumors of childhood: costs versus benefits.

The patterns of disease distribution at diagnosis and during follow-up were cataloged for the primary renal tumors of childhood. These data, derived from more than 1,500 patients, were used to define the most rewarding and cost-effective imaging methods required for patient management. The basic information needed prior to surgery includes whether there is a functioning kidney on the opposite side, and whether there are lung metastases or inferior vena cava thrombi. Simple X-ray examinations and ultrasonography (US) will provide the necessary data. Postoperatively, when the histology is known, examination of the brain (MRI or CT scan) is needed for patients with the rhabdoid tumor and clear cell sarcoma of the kidney (CCSK) who are prone to develop brain lesions; and the skeletal system (bone scan, X-ray skeletal survey) for CCSK and for renal cell carcinoma patients who tend to develop bone metastases. Continuing examination of the lung (chest films) is required for all histologies except perhaps for mesoblastic nephroma, which seldom metastasizes. The opposite kidney needs follow-up (US) for 5 or more years to exclude metachronous involvement if nephrogenic rests are present in either kidney. Sophisticated imaging studies, which cost five times or more than simple X-ray examinations or US, are not warranted routinely, and should be reserved for those cases where simpler, less expensive studies do not suffice for reaching patient management decisions.

Bone Neoplasms↗
PubMed1991

Analysis of proteins synthesized by 9.5 day mouse embryos: determination of cardiac and noncardiac proteins.

To catalog polypeptides that were specific to developing hearts, we separated 35S-methionine-labeled 9.5 day mouse embryos into cardiac and noncardiac (carcass) components. Two-dimensional gels were then used to analyze the polypeptides synthesized in these two fractions. As a result, we were able to distinguish polypeptides that were specific to or increased in the heart as well as those polypeptides that were specific to or increased in the embryo minus the dissected heart. Using this analysis, there were two polypeptides that were cardiac-specific and 17 that were expressed at increased levels by at least twofold in the heart. The cardiac-specific polypeptides may be used in further studies to identify early cardiac tissue. Conversely, there were 26 polypeptides unique to noncardiac structures and an additional 15 that were increased in the carcass more than twofold relative to the heart. The noncardiac-specific polypeptides may be used to define contamination of putative cardiac tissue with noncardiac material. Two of the polypeptides expressed more abundantly in the carcass appeared to correspond to known proteins in the mouse fibroblast database, cyclin and tropomyosin 4. Thus the heart at 9.5 days of murine development can be distinguished readily from the remainder of the embryonic mouse both macroscopically and on two-dimensional gels.

Animals↗
PubMed2006

Early embryonic death-associated changes in genome-wide gene expression profiles in the fetal placenta of the cow carrying somatic nuclear-derived cloned embryo.

Successful somatic nuclear transfer-derived cloning has been reported in cattle; however, the cloned embryo is highly susceptible to death around day 60 of gestation leading to early embryonic loss. The early embryonic death is postulated to possibly arise in part from an atypical placentation. We have performed cDNA macroarray analysis using 3,353 of the previously cataloged 4,165 genes, in order to characterize the early embryonic death-associated changes in genome-wide gene expression profiles in the fetal placenta of the cow carrying somatic nuclear transfer-derived cloned embryo. A more marked difference in the expression profiles was observed between the fetal placentas of the cows with the cloned immotile embryo (CD) and with the cloned motile embryo (CL) or artificial insemination-derived motile embryo (AI), as compared to between the CL and AI placentas, suggesting an aberration of the expression profile in the CD placenta among the three placentas. Further, 291 and 77 genes showed more than twofold elevation and less than 50% reduction, respectively, in either or both of two CD (CD1 and CD2) placentas in comparison with the CL placenta, but no differential expression between the CL and AI placentas. The expression patterns of six genes in the AI, CL, and CD placentas were confirmed in an experiment with an additional sample for each of the three placentas. Among the placental genes showing the early embryonic death-associated changes of expression in the cow with the cloned embryo, IGF2 (elevated gene), and HBA1, HBA2, SPTB, and SPTBN1 genes (reduced gene) are intriguing in that the changes of expression in these genes were observed in an additional sample of CD placenta as well as the CD1 and CD2 placentas, and in that overexpression (for IGF2) and dysfunction or deficiency (for HBA1, HBA2, SPTB, and SPTBN1) result in embryonic lethality.

Animals↗
PubMed2004

Role of CRMP-2 in neuronal polarity.

Of the several types of polarized cells, the neuron is one of the most dramatic examples. It extends two distinctive processes, axon and dendrite. Polarization in neurons enables the two processes to play their functionally different roles, sending and receiving electrical signals in a vectorial fashion. While a catalog of structural, molecular, and functional differences between axon and dendrite is accumulating, the mechanisms involved in establishment of neuronal polarity are not well understood. Neuronal polarity formation begins with the elongation of one process as an axon in a symmetric cell phase. In this review, we describe recent advances in the understanding of several cellular events in the early development of axon and dendrite. We also discuss the involvement of the Rho family small GTPases, their upstream and downstream molecules, and collapsin response mediator protein-2 (CRMP-2) in the regulation of neuronal polarity.

Animals↗
PubMed2007

Reporting adverse events in randomized controlled trials.

PURPOSE: How randomized controlled trial results are reported may minimize concerns and detection of adverse side effects. We aimed to describe the methods of reporting adverse events in these published trials. METHODS: Five frequently cited journals were investigated: Annals of Internal Medicine, British Medical Journal, JAMA, The Lancet, and the New England Journal of Medicine. For each journal, all randomized controlled trials conducted on the use of a medication were selected from January 2000 through June 2003. All issues of each journal were reviewed manually. Information retrieved included any mention of adverse events in the abstract, methods, results, or discussion section of the article; or inclusion of adverse events data in tables or figures. We also cataloged whether there was a separate subheading in the results section for reporting adverse events. Reports of trials that referred to methods described in a previous report were excluded. RESULTS: There were 521 eligible articles. Explicit mention of adverse events was in 328 (63%) of abstracts (range 47-66%), 380 (73%) of methods (range 51-81%), 464 (89%) of results (range 80-95%), and 250 (48%) of tables (range 31-49%). There was a separate subheading for adverse events in 240 (46%) (range 22-64%) of the eligible articles. CONCLUSION: There is variation among authors and journals as to the location of reporting adverse events and the means by which it is done. Authors and editors should include specific information on adverse events when reporting the results of randomized controlled trials. It would be ideal if there was more consistency among authors and journals as to how these adverse events are described.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry.

Human saliva contains a large number of proteins and peptides (salivary proteome) that help maintain homeostasis in the oral cavity. Global analysis of human salivary proteome is important for understanding oral health and disease pathogenesis. In this study, large-scale identification of salivary proteins was demonstrated by using shotgun proteomics and two-dimensinal gel electrophoresis-mass spectrometry (2-DE-MS). For the shotgun approach, whole saliva proteins were prefractionated according to molecular weight. The smallest fraction, presumably containing salivary peptides, was directly separated by capillary liquid chromatography (LC). However, the large protein fractions were digested into peptides for subsequent LC separation. Separated peptides were analyzed by on-line electrospray tandem mass spectrometry (MS/MS) using a quadrupole-time of flight mass spectrometer, and the obtained spectra were automatically processed to search human protein sequence database for protein identification. Additionally, 2-DE was used to map out the proteins in whole saliva. Protein spots 105 in number were excised and in-gel digested; and the resulting peptide fragments were measured by matrix-assisted laser desorption/ionization-mass spectrometry and sequenced by LC-MS/MS for protein identification. In total, we cataloged 309 proteins from human whole saliva by using these two proteomic approaches.

Chromatography, Liquid↗