Search PubMed⌕ Search

Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 577 records · Page 32Linked to original sources

An adenovirus E1a protein region required for transformation and transcriptional repression.

The adenovirus E1a region encodes two closely related gene products: 243 and 289 amino acid phosphoproteins. These proteins differ in their primary sequence only by 46 amino acids unique to the 289 amino acid protein. By constructing single-base substitution mutants we localized two functional regions of these E1a proteins: one required for efficient transcriptional activation, another required for efficient transcriptional repression. The 289 amino acid protein contains both regions and appears to function primarily as a transcriptional activator. The 243 amino acid protein lacks the transcriptional activation domain and appears to function primarily as a transcriptional repressor. Mutations within a highly conserved region define a novel class of transformation-defective mutants. These mutant E1a proteins can still efficiently activate transcription of early viral and cellular genes but cannot repress transcription of target genes. The fact that viral transformation may require a transcriptional repression function provides new insights into the mechanism by which adenovirus transforms cells.

Adenovirus Early Proteins↗

Correspondence matching in apparent motion: evidence for three-dimensional spatial representation.

The path of an object in apparent motion depends on correspondence matching, the decision that images seen at different places and at different times represent the same object. One determinant of correspondence is proximity. Still debated, however, is whether proximity is defined in a two- or three-dimensional spatial representation. Observers judged the motion path taken by an object with two neighbors of different apparent depth. Given similar two-dimensional distances, objects moved toward the neighbor of the same apparent depth. This is evidence that correspondence operates in a three-dimensional spatial representation.

Humans↗

Time for action.

Explore the source record for details and available documents.

Education, Nursing↗

Structure and assembly of the endoplasmic reticulum: biosynthesis and intracellular sorting of ERp61, ERp59, and ERp49, three protein components of murine endoplasmic reticulum.

Rabbit antibodies have been prepared against ERp61, ERp59, and ERp49, three protein components of rough endoplasmic reticulum (RER) purified from mineral oil-induced plasmacytoma 315 (MOPC-315) tissue. Analysis of subcellular fractions of MOPC-315 tissue by an immunoprecipitation procedure demonstrated that all three endoplasmic reticulum proteins (ERps) were most enriched in the RER. Immunologically cross-reacting proteins of similar molecular weight have been detected in other eucaryotic cell lines. We have used these antibodies to study the post-translational processing and biosynthetic sorting of the three ERps in pulse-labeled MOPC-315 cells. No larger precursor forms of the ERps were detected and none of the ERps were found to possess asparagine-linked oligosaccharide moieties. We have used a sucrose gradient analysis of pulse-labeled MOPC-315 cells to study the biosynthetic sorting of ERp61, ERp59 and ERp49 and have found no evidence to suggest that these proteins ever leave the endoplasmic reticulum. In addition, all three ERps appeared to have luminally exposed domains. ERp61 and ERp59 were entirely protected by the ER membrane in the absence of detergent, while ERp49 was a transmembrane protein that also possesses a cytoplasmically exposed domain. We have used the anti-ERp antibodies to quantitate the synthesis and accumulation of the three ERps during lipopolysaccharide (LPS)-induced lymphocyte differentiation. After 48 h of culture in the presence of LPS, the synthesis of ERp49 increased sixfold relative to that in control cells. The synthesis and membrane accumulation of ERp61 and ERp59 were less affected by the LPS treatment. Thus, membranes isolated from LPS-treated cells were enriched in ERp49 relative to those isolated from control cells.

Animals↗

Ocular toxicity following ethambutol in standard dosage.

We describe a patient who developed rapid irreversible blindness following treatment with ethambutol in the recommended dose of 15 mg/kg body weight which in clinical practice is widely considered to be safe. This case exemplifies the potential risks of ethambutol and re-emphasizes the importance of instructing patients to stop the drug at once if they develop visual symptoms.

Adult↗

What determines correspondence strength in apparent motion?

A sequence of static frames may produce the perception of coherent motion. The experiments described below investigated the psychophysical basis of this correspondence matching. Observers judged the direction of motion for "Gabor functions" which varied in spatial frequency, orientation or phase. The strongest determinant of correspondence was similarity of spatial frequency: objects tend to move toward neighbors of the same spatial frequency content. Orientation similarities also produced correspondence, although the effect was somewhat weaker than for spatial frequency. Phase played no role in determining correspondence.

Discrimination, Psychological↗

Detection of somatic mutations in man: evaluation of the microtitre cloning assay for T-lymphocytes.

A method of detecting 6-thioguanine-resistant lymphocytes by the cloning of T-lymphocytes in microtitre wells is evaluated for its usefulness in population monitoring. Factors shown to affect the cloning efficiency of lymphocytes include the strain and irradiation level of the lymphoblastoid feeder cells and the use of a pre-incubation period in bulk culture without mitogenic stimulus before plating at limiting dilutions. Cord blood samples have markedly lower mutant frequencies than adult blood samples. The adult range was 8.0 X 10(-7) to 1.8 X 10(-5). Seven males and seven females aged between 23 and 47 years were sampled. No effect of sex or age was found. Individual samples which were divided at collection and treated separately did not vary from each other, but repeat samples taken at different times showed up to a 2-fold variation. The application of this method in population monitoring is discussed.

Adult↗

Attentional performance in positive- and negative-symptom schizophrenia.

Two tasks designed to measure selective attention were administered to schizophrenics, patients with bipolar disorder, and normal subjects. Schizophrenics were divided into three subgroups: positive-, negative-, and mixed-symptom patients. Positive-symptom schizophrenics showed significant deficits on a digit-span task when compared to normal subjects. Furthermore, the positive group was the only one to show a significant performance decrement in the distraction condition of the digit-span task. There were no significant group differences in performance on a dichotic listening test. The results of the present study are contrary to the hypothesis that selective attention deficits are characteristic of negative-symptom schizophrenia. Instead, the findings suggest that positive symptoms are associated with greater susceptibility to distraction.

Adult↗

Biosynthesis and properties of the adenovirus 2 L1-encoded 52,000- and 55,000-Mr proteins.

The adenovirus type 2 L1 region, which is located at 30.7 to 39.2 map units on the viral genome, is transcribed from the major late promoter during both early and late stages of virus replication, and a 52,000-Mr (52K) protein-55K protein doublet has been translated in vitro on L1-specific RNA. To investigate the biosynthesis and properties of the L1 52K and 55K proteins, we prepared antibody against a synthetic peptide encoded near the predicted N terminus. As determined by immunoprecipitation and immunoblot analysis, the antipeptide antibody recognized major 52K and 55K proteins synthesized in adenovirus type 2-infected cells that appeared to be identical to the 52K-55K doublet translated in vitro. The immunoprecipitated 52K and 55K proteins were very closely related, as shown by a peptide map analysis. Both L1 proteins were phosphorylated, and they were phosphorylated at similar sites. No precursor-product relationship was detected between the 52K and 55K proteins by a pulse-chase analysis. Biosynthesis of the L1 52K and 55K proteins began about 6 to 7 h postinfection, after biosynthesis of the early region 1A and early region 1B 19K (175R) T antigens, and reached a maximum rate at about 15 h; the maximum rate was maintained until at least 25 h postinfection. At all times, the 55K protein appeared to be synthesized at a severalfold-higher level than the 52K protein. Both proteins were quite stable and accumulated until late times after infection. Viral DNA replication was not essential for formation of the L1 proteins. Thus, the L1 52K-55K gene appears to be regulated in a manner different from the classical early and late viral genes but similar to the protein encoded by the i-leader (Symington et al., J. Virol. 57:849-856, 1986). The L1 proteins were detected in the cell nucleus by immunofluorescence microscopy with antipeptide antibody and were found to be primarily associated with the nuclear membrane by an immunoblot analysis of subcellular fractions.

Adenoviridae Infections↗

Biosynthesis of adenovirus type 2 i-leader protein.

The i-leader is a 440-base-pair sequence located between 21.8 and 23.0 map units on the adenovirus type 2 genome and is spliced between the second and third segments of the major tripartite leader in certain viral mRNA molecules. The i-leader contains an open translational reading frame for a hypothetical protein of Mr about 16,600, and a 16,000-Mr polypeptide (16K protein) has been translated in vitro on mRNA selected with DNA containing the i-leader (A. Virtanen, P. Aleström, H. Persson, M. G. Katze, and U. Pettersson, Nucleic Acids Res. 10:2539-2548, 1982). To determine whether the i-leader protein is synthesized during productive infection and to provide an immunological reagent to study the properties and functions of the i-leader protein, we prepared antipeptide antibodies directed to a 16-amino acid synthetic peptide which is encoded near the N terminus of the hypothetical i-leader protein and contains a high acidic amino acid and proline content. Antipeptide antibodies immunoprecipitated from extracts of adenovirus type 2-infected cells a major 16K protein that comigrated with a 16K protein translated in vitro. Partial N-terminal amino acid sequence analysis by Edman degradation of radiolabeled 16K antigen showed that methionine is present at residue 1 and leucine is present at residues 8 and 10, as predicted from the DNA sequence, establishing that the 16K protein precipitated by this antibody is indeed the i-leader protein. Thus, the i-leader protein is a prominent species that is synthesized during productive infection. The i-leader protein is often seen as a doublet on polyacrylamide gels, suggesting that either two related forms of i-leader protein are synthesized in infected cells or that a posttranslational modification occurs. Time course studies using immunoprecipitation analysis with antipeptide antibodies revealed that the E1A 289R T antigen and the E1B-19K (175R) T antigen are synthesized beginning at 2 to 3 and 4 to 5 h postinfection, respectively, whereas the i-leader protein is synthesized starting at about 8 h postinfection and continues unabated until at least 25 h postinfection. The i-leader protein is very stable, as determined by pulse-chase labeling experiments, and accumulates continuously from 8 to 25 h postinfection, as shown by immunoblot analysis. The synthesis of i-leader protein does not depend upon viral DNA replication. Thus, the i-leader protein is a viral gene product of unknown function and high stability that is made in large quantities at intermediate times of productive infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoviridae Infections↗

Posttranslational modification at the N terminus of the human adenovirus type 12 E1A 235R tumor antigen.

The adenovirus E1A transforming region, which encodes immortalization, partial cell transformation, and gene activation functions, expresses two early mRNAs, 13S and 12S. Multiple-T antigen species with different electrophoretic mobilities are formed from each mRNA, presumably by unknown posttranslational modifications. The adenovirus type 12 (Ad12) 13S and 12S mRNAs encode E1A T antigens of 266 and 235 amino acid residues (266R and 235R), respectively. To study possible posttranslational processing at the N and C termini and to distinguish between the Ad12 266R and 235R T antigens, we prepared antibodies targeted to synthetic peptides encoded at the common C (peptide 204) and N (peptide 202) termini of the 266R and 235R T antigens and at the unique internal domain of the 266R T antigen (peptide 206). The specificity of each anti-peptide antibody was confirmed by immunoprecipitation of the 266R and 235R T antigens produced in Escherichia coli. Immunoprecipitation analysis of the E1A T antigens synthesized in Ad12-infected KB cells revealed the following. Antibody to the common C terminus recognized three T antigens with apparent Mrs of 43,000, 42,000, and 39,000 (43K, 42K, and 39K). All three forms were phosphorylated and were present in both the nucleus and the cytoplasm. The 43K and 42K T antigens were rapidly synthesized during a 10-min pulse with [35S]methionine in Ad12-infected cells. The 43K T antigen had a half-life of 20 min, the 42K T antigen had a longer half-life of about 40 min, and the 39K T antigen became the predominant E1A T antigen. Antibodies to the unique region immunoprecipitated the 43K T antigen but not the 42K and 39K T antigens. Antibody to the N terminus immunoprecipitated the 43K and 42K T antigens but not the 39K T antigen, suggesting that the 39K T antigen possessed a modified N terminus. Partial N-terminal amino acid sequence analysis showed that the 43K and 42K T antigens contain methionine at residues 1 and 5, as predicted from the DNA sequence, whereas no methionine was released from the 39K T antigen during the first six cycles of Edman degradation. We propose that the short-lived 43K T antigen is the primary product of the 13S mRNA, the 266R T antigen; the somewhat more stable 42K T antigen is the primary product of the 12S mRNA, the 235R T antigen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenovirus Early Proteins↗

Rat embryo fibroblast cells expressing human papillomavirus 1a genes exhibit altered growth properties and tumorigenicity.

Human papillomavirus 1a (HPV1a) induces benign tumors (papillomas or warts) in humans under natural conditions of infection but has not been found to replicate significantly in cell culture or in experimental animals. To establish model systems to study the oncogenic properties and expression of HPV genes, we established cell lines by cotransfecting the 3Y1 rat fibroblast cell line with HPV1a DNA constructs containing an intact early gene region and the Tn5 neomycin resistance gene. Most cell lines selected for expression of the neomycin resistance gene by treatment with the antibiotic G-418 contained viral DNA in a high-molecular-weight form. The growth characteristics of several cell lines containing high copy numbers of HPV1a DNA were studied further. They were shown to differ from the parental cell line and from G-418-resistant cell lines that did not incorporate viral DNA in the following properties: morphological alteration, increased cell density at confluence, growth in 0.5% serum, efficient anchorage-independent growth in soft agar, and rapid formation of tumors in nude mice. Those cell lines that possessed altered growth properties and tumorigenicity were found to express abundant quantities of polyadenylated virus-specific RNA species in the cytoplasm.

Animals↗

Symptom correlates of vulnerability to backward masking in schizophrenia.

The authors used the backward-masking procedure to investigate visual information processing in schizophrenic and bipolar patients, determining the critical interstimulus interval at which the masked target could be identified for each subject. Multiple regression analysis revealed that a negative symptom rating was a significant predictor of this interval among schizophrenic patients: greater negative symptoms were associated with longer intervals. Positive symptom ratings were not predictive of performance. Symptom ratings did not predict performance of bipolar patients. Group comparisons revealed that schizophrenic patients who had mixed positive and negative symptoms had significantly longer intervals than normal control subjects did. These results have implications for theories of information processing in schizophrenia.

Adult↗

Mental illness and the media: Part II. Content analysis of press coverage of mental health topics.

The public image of psychiatry has been tarnished in recent years. In order to determine the extent to which press coverage has contributed to negative attitudes towards psychiatry, we conducted a content analysis of a random selection of newspaper articles which appeared over a twenty-year period in two different newspapers. We found that although there had been some minor, cosmetic changes over the years, such as more appropriate headlines and more direct quotes from psychiatric experts, on the whole, content and attitudes had changed very little. An accuracy check of media reporting of forensic cases over a 20-year period revealed that when reporters have access to written material, the accuracy levels are greatly improved.

Attitude to Health↗