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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 361 records · Page 20Linked to original sources
PubMed1985

Identification and expression of a nuclear antigen from the genomic region of the Jijoye strain of Epstein-Barr virus that is missing in its nonimmortalizing deletion mutant, P3HR-1.

An Epstein-Barr virus (EBV) deletion mutant, HR-1, cannot immortalize lymphocytes. HR-1 was derived from a virus strain, Jijoye, that is immortalization competent. Using human antiserum from certain patients with chronic active EBV infection, we have identified in Jijoye cells a protein of apparent mass of 78-80 kDa that is missing in cells with the HR-1 genome. A protein of identical size and antigenicity has been stably expressed in mouse LTK- cells by gene transfer with cloned Jijoye EBV DNA that encompasses the deletion in the HR-1 genome. The expressed product is a nuclear neoantigen. The polypeptide we have identified is likely to be essential in the immortalization process.

Animals↗
PubMed1985

Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: the role of primary infection.

Fourteen patients who developed B cell lymphomas or lymphoproliferative lesions after kidney, liver, heart, or heart-lung transplantation in Pittsburgh during 1981-1983 had active infection with Epstein-Barr virus (EBV) of the primary (six patients), reactivated (seven patients), or chronic (one patient) type. In transplant patients without tumors, the incidence of EBV infection was 30% (39 of 128). Only three of these patients had primary infections. Thus the frequency of active infection was significantly higher in patients with tumors, and patients with primary infections were at greater risk of developing tumors. Five of 13 tumors tested contained EBV nuclear antigen (EBNA) and nine of 11 contained EBV genomes detected by DNA-DNA hybridization with BamHI K, BamHI W, or EcoRI B cloned probes. All EBNA-positive tumors, except one, were also positive by hybridization. Only one tumor was negative for both EBNA and EBV DNA. These data suggest that EBV plays an etiologic role in the development of these lesions.

Adolescent↗
PubMed1985

Predictors for survival and normal neurodevelopmental outcome of infants weighing less than 1001 grams at birth.

Between 1979 and 1981, 67 infants weighing 1000 g or less at birth were admitted to the Hammersmith Hospital Neonatal Intensive Care Unit. 29 survived the neonatal period. Low acidosis score, without a metabolic component, was the most powerful predictor of survival. Other factors were gestational age, five-minute Apgar score, the need for ventilatory support, hypoxia, hypercapnia, pneumothorax, hypotension and the presence of a larger PVH. Of the 24 survivors followed up to three years of age, 11 were optimal, nine had some neurodevelopmental deficits and three had moderate functional handicap. Only one child has cerebral palsy and global mental retardation. Five-minute Apgar score and the presence of PDA correlated with normal outcome. None of the 20 obstetrical factors examined appeared to influence either survival or neurological outcome.

Child Development↗
PubMed1985

Constitutive expression of Epstein-Barr virus-encoded RNAs and nuclear antigen during latency and after induction of Epstein-Barr virus replication.

We examined the fate of two major products of latency as Epstein-Barr virus was induced to replicate. We studied a superinducible clone of HR-1 cells in the presence and absence of induction by phorbol ester, and we analyzed the X50-7 line with and without superinfection by an HR-1 viral variant which disrupts latency. The two methods of induction yielded qualitatively similar results. After induction, there was abundant synthesis of viral transcripts, amplification of viral DNA, and the appearance of many new viral polypeptides. Nonetheless, there were no changes in the cytoplasmic abundance of Epstein-Barr virus-encoded RNAs and no alteration in the level of Epstein-Barr virus nuclear antigen mRNA or polypeptide. Thus, under conditions in which numerous other Epstein-Barr virus gene products are activated, the two major latent gene products are expressed at a constitutive level. Expression of Epstein-Barr virus-encoded RNAs and nuclear antigen must therefore be regulated in a manner completely different from expression of replicative functions.

Antigens, Viral↗
PubMed1985

P3HR-1 Epstein-Barr virus with heterogeneous DNA is an independent replicon maintained by cell-to-cell spread.

We present results of biological experiments which indicate that the subpopulation of Epstein-Barr virus strain P3HR-1 with heterogeneous (het) DNA consists of self-contained replicons which multiply alongside, but independently of, Epstein-Barr virus strain HR-1 containing standard DNA. When a population of HR-1 virions containing het DNA was introduced into X50-7 cells, the input heterogeneous DNA increased in abundance, as did the DNA of the endogenous virus of X50-7 cells. The input standard HR-1 viral DNA, however, was not amplified. When parental HR-1 cells or a cellular subclone containing het DNA were grown for several weeks in the presence of human serum with neutralizing antibody, the het DNA was lost from the culture; standard HR-1 DNA, however, was not affected by antiserum. Furthermore, virions containing het DNA could be serially propagated through cellular subclones of HR-1 cells which lack het DNA. After each serial passage, cells which acquired het DNA released virions with the ability to induce early antigens in Raji cells. These experiments define a novel in vitro life cycle of an Epstein-Barr virus variant which is maintained, not vertically by partitioning to daughter cells in cell division, but horizontally by cell-to-cell spread.

Antibodies, Viral↗
PubMed1985

Latent and viral replicative transcription in vivo from the BamHI K fragment of Epstein-Barr virus DNA.

We mapped one latent and two replicative messages transcribed in vivo from the BamHI K fragment of the Epstein-Barr virus genome. The exon encoding Epstein-Barr nuclear antigen (EBNA), a major latent product, is 2,028 bases; the 3' end of this exon occurs 30 bases after the polyadenylation signal AATAAA, and the 5' end occurs within a splice acceptor site. The open reading frame which encodes the EBNA peptide is completely contained within this coding exon. The exon was faithfully transcribed after transfection of cloned BamHI-K into either COS-1 or TK- mouse L cells. In lymphocytes the abundance of the EBNA message is increased after cycloheximide treatment. The two viral replicative genes completely contained in BamHI-K were not transcribed in line X50-7, in which the genome is tightly latent. In contrast to the EBNA message, these mRNAs of 1.3 and 2.1 kilobases are inducible with phorbol ester and are unspliced. Their promoter regions are similar to those of each other and to replicative promoters mapped in other regions of the Epstein-Barr virus genome (P. J. Farrell, A. Bankier, C. Seguin, P. Deininger, and B. G. Barrell, EMBO J. 2:1331-1338, 1983). An unusual feature of these replicative genes is that the smaller mRNA begins within a long open reading frame of the larger mRNA. The identification of the structure of latent and replicative genes within one DNA fragment will facilitate analysis of regulation of expression for the two life cycles of the virus.

Antigens, Viral↗
PubMed1985

Epstein-Barr virus genomes are restricted to secondary neoplastic cells following bone marrow transplantation.

DNA from mononuclear blood and tumor cells from 33 patients undergoing bone marrow transplantation for leukemia was examined for the presence of Epstein-Barr virus (EBV) genomes by blot hybridization. Four groups of patients were studied soon after engraftment, during long-term remission, after relapse of the original leukemia, and after development of secondary B cell neoplasms. Only the cells of patients with secondary neoplasms demonstrated EBV genomes, where all five adequately studied samples were positive. Samples from all other patient categories were negative for EBV genomes. We conclude that EBV genomes do not frequently persist in normal engrafted lymphocytes or in mononuclear cells of patients suffering recurrent leukemia. These results are consistent with EBV playing a role in the genesis of secondary B cell neoplasms following bone marrow transplantation.

B-Lymphocytes↗
PubMed1985

Buccal administration of fenoterol aerosol in childhood asthma.

We have studied 23 asthmatic children who were wheezy when attending a hospital clinic or following tests for exercise-induced asthma. Fenoterol was administered by metered dose aerosol against the buccal mucosa on the inside of the cheek. This produced marked improvement in peak-expiratory-flow-rate and relieved clinical symptoms. Buccal administration of fenoterol may be a useful treatment for children with mild asthma who have difficulty in using inhaled drugs.

Adolescent↗
PubMed1984

Arterial blood pressure and urinary electrolytes.

The relationship between blood pressure levels and urinary sodium and potassium concentrations were examined by sex and race in a random population sample of 1939 residents, aged 34-57. They were selected from three cities of the United States which had reported marked differences in morbidity and mortality due to stroke. We found that high blood pressure was associated with higher urinary sodium/potassium ratio and lower urinary potassium concentration. Part of this relationship might be due to obesity. Blacks had higher blood pressure than whites and they also had higher sodium and lower potassium concentrations in the urine. In addition, black women were much heavier than white women. Blood pressure was lower among individuals with higher education. Both obesity and urinary Na/K ratio were inversely related to the level of education among white women.

Adult↗