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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 271 records · Page 15Linked to original sources
PubMed1990

Differences in the extent of activation of Epstein-Barr virus replicative gene expression among four nonproducer cell lines stably transformed by oriP/BZLF1 plasmids.

Lymphoid cell lines were established which stably carry the Epstein-Barr viral (EBV) BZLF1 gene on an extrachromosomal plasmid. These lines, which spontaneously synthesize the BZLF1 gene product, ZEBRA, were examined for expression of EBV genes which were activated by ZEBRA. Cell lines which acquired oriP plasmids without BZLF1 served as controls. The extent of activation differed among derivatives of four cell lines. X50-7 cells, which harbor a standard latent EBV, could be induced by ZEBRA to produce transforming virus; a cellular subclone of this line was induced to express EBV late antigens but did not release transforming virus. In two other cell lines, Raji and ER, ZEBRA activated only a group of early antigens. Using immunofluorescence and immunoblotting with monoclonal antibodies and Northern analysis five EBV early genes were shown to be induced in cells stably transformed by oriP/BZLF1 plasmids. ZEBRA itself was activated; thus BZLF1 is autostimulatory. Four other activated genes were components of the diffuse (EA-D) and restricted (EA-R) early antigens (BMRF1, BMLF1, BHRF1, and BORF2). Stable cell lines with extrachromosomal BZLF1 expression vectors will ultimately be useful in a variety of experiments designed to study regulation of this gene, to analyze the effects of mutations on ZEBRA protein function, and to define the full spectrum of viral and cellular genes which are activated by and interact with the ZEBRA protein.

Cell Line↗
PubMed1990

Trace elements in soil and biota in confined disposal facilities for dredged material.

We studied the relation of trace element concentrations in soil to those in house mice (Mus musculus), common reed (Phragmites australis) and ladybugs (Coccinella septempunctata at five disposal facilities for dredged material. The sites had a wide range of soil trace element concentrations, acid soils and a depauperate fauna. They were very poor wildlife habitat because they were dominated by the common reed. Bioassay earthworms exposed to surface soils from three of the five sites died, whereas those exposed to four of five soils collected a meter deep survived, presumably because the deeper, unoxidized soil, was not as acid. Concentrations of Ni and Cr in the biota from each of the sites did not seem to be related to the concentrations of the same elements in soil. Although Pb, Zn and Cu concentrations in biota were correlated with those in soil, the range of concentrations in the biota was quite small compared to that in soil. The concentrations of Pb detected in mice were about as high as the concentrations previously reported in control mice from other studies. Mice from the most contaminated site (530 ppm Pb in soil) contained only slightly more Pb (8 ppm dry wt) than did mice (2-6 ppm dry wt) from sites containing much less Pb (22-92 ppm in soil). Despite the acid soil conditions, very little Cd was incorporated into food chains. Rather, Cd was leaching from the surface soil. We concluded that even the relatively high concentrations of trace elements in the acid dredged material studied did not cause high concentrations of trace elements in the biota.

Journal Article↗
PubMed1990

The switch between latency and replication of Epstein-Barr virus.

Latency is characteristic behavior of many viruses that persist in their hosts. During latency an intact viral genome resides in the cell, but most viral genes are silent. Diverse inducing stimuli, by which the environment interacts with the host cell, trigger the latent viral genome into replication. Experiments are described that led to the identification of a crucial Epstein-Barr virus (EBV) gene, called ZEBRA, which acts as a switch between latency and replication of this herpes virus. During latency of EBV, ZEBRA expression is repressed. Inducing stimuli cause synthesis of ZEBRA which, in turn, activates expression of several individual EBV early genes. The ZEBRA polypeptide is a site-specific DNA binding protein that is likely to function as a transcriptional transactivator. The recognition that a single viral product may control the latency-to-replication switch offers promise of a detailed understanding of a central process in virology.

Base Sequence↗
PubMed1990

Resistance mechanisms of multiresistant serotype 012 Pseudomonas aeruginosa isolated in Europe.

Serotype 012 Pseudomonas aeruginosa resistant to gentamicin (MIC greater than 4 mg/l) and carbenicillin (MIC greater than 128 mg/l) occur widely in Europe and are homogeneous in their phenotypic and genetic properties. It has been suggested that a single multiresistant strain of this serotype has become widespread. This study examined the resistance mechanisms present in multiresistant serotype 012 P. aeruginosa isolates from Austria, Belgium, France, Greece, Italy, Holland, West Germany and the UK. Disseminated isolates produced a PSE-1 type beta-lactamase, correlating with their resistance to the known substrates of this enzyme (carbenicillin, azlocillin and cefsulodin). These isolates also reacted with gene probes for the aminoglycoside modifying enzymes AAC(6')I and ANT(3'). The probe for AAC(6')I is known to cross-react with the gene for AAC(6')II. The fact that the organisms were resistant to netilmicin, gentamicin, sisomicin and tobramycin, but less so to amikacin, suggested that the latter enzyme was produced rather than AAC(6')I. PSE-1 beta-lactamase and the gene for AAC(6')I/AAC(6')II were absent from the International Antigenic Typing Scheme 012 reference strain, which was sensitive to beta-lactams and aminoglycosides, and also from a multiresistant serotype 012 strain isolated at a London burns unit in 1987. These organisms have been shown previously to be distinct from the disseminated multiresistant strain in their phenotypic properties. Two 012 isolates appeared to have additional resistance determinants to amikacin and isepamicin.

Aminoglycosides↗
PubMed1990

Persistent nonproductive infection of Epstein-Barr virus-transformed human B lymphocytes by human immunodeficiency virus type 1.

We have studied the interaction of different strains of human immunodeficiency virus type 1 (HIV-1) with an Epstein-Barr virus-transformed human B-lymphocyte line, X50-7. Previously we found that some HIV-1 strains replicated rapidly and were exclusively cytolytic; others induced persistent noncytopathic infection associated with continued shedding of extracellular virus (K. Dahl, K. Martin, and G. Miller, J. Virol. 61:1602-1608, 1987). We now describe a third form of cell-virus relationship in which infection by strain IIIB is maintained in a highly cell-associated state in a small subpopulation (less than 2%) of X50-7 cells. Neither viral subcomponents nor infectious virus was detectable in culture supernatants; however, the carrier lines were fusogenic and HIV-1 could be recovered following prolonged cocultivation with susceptible cells. In these chronic carrier cultures, virions were not seen budding at the cell surface, but a few were found within cytoplasmic vesicles. HIV-1 infection of first- and second-generation cell subclones of the carrier cell line rapidly evolved from a productive to a cell-associated state. There were low levels of HIV DNA, and RNA in the fusogenic secondary clones, but most clones lacked HIV-1 DNA, failed to express HIV-1 RNA, and exhibited no properties associated with HIV-1 infection. The experiments indicate that HIV-1 can be sequestered in human B lymphocytes. The cell cloning experiments introduce the possibility that the HIV-1 provirus may be lost from some lymphocytes.

B-Lymphocytes↗
PubMed1990

Acute myocardial infarction resulting from the migration of a Greenfield filter.

A paraplegic patient who underwent the placement of Greenfield filters to prevent pulmonary emboli had one of the filters migrate proximally to the junction of the inferior vena cava and right atrium, then into the right atrium a few months later. This resulted in an acute myocardial infarction by apparently causing an intimal dissection of the posterior descending artery. Treatment, follow-up and causes of filter migration are discussed.

Adult↗
PubMed1989

Sleep apnea syndrome in chronic renal disease.

PURPOSE: We performed this study in order to expand on an earlier report indicating a high prevalence of the sleep apnea syndrome in male patients with end-stage renal disease treated with hemodialysis and to determine whether patients with chronic renal insufficiency (prior to the initiation of therapy for end-stage renal disease) and female patients with end-stage renal disease treated with hemodialysis were affected. PATIENTS AND METHODS: Polysomnography was performed in 26 male and female patients with chronic renal insufficiency and end-stage renal disease treated with hemodialysis who were not receiving testosterone. They included 22 whose histories were suggestive of sleep apnea ("symptomatic") and four whose histories were not ("asymptomatic"). RESULTS: Sixteen of the symptomatic (73 percent) and none of the asymptomatic patients were found to have clinically significant sleep apnea syndrome (p less than 0.02). Both female patients and patients with chronic renal insufficiency had sleep apnea. In nine of these 16 cases, the disorder was primarily of the obstructive type. CONCLUSION: These preliminary data raise the possibility of an association of chronic renal disease and the sleep apnea syndrome, and suggest that some of the daytime sleepiness and disturbed nocturnal sleep in such patients may be related to sleep apnea. They also indicate that questioning patients with chronic renal disease and symptoms suggestive of a sleep disorder is useful in determining who are at high risk for the sleep apnea syndrome. Further study is required to establish a causal relationship between chronic renal disease and the sleep apnea syndrome, and to determine the prevalence of the latter in patients with end-stage renal disease.

Adult↗
PubMed1989

Autonomic function and the sinus tachycardia of Duchenne muscular dystrophy.

The cardiovascular autonomic function of 13 boys with Duchenne muscular dystrophy was examined in order to test the hypothesis that the labile sinus tachycardia of that disorder is due to autonomic dysfunction. Five non-invasive procedures evaluated the responses of heart rate and blood pressure to postural change, the Valsalva maneuver, sustained hand grip and deep breathing. No individual had sufficient evidence of autonomic dysfunction. Most tests were normal (76%), 16% were borderline, and 8% were abnormal. None had more than one abnormal test. Although most had some difficulty with the Valsalva maneuver, the study demonstrated that simple clinical non-invasive testing of autonomic function can be carried out on a young severely handicapped population.

Adolescent↗
PubMed1989

Ataxic cerebral palsy--clinico-radiologic correlations.

Clinico-radiologic correlations, using CT, were studied in 29 patients with ataxic cerebral palsy. The scans were normal or only slightly abnormal in 38%, posterior fossa abnormalities occurred in 28%, and 55% had obvious cerebral abnormalities which always involved the parietal lobes. There were only two cases where the changes were confined to the posterior fossa. Hydrocephalus was present in four, and there was one case of a Dandy-Walker malformation. An absolute association with any clinical subtype was unusual. All cases of simple ataxia had an obviously abnormal scan, but the changes were widespread. Where dysequilibrium was present the scans were either normal or showed widespread change. Only 25% involved the vermis. Although there was some association between hydrocephalus and ataxic diplegia, the majority of this subtype had a normal or only slightly abnormal scan. Most were hypotonic docile infants with delayed speech and motor skills, particularly those with posterior fossa abnormality. Although CT did not predict development well, those with lower IQ's were more likely to have obvious CT change. Where obvious supratentorial change was present, 75% had a history of epilepsy. In ataxic cerebral palsy CT findings are common, but variable. CT change correlates better with IQ and epilepsy than clinical subtype.

Adolescent↗
PubMed1989

Latent and replicating forms of Epstein-Barr virus DNA in lymphomas and lymphoproliferative diseases.

Epstein-Barr virus (EBV) is associated with lymphomas and lymphoproliferative diseases that occur mainly in immunocompromised patients, but the role EBV plays in their pathogenesis is unclear. The evidence linking EBV etiologically to these disorders includes the presence of EBV DNA and nuclear antigens in the lesions and serologic evidence that some patients with these lesions are experiencing primary or reactivated EBV infections. These syndromes may represent proliferation of cells latently infected with EBV, but the possibility of viral replication has not been rigorously studied. DNA extracted from biopsies of 35 lymphoproliferative diseases was probed with regions of the EBV genome capable of distinguishing circular, episomal DNA found in latency from linear, replicating EBV DNA. All samples contained restriction fragments characteristic of fused termini, indicative of circular, latent genomes. Thirteen samples contained additional restriction fragments diagnostic of linear EBV DNA. Therefore, replicating EBV DNA is found in approximately 40% of EBV-associated lymphoproliferative disorders.

Acyclovir↗
PubMed1989

Management of supracondylar fractures of the femur with Zickel supracondylar nails.

Twenty-one cases of supracondylar fracture of the femur treated at St Vincent's Hospital, Melbourne, during 1983-86, by intramedullary Zickel supracondylar nails were reviewed. The causes were high energy trauma in young patients (six), minor trauma in elderly patients (13), and metastatic malignant fracture (two). The functional results were considered excellent in 10, good in six and poor in five. There were two cases of superficial wound infection. All cases united after 3-6 months. The best functional results were in those patients below 60 years or with pathological fractures. It is concluded that internal fixation of supracondylar fractures of the femur with Zickel supracondylar nails is a successful technique and can be performed by open and closed methods. It is most useful in osteoporotic or pathological bone which is unsuitable for bone plating.

Aged↗
PubMed1989

Influence of Burkitt's lymphoma and primary B cells on latent gene expression by the nonimmortalizing P3J-HR-1 strain of Epstein-Barr virus.

The Epstein-Barr virus (EBV) genes expressed in B lymphocytes immortalized in vitro or in Burkitt's lymphoma (BL) cells infected in vivo have been characterized previously; however, the viral products which are essential for immortalization or for establishment of EBV latency are still not known. To approach this question, we compared the kinetics of expression of EBV nuclear antigens and the two EBV-encoded small RNAs, EBER1 and EBER2, after infection of primary B cells or EBV genome-negative BL cells with either an immortalizing EBV strain (B95-8) or the nonimmortalizing deletion mutant (HR-1). Following infection of primary cells with B95-8 virus, EBV nuclear antigen (EBNA)-2 was expressed first, followed by EBNA-1, -3, and -4 (also called leader protein [LP]) and the two small RNAs. Infection of EBV genome-negative BL cells with the same strain of virus resulted in a similar pattern of gene expression, except that the EBNAs appeared together and more rapidly. EBERs were not apparent in one BL cell line converted by B95-8. The only products detected after infection of primary B lymphocytes with the HR-1 deletion mutant were the EBNA-4 (LP) family and trace amounts of EBER1. Although HR-1 could express neither EBNA-1, EBNA-3, nor EBER2 in primary cells, all these products were expressed rapidly after HR-1 infection of EBV genome-negative BL cell lines. The results indicate that the mutation in HR-1 virus affects immortalization not only through failure to express EBNA-2, a gene which is deleted, but also indirectly by curtailing expression of several other EBV genes whose coding regions are intact in the HR-1 virus and normally expressed during latency. The pattern of latent EBV gene expression after HR-1 infection is dependent on the host cell, perhaps through products specific for the cell cycle or the state of B-cell differentiation.

Antigens, Viral↗