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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 289 records · Page 16Linked to original sources
PubMed1989

Expression of the BZLF1 latency-disrupting gene differs in standard and defective Epstein-Barr viruses.

Previous experiments using gene transfer of plasmids with heterologous promoters identified an Epstein-Barr virus (EBV) gene (BZLF1) whose product (ZEBRA) switches the virus from a latent to a replicative state. We have now studied expression of ZEBRA in lymphoid cells harboring either standard virus or a mixture of standard and defective (heterogeneous [het]) viruses. A high-titer rabbit antiserum to a TrpE-BZLF1 fusion protein was used to identify ZEBRA expressed from standard and het EBV DNA. These ZEBRA proteins could be distinguished from each other on the basis of their electrophoretic mobilities. ZEBRA could not be detected in cells latently infected with standard EBV. However, within 6 h after induction of replication by sodium butyrate, ZEBRA appeared and persisted long thereafter. Synthesis of ZEBRA was insensitive to phosphonoacetic acid or acycloguanosine, behavior characteristic of an early replicative protein. ZEBRA was constitutively expressed in cells containing both defective and standard EBV genomes. ZEBRA was made predominantly from the het genome but also from the standard genome. Control of BZLF1 expression appears to occur at the transcriptional level. No BZLF1-specific transcript was detected in cells containing only standard latent EBV. BZLF1 transcripts could be detected in these cells if virus replication was induced by treatment with butyrate. Cells bearing both standard and het genomes did not require addition of an exogenous inducing agent to transcribe the BZLF1 gene. The experiments suggest that regulation of transcription of the BZLF1 gene is a pivotal event in the control of EBV replication.

Burkitt Lymphoma↗
PubMed1989

Minor congenital anomalies and ataxic cerebral palsy.

The incidence of minor congenital anomalies was examined in 36 patients with ataxic cerebral palsy, in unaffected family members, and in 100 unrelated control subjects. None of the control subjects or family members had more than four anomalies, and 25 of 36 (69%) of the patients had more than four. The distribution of anomalies differed considerably, with 60% of the index cases having seven or more, and 94% of the controls having three or less. The number occurring in the patients was significantly more than in their relatives. Of the 25 patients with more than four anomalies, 16 (64%) had undergone potentially adverse perinatal or early postnatal events. Thus minor congenital anomalies were considerably more frequent in those with ataxic cerebral palsy than in related or unrelated control subjects. These anomalies may be markers of early prenatal factors that contributed to the adverse outcome either directly or by predisposing to perinatal difficulties.

Abnormalities, Multiple↗
PubMed1989

Smoking delays gastric emptying of solids.

Oesophageal transit and gastric emptying of liquids and solids was measured in eight normal subjects with a single test meal containing In113 labelled water and an omelette labelled with Tc99m sulphur colloid. Each volunteer was studied, basally, whilst continuously smoking, and while chewing nicotine gum. Neither liquid, nor solid oesophageal transit were affected by smoking, or gum. Liquid gastric emptying occurred exponentially and clearance was not affected by smoking nor gum (mean basal t1/2 17.4 (2.7) (SEM) min, smoking t1/2 16.6 (7.4) min, gum t1/2 12.5 (2.9) min). Gastric emptying of solid had three components. An initial mean lag phase increased from 17.5 (2.7) min, to 27.5 (6.1) min (p less than 0.05) during smoking, but was not prolonged by nicotine gum (17.5 (1.1) min). A subsequent linear emptying phase was also slowed by smoking from a mean of 1.01 (0.15)% min to 0.80 (0.15)% min (p less than 0.05), but was not affected by nicotine gum, 1.06 (0.2)% min. A third complex phase of solid gastric emptying was not analysed. Smoking delays gastric emptying of solids, but not liquids; nicotine is not responsible for this effect. This observation may partly explain the adverse effect of smoking in patients with gastro-oesophageal reflux.

Adult↗
PubMed1989

Controlled trial of external negative pressure ventilation in patients with severe chronic airflow obstruction.

The effect of intermittent external negative pressure ventilation (ENPV) with the Emerson Pulmowrap ventilator upon leg cycle endurance time (ET), maximal transdiaphragmatic pressure (Pdimax), breathing pattern as expressed by the tension time index (TTdi), and sense of well being was studied in 16 patients with severe chronic airflow obstruction (CAO). The patients were randomized to 3 wk of in-hospital pulmonary rehabilitation (Group I, seven patients) or the same program plus ENPV (Group II, nine patients). Both groups were similar in terms of age (65 +/- 8 versus 61 +/- 13 yr), severity of CAO (FEV1 of 0.64 +/- 0.14 versus 0.59 +/- 0.18 L), and PaCO2 (44 +/- 9 versus 45 +/- 7 mm Hg). Blood theophylline levels and nutritional status were also similar in both groups. Baseline ET (2.9 +/- 0.6 versus 3.8 +/- 1.6 min) and Pdimax (45 +/- 15 versus 56 +/- 18 cm H2O) were decreased in both groups. Baseline TTdi was high but similar in both groups; at rest the values were 0.15 +/- 0.05 versus 0.16 +/- 0.04, and at end-exercise they were 0.17 +/- 0.06 versus 0.21 +/- 0.12. After treatment FEV1 and Pdimax remained unchanged, but the patients in both groups manifested clinical improvement and had a significant increase in mean ET (Group I from 2.9 to 6.9 and Group II from 3.8 to 6 min, p less than 0.01). TTdi decreased both at rest (0.14 +/- 0.07 versus 0.13 +/- 0.04) and at end-exercise (0.14 +/- 0.06 versus 0.15 +/- 0.09) with no difference between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗
PubMed1989

Mesangiopathic glomerulonephritis in Zuni (New Mexico) Indians.

Zuni is a Pueblo Indian village having more than a sixfold greater incidence of nondiabetic end-stage renal disease than the rest of the United States. Renal biopsy specimens from 44 patients with nondiabetic renal disease were subdivided into two groups. In group 1, 21 patients with asymptomatic microscopic hematuria revealed a mild mesangiopathic glomerulonephritis in 18 cases. The predominantly staining immunoglobulin was IgM in ten specimens and IgA in eight specimens. In group 2, 23 patients with symptomatic renal disease presented with nephrotic range proteinuria (11), renal insufficiency (eight), and hypertension (four). A mesangiopathic glomerulonephritis was diagnosed in 16 cases, and in 11 was IgA predominant. Three cases of membranoproliferative glomerulonephritis occurred in group 2. Five cases revealed focal glomerulosclerosis without immune deposits (three in group 1 and two in group 2). More than half (57%) of the patients undergoing biopsy were related. Cases of symptomatic nondiabetic renal disease showed a significant tendency to cluster among the members of four families, suggesting a hereditary influence in the pathogenesis of immune-mediated glomerulonephritis in the Zuni.

Adolescent↗
PubMed1989

Project Canvas-Back in the Marshall Islands.

Using the catamaran boat "Canvas-Back" during May 1987, a whole-population ocular survey utilizing modern equipment and ophthalmic subspecialists was conducted on one of the atolls (Wotje) in the Marshall Islands. A relatively low prevalence of ocular pathology, especially of cataract, infectious disease, and nutritional blindness was found. A far greater need exists for refractive services than for surgical ophthalmic care. The only exception is related to the high incidence of hyperglycemia, which indicates that greater efforts in the treatment and prevention of retinopathy are required.

Adolescent↗
PubMed1988

Distinction of partially purified human natural killer cytotoxic factor from recombinant human tumor necrosis factor and recombinant human lymphotoxin.

Natural killer cell cytotoxic factor (NKCF), a cytotoxic factor contributing to human natural killer cell-mediated cytotoxicity, was generated from lymphocyte-conditioned medium using various stimuli. Crude NKCF activity was concentrated, and partially purified by ammonium sulfate precipitation and gel filtration. NKCF activities eluted as two molecular weight peaks, corresponding to Mr 33,000-43,000 (pool I) and approximately Mr 5,000 (pool II). The cytotoxic activity and target specificity of the partially purified NKCFs were found to be different from both recombinant human TNF and recombinant human lymphotoxin. In the NKCF assay, up to 10(6) units/ml of TNF and lymphotoxin had virtually no effect, whereas both NKCFs lysed 22% (range 17-33%) of the NK-sensitive target K562. In contrast, TNF and lymphotoxin were active in a standard assay against the sensitive murine L929 fibroblast cell line in all concentrations tested (10(-1)-10(6) units/ml). In addition, the effect of these cytotoxic factors in a short-term (4-h) chromium-release assay using peripheral blood mononuclear cells as effector cells was tested: only NKCF (pool I), but not TNF, lymphotoxin, or low molecular weight NKCF (pool II), enhanced NK and lymphokine-activated killer cell cytolysis, both against the NK-sensitive target K562 and the NK-resistant melanoma cell line SK-MEL 30. Results were not affected in the presence of neutralizing antibodies against TNF. NKCF could, therefore, be distinguished from TNF and lymphotoxin with respect to their biological activities.

Cell Line↗
PubMed1988

The bacteriophage lambda cohesive end site: isolation of spacing/substitution mutations that result in dependence on Escherichia coli integration host factor.

Substitution, insertion and deletion mutations have been constructed at the XmnI restriction site in cos lambda. The XmnI site is located between cosB, the site where terminase binds lambda DNA; and cosN, the site where terminase introduces staggered nicks to generate cohesive ends. Substitution mutations and deletion of a base pair (a -1 change) do not obviously affect lambda growth and DNA packaging. Changes of -2, +2 and -3 render lambda unable to grow on host cells lacking integration host factor (IHF). The -3 mutant has a reduced burst size in IHF+ cells, due to a defect in the initiation of packaging. A -7 deletion mutation is lethal. Models for the basis of these mutational effects are discussed.

Bacterial Proteins↗
PubMed1988

Cardiomyopathy of Duchenne muscular dystrophy.

A total of 18 male patients with Duchenne muscular dystrophy (DMD), aged 8-29 years (mean, 15.7 years), were prospectively studied to assess the cardiomyopathy associated with DMD, using clinical parameters and noninvasive cardiovascular investigations: electrocardiogram (ECG), Holter monitoring, and echocardiography. In addition, five clinical tests of cardiovascular autonomic function were used to assess the role of the autonomic nervous system in the pathogenesis of dysrhythmias. The majority of subjects were asymptomatic, but four had abnormal physical findings. All had abnormal ECG, the commonest abnormality (in 16) being tall R waves or increased R/S ratios in the right precordial leads; 14 had abnormal findings on echocardiography, including three with poor left ventricular function and five with mitral valve prolapse (MVP). Labile abrupt sinus tachycardia was present in 11, and four had high-grade ventricular ectopy. None had definite clinical evidence of autonomic dysfunction. The cardiomyopathy of DMD appears to be unrelated to disease severity. However, abnormal Q waves or Q/R ratios in ECG leads I, aVL9 and V5-V6 are significantly related to young age (p less than 0.05), and high-grade ventricular ectopy occurred significantly more frequently (p less than 0.05) in older subjects (greater than 15 years). Dysrhythmias were not related to the presence of MVP, poor left ventricular function, or autonomic dysfunction.

Adolescent↗
PubMed1988

Polymorphisms of the region of the Epstein-Barr virus genome which disrupts latency.

The nucleotide sequence of the portion of naturally occurring defective EBV (HR-1) DNA (designated het DNA) which is responsible for disruption of EBV latency has been determined and compared with the regions of the standard HR-1 viral genome from which it was derived. This rearranged 2.7-kbp DNA fragment represented an apparently nonhomologous recombination between sequences found in the BamHI W and BamHI Z fragments of the standard HR-1 genome. Only one intact open reading frame, comparable to standard HR-1 BZLF1, was present within this 2.7 kbp. No new open reading frames were created by the recombination. The BZLF1 sequence and predicted polypeptide products of standard HR-1 and het DNA were compared to B95-8 EBV. If an unspliced version of BZLF1 is used, the carboxy end of the BZLF1 polypeptides would differ considerably, principally due to an identical 28-bp insertion in both standard HR-1 and het BZLF1 relative to B95-8. However, if both virus strains use the same mRNA splicing strategy, the BZLF1 products from HR-1 and B95-8 would be similar, though distinguished by seventeen 1-bp differences which would result in nine amino acid changes. Both unspliced and spliced versions of het BZLF1 had five amino acid changes by comparison to standard HR-1 BZLF1. Differences in predicted secondary structure were found, consistent with dissimilar electrophoretic mobility of the polypeptide products. The amino acid differences between the BZLF1 polypeptide products of HR-1, het DNA, and B95-8 virus are all compatible with the creation of a protein which would function similarly to disrupt EBV latency. The differences in these polypeptides may account for some of the variation in the level of biologic activity of the BZLF1 products of different EBV strains. However, the major difference in activity between standard HR-1 and HR-1 het virus to disrupt EBV latency appears to be due to up-regulation of expression of het BZLF1 due to juxtaposition of BamHI W sequences upstream of het BZLF1.

Amino Acid Sequence↗
PubMed1988

Genome rearrangements activate the Epstein-Barr virus gene whose product disrupts latency.

A defective Epstein-Barr virus (EBV) containing a deleted and rearranged genome (het DNA) causes latent EBV to replicate. This activity maps to the 2.7-kilobase-pair WZhet fragment. The BZLF1 open reading frame, present within WZhet as well as in the standard viral BamHI Z fragment, encodes the protein ZEBRA, which induces viral replication. Using gene transfers into Burkitt lymphoma cells, we now demonstrate that rearranged sequences juxtaposed to BZLF1 in het DNA facilitate expression of ZEBRA protein. Two stretches of EBV sequences within a palindromic region of het DNA contain positive regulatory elements. One set, derived from the viral large internal repeat, is newly positioned upstream of BZLF1; the second set is downstream of BZLF1 in het DNA. The capacity of defective HR-1 viruses to disrupt latency of the standard EBV genome is due to abnormal regulation of the BZLF1 gene as a result of genomic rearrangements.

Base Sequence↗
PubMed1988

Fragment length polymorphisms among independent isolates of Epstein-Barr virus from immunocompromised and normal hosts.

DNA restriction fragment length polymorphisms of Epstein-Barr virus (EBV) DNA were used as a molecular epidemiological tool to study multiple isolates of virus from the same and different individuals. We studied 35 EBV isolates: 19 from seven immunocompromised children and 16 from seven college students with mononucleosis. Analysis of the fragment length polymorphisms in this collection of isolates permitted several conclusions. Sites of polymorphism were most often encountered in regions with repetitive DNA. Epidemiologically unrelated patients harbored viruses that could be readily distinguished; by contrast, two infants and their mothers harbored similar viruses. Isolates from different sites in the same patient were similar. Variations between different clinical isolates of EBV mimic those found between different laboratory strains of the virus. Fragment length polymorphisms thus provide a useful marker for studying transmission and pathogenesis of EBV infections.

Adolescent↗
PubMed1988

Fatty acids of liver, cardiac and adipose tissues from copper-deficient rats.

The effect of copper deficiency on liver, cardiac and adipose fatty acids was studied in the Long-Evans rat. Rats were fed diets adequate in copper (8.5 mg Cu/kg diet, group AC, n = 10) or with no added copper (0.4 mg Cu/kg diet, group NC, n = 9) or were pair-fed an adequate copper diet in amounts eaten by group NC rats (group PF, n = 10), from weaning until 8 wk thereafter. Group NC rats exhibited typical copper deficiency signs such as decreased body weight, hematocrit and liver copper levels but increased heart/body weight ratios. Adipose and cardiac triglycerides of group NC rats had greater 18:0 to 18:1n-9 ratios. All tissues in group NC rats had higher levels of longer-chain polyunsaturated fatty acids in triglycerides than those in AC or PF rats. Specifically, the following triglyceride fatty acids were in greater concentration in NC rats than in AC or PF rats: for liver, 18:2n-6, 22:5n-6, 22:5n-3 and 22:6n-3; for cardiac, 20:3n-6, 20:4n-6 and 22:5n-6. Liver phospholipids had lower levels of 20:4n-6 in NC rats than in AC or PF rats. These results suggest that copper deficiency results in the accumulation of both n-3 and n-6 longer-chain polyunsaturated fatty acids in triglycerides of various tissues.

Adipose Tissue↗