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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 163 records · Page 9Linked to original sources
PubMed1996

Comparing transcriptional activation and autostimulation by ZEBRA and ZEBRA/c-Fos chimeras.

The lytic cycle of Epstein-Barr virus (EBV) can be activated by transfection of the gene for ZEBRA, a viral basic-zipper (bZip) transcriptional activator. ZEBRA and cellular AP-1 bZip activators, such as c-Fos, have homologous DNA-binding domains, and their DNA-binding specificities overlap. Moreover, EBV latency can also be disrupted by phorbol esters, which act, in part, through AP-1 activators. It is not known whether ZEBRA and AP-1 factors play equivalent roles in the initial stages of reactivation. Here the contribution of ZEBRA's basic DNA recognition domain to disruption of latency was analyzed by comparing ZEBRA with chimeric mutants in which the DNA recognition domain of ZEBRA was replaced with the analogous domain of c-Fos. Chimeric ZEBRA/c-Fos proteins overexpressed in Escherichia coli bound DNA with the specificity of c-Fos; they bound a heptamer AP-1 site and an octamer TPA response element (TRE). ZEBRA bound the AP-1 site and an array of ZEBRA response elements (ZREs). In assays with reporter genes, both ZEBRA and ZEBRA/c-Fos chimeric mutants activated transcription from Zp, a promoter of the ZEBRA gene (BZLF1) that contains the TRE and multiple ZREs. However, despite their capacity to activate reporters bearing Zp, neither ZEBRA nor the c-Fos chimeras activated transcription from Zp in the context of the intact latent viral genome. In contrast, ZEBRA but not ZEBRA/c-Fos chimeras activated Rp, a second viral promoter that controls ZEBRA expression. Hence, transcriptional autostimulation by transfected ZEBRA occurred preferentially at Rp. Both ZEBRA and the ZEBRA/c-Fos chimeras activated transcription from reporters with multimerized AP-1 sites. However, in the context of the virus, only ZEBRA activated the promoters of two early lytic cycle genes, BMRF1 and BMLF1, that contain an AP-1 site. Thus, overexpression of an activator that recognized AP-1 and TRE sites was not sufficient to activate EBV early lytic cycle genes.

B-Lymphocytes↗
PubMed1996

Outcome after open-heart surgery in infants and children.

We have studied the neurodevelopmental outcome of 104 consecutive unselected children who underwent open-heart surgery from 1987 through 1989. Survivors had formal neurologic and psychometric examinations after 2 years of age. Mean IQ was 90, and 78% had scores above 70. Cerebral palsy occurred in 22%. Deep hypothermia for longer than 45 minutes was associated with IQ less than 85 (P < .001) and later cerebral palsy (P = .02). Those less than 1 month old at operation had a median IQ of 96, and 25% had cerebral palsy. Median IQ for survivors of hypoplastic left heart syndrome was 66, only one had an IQ above 70, and 57% had cerebral palsy. Median IQ for transposition of great arteries was 109, only one was less than 85, and all had normal neurologic examinations. Those between 1 and 6 months of age at operation had a median IQ of 93, with 64% above 85, and 5% had cerebral palsy. Those older than 6 months had a median IQ of 99, with 70% above 85, and 13% had cerebral palsy. For infants less than 1 month old at operation, a strong association existed between outcome, type of lesion, and duration of deep hypothermia (P < .01), although not in all cases. In those older than 1 month at operation, no association existed between outcome and any study variable. Although the majority of children have an uneventful outcome after open-heart surgery, a significant morbidity exists. This is related to several factors, including type of lesion and duration of hypothermia, particularly in neonates; preoperative congenital and acquired lesions; and possible perioperative cerebrovascular events.

Age Factors↗
PubMed1996

Cognitive dysfunction as the major presenting feature of Becker's muscular dystrophy.

We report four patients, currently aged 15, 17, 19, and 42 years, with X-linked dystrophinopathy who presented with mental retardation (IQ range, 60-68) and psychiatric disturbance in the absence of muscle weakness. All patients had elevated serum creatine kinase and dystrophic changes on muscle biopsy. There were alterations in the size and abundance of dystrophin on immunohistochemistry and immunoblotting in all cases, consistent with a molecular diagnosis of Becker's muscular dystrophy. Two patients had deletions of the dystrophin gene on DNA analysis. These findings suggest that Becker's muscular dystrophy may be associated with a predominantly neuropsychiatric presentation and that dystrophinopathy should be considered in the differential diagnosis of unexplained cognitive or psychiatric disturbance in males. Serum creatine kinase may provide an adequate screening test in this clinical situation.

Adolescent↗
PubMed1996

Late motor deficits of Chilean manganese miners: a blinded control study.

High-level chronic manganese (Mn) exposure produces dystonic rigidity and proximal tremor. The late effects of asymptomatic exposure are uncertain. To evaluate hand movements of asymptomatic Chilean miners, we utilized a manual tremormeter (EAP) and a digitizing tablet (MOVEMAP). In Andacollo, Chile, we examined 59 individuals aged > 50 years (mean age, 64.4 years). Twenty-seven exposed miners had heavy Mn dust exposure in Mn mines for more than 5 years (mean duration, 20.25 years), ending at least 5 years previously. Thirty-two control miners had never worked in Mn mines or had short-term Mn employment. Tests of resting tremor (EAP Tremormeter, MOVEMAP Steady paradigm), action tremor (MOVEMAP Square paradigm), and repetitive hand movements (EAP Tapping Test and Orthokinesimeter) differentiated performance of exposed miners from that of controls. Chronic asymptomatic Mn exposure results in detectable late-life abnormalities of movement.

Chile↗
PubMed1996

Excursion and strain of the median nerve.

Five fresh-frozen transthoracic cadaver specimens (ten upper extremities) were dissected in order to measure excursion and strain of the median nerve at the wrist and the elbow in association with different positions of the shoulder, elbow, wrist, and fingers. The relationships between motions of the joints and excursion and strain at the wrist and the elbow as well as between excursion and strain were also determined. When the wrist was moved from 60 degrees of extension to 65 degrees of flexion, the median nerve at the wrist underwent a mean total excursion of 19.6 millimeters (9.2 +/- 1.38 millimeters [mean and standard deviation] in extension and 10.4 +/- 1.50 millimeters in flexion). The change in strain was not measurable secondary to nerve-wrinkling. Motion of the fingers from hyperextension to full flexion caused a mean total excursion of 9.7 millimeters (6.3 +/- 1.31 millimeters in hyperextension and 3.4 +/- 1.04 millimeters in flexion) and a change in strain of 19.0 per cent. This change in strain became more pronounced when the wrist and the fingers moved in synergy. Such strain, if constant, has been shown to decrease microvascular perfusion and nerve conduction in rabbits. With motion of the shoulder, the mean total excursion of the median nerve at the elbow was 9.1 millimeters (4.4 +/- 1.64 millimeters in abduction and 4.7 +/- 1.81 millimeters in adduction) and the change in strain was 13.3 per cent. With motion of the elbow, the mean total excursion was 12.3 millimeters (12.3 +/- 4.20 millimeters in flexion and zero millimeters in the resting position) and the change in strain was not measurable because of the wrinkle effect in flexion. With motion of the wrist, the mean total excursion was 5.6 millimeters (4.3 +/- 1.95 millimeters in extension and 1.25 +/- 0.81 millimeters in flexion) and the change in strain was 14.8 per cent. With motion of the fingers, the mean total, excursion was 3.4 millimeters (2.6 +/- 1.13 millimeters in hyperextension and 0.80 +/- 0.92 millimeter in flexion) and the change in strain was 10.3 per cent. Motion of the wrist and the fingers induced profound excursion of the median nerve at the wrist, whereas motion of the shoulder and the elbow induced marked excursion of the median nerve at the elbow. These excursions were much more pronounced when a number of joints were moved in a composite manner. Any factor that might limit normal excursion, such as scarring, could induce strains that could adversely affect the function of the median nerve. The finding that the position and movement of the limb had a profound effect on excursion and strain of the median nerve at the wrist and the elbow may aid in the understanding of the pathophysiology of median-nerve neuropathy.

Cadaver↗
PubMed1996

Use of intravascular stents in the treatment of internal carotid and extracranial vertebral artery pseudoaneurysms.

The management of extracranial carotid or vertebral artery pseudoaneurysms is controversial. Although some of these lesions resolve spontaneously, many clinicians opt to treat them with trapping procedures that result in vessel sacrifice. We describe two cases in which an intravascular stent was used to obliterate an aneurysm of the extracranial vertebral artery and the internal carotid artery, respectively, while maintaining the patency of the parent vessel. The technique, which has been successful in experimental animal models, shows promise for application in humans.

Aneurysm, False↗
PubMed1996

Low plasma levels of factor VIIc and antigen are more strongly associated with the 10 base pair promoter (-323) insertion than the glutamine 353 variant.

In a group of 705 healthy middle-aged men, we have examined the relationship between plasma levels of Factor VII (FVII) c and Factor VII antigen (FVIIag) and two polymorphisms in the FVII gene. One polymorphism alters arginine at position 353 to glutamine (R/Q), and the other is the result of a 10 base pair (bp) insertion in the promoter region at position -323 from the start of translation (0/10bp). The frequency for the Q allele was 0.105 (95% CI 0.09-0.12) and for the 10bp allele was 0.117 (95% CI 0.10-0.13). Men who were carriers of either of the rare alleles had levels of FVIIc and FVIIag that were approximately 20% lower than non-carriers, and both of these effects were highly statistically significant (p < 0.0001). Strong allelic association was observed between the two polymorphisms, with R and 0 bp being on the same chromosome in 96% of cases, and Q and 10 bp being on the same chromosome in 90% of cases where this could be determined unambiguously (Delta = 0.92, chi 2 = 1206, p < 0.0001). This strong allelic association created three major genotype groups which were found to have significantly different levels of FVIIc (p < 0.001). In the 547 men homozygous for both common alleles (R/R & 0/0), mean (SD) FVIIc was 101 (29) as compared with 85 (30) in the 20 men with the genotype R/R & 0/10 and 81 (23) in the 126 men with the genotype R/Q & 0/10, suggesting a larger lowering effect associated with the 10 bp allele (16%) compared to the Q allele (an additional 4%). The lowering effect on FVII associated with the 10 bp allele remained statistically significant after adjusting for the effect of the Q allele (p = 0.004 for FVIIc and p = 0.06 for FVIIag), but the effect associated with the Q allele was no longer significant after adjusting for the 10 bp allele, suggesting that the strongest effect on levels of FVIIc was associated with the 0/10 bp genotype. In the sample overall, plasma FVIIc was associated positively with serum triglyceride concentration and the slope of this relationship was significantly greater in those with the genotype R/R compared to the other groups combined (0.12 versus 0.02, p = 0.008) with differences of similar size seen in the 0/0 compared to 0/10 + 10/10 groups. However, using the combined genotype, the slope of this relationship in the R/R & 0/10 group was 0.38 and was significantly steeper (p = 0.01) than in the other two groups who did not differ in this respect (slopes 0.11 and 0.08). This effect was seen on four subsequent annual examinations, and was also evident in the relationship between FVIIag and triglyceride concentration (p = 0.003 for difference between groups measured at baseline only). These data suggest that part of the previously described effects on FVIIc levels associated with the R/Q polymorphism may be explained by genetic variation in the promoter region of the FVII gene.

Antigens↗
PubMed1996

Warfarin prescribing.

The incident Monitoring in General Practice Project began as an initiative of the Professional Indemnity Review. Anonymous data from general practitioners about unintended, and possibly adverse events were collected in order to develop preventive strategies that might ultimately increase patient safety and therefore reduce litigation. Feedback and sharing of experiences and ideas about these events, possible management strategies or the project as a whole are invited from the readers.

Anticoagulants↗
PubMed1996

Clinical incidents in general practice. Communication between casualty departments and general practitioners.

The incident Monitoring in General Practice Project began as an initiative of the Professional Indemnity Review. Anonymous data from general practitioners about unintended, and possibly adverse events were collected in order to develop preventive strategies that might ultimately increase patient safety and therefore reduce litigation. Feedback and sharing of experiences and ideas about these events, possible management strategies or the project as a whole are invited from readers.

Australia↗
PubMed1996

Clinical incidents in general practice. A difficult paediatric diagnosis.

The Incident Monitoring in General Practice Project began as an initiative of the Professional Indemnity Review. Anonymous data from general practitioners about unintended, and possibly adverse events were collected in order to develop preventive strategies that might ultimately increase patient safety and therefore reduce litigation. Feedback and sharing of experiences and ideas about these events, possible management strategies or the project as a whole are invited from readers.

Child↗
PubMed1996

Clinical incidents in general practice. Prescription errors.

The incident Monitoring in General Practice Project began as an initiative of the Professional Indemnity Review. Anonymous data from general practitioners about unintended, and possibly adverse events were collected in order to develop preventive strategies that might ultimately increase patient safety and therefore reduce litigation. Feedback and sharing of experiences and ideas about these events, possible management strategies or the project as a whole are invited from the readers.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Clinical incidents in general practice. Keeping on track with test results.

The incident Monitoring in General Practice Project began as an initiative of the Professional Indemnity Review. Anonymous data from general practitioners about unintended and possibly adverse events were collected in order to develop preventive strategies that might ultimately increase patient safety and therefore reduce litigation. Feedback and sharing of experiences and ideas about these events, possible management strategies or about the project as a whole are invited from readers.

Australia↗
PubMed1995

Potent inhibitory effects of glial derived neurotrophic factor against kainic acid mediated seizures in the rat.

Recently messenger RNA (mRNA) for glial derived neurotrophic factor (GDNF), a recently discovered member of the TGF-beta superfamily, was shown to increase in the hippocampus after kainic acid-induced seizures. The possibility that exogenous recombinant human (rh) GDNF may have anticonvulsant properties was investigated using a model of temporal lobe epilepsy in the rat. rhGDNF, vehicle or inactive rhGDNF were injected intracerebroventricularly 1 h before peripheral administration of kainic acid. rhGDNF suppressed kainic acid-induced tonic-clonic convulsions when compared to animals treated with vehicle or inactive rhGDNF. The inhibition of kainic acid-induced seizure activity by rhGDNF also prevented the associated neuronal cell loss in hippocampal, thalamic and amygdaloid regions. These results suggest that rhGDNF should be evaluated in other seizure and acute neural disorders that are associated with excitotoxic processes.

Adrenergic Fibers↗
PubMed1995

Transmissible retrovirus in Epstein-Barr virus-producer B95-8 cells.

Epstein-Barr virus (EBV) released from the B95-8 marmoset cell line has served as a prototype for biologic and biochemical studies of EBV. Here we identify and characterize a retrovirus carried by many cultures of B95-8 cells. The experiments were stimulated by the isolation of a cDNA clone from B95-8 cells in which sequences from the EBV large internal repeat were linked to gag sequences similar to those of squirrel monkey retrovirus, human isolate, SMRV-H. However, among 413 amino acids predicted from the nucleotide sequence of the gag region of the B95-8 SMRV isolate there were 48 amino acid changes that distinguished this virus from SMRV-H originally isolated from a human lymphoid cell line by Oda et al. (1988, Virology 167, 468-476). Nucleic acid and antibody probes were developed for the B95-8 isolate of SMRV. Using such probes, we found that SMRV-B95-8 was readily transmissible, independent of EBV, as an infectious virus to human B and T cell lines. SMRV-B95-8 was highly fusogenic in the presence or absence of EBV. The ultrastructural appearance of the B95-8 retrovirus was characteristic of a type D retrovirus. Cells dually infected with EBV and SMRV-B95-8 did not demonstrate increased levels of lytic EB viral replication. SMRV-B95-8 did not by itself cause lymphocyte immortalization or enhance immortalization by EBV. Thus SMRV-B95-8 does not contribute to the major biologic properties of the B95-8 strain of EBV.

Amino Acid Sequence↗