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Biomedical subjects

P MacPherson

Publications and source records attributed to P MacPherson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes.

Culture of infectious virus, PCR amplification of viral DNA, and the appearance of genital skin lesions were used as markers to study the course of a recurrence of genital herpes in 40 patients treated with famciclovir or placebo. The highest frequency of patients with skin lesions occurred within the first 36 h following the onset of a recurrence, which also corresponded to the peak in the production of virus. While the timing of the peak in skin lesions was independent of the type of treatment, the frequency of lesions and the release of virus at the lesion site were both reduced by famciclovir treatment. Furthermore, patients receiving this antiviral agent showed a more rapid recovery time and a shorter period during which viral DNA could be detected at the lesion. PCR and then Southern blot hybridization greatly enhanced our ability to detect herpes simplex virus at the lesion site. This procedure proved to be of greater diagnostic value in assessing genital herpes than the standard culture method currently used. In addition, PCR was more sensitive in evaluating treatment effectiveness.

2-Aminopurine↗
PubMed1995

Glutamate receptor-mediated calcium surges in neurons derived from P19 cells.

Retinoic acid-treated murine P19 embryonal carcinoma cells differentiate into cells with neuronal morphology that display typical neuronal markers. In this study, the presence of glutamate receptors linked to Ca(2+)-signaling mechanisms on these neurons was demonstrated by testing the effects of glutamate agonists and antagonists on the intracellular calcium ion concentration ([Ca2+]i). Glutamate (1 mM) induced either sustained or transient increases in [Ca2+]i. The sustained glutamate-induced increase in [Ca2+]i was mimicked by NMDA (40 microM). The NMDA-triggered [Ca2+]i response was abolished by incubating the cells in Ca(2+)-free medium or by pretreating them with Mg2+ (2 mM) or MK-801 (0.1 microM). These responses were unaffected by the non-NMDA antagonist CNQX (10 microM), but they required glycine (3-30 microM). Kainate (40 microM) and AMPA (40 microM) did not affect [Ca2+]i. Without external Ca2+, glutamate triggered transient, sometimes oscillating, increases in [Ca2+]i. These responses were mimicked by the metabotropic agonist trans-(1S, 3R)-1-amino-1,3-cyclopentanedicarboxylic acid (300 microM). These results suggest that neurons derived from P19 embryonal carcinoma cells have NMDA and metabotropic, but not AMPA/kainate receptors, which are linked to Ca(2+)-signaling mechanisms. These cells could provide a consistent and reproducible model with which to study neuronal differentiation, neurotoxicity, and glutamate receptor-signaling mechanisms.

Animals↗
PubMed1994

The bovine papilloma virus E1 protein has ATPase activity essential to viral DNA replication and efficient transformation in cells.

The bovine papilloma virus (BPV) E1 protein essential to viral DNA replication has recently been shown to associate via direct protein-DNA interactions with the viral origin of replication and to be an ATP-dependent helicase. We show here that in accordance with the latter function, the E1 gene product has intrinsic ATPase activity. Mutations placed throughout the nucleotide binding consensus element abolish the ATPase activity of E1 and render BPV genomes harboring such mutations defective for episomal replication and impaired for oncogenic transformation.

Adenosine Triphosphatases↗
PubMed1990

Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator.

The mechanism by which transcription factors stimulate DNA replication in eukaryotes is unknown. Bovine papillomavirus DNA synthesis requires the products of the viral E1 gene and the transcriptional activator protein encoded by the E2 gene. Experimental data showed that the 68-kilodalton (kD) E1 protein formed a complex with the 48-kD E2 transcription factor. This complex bound specifically to the viral origin of replication, which contains multiple binding sites for E2. Repressor proteins encoded by the E2 open reading frame failed to complex with E1 suggesting that the 162-amino acid region of E2 that participates in transactivation contained critical determinants for interaction with E1. The physical association between a replication protein and a transcription factor suggests that transcriptional activator proteins may function in targeting replication initiator proteins to their respective origins of replication.

Animals↗
PubMed1990

CT evidence of intracranial contusion and haematoma in relation to the presence, site and type of skull fracture.

The skull films and CT scans of 1383 patients with acute head injury transferred to a regional neurosurgical unit were reviewed. Of the 850 patients with a skull fracture, contusion and/or haematoma was found in 71%, compared with 46% of the 533 patients with no fracture. Thirty-nine per cent of patients had neither contusion nor haematoma, and 21% had neither skull fracture nor contusion/haematoma. Haematomas occurred more frequently in association with lateral and occipital fracture than with frontal fracture, but the incidence of contusion was similar for all fracture sites. Linear fractures were more often associated with extra- and subdural haematomas than were depressed fractures. Intracranial damage associated with depressed fractures was localized more frequently than with linear fractures. Frontal fractures were rarely associated with posterior damage alone, but with occipital fractures anterior contusion was more frequent than posterior. Damage associated with lateral fracture was solely contralateral in 26%. Skull fracture was present in 77% of patients with contusion, 87% of those with an extradural, 72% with a subdural, and 66% with an intracerebral haematoma (70% of all those with an intracranial haematoma).

Brain Concussion↗
PubMed1990

Identification of a 68-kilodalton nuclear ATP-binding phosphoprotein encoded by bovine papillomavirus type 1.

E1 is the largest open reading frame (ORF) of bovine papillomavirus type 1 (BPV-1) and is highly conserved among all papillomaviruses, maintaining its size, amino acid composition, and location in the viral genome with respect to other early genes. Multiple viral replication functions have been mapped to the E1 ORF of BPV-1, and evidence suggested that more than one protein was encoded by this ORF. We previously identified a small protein (M) whose gene consists of two exons, one encoded by the 5' end of the E1 ORF. We show here that a 68-kilodalton (kDa) phosphoprotein made from the E1 ORF can be detected in BPV-1-transformed cells, and we present evidence that this protein is encoded by sequences colinear with the entire E1 ORF. The full-length E1 protein immunoprecipitated from virally transformed cells and identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis comigrates with a protein expressed from a recombinant DNA construct capable of producing only the complete E1 protein. In addition, two different antisera directed against polypeptides encoded from either the 3' or the 5' end of the E1 ORF both recognize the full-length E1 product. A mutation converting the first methionine codon in the ORF to an isoleucine codon abolishes BPV-1 plasmid replication and E1 protein production. Consistent with the notion that this methionine codon is the start site for E1, a mutant with a termination codon placed after the splice donor at nucleotide 1235 in E1 produces a truncated protein with the molecular mass predicted from the primary sequence as well as the previously identified M protein. When visualized by immunostaining, the E1 protein expressed in COS cells is localized to the cell nucleus. A high degree of similarity exists between the BPV-1 E1 protein and polyomavirus and simian virus 40 large-T antigens in regions of the T antigens that bind ATP. We show by ATP affinity labeling that the E1 protein produced in COS cells binds ATP and that this activity is abolished by a point mutation which converts the codon for proline 434 to serine. Furthermore, this mutation renders the viral genome defective for DNA replication, suggesting that the ATP-binding activity of E1 is necessary for its putative role in viral DNA replication.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1988

Magnetic resonance imaging in acute head injury.

Using cardiorespiratory monitoring and support equipment compatible with a low field (0.15 T) system, magnetic resonance imaging (MRI) of patients suffering acute head injuries proved to be both feasible and safe. An abnormality was demonstrated by magnetic resonance imaging in 46 of 50 patients examined within 7 days of head injury using T2 weighted (SE2200/80) and T1 weighted (IR2000/600/40) multislice sequences. IN contrast, computed tomography (CT) demonstrated abnormalities in only 31 of the 50 patients. Intracranial extracerebral space-occupying collections of blood were well shown by magnetic resonance imaging which provided especially clear definition in the posterior fossa, subtemporal and subfrontal regions. Magnetic resonance imaging was more sensitive to cerebral abnormalities associated with traumatic unconsciousness and detected parenchymal lesions both in patients in coma and in those who had lost consciousness for only a few minutes. Lesions seen with MRI but not with CT included non-haemorrhagic contusions and abnormalities thought to reflect shearing injuries of white matter and intracerebral vessels. Magnetic resonance imaging is an effective alternative to CT; the additional information it can provide should be valuable in increasing the understanding of the early effects and late consequences of a head injury.

Acute Disease↗
PubMed1986

Elevated amounts of a 7S nuclear RNA with sequence homology to a tumor virus promoter in transformed and tumorigenic cells.

A small nuclear RNA (7S-K) from cultured mammalian cells has been shown, in previous studies, to have the characteristics expected of a gene regulatory molecule, i.e., a tissue- and species-specific stimulatory activity for initiation of transcription of protein-coding genes. Moreover, in simian virus 40 (SV40)-transformed mouse cells, this RNA was shown, by S1-analysis, to bear an extensive homology to the SV40 promoter, suggesting that it acts by base-pairing to DNA in this region to facilitate the formation of the transcription-initiation complex. In order to investigate whether or not this homology is restricted to SV40-transformed cells and in any way related to transformation, a series of normal and transformed cell lines were examined for the degree of homology between their 7S-K RNAs and the SV40 promoter. Results show that the amount of 7S-K RNA hybridizable to the promoter varies as a direct function of the established degree of tumorigenic activity of the cells and is not dependent on the presence of SV 40 sequences. Taken together with the known overexpression of some cellular oncogenes in tumor tissues, these results suggest that this particular RNA may be involved in stimulating transcription of, at least, some of these genes.

Animals↗
PubMed1985

Protein binding and CSF penetration of phenytoin following acute oral dosing in man.

Prophylactic phenytoin (DPH) has been evaluated in 20 patients undergoing diagnostic myelography. DPH (0.75 g) was ingested at 20.00 h the night before and 0.5 g at 08.00 h on the morning of the procedure. Total DPH concentrations at myelography (mean +/- s.d.: 12.7 +/- 4.3 mg l-1; range 6.3-21.5 mg l-1) correlated with CSF values (1.3 +/- 0.46 mg l-1; range 0.7-2.2 mg l-1; r = 0.83, P less than 0.001). DPH protein binding at that time varied two-fold (9.2-18.5%) and free drug levels (1.7 +/- 0.6 mg l-1) correlated with CSF (r = 0.83, P less than 0.001) and total (r = 0.89, P less than 0.001) plasma DPH concentrations. There were significant negative correlations between patient weight (n = 17) and total (r = 0.57, P less than 0.05) and CSF (r = -0.55, P less than 0.05) DPH concentrations at myelography. Total plasma DPH levels 8 h (14.5 +/- 3.9 mg l-1; range 7.3-20.6 mg l-1) and 24 h (12.3 +/- 3.8 mg l-1; range 5.0-19.8 mg l-1) after myelography were largely within the 'therapeutic range' of 10-20 mg l-1 for the drug. No patient suffered a seizure although, in two, spike discharges were seen on a post-myelography electroencephalogram. A simple regime involving two doses of DPH would provide acceptable plasma CSF concentrations as a basis for controlled studies in seizure prophylaxis following neuroradiological investigations involving intrathecal contrast.

Administration, Oral↗