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Biomedical subjects

M R Scott

Publications and source records attributed to M R Scott.

33 records · Page 2Linked to original sources
PubMed1993

Extracranial absorbed doses with Gamma Knife radiosurgery.

Radiosurgery is used with increasing frequency, not only for the treatment of cerebral arteriovenous malformations (AVMs), but also for the treatment of other well-defined lesions including acoustic neuromas, meningiomas, pituitary adenomas as well as solitary metastases. Although investigators have addressed dosimetric aspects of stereotactic radiosurgery in terms of target volume, little if any attention has been focused on the absorbed doses received at extracranial sites. Therefore, absorbed doses to the eye, thyroid, sternum and gonads were measured in 111 patients (100 adults and 11 children) using thermoluminescent dosimetry (TLDs). For the 100 adults, the average maximum target absorbed dose was 35 +/- 8 Gy. The measured absorbed dose in selected organs of adults from Gamma Knife radiosurgery using one or more isocenters was 9 +/- 8 cGy for the eye, 15 +/- 7 cGy for the thyroid, 20 +/- 10 cGy for the sternum and 3 +/- 2 cGy for the gonads. The absorbed doses received by the children (13 years and younger) was similar with the exception of a marked increase in gonadal dose. The use of multiple isocenters is associated with higher absorbed doses to extracranial sites.

Adolescent↗
PubMed1992

Chimeric prion protein expression in cultured cells and transgenic mice.

The efficient expression of exogenous prion protein (PrP) molecules in mouse neuroblastoma cells that are chronically infected with murine scrapie prions (ScN2a cells; Butler, D.A., et al., 1988, J. Virol. 62, 1558-1564) and in transgenic mice is described. This technology allows investigation of the PrP molecule for structural regions involved in determining species specificity, as well as ablation experiments designed to address the functionality of particular regions of the PrP molecule. Previous reports demonstrated that the PrP gene specifies the host range for susceptibility of transgenic animals to prions (Scott, M., et al., 1989, Cell 59, 847-857; Prusiner, S.B., et al., 1990, Cell 63, 673-686). Consistent with these results, we showed that Syrian hamster (SHa) PrP is ineligible for efficient conversion to PrPSc in ScN2a cells. By constructing a series of chimeric mouse (Mo)/SHaPrP genes, we developed an epitopically tagged functional variant of the MoPrP gene, which can efficiently form protease-resistant PrP molecules upon expression in ScN2a cells. The presence of a defined epitope for an SHa-specific monoclonal antibody allows the products of this chimeric gene to be discriminated from endogenous MoPrP and creates a useful reagent for exploring structure/function relationships via targeted mutagenesis. In addition, we developed a transgenic mouse expression vector by manipulation of an SHaPrP cosmid clone. This vector permits the efficient expression of foreign PrP genes in the brains of transgenic animals, enabling pathological consequences of in vitro mutagenesis to be studied.

Animals↗
PubMed1992

Dandy-Walker variant: prenatal sonographic features and clinical outcome.

The Dandy-Walker variant is a less severe posterior fossa anomaly than the classic Dandy-Walker malformation. In 17 consecutive fetuses, the Dandy-Walker variant was diagnosed at sonography, and associated defects, karyotypic anomalies, and outcomes were evaluated. Four of the 17 fetuses (24%) had mild ventriculomegaly. Eight of the 17 (47%) had concurrent non-central nervous system (CNS) anomalies. Five fetuses (29%) had an abnormal karyotype (two with trisomy 18, one each with trisomy 13, 21, and 11q+) and associated sonographic anomalies. Six of the 17 fetuses (35%) died in utero or during the neonatal period, two are severely handicapped, and the other nine are developing normally at ages 4 months to 4 years. Six of the nine normally developing infants (53%) lacked non-CNS sonographic findings. Because the prognosis is uncertain for an infant born with the prenatal diagnosis of Dandy-Walker variant, prenatal recognition of the anomaly allows for the option of fetal karyotyping and for arrangement for postnatal follow-up.

Abnormalities, Multiple↗
PubMed1988

Prion protein gene expression in cultured cells.

A single copy gene encodes both the scrapie (PrPSc) and cellular (PrPC) isoforms of the prion protein (PrP). Cultured cell lines were found to express the endogenous PrP mRNA at levels comparable to those observed in the brains of adult rodents; however, these cells were invariably found to express greatly reduced levels of PrP. In all the cell lines examined, PrP was undetectable by Western immunoblot analysis. These cells were also poor recipients for expression constructs linking the hamster PrP gene open reading frame to several strong eukaryotic promoters; stable clones derived by transfection of these expression vectors failed to show elevated expression of PrP. When extremely high levels of PrP mRNA were produced using either an insect baculovirus or a mammalian SV40 based vector, significant quantities of PrP were produced, although in both cases the proteins were apparently processed differently from the PrPC observed in brains. In an expression system using an SV40 late promoter vector in monkey COS-7 cells, a significant fraction of PrP was transported to the cell surface where PrPC is found in vivo. PrP synthesized by the baculovirus vector failed to induce scrapie in hamsters and did not possess the characteristics of the PrPSc isoform associated with infectivity. The SV40 late promoter vector system may permit experiments designed to elucidate the role of PrPSc during scrapie infection as well as the function of PrPC in normal metabolism.

Animals↗
PubMed1988

Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins.

Scrapie and Creutzfeldt-Jakob disease are transmissible, degenerative neurological diseases caused by prions. Considerable evidence argues that prions contain protease-resistant sialoglycoproteins, designated PrPSc, encoded by a cellular gene. The prion protein (PrP) gene also encodes a normal cellular protein designated PrPC. We established clonal cell lines which support the replication of mouse scrapie or Creutzfeldt-Jakob disease prions. Mouse neuroblastoma N2a cells were exposed to mouse scrapie prions and subsequently cloned. After limited proteinase K digestion, three PrP-immunoreactive proteins with apparent molecular masses ranging between 20 and 30 kilodaltons were detected in extracts of scrapie-infected N2a cells by Western (immuno-) blotting. The authenticity of these PrPSc molecules was established by using monospecific antiserum raised against a synthetic peptide corresponding to a portion of the prion protein. Those clones synthesizing PrPSc molecules possessed scrapie prion infectivity as measured by bioassay; clones without PrPSc failed to demonstrate infectivity. Detection of PrPSc molecules in scrapie-infected N2a cells supports the contention that PrPSc is a component of the infectious scrapie particle and opens new approaches to the study of prion diseases.

Animals↗
PubMed1983

Activation of mouse genes in transformed cells.

We have used molecular hybridization and cDNA cloning techniques to isolate mouse cellular genes activated in SV40-transformed cells and we show that many of the clones belong to one of four sets. We characterize the cytoplasmic transcripts and genomic sequences homologous to two of these sets. The Set 1 transcription unit(s) is activated in all SV40-transformed cell lines analyzed, and experiments with tsA-mutant-transformed lines show that activation appears to require functional large T-antigen. This transcription unit(s) is also activated in mouse fibroblasts transformed by other agents, including retroviruses and chemical carcinogens. Activation of the Set 2 transcription unit(s) is more restricted, being confined to cell lines transformed by SV40 and retroviruses with distinctive biological properties.

Animals↗
PubMed1982

The construction of cosmid libraries of eukaryotic DNA using the Homer series of vectors.

We have constructed and characterised a series of approved, disabled cosmid vectors which we call Homer cosmids and have examined the optimal conditions for the construction of libraries of eukaryotic DNA segments using these vectors. Analysis of these libraries shows that most of the sequences we have tested for are present at the expected frequency and that the libraries can be stably propagated. We have also directly tested the stability of cosmid clones carrying tandemly repeated inserts. This work shows that it should be possible to clone most eukaryotic genes using cosmid vectors and that such cloning systems have considerable advantages over those more commonly used.

Animals↗
PubMed1976

Comparison of hydrophilic polymer-coated latex, uncoated latex and PVC indwelling balloon catheters in the prevention of urinary infection.

Latex, hydrophilic polymer-coated latex and PVC balloon indwelling urethral catheters were compared in respect of the urinary tract infections arising in association with their use in male patients. The polymer (Hydron) coating conferred no benefit over uncoated latex which in turn was indistinguishable from PVC. No significant differences in the spectra of infecting organismns were observed between the 3 catheter types.

Adult↗