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Biomedical subjects

A M Lewis

Publications and source records attributed to A M Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1998

FDA "reform"?

Explore the source record for details and available documents.

Budgets↗
PubMed1998

Safety of viral DNA in biological products.

Data from studies of the infectivity of DNA injected directly into laboratory animals are used to estimate the potential infectivity risk of residual DNA in biological products. The potential for some novel products to contain infectious quantities of residual cellular DNA is discussed, and further study of this subject is suggested.

Animals↗
PubMed1998

A community outbreak of invasive and non-invasive group A beta-haemolytic streptococcal disease in a town in South Wales.

An increase in the incidence of invasive and non-invasive infections caused by group A beta-haemolytic streptococci (GAS) was noted in and around the town of Glynneath (population approx. 4000) in West Glamorgan, South Wales between 1 January and 30 June 1995. A total of 133 cases was ascertained with 127 (96%) occurring between 1 March and 30 June 1995. Six patients had invasive disease (one died) and all presented at the peak of the outbreak. There were 127 non-invasive cases of whom 7 were hospitalized. The outbreak was investigated to determine its extent and whether it was caused by a single M-serotype of GAS. Serotyping showed that 13 different M-serotypes were involved with the M1 serotype predominating. The overall incidence of GAS invasive disease in West Glamorgan (population 365,000) increased sevenfold from a crude incidence of 0.5/10(5) per year in 1994 to 3.5/10(5) per year in 1995, but fell back to 0.75/10(5) per year in 1996. Eighty-two (80%) out of 102 individuals affected by GAS replied to a health questionnaire; sore throat was the commonest symptom reported (97%). Thirty-nine of these index cases identified at least one other member of their household who had experienced similar symptoms. The interval between the onset of illness in members of a single household was 0-83 days with a mean of 22 days. The mean duration of illness was 13.5 days and 61% of patients were treated with penicillin V for a mean duration of 9.3 days. Twenty-one per cent of GAS isolates were erythromycin-resistant and the M4 and M6 serotypes were especially resistant to erythromycin (87.5 and 100% resistance, respectively). Penicillin V failed to eradicate GAS from the throats of 25% of assessable patients. In this community, an outbreak of non-invasive disease caused by GAS was linked in time and place with an outbreak of serious invasive disease.

Adolescent↗
PubMed1998

SV40 in adenovirus vaccines and adenovirus-SV40 recombinants.

During the development of adenovirus (Ad) vaccines in the 1950s, Ad strains 1-5 and 7 recombined with SV40 during adaptation to growth in rhesus monkey kidney cells. The recombination events between the Ad and SV40 genomes produced hybrid viruses that contained, within the Ad genome, either portions of the early region of the SV40 genome or single or multiple copies of the entire SV40 genome inserted in a configuration that permitted the generation of SV40 progeny. When portions of the SV40 early region were inserted into the Ad2 E3 region, a region non-essential for viral replication, the resulting Ad-SV40 hybrids were non-defective in that they were capable of independent replication. Such hybrids have no known selective advantage for replication in human tissues; however, through inadvertent human exposure it is theoretically possibly that they could be induced to spread in the environment. Because of deletions in the Ad genome, the Ad-SV40 hybrids that contain infectious SV40 DNA were defective and were not capable of replication without a helper virus. Due to the low frequency with which cells in an infected individual could be co-infected with both defective hybrid and helper virions, it is unlikely that such defective viruses could be established in the population. Based on the Ad-SV40 model, it is theoretically possible that SV40 could recombine with other DNA viruses that infect humans. The introduction of Ad-SV40 hybrids or SV40-other virus hybrids into the environment could contribute to establishing SV40 as a human polyomavirus and to the SV40 DNA sequences that are being detected in human tissues.

Adenoviridae↗
PubMed1997

Downregulation of Waf1, C2, C3, and major histocompatibility complex class I loci within an 18-cM region of chromosome 17 in adenovirus-transformed mouse cells.

In this study, the expression of the p53 tumor suppressor gene and the p53-regulated Mdm2 and Waf1 genes was evaluated in adenovirus (Ad)-transformed mouse cells. The expected levels of p53 mRNA and protein and Mdm2 mRNA were detected in all transformed cells. However, the level of Waf1 mRNA was markedly reduced in Ad12-transformed cells and in some Ad5-transformed cells. Waf1 expression was not reduced in untransformed mouse cells infected with Ad12 or Ad5. Expression of the class I major histocompatibility complex (MHC) locus was downregulated in 13 Ad-transformed cell lines (derived from four different strains of mice) that exhibited reduced expression of Waf1. Waf1 is located on mouse chromosome 17 proximal to the MHC class I locus. To determine whether other chromosome 17 genes were downregulated, the cells were examined for expression of other genetic loci. Of those tested, only the C2 and C3 complement loci were expressed in mouse fibroblasts. Expression of C2 (which is within the MHC) and expression of C3 (which is 15 cM distal to the MHC) were downregulated in those transformed cells in which Waf1 and MHC class I were downregulated. The Ad12- and Ad5-transformed cells that expressed low levels of Waf1, MHC class I, C2, and C3 formed tumors in syngeneic adult mice. These data suggest that the downregulation of multiple genes within the 32 Mb of mouse chromosome 17 that includes the Waf1 locus to the C3 locus occurs in Ad mouse-cell transformation and may contribute to the tumorigenicity of transformed cells.

Adenoviridae↗
PubMed1996

Relationship between intrinsic radiation sensitivity and metastatic potential.

PURPOSE: Prior studies emphasized genetic modulation of tumorigenicity, and experimental metastatic potential in cells transfected with oncogenes. Whether the intrinsic radiaton sensitivity of cells might correlate with parallel changes in metastatic potential is unknown. METHODS AND MATERIALS: Rat embryo cells (REC) were transfected with the following oncogenes, and where appropriate, with corresponding selection markers: pCMVneopEJ6.6ras, pEJ6.6ras/v-myc, pEla, and pEJ6.6ras/Ela. Individual transfectant clones and corresponding pooled cellular populations were propagated in selective medium. In vitro cellular radiation sensitivity was determined via clonogenic assays, a minimum of three, by standard techniques and individual SF2 and MID parameters determined. Tumorigenicity was defined as the number of tumors forming following the injection of 1 x 10(5) - 1 x 10(6) cells into the axillary pouch of three different strains of immune-deficient mice. Animals were killed once resultant tumors reached a maximum size of 1.5-2.0 cm in maximum diameter. For determination of experimental metastatic potential, between 1 x 10(5) - 1 x 10(6) cells were injected into the tail veins of litter-matched sibling mice in parallel to the tumorigenicity studies. RESULTS: Radiobiologic studies indicate similar levels of radiation sensitivity among REC, mock-transfected REC, Ela, and combined E1a/ras transfectants. pEJ6.6ras, and combined ras/myc transfected pooled cellular populations demonstrated increases in radiation resistance when compared to the pooled radiobiologic data from untransfected and mock-transfected corresponding pooled cellular populations (p <0.05, two-tailed test, SF2, MID). Rat embryo cells, Ela, and mock-transfectants were relatively radiation sensitive and nontumorigenic. pEla/ras was tumorigenic but demonstrated relatively low experimental metastatic potential. Ras, and ras/myc transfectants, demonstrated similar levels of experimental metastatic potential on lung colonization assays. CONCLUSIONS: A good correlation exists between the intrinsic radiation sensitivity and the experimental metastatic potential of transfected REC. The highest levels of radiation resistance in vitro and experimental metastatic potential in vivo were found among REC transfected with ras/myc or activated ras alone. E1a/ ras cotransfected cellular populations, although tumorigenic, were relatively radiation sensitive and nonmetastatic. Further study is needed to formulate a mechanistic explanation for the intriguing correlation between intrinsic radiation sensitivity in vitro and metastatic potential in vivo.

Adenovirus E1A Proteins↗
PubMed1996

Cleavage in vivo and in vitro in the Marsupial Macropus eugenii.

In the tammar wallaby, transport down the oviduct takes less than 24 h after fertilization and a mucoid coat is deposited within a few hours of fertilization, with excess spermatozoa trapped in the mucoid layer. The mucin coat thickens as the zygote passes down the oviduct. A proteinaceous shell is laid down outside the mucin coat in the utero-tubal region of the tract. The fertilized zygote enters the uterus in the pronuclear stage with cleavage proceeding in the uterus. In vivo, the first cleavage takes place two days post coitum (p.c.) (approximately 24 h after ovulation) but the next three cleavage stages may be completed within 24 h (between 48 h and 72 h p.c.). Thus, cell-doubling time appears to be around 8 h for 2-8-cell stages. Cleavage in vitro can occur with, or without, the shell membrane. Cleavage in early embryos of the tammar in vitro is slower than that occurring in vivo, and in vitro there may be a '4-cell block' in early development, as in dasyurids. The pattern of cleavage differs markedly from that of dasyurid marsupials in that there is no extrusion of yolk material from the cells and no separation of the blastomeres during the first cleavage stages to the 8-cell stage. The blastomeres are characterized by numerous vesicular structures and lipid droplets, but no yolk bodies. Polarity is not marked in early cleavage, but by the 8-cell stage polarity has developed with surface microvilli and numerous granular vesicles and mitochondria in the cortical regions at one pole of the cells, but sparse microvilli on the inner surfaces and at the other pole. There are complex intervillous interdigitations of microvilli between cells. However, clear identification of cells as pluriblast or trophoblast cells is not possible up to the 8-cell stage examined. These results demonstrate that this macropodid marsupial has a distinctive pattern of early development which differs from that of Didelphis and of the dasyurid marsupials so far described.

Animals↗
PubMed1995

The effects of end point overdispersions on the validity of single-dose tumorigenicity assays.

Overdispersion can be found in tumor incidence and tumor latency end point values obtained by the conventional assays that are being used to assess the tumorigenicity of neoplastic cells growing in tissue culture. Failure to account for such wide variations in end point data can lead to incorrect assessments of the neoplastic cell tumorigenic phenotype and misinterpretations of data relating genetic functions to tumor-forming capacity. This problem suggests the need for more detailed analyses of the relationships that exist between tumor cell dose and the parameters being used to measure tumorigenicity.

Animals↗
PubMed1995

A p53 mutation in exon 5 associated with adenovirus transformation.

The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form complexes with the p53 tumor suppressor protein. These complexes are thought to interfere with normal p53 activity and may be responsible for the paucity of p53 mutations in cells transformed by these viruses. This report describes an example of a p53 mutation in exon 5 in an Ad5-transformed cell line that exhibited less expression of E1B 55-kDa protein and a longer tumor-latency phenotype than another Ad5-transformed cell line expressing wild-type p53. The finding of a p53 mutation in an Ad5-transformed cell line is unusual, especially considering the current theory that p53-E1B interactions play an important role in adenovirus transformation. This mutation could represent an alternative method of inactivating p53 function in the absence of sufficient levels of E1B 55-kDa oncoprotein.

Adenovirus E1B Proteins↗
PubMed1994

Flow cytometric detection of DNA tumor virus nuclear oncogene products in unfixed cells: saponin FACS of viral oncogene products.

Immunofluorescent analysis is a standard method for detecting DNA virus oncoproteins in transformed cells. Here we demonstrate the detection of DNA virus nuclear oncoproteins by flow cytometry of unfixed cells, after saponin permeabilization. This method could to be of value in the evaluation and quantitation of oncogene products in transformed cells.

Adenovirus E1 Proteins↗