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Biomedical subjects

N W Fraser

Publications and source records attributed to N W Fraser.

At least 109 records · Page 6Linked to original sources
PubMed1985

Possible relationship between antigenic properties and isolation history of HSV-1 strains.

29 monoclonal anti-herpes simplex virus (HSV)-1 antibodies were produced and characterized with regard to virus neutralizing activity, intracellular or cell-surface location of viral antigens and, where possible, molecular weight of the viral protein recognized. 13 antibodies recognized viral antigens expressed on the surface of infected cells and 16 were directed to intracellular viral components. Only two antibodies exhibited virus neutralizing activity. Application of these antibodies to an antigenic comparison of standard laboratory HSV-1 strains F, HFEM, mP, Glasgow-17 and MAC revealed unique antigenic differences among these strains. The antibodies were further used in an antigenic comparison of 45 human HSV-1 isolates with defined isolation history. Except for two paired isolates from left and right trigeminal ganglia of two human cadavers, the antibody panel revealed antigenic differences among all isolates, including paired isolates from three additional cadavers. Overall, isolates from different human donors showed greater antigenic dissimilarity from each other in cell-surface associated than in intracellular antigens. The data suggest the possibility of a correlation between antigenic and biologic properties of HSV-1.

Animals↗
PubMed1984

Localization of herpes simplex virus in the trigeminal and olfactory systems of the mouse central nervous system during acute and latent infections by in situ hybridization.

The precise anatomical location of latent herpes simplex virus (HSV) infection of the mouse central nervous system (CNS) has been identified by application of a 3H-labeled HSV-specific probe to deparaffinized sections of mouse brain tissue in situ. At times after corneal inoculation with HSV type 1 (HSV-1), strain F, representing the acute and latent phases of infection, BALB/c mice were perfused with a fixative containing sodium m-periodate, lysine, and paraformaldehyde and their CNS tissues and trigeminal ganglia embedded in paraffin, sectioned, and and subjected to hybridization. During the acute phase, HSV-1 was localized to neurons and some small supporting cells in the sensory portion of the 5th cranial nerve including the trigeminal ganglia and nerve root, principal sensory nucleus, mesencephalic nucleus, descending tract and nuclei, and cerebral cortex. During the latent phase, HSV-1 was found only in neurons located primarily in the descending nuclei and mesencephalic nucleus. Evidence was also obtained that implicated the olfactory tract as an additional route of entry into the CNS, in that positive hybridization was found in the olfactory bulb, the entorhinal cortex, and adjacent cerebral cortex. Additionally, HSV-1 established latent infections in neurons of the olfactory system. HSV-1-specific RNA was detected in ganglionic and CNS neurons throughout the acute and latent phases of infection, whereas HSV-1-specific DNA was detected only during the acute phase, indicating that the relationship between HSV and latently infected CNS and ganglionic neurons involves limited transcription of the viral genome.

Acute Disease↗
PubMed1983

Detection of HSV-1 genome in central nervous system of latently infected mice.

Herpes simplex virus type 1 (HSV-1) can establish latent infections in peripheral nerve ganglia and the central nervous system (CNS) of experimentally infected mice. Latent infections of peripheral nervous tissue are characterized by the ability to recover infectious virus from explant cultures of most of the latently infected ganglia. In contrast, infectious virus is infrequently recovered from the CNS of latently infected mice following explant culture, although viral DNA can be detected in CNS tissue. The presence of incomplete or defective viral genomes during the latent CNS infections has been proposed to explain this difference between the two latent infections. To characterize the completeness and the physical state of the latent viral genome, we used Southern blot hybridization to analyse the viral DNA from latently infected mouse ganglia and brains. Our results, reported here, indicate that most, if not all, of the HSV-1 genome is present in latently infected CNS tissue and that the latent viral genome exists in a form other than linear, unit length DNA.

Animals↗
PubMed1983

CpG frequency in large DNA segments.

The relationship between the deficiency of CpG dinucleotides and the coding-noncoding segments of DNA has been examined. Analysis of five human alpha-like globin DNA sequences and five human beta-like globin DNA sequences reveal that there is no apparent difference between protein coding and non-coding portions of DNA. Rather CpG deficiency appears to be a property of long contiguous segments of DNA consisting of several genes and their intergenic regions. Thus we propose that CpG deficiency is not involved with translation or transcription but rather is related to chromosomal constraints.

Adult↗
PubMed1981

Gadusol, an enolic derivative of cyclohexane-1,3-dione present in the roes of cod and other marine fish. Isolation, properties and occurrence compared with ascorbic acid.

Gadusol, C8H12O6, has been isolated from roes of the cod (Gadus morhua L.), i.e., ovaries that contain ripe eggs just before spawning. The concentration is about 4 g/kg dry wt. It has been identified as 1,4,5-trihydroxy-5-hydroxymethyl-2-methoxycyclo-hex-1-en-3-one and this structure was confirmed by synthesis of the anhydro tetra-acetate derivative from methyl 3,5-diacetoxy-4-methoxybenzoate. Concentrations of gadusol in the roes of other marine teleost fish examined are of the same order as in cod roes. Gadusol has some properties similar to ascorbic acid and both compounds, after oxidation, react with 2,4-dinitrophenylhydrazine in the commonly-used assay procedure for ascorbic acid. Specific assays showed that the concentrations of gadusol in the roes of marine fish are severalfold greater than those of ascorbic acid. Gadusol is structurally related to the mycosporines previously reported from a number of different organisms.

Animals↗
PubMed1981

Herpes simplex type 1 DNA in human brain tissue.

Herpes simplex virus type 1 (HSV-1) is known to reside latently in the trigeminal ganglia of man. Reactivation of this virus causes skin lesions and may occasionally infect other tissues, including the brain. To determine whether the brain tissue of humans free of clinical signs of HSV-1 infection contains any trace of HSV-1, we examined the DNA from brain tissue by endonuclease digestion, separation of the fragments by gel electrophoresis, and hybridization with labeled HSV-1 DNA probes. Hybrid bands were detected autoradiographically in experiments using cloned and virion-purified fragments of the HSV-1 genome. HSV-1 DNA sequences were found in 6 of 11 human brain DNA samples tested. In some cases, these bands corresponded to the bands expected for the complete viral genome, whereas others contained bands representing only a part of the genome. In some cases, the terminal fragments could be found, suggesting that the DNA was in a linear, nonintegrated form.

Brain↗
PubMed1979

Multiple discrete sites for premature RNA chain termination late in adenovirus-2 infection: enhancement by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

Discrete-sized short RNA chains that contain the distinctive oligonucleotides, including the 5'-capped oligonucleotide, characteristic of the first 600 nucleotides of the adenovirus type 2 (Ad-2) large, late, rightward-reading transcriptional unit (16.4-99) accumulate in Ad-2-infected HeLa cells. In the presence of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole the accumulation of these chains is enhanced, as is the accumulation of short chains from a neighbouring rightward-reading transcriptional unit (3.0-10.7). These short chains appear to represent prematurely terminated transcripts. Late in infection there is a marked increase in RNA synthesis, including that of prematurely terminated short chains, from the large late transcriptional unit. This suggests that the increase in transcription and mRNA production from this region late in infection is not due to reduced "attenuation" of RNA synthesis.

Adenoviruses, Human↗
PubMed1978

DRB-induced premature termination of late adenovirus transcription.

Exposure of HeLa cells to 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazde (DRB) late in the course of adenovirus 2 infection results in the inhibition of virus-specific RNA synthesis from all parts of the previously identified, very long (approximately 28 kilobases) late transcriptional unit, except for the first approximately 400-800 nucleotides. It is suggested that DRB acts not as an inhibitor of RNA chain initiation, but rather causes "premature" chain termination close to the promoter. A practical aspect of these findings may be that RNA sequences near promoter sites that are responsible for mRNA formation can be isolated from DRB-treated cells.

Adenoviruses, Human↗
PubMed1975

Comparison of nucleotide sequences in HeLa cell mRNA and hnRNA.

Nearest neighbour analysis of nucleotides in vertebrate DNA has revealed a marked deficiency in the frequency of occurrence of the sequence CpGp. By use of the fingerprinting technique of Sanger et al. (1965) to characterise the nucleotide sequences of HeLa cell hnRNA after T1 RNAase digestion, we have shown that this deficiency also occurs in hnRNA and that it appears to be a general transcript of DNA. This is also true of the hnRNA that contains poly(A). Whilst a deficiency of CpGp occurs also in poly(A) containing mRNA from HeLa cells the deficiency is less marked than in the case of total hnRNA, or poly(A) containing hnRNA. Another difference between mRNA and hnRNA lies in the level of occurrence of the sequence UpApGp. These results are discussed with reference to the possible relationship of hnRNA to mRNA.

Base Sequence↗
PubMed1971

Egg proteins in cod serum. Natural occurrence and induction by injections of oestradiol 3-benzoate.

1. Before the uptake of water that precedes spawning, eggs of cod (Gadus morhua L.) contained 30% dry matter, of which 80% was protein. Some 75% of this protein was soluble in 0.5m-sodium chloride. The major components in the extract were two similar lipoproteins, of molecular weight about 400000, containing 21% lipid, some two-thirds of which was phospholipid, and about 0.5% protein phosphorus. 2. These lipoproteins were identified by immunochemical methods in the serum of female cod with developing ovaries, but not in the serum of male or of immature female fish. 3. The concentrations of egg proteins in the serum of female cod were determined by a serial-dilution double-diffusion immunological method, and were shown to increase with development of the ovaries, reaching a value of about 32mg/ml when the weight of the ovaries was 10% of the weight of the fish. 4. Immature male and female cod were injected intramuscularly with a solution of oestradiol-17beta 3-benzoate in oil and the concentration of egg proteins in their serum was measured by the immunodiffusion method. The serum contained no detectable egg proteins before injection of the fish, but 30mug of oestradiol benzoate/kg gave rise to detectable amounts of egg proteins in 10 days, and with 300mug or 1mg of oestradiol benzoate/kg the concentration of egg proteins rose to 32mg/ml. The values for male and female cod were similar and represented about one-half of the total serum protein. 5. With a dose of 1mg of oestradiol benzoate/kg, egg proteins were first detected in the serum 2 days after injection and the concentration increased up to 10 days. 6. Serum samples taken before and 10 days after an injection of 1mg of oestradiol benzoate/kg were fractionated by gel-filtration on Sephadex G-200. The difference curves obtained from fractionation curves after and before injection confirmed the values of the concentrations of egg proteins obtained from the immunodiffusion test and showed that the concentrations of the normal serum components fell by 20-50% of the initial value, the high-molecular-weight globulins showing the most marked fall. 7. Egg proteins were detected in the liver and testes of the injected fish, but not in the ovaries.

Animals↗
PubMed1971

Incorporation of l-[C]leucine into egg proteins by liver slices from cod.

1. Liver slices from cod (Gadus morhua L.) were incubated with l-[(14)C]leucine and the incorporation of label into total protein, precipitated with trichloroacetic acid, and into egg proteins, precipitated with an antibody after addition of carrier egg proteins, was measured. 2. Liver slices from immature male or female cod, and from male fish with developing testes, did not incorporate significant amounts of l-[(14)C]leucine into egg proteins, whereas with slices from female cod with developing ovaries the rate of incorporation into egg proteins was 8% of the rate of incorporation into total protein. 3. Liver slices from immature male or female fish that had received an intramuscular injection of oestradiol benzoate (1mg/kg) 5-8 days previously incorporated l-[(14)C]leucine into egg proteins at about 26% of the rate of incorporation into total protein. 4. Incorporation into total protein and into egg proteins was inhibited by puromycin, and 1.2 and 0.13mug of puromycin/mg of tissue protein, respectively, gave 50% inhibition.

Journal Article↗