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Biomedical subjects

M Dawson

Publications and source records attributed to M Dawson.

At least 127 records · Page 7Linked to original sources
PubMed1987

Genetic mapping of the amino-terminal domain of bacteriophage T4 DNA polymerase.

The DNA polymerase of bacteriophage T4 is a multifunctional enzyme that harbors DNA-binding, DNA-synthesizing and exonucleolytic activities. We have cloned in bacterial plasmids about 99% of the structural gene for this enzyme (T4 gene 43). The gene was cloned in six contiguous 5'-terminal DNA fragments that defined seven intragenic mapping regions. Escherichia coli hosts harboring recombinant plasmids carrying the gene 43 subsegments were used in marker-rescue experiments that assigned a large number of ts and nonsense polymerase mutations to different physical domains of the structural gene. Conspicuously, only one missense mutation in a large collection of mutants mapped in the 5'-terminal 450 base-pair segment of the approximately 2700 base-pair gene. To test if this indicated a DNA polymerase domain that is relatively noncritical for biological activity, we mutagenized a recombinant plasmid carrying this 5'-terminal region and generated new conditional-lethal mutations that mapped therein. We identified five new ts sites, some having mutated at high frequency (nitrosoguanidine hot spots). New ts mutations were also isolated in phage genes 62 and 44, which map upstream of gene 43 on the T4 chromosome. A preliminary examination of physiological consequences of the ts gene 43 mutations showed that they exhibit effects similar to those of ts lesions that map in other gene 43 segments: some were mutators, some derepressed gene 43 protein synthesis and they varied in the severity of their effects on T4-induced DNA synthesis at nonpermissive temperatures. The availability of the gene 43 clones should make it possible to isolate a variety of lesions that affect different activities of the T4 DNA polymerase and help to define the different domains of this multifunctional protein.

Cloning, Molecular↗
PubMed1987

Identification of two new bacteriophage T4 genes that may have roles in transcription and DNA replication.

We have identified two bacteriophage T4 genes, 45.1 and 45.2, that map in the intergenic space between phage replication genes 46 (which encodes a recombination initiation protein) and 45 (which encodes a bifunctional protein required in replication and transcription). The existence of genes 45.1 and 45.2 had not been previously recognized by mutation analysis of the T4 genome. We cloned the T4 gene 45.1/45.2 segment, determined its nucleotide sequence, and expressed its two reading frames at high levels in bacterial plasmids. The results predicted molecular weights of 11,400 (100 amino acids) for gp45.1 and 7,500 (62 amino acids) for gp45.2. We also determined that in T4-infected Escherichia coli, genes 45.1 and 45.2 are cotranscribed with their distal neighbor, gene 45, by at least one mode of transcription. In an accompanying report (K. P. Williams, G. A. Kassavetis, F. S. Esch, and E. P. Geiduschek, J. Virol. 61:600-603, 1987), it is shown that the product of gene 45.1 is the so-called T4-induced 15K protein, an RNA polymerase-binding protein of unknown role in phage development. Possibly, T4 genes 45.2, 45.1, and 45 constitute an operon for host RNA polymerase-binding phage proteins. Jointly with Williams et al., we propose the term rpb (RNA polymerase-binding) to refer to T4 genes whose products bind to the host RNA polymerase and have adopted the name rpbA for T4 gene 45.1.

Amino Acid Sequence↗
PubMed1987

Caprine arthritis-encephalitis. Virus isolation and identification in goat herds in Italy.

Caprine arthritis-encephalitis virus (CAEV) was isolated by explant cultures of carpal synovial membrane, udder, lymph-nodes, lung and choroid plexus from six goats in two different herds with histories of arthritis-encephalitis. The virus was also isolated from milk, heparinized blood and carpal synovial fluid, using secondary goat synovial membrane cells. Virus identification was made by means of cytopathology, agar gel immunodiffusion test, immunofluorescence, in vitro host range and electron microscopy. Efficacy of different virus isolation procedures from live and necropsied animals are discussed.

Animals↗
PubMed1986

Keutel syndrome: clinical report and literature review.

In 1972 Keutel et al described a brother and sister with brachytelephalangism, hearing loss, peripheral pulmonary stenosis and abnormal cartilage calcification. Since then, three additional cases have been reported. We report a sixth case and discuss the clinical findings and cause.

Abnormalities, Multiple↗
PubMed1986

Ovine enzootic abortion: experimental studies of immune responses.

Eight pregnant and four non-pregnant ewes were exposed to experimental oral infection with the chlamydial agent of ovine enzootic abortion. Four non-pregnant ewes received a sham inoculum. Immune responses were investigated using a complement fixation test (CFT), a delayed-type hypersensitivity (DTH) skin test and a lymphocyte transformation assay (LTA). When these responses were correlated with clinical observations it was concluded that fetopathy occurred in those ewes which failed to mount or mounted only weak DTH responses. High antibody titres were not an indication of protective immunity; in pregnant animals there was evidence of an inverse correlation between DTH and humoral responses as detected by the CFT. In the LTAs, chlamydia specific blastogenesis was recorded in all infected sheep but there was little correlation with clinical findings.

Abortion, Veterinary↗
PubMed1985

Serological survey of lentivirus (maedi-visna/caprine arthritis-encephalitis) infection in British goat herds.

A serological survey for lentivirus infection was undertaken on a volunteer sample of 331 British goat herds. The prevalence of infected herds was 10.3 per cent and the prevalence of seropositive individual animals was 4.3 per cent. There was evidence of a geographical variation in the distribution of infection. Herds consuming pooled colostrum appeared to be at greater risk from infection. Approximately half the herds sampled had been established within the past six years. There was evidence of recently introduced infection in a relatively high proportion of infected herds.

Animals↗
PubMed1985

Use of cultured human conjunctival and other cells to assess the relative toxicity of six local anaesthetics.

The effects of six local anaesthetics on five cell types were investigated in vitro, with the objectives of assessing their toxicity to the cell types with which they would be likely to come into contact, ranking them in order of toxicity, determining whether toxicity was related to potency, and investigating a range of indices of toxicity. Procaine, lignocaine, piperocaine, amylocaine, amethocaine and cinchocaine all showed some toxicity increasing in that order. The indices of toxicity studied all led to the same ranking order of the drugs, and this order was also the order of their anaesthetic potencies. Thus cell culture was shown to be a useful means of investigating local anaesthetics for toxicity.

Anesthetics, Local↗
PubMed1985

The pharmacokinetics and bioavailability of a tracer dose of [3H]-mebendazole in man.

Five volunteers, whose ages ranged between 37 and 64 years, took part in a crossover study to determine the pharmacokinetics and bioavailability of mebendazole in man following intravenous and oral administration of a tracer dose of [3H]-mebendazole. Following intravenous administration, the average distribution half-life, elimination half-life and rate of clearance were 0.20 h, 1.12 h, and 1.063 min respectively. After oral administration of the solution, the average elimination half-life was 0.93 h, the apparent rate of clearance was 0.846 l/min, the average time to peak plasma concentration was 0.42 h, and the bioavailability of mebendazole was 22%. Comparison of metabolite area under the plasma concentration vs time data from each route of administration indicates that absorption of mebendazole from the gastrointestinal tract at this dose level is almost complete. The low bioavailability observed following oral administration at this dose level is postulated to be due to high first pass elimination. Approximately half of the administered dose of radioactivity following intravenous and oral administration was detected in the urine, and the major unconjugated metabolite of mebendazole was found to be 2-amino-5(6) [alpha-hydroxybenzyl]benzimidazole (IV), not 2-amino-5(6)benzoylbenzimidazole (II), as previously reported.

Absorption↗
PubMed1985

The effect of dose form on the bioavailability of mebendazole in man.

Four different dose forms of mebendazole were administered to human volunteers, and urine was collected and assayed for mebendazole and unconjugated metabolites of mebendazole. Oral administration of mebendazole as an oily suspension slightly enhances the bioavailability of the drug, however mebendazole is not absorbed following rectal administration. The major urinary metabolite of mebendazole in humans is 2-amino-5(6)[alpha-hydroxybenzyl]benzimidazole (IV), not 2-amino-5(6) benzoylbenzimidazole (II), as previously reported.

Administration, Oral↗
PubMed1985

Electrophoretic separation and molecular weight characterization of Pseudomonas aeruginosa H-antigen flagellins.

We found that preparations of Pseudomonas aeruginosa flagellar antigens protected against P. aeruginosa challenge in a burned-mouse model. To determine the extent of similarity among known flagellar antigen types, we compared flagellins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A majority of our laboratory strains and clinical isolates, including PAO strains and their derivative mutants RM46 and PJ108, as well as virulent strains M-2 and 1244, had flagellins of 53,000 Mr. These flagellins had the same Mrs as those of type b-standard strains 170001 and 15084. The heterogeneous group of a-type H-antigen flagellins were of smaller molecular weights, ranging from 52,000 Mr for standard strain 5939 (a0, a3) to 45,000 Mr for standard strain 170018 (a0, a3, a4). Standard strains 5933 (a0, a1, a2) and 5940 (a0, a2) had intermediate Mrs of 51,000 and 47,000, respectively. Differences in Mr of 1,000 to 2,000 could be resolved by coelectrophoresis. A series of 26 unknown strains were categorized. Correlations among typing by molecular weight, cross-agglutination reactions with O-adsorbed H antisera, and previous results for H-serum typing are reported.

Animals↗
PubMed1984

Global survey of serological evidence of caprine arthritis-encephalitis virus infection.

Using caprine arthritis-encephalitis virus antigen in the agar gel immunodiffusion test, 3729 serum samples from goats in over 112 locations around the world were tested for precipitating antibodies. Over 90 per cent of the 1265 positive samples came from Canada, France, Norway, Switzerland and the USA, all of which had 65 per cent reactors or greater. Fiji, Great Britain, Kenya, Mexico, New Zealand and Peru had fewer than 10 per cent positive samples; the majority of these could be traced to importations of goats from countries where there was a high occurrence of precipitating antibody. Somalia, Sudan and South Africa had no reactors among 306 samples. No reactors were found among 1116 samples from domestic and indigenous goats which were known to have had no contact with imported goats from countries which had a high occurrence.

Africa↗