Biomedical subjects
Publications and source records attributed to G Webb.
A simplified protocol for the hybridization of labeled oligonucleotides and other radiolabeled DNAs to membranes is described and used for the detection of specific recombinant phage in the ordered miniset collection representing virtually the entire E. coli genome.
Proliferating cell nuclear antigen (PCNA)/cyclin has been localized by in situ hybridization to the short arm of human chromosome 20 with a peak of grains over band 20p13. In addition, there were two strong secondary peaks of grains over 11p15.1 and Xp11.4 indicating the presence of two related genes in man.
The glutathione transferases (GSTs) are involved in the metabolism of a wide range of compounds of both exogenous and endogenous origin. There is evidence that deficiency of GST may increase sensitivity to certain environmentally derived carcinogens. In contrast, elevated expression has been implicated in resistance to therapeutic drugs. The GSTs are the products of several gene families. This review summarizes the present knowledge of the genetic interrelationships between the various isoenzymes, their deficiencies and the physical locations of their genes.
Recombinant inbred strains of mice were used to localize the genes coding for the class alpha glutathione S-transferase 2 (Gst-2). The genes showed three distinct strain distribution patterns, indicating that they occur in at least three clusters separable by recombination. All three clusters are located in the vicinity of the d locus on mouse chromosome 9, but two of them are closer to d than the third. Linked to Gst-2 on mouse chromosome 9 are two enzyme-encoding loci, Pgm-3 and Mod-1. The human counterparts of Gst-2, Pgm-3, and Mod-1 map to 6p12, 6q12, and 6q12, respectively. Thus, the pericentric region of human chromosome 6 has its homolog in the segment spanning Gst-2, Pgm-3, and Mod-1 on mouse chromosome 9. The fact that the syntenic group extends across the centromere of human chromosome 6 can best be explained by a pericentric inversion postulated to have taken place in the primate lineage leading to Catarhini.
Because of the potential benefits of primary prevention and early detection of cancer, a considerable proportion of the efforts of State cancer organizations has been directed towards public educational programs. The study aimed to determine the level of agreement in the messages contained in the written educational material of the State and Territory cancer organizations in Australia. Pamphlets and brochures dealing with primary and secondary prevention of breast, cervical, skin and bowel cancers were obtained. The materials were compared on a number of dimensions: the characteristics of people who are at increased risk of contracting the cancer, how to avoid the cancer through primary prevention, how and when to screen in the case of secondary prevention, and action to be taken if a sign or symptom indicative of cancer is discovered. The study found a lack of agreement in the messages of the State cancer organizations. Some hypotheses are suggested to explain the discrepancies. In addition, some suggestions for remedying this situation are provided.
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Computer-aided learning is considered to be useful in the teaching of host/parasite population modelling. The STELLA programme for the Apple Macintosh microcomputer allows dynamic models to be developed by drawing a diagram of the interactions and then defining the relationships between variables in terms of simple mathematics or as graphs. Our experience in using this programme for project-based teaching is described.
The views of politicians, experts in the field of drug abuse and randomly-selected members of the community were sought concerning the burden of illness that is imposed by the abuse of alcohol, tobacco, narcotic agents, prescribed drugs, cocaine, volatile substances, over-the-counter drugs and cannabis. Politicians and community members perceived illicit drugs to have the greatest associated burden. Experts ranked in descending order alcohol, tobacco, narcotic agents, prescribed drugs, cocaine, volatile substances, over-the-counter drugs and then cannabis to have the greatest burden of illness. Priorities that were perceived by each group for research funding corresponded with their judgements of the burden of illness. Experts' views on the burden of illness most closely matched the data that are available on drug-associated mortality. It is suggested that unless a close correspondence among the views of the three groups is present, conflict in regards to allocation of resources is likely.
The selection of ofloxacin-resistant mutants from susceptible wild-type bacterial populations was investigated by three methods. Resistant mutants selected from populations of Escherichia coli (NCTC 10418) and Staphylococcus aureus (NCTC 6571) by single-step passage at either four or eight times the MIC occurred at a frequency of less than 1 x 10(-10). Ofloxacin-resistant mutants of Pseudomonas aeruginosa (NCTC 10662), selected at four times the MIC, occurred with a 100-fold greater frequency at 3.3 X 10(-8), however, mutants of this species selected at eight times the MIC, occurred at a frequency of less than 1 X 10(-10). Sequential selection of ofloxacin-resistant mutants during multiple passages at 1/2 MIC, resulted in a 16- to 32-fold increase in MICs for isolates of P. aeruginosa and Klebsiella aerogenes, a four- to eight-fold increase in MICs for some strains of E. coli and a two- to four-fold increase in MICs for Staph. aureus and Streptococcus spp. During prolonged exposure of populations of E. coli (NCTC 10418) and Staph. aureus (NCTC 6571) to concentrations of ofloxacin at 1, 10 and 100 times the MIC no resistant-mutants were selected after seven days incubation. In similar experiments with P. aeruginosa (NCTC 10662) ofloxacin-resistant mutants were selected from populations exposed to the MIC which required 64 mg/l ofloxacin for inhibition. No ofloxacin-resistant mutants were selected from populations of P. aeruginosa (NCTC 10662) exposed to either ten or 100 times the MIC.(ABSTRACT TRUNCATED AT 250 WORDS)
We characterized a recombinant clone E7 containing a 1.6-kb Eco RI insert of human alpha satellite DNA (alpha DNA) which hybridized in situ predominantly to the centromere of chromosome 17. Three thousand copies of this sequence were detected on chromosome 17, although a lesser number of copies were also found on the centromeres of chromosomes 11, X, and the other human chromosomes, except Y. In the human genome, sequences homologous to E7 were organized principally as five major polymorphic (Pst I) forms of tandem alpha DNA repeats with molecular weights between 2.0 and 2.7 kb. We We studied the higher-order organization of these major forms using a series of 12 cosmid clones. Close linkage of the different polymorphic forms was demonstrated, with no two cosmids showing an identical linkage pattern. Six of the cosmid clones carried a considerable amount (20-25%) of nonhomologous (non-alpha) DNA, indicating that the repeat arrays are relatively frequently interrupted by other genomic DNA. In none of the cosmid inserts were the repeat arrays bound on both sides by non-alpha DNA, suggesting that short arrays are not common. However, some of the intervening non-alpha DNA sequences were relatively short, and vary in size from 6 to 24 kb. Our results suggest an irregular and complex pattern of organization of alpha DNA in the human genome.
The in vitro activity of aztreonam, cefuroxime and ceftazidime was determined against 2,372 Gram-negative rods (including Pseudomonas spp.) isolated from hospital patients with urinary tract infections during 1985. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique in Mueller-Hinton agar. The inoculum used was approximately 10(5) colony forming units (cfu) contained in 10 microliter Mueller-Hinton broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation plates were incubated aerobically at 37 degrees C for 18 h. The MIC of each antimicrobial for each organism examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentration required to inhibit the growth of 90% (MIC90) of the bacterial isolates in each genus or species examined was also determined. In general the antibacterial spectrum of aztreonam was comparable to that of ceftazidime and superior to that of cefuroxime. Against Escherichia coli, which accounted for 72% of the isolates examined, aztreonam (MIC90 less than or equal to 0.25 microgram/ml) was slightly more active than ceftazidime (MIC90 0.5 microgram/ml) and considerably more active than cefuroxime (MIC90 8 micrograms/ml). Aztreonam was active against Pseudomonas spp. (MIC90 16 micrograms/ml), although somewhat less so than ceftazidime (MIC90 4 micrograms/ml). Cefuroxime showed low activity against this genus (MIC90 greater than 128 micrograms/ml).
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We modified the Sandoz cyclosporine radioimmunoassay because of our need for frequent clinical monitoring of cyclosporine drug levels in allo- and xenograft pediatric cardiac transplant patients. With application of a commercially available [125I]cyclosporine label in place of [3H]cyclosporine and a second antibody/polyethylene glycol (PEG) method of separation in place of charcoal separation, we simplified and enhanced the speed and precision of assay performance. Studies of 140 whole blood samples comparing this new method to the [3H]cyclosporine radioimmunoassay (RIA) method of Berk and colleagues yielded a coefficient of correlation of 0.96 (p less than 0.00001) with means of 626 and 667 ng/ml for [3H]RIA and [125I]RIA, respectively, and a regression equation of y = 28 + 1.02x. The major advantages are that total assay time is reduced to approximately 1 h; [125I]cyclosporine label is used, avoiding the problems associated with liquid scintillation counting; and precision is enhanced by separating bound and free fractions with second antibody/PEG. These modifications should provide for greater ease of assay performance and improved clinical utility of cyclosporine monitoring not only in the pediatric but also in the adult transplant patient.
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The karyotypes of a female and of a male Presbytis cristatus are analysed. In the latter, there is a complex Y-autosome rearrangement. The phyletic position of this species, in relation to genus Colobus, previously studied, is proposed, considering the sequence of chromosomal rearrangements which occurred during their evolution. These rearrangements, in addition to the t(Y-autosome), are characterized by a high frequency of inversions, and above all, by several non-Robertsonian translocations which occurred very rarely during evolution of other Primates.
A 46-component neurological exam was administered to 119 learning-disabled children and to 152 control children, and a Neuroimmaturity Index (NI) was constructed. The results were compared by age and sex. Neuroimmaturity decreased significantly with age, and after controlling for age and sex there were statistically significant differences in NI between the learning-disabled and control children. Male children from both groups, controlling for age, tended to have a higher NI than females. Patterns of disability were related to communication skills; older learning-disabled males had difficulty writing and spelling, whereas younger female learning-disabled children had difficulty with spoken language.
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The retention and elution of acetylcholinesterase from bovine erythrocytes and electric eel on N-methylacridinium affinity columns have been compared at various ligand concentrations. A soluble 7.7 S dimeric form of bovine erythrocyte acetylcholinesterase required a ligand concentration of 2.0-2.8 mumol/ml in 0.1 M NaCl for retention, compared to 0.44 mumol/ml for various forms of the electric eel acetylcholinesterase. The difference in the retention of acetylcholinesterase from these two sources could not be explained by differences in their oligomeric structure. The affinity of bovine erythrocyte acetylcholinesterase for N-methylacridinium was 13-fold or more lower than the electric eel acetylcholinesterase at similar ionic strengths. N-Methylacridinium appeared to react selectively with the catalytic anionic site of both enzymes. It was concluded that the affinity of the side arm ligand was the major determinant of the differences in the retention properties of the eel and erythrocyte acetylcholinesterase. The difference in affinity for N-methylacridinium probably reflects differences in the organic cation binding region of the two enzymes.