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D J Brenner

Publications and source records attributed to D J Brenner.

340 records · Page 19Linked to original sources
PubMed1970

Lack of nucleotide sequence relationship among the temperate bacteriophage SPO2, Bacillus subtilis, and virulent bacteriophages beta 3 and beta 22.

Radiolabeled phage SPO2 fragments were tested for the abiity to form interspecies deoxyribonucleic acid (DNA) duplexes with DNA from Bacillus subtilis and from phages beta3 and beta22. No reassociation, above control values, occurred between the DNA of phage SPO2 and that of its host or either of the virulent B. subtilis phages. It appears that extensive nucleotide sequence similarities between portions of host and phage DNA species are not necessary for the formation of the lysogenic state. The thermal elution profile of reassociated SPO2 DNA exhibited a normal distribution, indicating no heterogeneity in base composition. This differs from temperate enterophages whose DNA molecules contain regions of differing base composition.

Bacillus subtilis↗
PubMed1969

Polynucleotide sequence relationships among members of Enterobacteriaceae.

Polynucleotide relationships were examined among many representatives of the Enterobacteriaceae by means of agar, membrane filter, and hydroxyapatite procedures. The amount of deoxyribonucleic acid (DNA) that reassociated was dependent, especially in interspecific reactions, on the annealing temperature. In only three cases: Escherichia coli-Shigella flexneri, Salmonella typhimurium-S. typhi, and Proteus mirabilis-P. vulgaris, was relative interspecific duplex formation 80% or higher. In most cases interspecies DNA duplex formation was 40% or less of that obtained from intraspecies DNA reassociation reactions. The stability of E. coli-S. flexneri DNA duplexes formed at either 60 or 75 C was virtually identical to that of homologous E. coli DNA duplexes, and the degree of interspecies duplex formation was minimally affected by the temperature increase (86% at 60 C; 77% at 75 C). The thermal stability of DNA duplexes formed at 60 C between DNA from E. coli and DNA from strains of Aerobacter aerogenes, S. typhimurium, S. typhi, and P. mirabilis was about 12 to 14 C below that of reassociated E. coli DNA. At 75 C, the formation of the interspecific DNA duplexes was markedly decreased, but the stability of the DNA able to reassociate at this temperature approximated that of reassociated E. coli DNA. The degree of reassociation and the thermal stability of E. coli-S. flexneri DNA duplexes suggests relatively little evolutionary divergence in these organisms. The other enterobacteria tested, however, have diverged to a point where less than one-half of their DNA can reanneal with E. coli DNA at 60 C and less than 10% reacts at 75 C. The degree of divergence between various enterobacteria does not appear to be uniform along the DNA molecule. Ribosomal ribonucleic acid (RNA)-specific sequences are conserved among most enterobacteria. An examination of messenger RNA relatively specific for the lactose operon suggests that specific chromosomal genes may diverge more or less than the genome as a whole.

Carbon Isotopes↗
PubMed1968

Thermal stability of Escherichia coli-Salmonella typhimurium deoxyribocleic acid duplexes.

Single-stranded, labeled deoxyribonucleic acid (DNA) fragments from Escherichia coli were incubated at 60 and 66 C with a large excess of single-stranded, unlabeled DNA fragments from E. coli and Salmonella typhimurium. The resulting reassociated DNA was adsorbed to hydroxylapatite and eluted in a series of washes at increasing temperatures. The thermal stability of the reassociated DNA was determined by means of this procedure. Neither the extent of reassociation nor stability of the reassociated E. coli DNA was affected by increasing the incubation temperature from 60 to 66 C. The double-stranded molecules resulting from the reassociation of E. coli DNA with S. typhimurium DNA had a markedly lower thermal stability than reassociated E. coli DNA. More reassociation occurred between E. coli and S. typhimurium at 60 C than at 66 C. In addition, the product of interspecies reassociation occurring at 66 C had a higher thermal stability than that occurring at 60 C. Preliminary results indicate that the decreased thermal stability of the interspecies duplex is in part the result of unpaired bases.

Agar↗
PubMed1966

Inhibition of coliphage reproduction after superinfection of induced lysogens.

Brenner, Don J. (University of Washington, Seattle), and Neal B. Groman. Inhibition of coliphage reproduction after superinfection of induced lysogens. J. Bacteriol. 92:1727-1734. 1966.-Purified preparations of phages lambda and lambda112 inhibited lysis, phage reproduction, and endolysin synthesis by ultraviolet-induced strains of K-12 (lambda) and K-12 (lambda112). Structural and partial functional integrity of phage was required for inhibition, and the role of phage deoxyribonucleic acid (DNA) in inhibition was demonstrated. Both ultraviolet-irradiated and host-modified lysates of lambda were inhibitory, suggesting that replication of superinfecting phage DNA was not essential for inhibition. Using various combinations of superinfecting and resident phage, including lambda, 434, 434hy, and C-mutant derivatives, we observed that all three C region cistrons played some role in inhibition. Of the three, the C(1) cistron was the most critical. With certain phage combinations, inhibition was observed even though the resident and superinfecting phage differed in immune specificity. Both the medium and the method of superinfection determined whether lysis or lysis inhibition would occur. These and other observations with K-12(lambda)thy(-) indicated that many factors influence the outcome of superinfection. The data are compatible with the view that superinfection inhibition is due to the establishment or re-establishment of phage repressor activity, with the result that replication of both superinfecting and resident phage is blocked.

Antibodies↗
PubMedDate not supplied

Ewingella americana gen.nov., sp.nov., a new Enterobacteriaceae isolated from clinical specimens.

We propose the name Ewingella gen.nov. for a new group in the Enterobacteriaceae. Ewingella is phenotypically distinct from all other groups of Enterobacteriaceae. The members of this genus are lipase- and deoxyribonuclease-negative; Voges-Proskauer-positive; lysine-, ornithine- and arginine-decarboxylase-negative; anaerogenic; they produce acid from glucose in the presence (and absence) of iodoacetate, but fail to produce acid from L-arabinose, melibiose, raffinose, D-sorbitol or sucrose. DNA-relatedness studies (S1-nuclease method) showed that the 10 Ewingella strains studied form a single DNA-hybridization group which is less than 21% related to other members of the Enterobacteriaceae. This single DNA-hybridization group is named Ewingella americana sp. nov. The type strain of E. americana is CDC 1468-78 (= ATCC 33852 = CIP 8194). Although the 10 strains of E. americana were isolated from clinical sources in the United States, the clinical significance of these organisms is not known.

Base Composition↗
PubMedDate not supplied

Legionella moravica sp. nov. and Legionella brunensis sp. nov. isolated from cooling-tower water.

Two Legionella-like organisms were isolated from cooling-tower water samples in Czechoslovakia. They were presumptively identified as legionellae by their growth on buffered charcoal-yeast extract agar (BCYE) containing L-cysteine and their absence of growth on BCYE without L-cysteine. Both strains contained predominately branch-chained cellular fatty acids and were therefore definitively placed in the genus Legionella. They were serologically distinct from other described Legionella species and were shown by DNA studies to constitute two new Legionella species, Legionella moravica (type strain 316-36; ATCC 43877) and Legionella brunensis (type strain 441-1; ATCC 43878).

Czechoslovakia↗
PubMedDate not supplied

Radiobiological principles in intravascular irradiation.

BACKGROUND: There is wide interest in the use of intravascular irradiation to control restenosis following balloon angioplasty. Part of the mechanism of restenosis appears to be the proliferation of smooth muscle cells (SMCs), triggered to divide by the damage caused by the angioplasty, and this proliferation can be inhibited by irradiation with y-rays or beta-rays. METHODS: In vitro data for the survival of smooth muscle cells exposed to radiation was used to model the likely control of restenosis by radiation. Physical and biological data were used to estimate differences in biological effectiveness of gamma-rays and beta3-rays, as well as the effect on cell killing of extending the exposure time. RESULTS: Based on the radiosensitivity of SMCs, measured in vitro, and the limited proliferative potential of these normal somatic cells, it is possible to understand and to model quantitatively how a single acute gamma-ray dose in the range of 15-20 Gy can inhibit restenosis. The few successful trials carried out to date where radiation has been shown to inhibit restenosis have all involved the gamma-emitter Iridium-192. The use of this radionuclide involves radiation safety problems and an inconveniently long treatment time. Consequently, there is much interest in developing a beta-emitting source that would solve both problems, and a number of different possibilities are being pursued. This development introduces two new problems discussed in this paper. First, beta-rays in the megavoltage range are less effective biologically than gamma-rays in the kilovoltage range, but the magnitude of the difference is not well known. Second, in the case of a single large dose, such as that proposed to inhibit restenosis, the biological effect will vary substantially as the exposure time varies from 1 to 20 min. If the clinical data are to be compared between centers using a variety of beta and y-emitting radionuclides, these factors will need to be taken into account. CONCLUSIONS: Doses of > 15 Gy are unlikely to result in elimination of the restenosis problem but should delay onset of restenosis for a significant period; the larger the dose, the longer the delay. Successful trials of endovascular radiation completed to date involve y-rays, while many systems being developed are based on beta-emitting radionuclides. Experimental data are urgently needed so that allowances can be made for the difference in dose-rate and radiation quality between gamma and beta-emitting radionuclides.

Angioplasty, Balloon↗
PubMedDate not supplied

Profiles of obese children presenting for metabolic evaluation.

BACKGROUND: Obesity, increasingly prevalent among children, causes major morbidities, among which is earlier onset of type 2 diabetes mellitus (DM). METHODS: We reviewed charts of children aged 3 to 18 years (n=106). The population was divided into four age groups. Anthropomorphic measurements, family history, diet and exercise patterns, and selected endocrine/metabolic measurements were recorded, and descriptive statistics were calculated. RESULTS: Obesity in one or both parents correlated with a higher percent of ideal body weight (IBW) (p = 0.01). Fifty-eight percent of the children had first- or second-degree relatives with a history of type 2 DM; 9% had relatives with type 1 DM. Fifty-four percent had dieted and exercised regularly. Mean onset of obesity was at 4.2 +/- 0.9 years. Mean cholesterol was elevated at 176 mg/dl. Average BMI was 26.6 in the youngest children (Group 1; normal mean for this age approximately 15.5), and increased to 37.8 in adolescents (Group 4; normal mean approximately 21). Elevated TSH was present in <1% of the population. The number of patients with an abnormal insulin: glucose ratio (>1:4) increased with age. CONCLUSIONS: Childhood obesity in children is correlated with family histories of obesity and DM. Thyroid dysfunction is seldom found, although mild hypercholesterolemia and insulin insensitivity are prevalent, especially among adolescents.

Adolescent↗
PubMedDate not supplied

DNA characterization of Lyme disease spirochetes.

Lyme disease spirochetes (LDS) have phenotypic characteristics of both treponemes and borreliae. To ascertain whether one or more species of LDS exist, as well as their taxonomic status, we determined the DNA base (G + C) content for three strains of LDS, the DNA relatedness of ten strains isolated in the United States or Europe, and the DNA relatedness of LDS to other spirochetes. The G + C content of the three LDS strains was 28.1-29.0 mol%, most similar to those of Borellia hermsii (30.6 mol %) and Treponema hyodysenteriae (25.6 mol %) among the other spirochetes tested. DNA hybridization studies of nine LDS strains to a reference strain isolated from human blood revealed divergence (unpaired bases) within related nucleotide sequences of only 0.0-1.0 percent, indicating the strains were one species. Similarly, relatedness values of seven strains to the reference strain were high: 58-98 percent (mean, 71 percent) in 50 degrees C reactions and 50-93 percent (mean, 69 percent) in 65 degrees C reactions. Labeled DNA from B. hermsii was 30-40 percent related to three Lyme disease spirochete strains in 50 degrees C reactions and 8-10 percent related in 65 degrees C reactions. In contrast, DNA from the reference LDS strain showed relatedness of only 1 percent to DNAs of two leptospires and only 16 percent to DNA from T. hyodysenteriae. We conclude that LDS are a single species, genetically unlike treponemes or leptospires, which belong in the genus Borrelia.

Borrelia↗
PubMedDate not supplied

A preliminary report: frequency of A-T heterozygotes among prostate cancer patients with severe late responses to radiation therapy.

PURPOSE: To investigate whether a significant proportion of prostate cancer patients who have late sequelae after high-dose external-beam conformal radiation therapy are radio-sensitive because they are carriers of ataxia-telangiectasia, that is, are heterozygous for mutations in the ATM gene. PATIENTS AND METHODS: A group of prostate cancer patients were selected who experienced severe late sequelae, specifically proctitis or cystitis, after high-dose external-beam conformal radiation therapy, together with a control group of patients treated in the same way but who did not have severe late effects. Blood samples were taken from these patients, genomic DNA extracted, and mutations sought in the ATM gene. RESULTS: Of 17 late-effect patients in whom most or all of the ATM gene has been examined, significant mutations (17.6%) were identified in three. No significant mutations were found in the control group. The incidence of ataxia- telangiectasia heterozygotes in the United States population is 1% to 2%. DISCUSSION: These preliminary data suggest that a disproportionate number, but by no means all, of prostate cancer radiotherapy patients who experience severe late effects are ataxia-telangiectasia heterozygotes. If this conclusion is confirmed, these individuals could be identified prospectively and, with dose de-escalation, spared a great deal of discomfort and suffering. As a corollary, if most of the small late-effects population were prospectively identifiable, the dose to the remaining population could potentially be escalated. Present methods of identifying mutations in a large gene, such as ATM, are cumbersome and expensive, but the technology is evolving rapidly, so that rapid screening of the ATM gene is imminent.

Ataxia Telangiectasia↗