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D J Brenner

Publications and source records attributed to D J Brenner.

At least 73 records · Page 4Linked to original sources
PubMed1998

Genetic relationships among the different phenotypes of Streptococcus dysgalactiae strains.

The species Streptococcus dysgalactiae was proposed to accommodate a heterogeneous group of streptococci associated with infections in animals and human beings. This taxon is now considered to include animal isolates of alpha-haemolytic group C streptococci, previously called S. dysgalactiae; animal and human isolates of beta-haemolytic group C streptococci, previously called 'S. equisimilis'; beta-haemolytic group L strains associated with infections in animals and, rarely, in humans; and beta-haemolytic group G strains isolated from humans. DNA-DNA reassociation experiments (hydroxyapatite method) and multilocus enzyme electrophoresis (MEE) were performed on reference strains and clinical isolates to determine the genetic relationships among these different phenotypic categories. DNA-DNA hybridization tests showed that they were related at the species level, despite the phenotypic and host heterogeneity. Both genotypic and phenotypic characterization indicated that S. dysgalactiae could be separated into two major sub-groups. The first sub-group contained alpha-haemolytic strains that showed levels of DNA relatedness with the type strain of S. dysgalactiae ranging from 84 to 90% and from 82 to 88% under optimal (55 degrees C) and stringent (70 degrees C) conditions, respectively. The second sub-group contained beta-haemolytic strains showing levels of relatedness ranging from 71 to 79% (55 degrees C) and from 62 to 73% (70 degrees C). Percentage divergence varied from 0.5 to 1.0% (alpha-haemolytic group) and from 2.0 to 3.5% (beta-haemolytic group). A dendrogram based on phenotypic similarity between the enzyme bands produced by MEE showed a Jaccard similarity coefficient of 0.45 between the subclusters formed by the two sub-groups. The results of phenotypic and genotypic characterization were consistent with a published proposal to divide S. dysgalactiae into two subspecies, S. dysgalactiae subsp. dysgalactiae and S. dysgalactiae subsp. equisimilis, with a few modifications.

Animals↗
PubMed1998

A practical target system for accelerator-based BNCT which may effectively double the dose rate.

A dose-limiting component of a proton accelerator-based source of epithermal neutrons is the neutron production target. Possible targets are lithium, producing high yield but having low melting point and thermal conductivity, and beryllium, presenting less engineering problems but a much smaller neutron yield. We propose that a hybrid Be-Li target would provide the best of both worlds, with the upstream beryllium component producing neutrons and providing containment to the lithium, and the downstream liquid lithium in turn producing further neutrons as well as cooling the beryllium. The engineering considerations associated with such a target system are within the range of current technology. Calculations suggest a yield of such a practical target that is at least double that from pure beryllium.

Beryllium↗
PubMed1998

First report of a human isolate of Erwinia persicinus.

Erwinia persicinus was first described in 1990 after being isolated from a variety of fruits and vegetables, including bananas, cucumbers, and tomatoes. In 1994, it was shown to be the causative agent of necrosis of bean pods. We now report the first human isolate of E. persicinus. The strain was isolated from the urine of an 88-year-old woman who presented with a urinary tract infection. By the hydroxyapatite method, DNA from this strain was shown to be 94.5% related at 60 degrees C and 86% related at 75 degrees C to the type strain of E. persicinus. The biochemical profile of E. persicinus is most similar to those of Erwinia rhapontici, Pantoea agglomerans, and Enterobacter species. It is negative in tests for lysine, arginine, ornithine, dulcitol, and urea. It is motile and positive in tests for D-sorbitol and sucrose. It is susceptible to the expanded-spectrum cephalosporins, aminoglycosides, and fluoroquinolones, but it is resistant to ampicillin, ticarcillin, and cefazolin.

Aged↗
PubMed1998

Cat scratch disease: the rare role of Afipia felis.

Since its isolation in 1988, Afipia felis has been associated with cat scratch disease (CSD) in only one report and its role in CSD has been questioned. We have cultured A. felis from a lymph node of a patient with CSD. 16S rRNA gene sequencing, DNA relatedness studies, fatty acid analysis, and PCR of the A. felis ferredoxin gene showed that the isolate is identical to the previously reported A. felis isolate. To determine the role of A. felis in CSD, PCR of the 16S rRNA gene followed by hybridizations with specific probes were performed with lymph node specimens from CSD patients. All 32 specimens tested positive for Bartonella henselae and negative for A. felis. We conclude that A. felis is a rare cause of CSD. Diagnostic tests not conducive to the identification of A. felis might cause the diagnosis of CSD due to A. felis to be missed.

Adult↗
PubMed1998

The linear-quadratic model and most other common radiobiological models result in similar predictions of time-dose relationships.

One of the fundamental tools in radiation biology is a formalism describing time-dose relationships. For example, there is a need for reliable predictions of radiotherapeutic isoeffect doses when the temporal exposure pattern is changed. The most commonly used tool is now the linear-quadratic (LQ) formalism, which describes fractionation and dose-protraction effects through a particular functional form, the generalized Lea-Catcheside time factor, G. We investigate the relationship of the LQ formalism to those describing other commonly discussed radiobiological models in terms of their predicted time-dose relationships. We show that a broad range of radiobiological models are described by formalisms in which a perturbation calculation produces the standard LQ relationship for dose fractionation/protraction, including the same generalized time factor, G. This approximate equivalence holds not only for the formalisms describing binary misrepair models, which are conceptually similar to LQ, but also for formalisms describing models embodying a very different explanation for time-dose effects, namely saturation of repair capacity. In terms of applications to radiotherapy, we show that a typical saturable repair formalism predicts practically the same dependences for protraction effects as does the LQ formalism, at clinically relevant doses per fraction. For low-dose-rate exposure, the same equivalence between predictions holds for early-responding end points such as tumor control, but less so for late-responding end points. Overall, use of the LQ formalism to predict dose-time relationships is a notably robust procedure, depending less than previously thought on knowledge of detailed biophysical mechanisms, since various conceptually different biophysical models lead, in a reasonable approximation, to the LQ relationship including the standard form of the generalized time factor, G.

Brachytherapy↗
PubMed1997

Pulsed-dose-rate brachytherapy: design of convenient (daytime-only) schedules.

PURPOSE: To design pulsed-brachytherapy (PDR) protocols that are expected to be at least as clinically efficacious (in terms of both tumor control and late sequelae) as continuous low-dose-rate (CLDR) regimens, but that involve irradiation only during extended office hours. Both interstitial and intracavitary brachytherapy protocols are considered. METHODS AND MATERIALS: The linear quadratic formalism was used in which the late normal tissue damage and tumor control for one protocol relative to another are assumed to be determined primarily by the level of cellular survival. PDR schedules were designed in which pulses are delivered during "extended office hours" (8 A.M. to 8 P.M.) with no irradiation overnight. Generally, the proposed PDR regimes last the same number of treatment days as the corresponding CLDR regimen, but the PDR treatment lasts longer on the final day (i.e., until 8 P.M.). PDR doses were calculated such as to produce a tumor control which is equivalent to standard CLDR protocols, and the corresponding predicted late complication rate was compared with that for CLDR. Ranges of plausible values for the half-times of sublethal damage repair for tumors and for late-responding normal tissues were considered. RESULTS: As has been previously shown, the efficacy of PDR relative to CLDR depends considerably on the repair rates for sublethal damage repair. Clinical and experimental evidence suggests that average repair half-times for early effects (e.g., tumor control) are less than about a half hour, and for late sequelae are more than about an hour. If these estimates are correct, daytime PDR regimes can usually be designed which take the same number of days as the corresponding CLDR regimen, but have comparable or better therapeutic ratios than CLDR. CONCLUSION: Protocols for PDR can be designed to involve irradiation only during extended office hours, that are likely to result in clinical results comparable or better than CLDR, for any expected combination of the repair half-times of early- and late-responding tissues. The suggested protocols allow all of the advantages of a computerized remote-controlled afterloader while preserving the benefits of low dose rate. In addition, the protocols could allow the patient to go home overnight, or to stay overnight in an adjacent medical inn or hospital-associated hotel, rather than in a hospital bed-which could have major economic benefits. In such an economic situation, an extra treatment day for the daytime PDR could well be considered, which would virtually guarantee an improved clinical advantage relative to CLDR.

Brachytherapy↗
PubMed1997

Pulsed brachytherapy as a substitute for continuous low dose rate: an in vitro study with human carcinoma cells.

PURPOSE: Pulsed dose rate (PDR) brachytherapy as a substitute for continuous low dose rate (CLDR) has the potential to be a useful option in brachytherapy. However, the frequency and duration of pulses that will produce results practically equivalent to CLDR is still an open and important question. This study was designed to compare the survival of human tumor cells, cultured in vitro, and exposed to continuous or pulsed irradiation where the pulse frequency was varied. METHODS AND MATERIALS: Three different human carcinoma cells, derived from cervical and breast cancers, were exposed to CLDR gamma rays, or to pulsed irradiations with the same overall dose rate. Pulsed regimens used were 3.8 min every hour, 7.6 min every 2 h, 11.4 min every 3 h, 15.2 min every 4 h, 22.8 min every 6 h, and 45.6 min every 12 h. For each comparison between CLDR and PDR, the overall dose and the overall time were the same. Experimental design was such that significant differences in biological effectiveness, if present, would be detected. RESULTS: For the cell lines investigated, hourly pulses resulted in cell survival indistinguishable from CLDR. However, as the pulse interval was increased, cell survival progressively decreased compared with CLDR, and the pulsed regimes were no longer equivalent to continuous low dose rate. CONCLUSIONS: This study provides some evidence to support the suggestion that a 10-min pulse, repeated every 1 to 2 h, would be functionally equivalent to a continuous low dose rate irradiation, at least in terms of early responding endpoints. Longer intervals between pulses might result in loss of equivalence in some cases.

Brachytherapy↗
PubMed1997

A cluster of atypical Yersinia strains with a distinctive 16S rRNA signature.

Thirty-eight bacterial isolates from raw milk samples in Queensland, Australia were identified as members of the genus Yersinia on the basis of biochemical profile, ability to hybridize with a genus-specific DNA probe, comparative 16S rDNA sequence analysis, and the presence of characteristic 16S rDNA signature nucleotides which occur in all Yersinia spp. Twenty-five of these isolates reacted with typing sera (O:22 or O:58) of Y. enterocolitica; the remainder were non-typable. None of the isolates displayed any of the phenotypic or genetic virulence-associated characteristics of Y. enterocolitica. Comparative 16S rDNA sequence analysis revealed that members of this group appear to represent a new sub-line within the genus Yersinia, most closely related to Y. frederiksenii hybridization group 2 (unnamed genomospecies 2). This findings was confirmed by DNA hybridization studies which indicated that the strains belonged to the unnamed genomospecies, Yersinia frederiksenii genomospecies 2, which is biochemically indistinguishable from Y. frederiksenii (Y. frederiksenii genomospecies 1). A 23-nucleotide 16S rDNA signature stretch which characterised these strains was identified.

Animals↗
PubMed1997

Radiation biology in brachytherapy.

The biological rationale for the use of brachytherapy, which is undergoing a significant resurgence in the United States, is reviewed with emphasis on low dose rate (LDR brachytherapy). Some of the newer alternatives that have recently been developed, such as pulsed dose rate (PDR) brachytherapy, are discussed.

Brachytherapy↗
PubMed1997

The link between low-LET dose-response relations and the underlying kinetics of damage production/repair/misrepair.

PURPOSE: To review current opinion on the production and temporal evolution of low-LET radiobiological damage. METHODS: Standard cell survival models which model repair/misrepair kinetics in order to quantify dose-response relations and dose-protraction effects are reviewed and interrelated. Extensions of the models to endpoints other than cell survival, to multiple or compound damage processing pathways, and to stochastic intercellular damage fluctuations are surveyed. Various molecular mechanisms are considered, including double strand breaks restitution and binary misrepair. CONCLUSIONS: (1) Linking dose-response curves to the underlying damage production/processing kinetics allows mechanistic biological interpretations of observed curve parameters. (2) Various damage processing pathways, with different kinetics, occur. (3) Almost every current kinetic model, whether based on binary misrepair or saturable repair, leads at low or intermediate doses to the LQ (linear-quadratic) formalism, including the standard (generalized Lea-Catcheside) dependence on dose protraction. (4) Two-track (beta) lethal damage is largely due to dicentric chromosome aberrations, but one-track (alpha) lethal damage is largely caused by other mechanisms such as point mutations in a vital gene, small deletions, residual chromosome breaks, induced apoptosis, etc. (5) A major payoff for 50 years of radiobiological modelling is identifying molecular mechanisms which underly the broadly applicable LQ formalism.

Animals↗
PubMed1997

Review: proximity effects in the production of chromosome aberrations by ionizing radiation.

After ionizing radiation has induced double-strand DNA breaks (dsb), misrejoining produces chromosome aberrations. Aberration yields are influenced by "proximity' effects, i.e., by the dependence of misrejoining probabilities on initial dsb separations. We survey proximity effects, emphasizing implications for chromosome aberration-formation mechanisms, for chromatin geometry, and for dose-response relations. Evidence for proximity effects comes from observed biases for centric rings and against three-way interchanges, relative to dicentrics or translocations. Other evidence comes from the way aberration yields depend on radiation dose and quality, tightly bunched ionizations being relatively effective. We concludes (1) that misrejoining probabilities decrease as the distance between dsb at the time of their formation increases, and almost all misrejoining occurs among dsb initially separated by < 1/3 of a cell nucleus diameter; (2) that chromosomes occupy (irregular) territories during the G0/G1 phase of the cell cycle, having dimensions also roughly 1/3 of a cell nucleus diameter, (3) that proximity effects have the potential to probe how much different chromosomes intertwine on move relative to each other: and (4) that incorporation of proximity effects into the classic random breakage-and-reunion model allows quantitative interrelation of yields for many different aberration types and of data obtained with various FISH painting methods or whole-genome scoring.

Chromosome Aberrations↗
PubMed1997

Aerococcus urinae: intraspecies genetic and phenotypic relatedness.

A number of Aerococcus-like organisms were recently recognized as human pathogens. Five Aerococcus-like strains were proposed as members of the new species Aerococcus urinae (with type strain E2 [= NCTC 12142]) on the basis of the results of a 16S rRNA sequence analysis. The intraspecies phenotypic and genetic relatedness of 22 selected A. urinae strains was investigated, and a hitherto unrecognized esculin hydrolysis-positive biotype was identified. A total of 14 of the 15 more common esculin-negative strains exhibited very high DNA relatedness as determined by the hydroxyapatite method (the levels of relatedness were greater than 90% in 55 and 70 degrees C reactions, with 1.5% or less divergence in related sequences). The DNA relatedness among the six esculin-positive strains was more heterogeneous, and two DNA hybridization subgroups were formed. Our results are compatible with the hypothesis that both biotypes are members of the single species A. urinae, which contains two or more genetic subspecies. The putative subspecies have not been formally proposed since they cannot be definitively differentiated. The inclusion of A. urinae in the genus Aerococcus is supported by the results of 16S rRNA sequencing. The rRNA sequence data also is compatible with placing both biotypes in a single species.

Bacteriological Techniques↗
PubMed1997

Phenotypic and genotypic characterization of Vagococcus fluvialis, including strains isolated from human sources.

This study presents phenotypic and genotypic data for seven isolates of Vagococcus fluvialis, including four strains recovered from human clinical sources, one strain isolated from an environmental source, and two strains isolated from pigs. On the basis of phenotypic characteristics, most isolates were initially classified as "unidentified enterococci," because they resembled atypical arginine-negative enterococcal species. All seven strains as well as the type strain of V. fluvialis reacted with the AccuProbe Enterococcus genetic probe. The seven isolates had virtually indistinguishable whole-cell protein profiles that were similar to that of the V. fluvialis type strain and distinct from those of Enterococcus and Lactococcus species. DNA-DNA reassociation experiments confirmed that the strains were V. fluvialis. They were 71% or more related to the V. fluvialis type strain under optimum and stringent conditions, with 2.5% or less divergence within related sequences. All strains were susceptible to ampicillin, cefotaxime, trimethoprim-sulfamethoxazole, and vancomycin and were resistant to clindamycin, lomefloxacin, and ofloxacin. Strain-to-strain variation was observed in relation to susceptibilities to 18 other antimicrobial agents. Chromosomal DNA was analyzed by pulsed-field gel electrophoresis (PFGE) after digestion with SmaI. Distinctive PFGE patterns were generated, suggesting the nonclonal nature of V. fluvialis strains. Although the number of strains was small, this report provides molecular characterization of V. fluvialis and the first evidence of a possible connection of this species with human infections.

Animals↗