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D J Brenner

Publications and source records attributed to D J Brenner.

At least 91 records · Page 5Linked to original sources
PubMed1997

A new agent of mycobacterial lymphadenitis in children: Mycobacterium heidelbergense sp. nov.

Nontuberculous mycobacterial lymphadenitis presents an increasing clinical problem in immunocompetent young children. A slowly growing, nonphotochromogenic mycobacterium was recovered twice (isolates 2553/91 and 2554/91) from the lymphatic tissue of a child with recurrent cervical lymphadenitis. It could be differentiated biochemically from described Mycobacterium species, although it most closely resembled Mycobacterium malmoense by thin-layer chromatography and high-performance liquid chromatography of mycolic acids. A striking characteristic of the isolate was its high degree of susceptibility to antituberculous drugs in vitro, including isoniazid. Direct determination of the 16S rRNA gene sequence revealed a unique sequence and positioned the strain phylogenetically on a branch separate from M. malmoense within a group of slowly growing mycobacteria that show a high degree of similarity to M. simiae at the 16S rRNA gene level. Despite 99.6% sequence identity with M. simiae at the 16S rRNA gene level, DNA-DNA hybridization studies (hydroxyapatite method) demonstrated DNA relatedness of less than 40%. We conclude that this organism is a new species for which we propose the name M. heidelbergense. A culture of the type strain, strain 2554/91, has been deposited in the American Type Culture Collection as strain ATCC 51253.

Antitubercular Agents↗
PubMed1997

Bartonella clarridgeiae, a newly recognized zoonotic pathogen causing inoculation papules, fever, and lymphadenopathy (cat scratch disease).

Shortly after adopting a 6-week-old cat, a veterinarian was bitten on the left index finger. Within 3 weeks, he developed headache, fever, and left axillary lymphadenopathy. Initial blood cultures from the cat and veterinarian were sterile. Repeat cultures from the cat grew Bartonella-like organisms with lophotrichous flagella. Sera from the veterinarian were not reactive against Bartonella henselae, B. quintana, or B. elizabethae antigens but were seroreactive (reciprocal titer, 1,024) against the feline isolate. Sequential serum samples from the cat were reactive against antigens of B. henselae (titer, 1,024), B. quintana (titer, 128), and the feline isolate (titer, 2,048). Phenotypic and genotypic characterization of this and six additional feline isolates, including microscopic evaluation, biochemical analysis, 16S rRNA gene sequencing, DNA-DNA hybridization, and PCR-restriction fragment length polymorphism of the 16S gene, 16S-23S intergenic spacer region, and citrate synthase gene identified the isolates as B. clarridgeiae. This is the first report of cat scratch disease associated with B. clarridgeiae.

Animals↗
PubMed1997

Intra-arm and interarm chromosome intrachanges: tools for probing the geometry and dynamics of chromatin.

Many chromosome-type, exchange-type chromosomal aberrations produced by radiation are intrachanges, i.e. involve only one chromosome. It is assumed such intrachanges are formed by illegitimate reunion of two double-strand breaks (DSBs) on the chromosome. The yield of intra-arm intrachanges (acentric rings or paracentric inversions) relative to that of interarm intrachanges (centric rings or pericentric inversions) is larger than would occur if production and illegitimate reunion of DSBs were spatially random. The excess of intra-arm intrachanges is presumably due to proximity effects for illegitimate reunions, i.e. enhancement of the intrachange probability when two DSBs are formed close to one another. Radiation track structure may also play a role. Using a polymer description for "large-scale" chromatin geometry (>2 Mb), and using two alternate (rapid or slow motion) models for the way that DSBs move after they are produced, theoretical estimates are given for size distributions of intrachanges at low or high linear energy transfer (LET). The ratio of intra-arm to interarm intrachanges is derived from the size distribution and compared with data from the literature on centric rings, inversions, interstitial deletions and excess acentric fragments. Proximity effects enhance yields of intra-arm relative to interarm intrachanges at least severalfold and perhaps as much as 10-fold compared to expectations based on spatial randomness. We argue that further measurements of intra-arm and interarm intrachanges would be informative about large-scale chromatin structure and chromosome motion. Because inversions are more frequent than estimates of randomness would indicate, and are transmissible to daughter cells, their size distribution could also help characterize past exposure to high-LET radiation.

Chromatin↗
PubMed1997

Computer simulation of data on chromosome aberrations produced by X rays or alpha particles and detected by fluorescence in situ hybridization.

With fluorescence in situ hybridization (FISH), many different categories of chromosome aberrations can be recognized-dicentrics, translocations, rings and various complex aberrations such as insertions or three-way interchanges. Relative frequencies for the various aberration categories indicate mechanisms of radiation-induced damage and reflect radiation quality. Data obtained with FISH support a proximity version of the classic random breakage-and-reunion model for the formation of aberrations. A Monte Carlo computer implementation of the model, called the CAS (chromosome aberration simulator), is generalized here to high linear energy transfer (LET) and compared to published data for human cells irradiated with X rays or 238Pu alpha particles. For each kind of radiation, the CAS has two adjustable parameters: the number of interaction sites per cell nucleus and the number of reactive double-strand breaks (DSBs) per gray. Aberration frequencies for various painted chromosomes, of varying lengths, and for 11 different categories of simple or complex aberrations were simulated and compared to the data. The optimal number of interaction sites was found to be approximately 13 for X irradiation and approximately 25 for alpha-particle irradiation. The relative biological effectiveness (RBE) of alpha particles for the induction of reactive DSBs (which are a minority of all DSBs) was found to be approximately 4. The two-parameter CAS model adequately matches data for many different categories of aberrations. It can use data obtained with FISH for any one painting pattern to predict results for any other kind of painting pattern or whole-genome staining, and to estimate a suggested overall numerical damage indicator for chromosome aberration studies, the total misrejoining number.

Alpha Particles↗
PubMed1996

The radiobiology of intravascular irradiation.

PURPOSE: There is increasing interest in the use of vascular irradiation, from an internally introduced radioactive source to control restenosis after balloon angioplasty. Both animal experiments and early clinical studies appear to show promising results in this regard. We consider various mechanistic interpretations of the experimental and clinical observations that doses of 12-20 Gy appear to be efficacious in preventing restenosis. We develop and investigate simple models, both experimental and theoretical, of the kinetics of radiation-induced smooth muscle cell (SMC) inactivation and regrowth, as a first step toward optimizing the design of clinical vascular irradiation. METHODS AND MATERIALS: Using in vitro models of human SMCs, we investigate the relative radiosensitivity of SMCs compared with endothelial cells and measure the dose-dependent ability of SMCs to repopulate a denuded region in a confluent layer of cells. We then use quantitative information on the number, radiation sensitivity, and growth rate of the potential arterial target cells to model the time course of the SMC population after irradiation. RESULTS AND CONCLUSION: Doses >20 Gy, which would be required to completely eliminate the SMC population which has the potential to cause restenosis, are too large to be practical because of the unacceptable risk of late complications. However, doses that can be practically given in vascular irradiation (<20 Gy) will certainly delay restenosis by 1-3 years, with larger doses producing longer delays. Whether such doses can avert restenosis permanently is unclear, as permanent prevention at realistic doses depends critically on the assumption that those SMCs which survive irradiation have a significantly limited capacity for proliferation. With regard to current animal model experiments, routine follow-up of <1 year, which is standard practice, is probably too short to address some of the key mechanistic question in intravascular radiation therapy.

Angioplasty, Balloon, Coronary↗
PubMed1996

Quantitative comparisons of continuous and pulsed low dose rate regimens in a model late-effect system.

PURPOSE: There is increasing interest and usage of pulsed low dose rate (PDR) brachytherapy, in which a single source is shuttled through the catheters of an implant, typically for about 10 min each hour. This study was designed to compare the late effects produced in various PDR regimens with those from the corresponding continuous low dose rate (CLDR) regimens. METHODS AND MATERIALS: A model late-responding system was used, namely, cataract induction in the rat lens. This system has the advantage of being highly quantifiable. The rats eyes were exposed to a total dose of 15 Gy either continuously over 24 h, or with three different PDR regimens, all with the same total dose and overall time. We addressed three questions: (a) are late effects increased when a CLDR regimen is replaced with 10-min pulses repeated every hour? (b) Are late effects increased if hourly 10-min pulses are replaced with 10-min pulses repeated every 4 h? (c) Are late effects increased if 10-min pulses are replaced with 100-s pulses? RESULTS: We found that the four regimens under test, continuous, 10-min pulses each hour, 10-min pulses every 4 h, and 100-s pulses every hour, showed no significant differences in cataractogenic potential, as estimated with the Wilcoxon-Gehan test. Power tests indicated that the experimental design was adequate to detect relatively small differences in cataractogenicity between regimens. CONCLUSIONS: The equality of late effects from CLDR and PDR in these experiments must imply that sublethal damage repair is quite slow in this model late-responding system, in agreement with trends observed in the clinic for sublethal damage repair of late sequelae. Such trends would suggest that PDR is unlikely to produce significantly worse late effects than the corresponding CLDR regimen, which is in agreement with early clinical data using PDR. Caution, however, is strongly recommended.

Animals↗
PubMed1996

Dose timing in tumor radiotherapy: considerations of cell number stochasticity.

A typical tumor radiotherapy regimen using external beam X rays consists of doses on weekdays for 4-7 weeks. During the final weeks, the tumor may contain only a few cells capable of regenerating the tumor and may be growing exponentially between doses. Stochastic fluctuations of the cell number can influence the optimal time pattern of dose delivery. If the total dose is fixed, a deterministic model of exponential tumor growth, neglecting stochastic effects, predicts that the way the radiation dose is spread out in time does not affect the average number of tumor cells at the end. However, we here show, within the framework of a birth-death model, that when stochastics are taken into account, the earlier the dose is given (consistent with other constraints imposed by quite different considerations), the better. The proof uses a transformation that simplifies the characteristic equation of the partial differential equation governing the probability generating function for a birth-death process with time-dependent rates. The theorem that earlier is better holds for any statistical distribution of cell number from patient to patient at the start of the exponential growth phase and for virtually any cell-killing model. Numerical results indicate the stochastic effects, although not dominant, are not negligible.

Cell Count↗
PubMed1996

Interpretation of inverse dose-rate effects for mutagenesis by sparsely ionizing radiation.

An inverse dose-rate effect has sometimes been observed for mutagenesis in cells exposed to gamma-rays. We model such data quantitatively with the key assumption that the effect is caused in cycling cells by correlated variations in sensitivity across the cell cycle, for both mutation and killing. We quantify this approach using the LQR (linear-quadratic + resensitization) formalism, which describes the response to radiation of a heterogeneous cell population. This model is applied to an exponentially growing population. We compare its predictions with dose- and dose-rate dependent mutation data and show that it can well fit the observed inverse dose-rate effect, as well as providing an explanation of why inverse dose-rate effects have been seen in some experiments, but not in others. The actual values of the model parameters emerging from the analysis are reasonable in magnitude, based on their biological interpretations. We conclude that the LQR model can quantify cell-cycle redistribution effects without overparameterization, and that the data favour a correlation explanation of inverse dose-rate effects for mutagenesis by low-LET radiation. It is less clear that this explanation is appropriate to high-LET radiation-induced oncogenic transformation, although all potential explanations of inverse dose-rate effects predict that, at appropriately low doses, no dose-rate effects of any kind are expected.

Cell Cycle↗
PubMed1996

Proximity effects for chromosome aberrations measured by FISH.

A Monte Carlo simulation computer program for radiation-produced chromosome aberrations, based on the breakage-and-reunion model, was extended to include proximity effects due to localization of chromosomes and limited range for break-break interactions. Two adjustable parameters were used. One corresponds to total dose: the other determines proximity effects by specifying the number of 'interaction regions' in a cell nucleus. The use of additional adjustable parameters was avoided by assuming randomness of break induction and aberration production. FISH chromosome painting data were obtained from 1.9 Gy 60Co gamma-rays-irradiated human lymphocytes. The data were compared with the computer simulation results, taking individual chromosome lengths into account. With about 13 interaction regions, agreement between the experiment and the simulation was good, even when detailed categories of damage were scored. An estimated average dsb-dsb interaction distance, based on 13 interaction regions, is about 1.3 micron. Monte Carlo methods give useful quantitative estimates of relative aberration yields, with a minimum of adjustable parameters and the theoretical assumptions, and indicated proximity effects. Computer simulation of FISH experiments can be adapted to any number of colours, any scoring criteria and any method of grouping aberrations into categories. Simulation allows systematic extrapolation of aberration data on painted chromosomes to whole-genome aberration frequencies.

Chromosome Aberrations↗
PubMed1996

Emended description of Buttiauxella agrestis with recognition of six new species of Buttiauxella and two new species of Kluyvera: Buttiauxella ferragutiae sp. nov., Buttiauxella gaviniae sp. nov., Buttiauxella brennerae sp. nov., Buttiauxella izardii sp. nov., Buttiauxella noackiae sp. nov., Buttiauxella warmboldiae sp. nov., Kluyvera cochleae sp. nov., and Kluyvera georgiana sp. nov.

A total of 219 strains belonging to the genera Buttiauxella and Kluyvera were studied; 171 of these strains were isolated from mollusks, mainly snails and slugs, obtained from around the world. On the basis of DNA-DNA hybridization data, the strains were grouped into 11 genomospecies. A total of 44 phenotypic characters were used to differentiate the genera Buttiauxella and Kluyvera at the genus level and to identify genomospecies. There were significantly higher phenotypic probability distances between the genomospecies in the genus Battiauxella and the genomospecies in the genus Kluyvera than between the genomospecies in the same genus. Therefore, the existence of Buttiauxella and Kluyvera as different genera was confirmed. The existence of new species necessitated broadening the definitions of both genera. In two cases, Buttiauxella species could not be quantitatively differentiated biochemically, and several other pairs of species could be separated only by the results of one biochemical test. Nonetheless, combinations of several characteristics were used in differentiate all of the species with levels of certainly ranging from log 10.79 to log 57.77 (calculated as probability distances). The following new species are proposed: Buttiauxella ferragutiae (type strain, ATCC 51602 [DSM 9390]), Buttiauxella gaviniae (type strain, ATCC 51604 [DSM 9393]), Buttiauxella brennerae (type strain, ATCC 51605 [DSM 9396]), Buttiauxella izardii (type strain, ATCC 51606 [DSM 9397]), Buttiauxella noackiae (type strain, ATCC 51607 [DSM 9401]), Buttiauxella warmboldiae (type strain, ATCC 51608 [DSM 9404]), Kluyvera cochleae (type strain, ATCC 51609 [DSM 9406]), and Kluyvera georgiana (type strain, ATCC 51603 [DSM 9409]).

Animals↗
PubMed1996

Legionella waltersii sp. nov. and an unnamed Legionella genomospecies isolated from water in Australia.

Two Legionella-like organisms were isolated from water samples obtained in Adelaide, Australia. One organisms was isolated from a drinking water distribution system, and the other was isolated from a cooling tower at a sewage treatment plant. Both strains required L-cysteine for growth and contained cellular branched-chain fatty acids and ubiquinones typical of the genus Legionella. These strains were serologically distinct from each other as determined by a slide agglutination test. STrain 2074-AUS-ET (T = type strain) was serologically distinct from all previously described Legionella species and serotypes. Strain 2055-AUS-E could not be differentiated biochemically or serologically from Legionella quinlivanii. Both strains were shown by DNA hybridization studies (Hydroxyapatite method) to be members of new Legionella species. Legionella waltersii sp. nov. is the name proposed for strain 2074-AUS-ET (= ATCC 51914T). L. waltersii was less than 10% related to other Legionella species. Strain 2055-AUS-E (= ATCC 51913) was informally named Legionella genomospecies 1, since it could not be phenotypically distinguished from L. quinlivanii. Legionella genomospecies 1 was closely related to L. quinlivanii strains (53 to 69% related with 4.5 to 6.5% divergence at 60 degrees C and 31 to 52% related at 75 degrees C).

Agglutination Tests↗
PubMed1996

Phenotypic and genotypic characterization of atypical Lactococcus garvieae strains isolated from water buffalos with subclinical mastitis and confirmation of L. garvieae as a senior subjective synonym of Enterococcus seriolicida.

During a survey of bacterial agents that cause subclinical mastitis in water buffalos, we isolated several strains of gram-positive cocci that appeared to be enterococci except that they grew very slowly at 45 degrees C and grew slowly in broth containing 6.5% NaCl. On the basis of the results of conventional physiologic tests, these strains were identified as Enterococcus durans. However, none of the strains reacted with the AccuProbe Enterococcus genetic probe. The whole-cell protein profiles of these organisms were compared with the profiles of Enterococcus and Lactococcus reference strains. apart from minor quantitative differences, the mastitis isolates had indistinguishable protein profiles that were similar to the profiles of the Lactococcus garvieae and Enterococcus seriolicida type strains. The results of DNA relatedness studies performed by using the hydroxyapatite method at 55 and 70 degrees C indicated that all of the mastitis isolates were related to the type strain of L. garvieae at the species level, despite the fact that they exhibited several uncommon phenotypic characteristics (growth at 45 degrees C, growth in broth containing 6.5% NaCl, and failure to produce acid from mannitol and sucrose). The high levels of DNA relatedness between strains of L. garvieae is a senior synonym of E. seriolicida, L. garvieae should be retained as the species name and strain ATCC 43921 should remain the type strain of this species.

Animals↗
PubMed1996

Bartonella vinsonii subsp. berkhoffii subsp. nov., isolated from dogs; Bartonella vinsonii subsp. vinsonii; and emended description of Bartonella vinsonii.

Two bacterial strains, one isolated from the blood of a dog with valvular endocarditis and one isolated from the blood of a healthy dog, were similar to Bartonella species, as determined by a number of phenotypic criteria, including growth characteristics, biochemical reactions, and cell wall fatty acid composition. The results of 16S rRNA gene sequence similarity studies confirmed that these strains are closely related and belong in the genus Bartonella and that Bartonella vinsonii is their closest relative (the 16S rRNA of isolate 93-C01T [T = type strain] was 99.37% identical to the 16S rRNA of the type strain of B. vinsonii, the 16S rRNA of isolate G7464 was 99.61% identical to the 16S rRNA of the type strain, and the 16S rRNAs of the dog isolates were 99.77% identical to each other). The 16S rRNAs of both strains contained a 12-base insertion that was not present in the 16S rRNA of the type strain of any Bartonella species. DNA relatedness tests revealed that these strains were related at the species level to the type strain of B. vinsonii. They were, however, significantly more closely related to each other than to B. vinsonii. On the basis of their unique 16S rRNA sequence insertion, their preferentially high level of relatedness, and their similar origins (dogs), we believe that strains 93-C01(T) and G7464 should be placed in a separate subspecies of B. vinsonii, for which we propose the name B. vinsonii subsp. berkhoffii subsp. nov. The type strain of B. vinsonii subsp. berkhoffii is strain 93-C01 (= ATCC 51672). The description of B. vinsonii is emended to accommodate the new subspecies, and B. vinsonii subsp. vinsonii is described.

Animals↗
PubMed1996

Rapid identification of Campylobacter species by restriction fragment length polymorphism analysis of a PCR-amplified fragment of the gene coding for 16S rRNA.

Restriction fragment length polymorphism analysis of a PCR-amplified DNA fragment of the gene coding for 16S rRNA was performed on 148 previously characterized strains of Campylobacter, Helicobacter, Arcobacter, and Wolinella succinogenes and 13 Campylobacter-like isolates. These strains included clinical, animal, and environmental isolates. PCR amplification generated a 283-bp fragment from all species. The amplicon from each strain was digested with six restriction endonucleases (AccI, AvaI, DdeI, HaeIII, HpaII, XhoI). DdeI was useful for the initial grouping of the strains. Additional discrimination within the different DdeI groups was obtained with AccI, HaeIII, HpaII, and XhoI digestions. The PCR-restriction fragment length polymorphism analysis allowed for the discrimination of members of the genus Campylobacter from members of closely related genera and discrimination between Campylobacter species. The proposed method is simple and rapid and can be useful for the routine identification of Campylobacter-like organisms in clinical or epidemiologic studies.

Animals↗
PubMed1996

Direct biological evidence for a significant neutron dose to survivors of the Hiroshima atomic bomb.

In the past few years much physical evidence has accumulated that the A-bomb survivors at Hiroshima were exposed to significant doses of neutrons, in contrast to the predictions of the current DS86 dosimetry. We discuss some biological measurements of exchange-type chromosomal aberrations in survivors at Hiroshima, which also strongly imply that the survivors received a significant neutron dose. Specifically, the ratio of translocations (an interchromosomal aberration) to pericentric inversions (intrachromosomal interarm aberration), the F value, was significantly smaller than would be expected from a gamma-ray exposure, and was consistent with the majority of the effective dose coming from neutrons. If this biological evidence and the previous physical evidence are correct, the effective neutron dose at relevant locations at Hiroshima dominated the total effective dose, from which it may be concluded that (1) the risk coefficient for gamma rays may have been considerably overestimated, and (2) there is a possibility of deriving from the A-bomb data, with reasonable confidence limits, the relative biological effectiveness (RBE) for carcinogenesis by neutrons.

Chromosome Aberrations↗
PubMed1996

The biological effectiveness of radon-progeny alpha particles. V. Comparison of oncogenic transformation by accelerator-produced monoenergetic alpha particles and by polyenergetic alpha particles from radon progeny.

Generation of estimates of risk caused by exposure to radon in the home, either from miner data or from A-bomb data, requires several scaling factors such as for dose, dose rate and radiation quality, and possible synergisms. Such scaling factors are best developed from laboratory-based studies. Two possible sources of alpha particles for such studies are (1) a polyenergetic spectrum, generated directly by radon and its progeny, or (2) a series of monoenergetic alpha particles. We compare here the results of oncogenic transformation from studies using both systems. At the Columbia University Radiological Research Accelerator Facility (RARAF), C3H 10T1/2 cells were irradiated with alpha particles of various energies, with defined LETs from 70 to 200 keV/mum. At Pacific Northwest Laboratory, cells from the same stock were exposed to alpha particles from radon gas and its progeny, which were in equilibrium with the culture medium. There was good agreement between the results of oncogenic transformation experiments using the two different exposure systems. Apart from the experimental transformation frequencies themselves, such a comparison requires (1) reliable dosimetry at both facilities and (2) estimated LET distributions for the polyenergetic alpha-particle irradiator. Thus this good agreement gives some confirmation to the technique which is used to fold together oncogenic transformation rates from monoenergetic alpha particles to yield a predicted rate for a spectrum of alpha particles.

Alpha Particles↗