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R Cox

Publications and source records attributed to R Cox.

At least 37 records · Page 2Linked to original sources
PubMed2001

The Rhodobacter capsulatus genome.

The genome of Rhodobacter capsulatus has been completely sequenced. It consists of a single chromosome containing 3.5 Mb and a circular plasmid of 134 kb. This effort, started in 1992, began with a fine-structure restriction map of an overlapping set of cosmids that covered the genome. Cosmid sequencing led to a gapped genome that was filled by primer walking on the chromosome and by using lambda clones. Methods had to be developed to handle strong stops in the high GC (68%) inserts. Annotation was done with the ERGO system at Integrated Genomics, as was the reconstruction of the cell's metabolism. It was possible to recognize 3709 orfs of which functional assignments could be made with high confidence to 2392 (65%). Unusual features include the presence of numerous cryptic phage genomes embedded in the chromosome.

Journal Article↗
PubMed2001

Undiagnosed macroscopic haematuria revisited: a follow-up of 146 patients.

OBJECTIVE: To further investigate a group of patients with macroscopic haematuria who had no abnormalities on upper tract imaging and cystoscopy, to determine the appropriate follow up. PATIENTS AND METHODS: The hospital notes of patients who presented with frank haematuria between 1990 and 1998 and had no abnormality on cystoscopy and/or upper tract imaging were reviewed, with particular note made of any further bleeding or any other further urological problems. Those with < 2 years of follow-up in the hospital notes were investigated by telephone or via their general practitioner to ensure that all patients had at least 2 years of follow-up after the initial investigation. RESULTS: Of the 146 patients in the study, 98 were alive and had no more bleeding after the initial investigation. None of them were found to have renal or urothelial tumours during the follow-up. Thirty-three patients had recurrent episodes of bleeding after the initial investigation; 26 of these had repeat investigations and one was found to have a renal pelvic transitional cell carcinoma on repeat intravenous urography. One patient in this subgroup had died from a subarachnoid haemorrhage; 15 other patients had died, 13 of non-urological causes and two of unknown causes. CONCLUSIONS: Of 146 patients with undiagnosed macroscopic haematuria, only one had a missed tumour and this was detected on further investigation for recurrent bleeding. These results confirm that repeat cystoscopy and upper tract imaging is only warranted in patients who have recurrent bleeding after initial investigation.

Cystoscopy↗
PubMed2001

In utero haemopoietic sensitivity to alpha, beta or X-irradiation in CBA/H mice.

PURPOSE: To assess in utero sensitivity to x-rays, alpha-emissions from plutonium-239 and beta-emissions from tritium in terms of induction of chromosomal aberrations in bone marrow cells. MATERIALS AND METHODS: CBA/H mice were exposed to a single dose of X-rays (0.5Gy) on either day 7 or day 14 of pregnancy or given (239)Pu (100 kBq kg(-1)) by intraperitoneal injection on either day 6 or day 13. Tritium was administered to mice throughout pregnancy as either tritiated water, ad libitum in drinking water (total intake averaged 130 MBq), or as homogenized tritiated cress, administered by gastric intubation (total 60 MBq). Irradiated and unexposed control mice and their offspring were sacrificed at 2-8 weeks after birth. Direct metaphase preparations from femoral bone marrow cells from mothers and offspring were used for G-band analysis. RESULTS: The incidence of stable aberrations was significantly and similarly increased in neonatal and maternal marrow samples after exposure to X-rays, (239)Pu or (3)H. The estimated average bone absorbed doses from (239)Pu in pregnant females were similar to the X-ray dose of 0.5 Gy, suggesting a low RBE for alpha-irradiation in adults. The similar levels of damage observed in neonates after X-irradiation and 239Pu exposure are indicative of greater in utero sensitivity to alpha-irradiation since the overall estimated in utero alpha-particle doses to haemopoietic tissue were much lower. In utero doses from (3)H and corresponding maternal doses were around 0.5Gy, showing no evidence of greater in utero sensitivity, no significant difference between the effects of the two forms of tritium, and were consistent with an RBE value of 1-2. CONCLUSIONS: Comparison of stable aberration yields in haemopoietic cells suggests a greater sensitivity to alpha-particles from (239)Pu than X-rays or beta-particles from (3)H for irradiation in utero but a low RBE value in adults.

Age Factors↗
PubMed2001

Telomeric sequences, radiation sensitivity and genomic instability.

PURPOSE: To review the basic features of telomeres with particular emphasis on their potential importance in radiation biology. Recent findings suggest that telomere length can influence radiation sensitivity in mouse and that several human radiosensitive disorders also show abnormalities in telomere dynamics. Numerous studies indicate that telomeric sequences may play a role in determining the stability of certain genomic regions both spontaneously and following irradiation. Furthermore, a number of transmissible genomic instability systems have been described in which it appears that telomere metabolism may be contributing to the delayed effects observed. Features of telomeres and telomere biology relevant to these topics are reviewed. CONCLUSIONS: The evidence that telomeres and the molecular pathways of telomere maintenance can play a role in determining the outcome of radiation exposure is now substantial. Thus, the field of telomere biology deserves continued attention from radiobiologists.

Animals↗
PubMed2001

Resolving the molecular mechanisms of radiation tumorigenesis: past problems and future prospects.

Major goals in experimental radiobiology continue to be the resolution of the fundamental mechanisms of cellular radiation response and to gain detailed understanding of the contribution made by these responses to the complex in vivo processes of tumor development. The coupling of this framework of fundamental knowledge to epidemiological measures of risk greatly strengthens the biological basis of radiological protection. A selective overview is provided of recent advances in the understanding of the mechanisms and genetics of radiation tumorigenesis and their possible implications. It is suggested that rapid technical and academic advances in biology greatly expand the opportunities to further refine scientific knowledge on tumor risk after radiation.

Animals↗
PubMed2001

Swallow-related cerebral cortical activity maps are not specific to deglutition.

Cortical representation of swallow-related motor tasks has not been systematically investigated. In this study, we elucidated and compared these cortical representations to those of volitional swallow using block-trial and single-trial methods. Fourteen volunteers were studied by functional magnetic resonance imaging. Cortical activation during both swallowing and swallow-related motor tasks that can be performed independent of swallowing, such as jaw clenching, lip pursing, and tongue rolling, was found in four general areas: the anterior cingulate, motor/premotor cortex, insula, and occipital/parietal region corresponding to Brodmann's areas 7, 19, and 31. Regions of activity, volume of activated voxels, and increases in signal intensity were found to be similar between volitional swallow and swallow-related motor tasks. These findings, using both block-trial and single-trial techniques, suggest that cerebral cortical regions activated during swallowing may not be specific to deglutitive function.

Adult↗
PubMed2001

Lack of detectable transmissible chromosomal instability after in vivo or in vitro exposure of mouse bone marrow cells to 224Ra alpha particles.

Several studies over recent years have highlighted the possibility that radiation can induce transmissible genomic instability. Most of these involve in vitro irradiation and usually in vitro culture. Here it is reported that the short-half-life bone-seeking alpha-particle emitter (224)Ra did not induce excess transmissible chromosomal instability in CBA/H mouse bone marrow cells in a 100-day period after in vivo or in vitro exposure. Similarly, no excess transmissible chromosomal instability could be detected after in vivo whole-body X irradiation. It was noted, however, that short-term culture of murine bone marrow cells elevated yields of aberrations, as did transplantation of untreated marrow into radiation-ablated hosts. These findings emphasize the sensitivity of murine hemopoietic tissue to experimental manipulation and reinforce the importance of appropriate concurrent control experiments in any investigation of transmissible genomic instability.

Alpha Particles↗
PubMed2001

221st ACS. Division of Medicinal Chemistry - first-time disclosure of clinical candidates.

The 221st ACS meeting in San Diego, USA, saw a symposium entitled 'First-time disclosure of clinical candidates', the inaugural presentation of this symposium in the society's 125-year history. Dr Balu N Balasubramanian (Bristol-Myers Squibb Co, USA), Chair of this well-attended symposium of five papers, remarked that he hoped that this symposium will become a regular event at ACS conferences.

Journal Article↗
PubMed2000

A high-density genetic map of the chromosome 13q14 atopy locus.

Atopy describes a syndrome of immunoglobulin E (IgE)-mediated allergy that underlies asthma and infantile eczema. We have previously identified a locus on chromosome 13q14 that is linked to atopy and to the total serum immunoglobulin A concentration. We have therefore made a saturation genetic map of the region by typing 59 polymorphic microsatellite loci on chromosome 13q. Multipoint linkage analysis identified a 1-LOD support unit for the location of the atopy locus with a 7.5-cM region flanked by the loci D13S328 and D13S1269. The peak of linkage was at locus D13S161 with a nonparametric -log of P score of approximately 4.5. Parent of origin effects were present, with linkage primarily observed to paternally derived alleles. The genetic map of this region provides a basis for the effective identification of the chromosome 13 atopy gene.

Adolescent↗
PubMed2000

A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse.

We have studied the efficiency of DNA double strand break (DSB) rejoining in primary cells from mouse strains that show large differences in in vivo radiosensitivity and tumor susceptibility. Cells from radiosensitive, cancer-prone BALB/c mice showed inefficient end joining of gamma ray-induced DSBs as compared with cells from all of the other commonly used strains and F1 hybrids of C57BL/6 and BALB/c mice. The BALB/c repair phenotype was accompanied by a significantly reduced expression level of DNA-PKcs protein as well as a lowered DNA-PK activity level as compared with the other strains. In conjunction with published reports, these data suggest that natural genetic variation in nonhomologous end joining processes may have a significant impact on the in vivo radiation response of mice.

Animals↗
PubMed2000

Loss of heterozygosity in spontaneous and X-ray-induced intestinal tumors arising in F1 hybrid min mice: evidence for sequential loss of APC(+) and Dpc4 in tumor development.

Min (multiple intestinal neoplasia) mice carry a mutant allele of the murine Apc (adenomatous polyposis coli) locus and are predisposed to intestinal adenoma formation in the intestinal tract. Early studies have shown complete loss of function of Apc by whole chromosome loss on the tumor-sensitive C57BL/6J genetic background and in AKR x B6 F1 hybrids. Gamma-radiation-induced chromosomal losses focus the critical region on wt Apc, but because of the limited number of polymorphic markers used, no other critical regions of loss on chromosome 18 were identified. Using intestinal tumors arising spontaneously and induced by X-rays in CBA/H x C57BL/6J F1 hybrid mice and high-resolution microsatellite loss of heterozygosity (LOH) techniques, we provide mapping data for wt Apc loss, which confirms and extends earlier observations. In addition, high-frequency loss events at the Dpc4 locus were found in both spontaneous and radiation-induced tumors. These data identified LOH of Dpc4 as a critical secondary event following complete functional loss of Apc. LOH across the Trp53 genomic region of chromosome 11 was not observed. No LOH was recorded for the Mom1 candidate gene Pla2g2a or for 9 out of 10 polymorphic markers from the Mom1 genomic region on murine chromosome 4. One marker mapping distal to Pla2g2a showed LOH in a small minority of spontaneous tumors. These data support the contention that Mom1 does not act as a classical tumor suppressor. Overall, our data indicates a significant role for Dpc4 mutation in intestinal tumor progression in the mouse and provides further evidence for the importance of interstitial chromosome losses in radiation tumorigenesis.

Animals↗
PubMed2000

Metacarpal morphometry using a semi-automated technique in the assessment of osteoporosis and vertebral fracture risk.

Metacarpal morphometry represents a potentially cheap and widely available non-invasive assessment of skeletal status. In two cross-sectional studies, we compared the performance characteristics of a semiautomated technique (the Teijin Bonalyzer) with an in-house manual measurement, and with measures of skeletal strength at other sites. The metacarpal cortical index (mCI) was measured on hand radiographs of 178 osteoporotic women using both the Teijin Bonalyzer and a digitizing tablet. Measurements on the latter were consistently lower than with the Bonalyzer except for mCI (0.443+/-0.080 vs 0.364+/-0.060, p<0.001), although correlation coefficients between these two methods were highly significant (r = 0.62-0.83, p<0.001). The reproducibility errors of metacarpal bone mineral density (mBMD) were constant (1.1-1.2%) whilst those for mCI showed a marked operator-dependency (2.0-7.9%). In 379 elderly community-dwelling women, Bonalyzer mCI and mBMD showed a significant decline with age (r = -0.30 and -0.27 respectively, p<0.05). Both mCI and mBMD correlated significantly with forearm BMD (r = 0.50 and 0.57 respectively, p<0.001) and hip BMD (r = 0.48 and 0.53 respectively, p<0.001). After adjustment for age and weight, hip BMD demonstrated the best discrimination for prevalent vertebral fractures as judged by the gradient of risk for a 1 SD decrease in measurement (odds ratio (OR) 2.17, 95% CI 1.56-3.01). Similar but smaller gradients of risk were shown by Bonalyzer mCI (OR 1.32, 95% CI 1.00-1.75), mBMD (OR 1.35, 95% CI 1.02-1.78) and forearm BMD (OR 1.39, 95% CI 1.08-1.80). MCI, and in particular mBMD, may be useful assessments of bone mass and fracture risk. In our study, it is comparable to peripheral assessment of skeletal status by forearm densitometry.

Absorptiometry, Photon↗
PubMed2000

Evidence for Msh2 haploinsufficiency in mice revealed by MNU-induced sister-chromatid exchange analysis.

The role of Msh2 in chromosome stability has been investigated in a targeted mouse model for HNPCC, Msh2Delta7N. Chromosome aberration frequencies were similar in bone marrow of Msh2(+/+), Msh2(+/-)and Msh2(-/-)mice and no differential effects of in vivo X-irradiation were noted. By contrast, the induction of sister-chromatid exchanges (SCEs) by methyl nitrosourea (MNU) was reduced in Msh2(-/-)and Msh2(+/-)cells to approximately 20% and approximately 45% wild-type levels respectively indicating a phenotypic effect of haploinsufficiency of the mouse Msh2 gene.

Animals↗