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R G Bristow

Publications and source records attributed to R G Bristow.

18 recordsLinked to original sources
PubMed2005

Radiotherapy and Marfan syndrome: a report of two cases.

Marfan syndrome (MFS) is a heritable disorder of the connective tissue which has been linked to mutations in the FBN (fibrillin-1) gene. Murine knockouts of the FBN gene show increased interstitial fibrosis and TGF-beta (tumor growth factor-beta) gene activation. Abnormal TGF-beta expression has previously been linked to radiation-induced fibrosis, suggesting a possible link between MFS and increased late effects following radiotherapy. Herein we report two cases in which MFS patients treated with radical radiotherapy without undue acute or late radiotherapy toxicity suggesting that radiotherapy should not be withheld from MFS patients. MFS patients may provide a unique clinico-translational setting to test associations between FBN mutations, TGF-beta activation and the risk of tissue fibrosis.

Adolescent↗
PubMed2003

Cell death in irradiated prostate epithelial cells: role of apoptotic and clonogenic cell kill.

Dose-escalated conformal radiotherapy is increasingly being used to radically treat prostate cancer with encouraging results and minimal long-term toxicity, yet little is known regarding the response of normal or malignant prostate cells to ionizing radiation (IR). To clarify the basis for cell killing during prostate cancer radiotherapy, we determined the IR-induced expression of several apoptotic- (bax, bcl-2, survivin and PARP) and G1-cell cycle checkpoint- (p53 and p21(WAF1/Cip1)) related proteins, in both normal (PrEC-epithelial and PrSC-stromal) and malignant (LNCaP, DU-145 and PC-3; all epithelial) prostate cells. For these experiments, we chose doses ranging from 2 to 10 Gy, to be representative of the 1.8-2 Gy daily clinical fractions given during curative radiotherapy and the 8-10 Gy single doses given in palliative radiotherapy. We observed that IR-induced bax and p21(WAF1/Cip1) protein expression were attenuated selectively in normal stromal and epithelial cell cultures, yet maintained their p53-dependency in malignant cell lines. For each cell culture, we also determined total apoptotic and overall radiation cell kill using a short-term nuclear morphologic assay and a long-term clonogenic survival assay, respectively. Clonogenic survival, as measured by the surviving fraction at 2 Gy (SF2), ranged from 0.05 (PrEC) to 0.55 (DU-145), suggesting that malignant prostate cells are more radioresistant than normal prostate cells, for this series. IR-induced apoptotic cell kill was minimal (less than 6% cell after a dose of 10 Gy at times of 24-96 h) and was not dose-dependent. Furthermore, apoptotic kill was not correlated with either molecular apoptotic response or clonogenic cell kill. Using a flow cytometric proliferation assay with the PrSC (stromal) and DU-145 (epithelial) representative cultures, we observed that a senescent-like phenotype (SLP) emerges within a sub-population of cells post-irradiation that is non-clonogenic. Terminal growth arrest was dose-responsive at 96 h following irradiation and associated with long-term expression of both p21(WAF1/Cip1) and p16(INK4a) genes. Future strategies for prostate radiotherapy prediction or novel treatments should additionally focus on terminal growth arrest as an important endpoint in prostate cancer therapy.

Apoptosis↗
PubMed1999

Enhanced replication of M-tropic HIV-1 strains in Herpesvirus saimiri immortalised T-cells which express CCR5.

A better characterisation of mononuclear cell-tropic (M-tropic) HIV-1 is central to disease control as these viruses predominate in disease transmission. M-tropic viruses do not replicate in conventional T-cell lines, and virus titres obtained in peripheral blood mononuclear cells (PBMC) are low. Human T-lymphocytes which have been immortalised by Herpesvirus saimiri strain C488 (HVS T-cells) are highly permissive to the replication of T-cell tropic strains of HIV. This study aimed to determine if HVS T-cells support replication of M-tropic HIV isolates that have not been adapted to conventional T-cell lines. A panel of PBMC low passage/primary field isolates and their molecular clones was used. Results show that infection in HVS T-cells was longer lived than in PBMC. In terms of peak virus titre and duration of productive infection, the two HVS T-cell lines studied were superior to PBMC, and one supported enhanced replication of all M-tropic isolates. This is important for generating M-tropic virus pools of sufficient titre for further biological studies such as virus neutralisation, co receptor usage and testing of antivirals. Phenotypic analysis showed that HVS T-cells are CD4+-activated memory cells expressing both CXCR-4 and CCR5 co receptors. Thus, HVS immortalisation appears to select for the T-cell subset targeted by HIV-1 in vivo.

CD4-Positive T-Lymphocytes↗
PubMed1998

T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control.

PURPOSE: Pretreatment hemoglobin (Hb) level has been reported to be an important prognostic factor for local control and survival in various malignancies. However, in many settings, the adverse effect of a low Hb may be related to more advanced disease. The purpose of this analysis was to assess the influence of pretreatment Hb on local control in a large series of patients with a localized cancer (T1/T2 glottic cancer, AJCC 1992) treated in a standard fashion. MATERIALS AND METHODS: Between January 1981 and December 1989, 735 patients (median age 63; 657 males, 78 females) with T1/T2 glottic cancer were treated with radiation therapy (RT). The standard RT prescription was 50 Gy in 20 fractions over 4 weeks (97% of patients). Factors studied for prognostic importance for local failure included pretreatment Hb, age, sex, T category, anterior commissure involvement, subglottic extension, and tumor bulk (presence of visible tumor vs. subclinical disease). RESULTS: With a median follow-up of 6.8 years (range 0.2-14.3), 131 patients have locally relapsed for an actuarial 5-year relapse-free rate of 81.7%. The 5-year actuarial survival was 75.8%. The mean pretreatment hemoglobin level was 14.8 g/dl and was similar in all prognostic categories. On multivariate analysis, using the Cox proportional hazards model, pretreatment Hb predicted for local failure after RT. The hazard ratio (HR) for relapse was calculated for various Hb levels. For example, the HR for a Hb of 12 g/dl vs. a Hb of 15 g/dl was 1.8 (95% confidence interval 1.2-2.5). Previously established factors, including gender, T category, subglottic extension, as well as tumor bulk, were also prognostically important for local control. CONCLUSIONS: This analysis, in a large number of similarly treated patients, indicates that pretreatment Hb is an independent prognostic factor for local control in patients with T1/T2 carcinoma of the glottis treated with RT. The underlying biology of this observation needs to be explored, and using this information, it may be possible to develop strategies to improve treatment outcome.

Carcinoma, Squamous Cell↗
PubMed1998

Radioresistant MTp53-expressing rat embryo cell transformants exhibit increased DNA-dsb rejoining during exposure to ionizing radiation.

Recent data suggest that aberrant function of the wild type p53 protein (WTp53) may alter cellular survival following DNA damage through cellular pathways involving apoptosis and cell-cycle checkpoints, but little is known concerning it's possible role in DNA repair. In the present study, the ionizing radiation sensitivity was determined for a series of rat embryo fibroblast (REF) cell lines transfected with an activated form of the H-ras oncogene alone, or in combination with a variety of missense-mutant p53 (MTp53) alleles. Transformed REF clones which expressed exogenous MTp53 and p21ras proteins (CLASS II clones) were generally radioresistant in culture as determined by higher values for the surviving fraction after 2 Gy (SF2 value) and the radiation dose required to reduce survival to a fraction of 0.1 (D10 value), compared either to transformed REF clones expressing p21ras protein alone (CLASS I clones), or to non-transfected REF control cell lines expressing baseline endogenous levels of p21ras and WTp53 protein. The increased radioresistance observed in the CLASS II clones (following both HDR- and LDR-irradiation), was significantly correlated with increased expression of MTp53 protein, and a decreased radiation-induced G1 arrest response. The variability observed in clonogenic radiosensitivity among REF clones was not explained by differential radiation-induced apoptosis. Using the Comet assay performed after continuous low dose-rate (LDR)-irradiation, MTp53-expressing REF clones were also found to be more proficient at the rejoining of DNA double-strand breaks (DNA-dsb), compared to WTp53-expressing REF clones. These results suggest that an enhanced DNA and cellular repair capacity may, in part, explain the increased radiation survival observed in some MTp53-expressing transformed fibroblasts and tumours.

Animals↗
PubMed1997

Mutator phenotype in Msh2-deficient murine embryonic fibroblasts.

Embryonic fibroblast cell lines were established from mice deficient, heterozygous, or proficient for Msh2, one of the three known DNA mismatch repair genes involved in hereditary nonpolyposis colon cancer (HNPCC). Cell lines were established by transfection of primary mouse embryo fibroblasts with E7 and Ras oncogenes or mutant p53. Spontaneously immortalized cells derived from the primary cultures were also studied. To determine whether these cells developed a mutator phenotype similar to that found in colon cancer cells deficient in mismatch repair, we measured mutation rates, microsatellite instability, and sensitivities to a range of DNA-damaging agents. The mutator phenotype detected in the E7 and Ras or mutant p53-immortalized Msh2-/- mouse cells was similar to that found in human mismatch repair-deficient colorectal carcinoma cell lines. Mutation rates to ouabain resistance were increased 8-12-fold relative to lines from Msh2+/+ mice, and microsatellite instability was detectable in 12-18% of subclones derived from the Msh2-/- line but was undetectable in subclones developed from the Msh2+/+ line. Furthermore, E7 and Ras or spontaneously immortalized Msh2-/- cells were significantly more resistant to the cytotoxic effects of 6-thioguanine relative to Msh2+/+ cells. In contrast, these lines showed various responses to UV light and cis-platinum, suggesting that mismatch repair deficiency was not the sole determinant for sensitivity to these DNA-damaging agents. Particular attention was paid to the properties of cells heterozygous for the Msh2 mutant gene, which would mimic the situation of an HNPCC carrier. However, our studies failed to reveal any properties of these cells that might provide a growth advantage or predispose them for the acquisition of further mutations. This observation is consistent with the model that inactivation of the wild-type Msh2 allele is a critical step for tumorigenesis in HNPCC patients.

Animals↗
PubMed1997

Post-operative radiotherapy for recurrent dermoid cysts of the spine: a report of 3 cases.

We report three cases of recurrent, intraspinal dermoid cysts managed with post-operative radical radiotherapy. In all cases, the period between last surgery and cystic re-accumulation has been lengthened by the use of involved-field radiotherapy. This combined-modality approach could be beneficial in decreasing the probability of recurrence associated with incompletely-resected tumours, or in patients whose co-morbidities put them at increased operative risk for serial neurosurgical procedures.

Adult↗
PubMed1996

P53-mediated radioresistance does not correlate with metastatic potential in tumorigenic rat embryo cell lines following oncogene transfection.

PURPOSE: Changes in wild-type p53 protein function occur in the majority of human tumors, and may alter genomic stability and the cellular response to ionizing radiation. Whether oncoproteins can render tumor cells both radioresistant and metastatic, may have implications for clinical strategies designed to improve local tumor control. In the studies reported here, we tested the hypothesis that acquired radioresistance correlates with metastatic potential within a large panel of transformed rat embryo cell (REF) lines following transfection with activated H-ras, mutant p53, and HPV16-E7 alleles. METHODS AND MATERIALS: Rat embryo cells (REF cells) were transfected using the calcium-phosphate technique with an activated H-ras gene alone, or in combination with human papillomavirus HPV16-E7 and/or human or murine mutant p53 sequences. Other rat embryo cell clones expressing transfected HPV-E7 and activated ras sequences subsequently acquired endogenous p53 gene mutations during culture in vitro. The relative expression of p21ras and p53 protein for each REF transformant was determined by Western blot analysis following transfection. REF clones were phenotypically characterized at early passage (i.e., passages 5-7) and late passage (i.e., passages 10-20) for their: (a) relative tumor growth rate, and (b) their ability to undergo spontaneous metastasis following intramuscular injection into the hind legs of SCID mice. In vivo phenotypic end points were then compared to previously measured parameters of in vitro radiosensitivity for each cell line. Additionally, the expression of the cellular protease, plasminogen activator, was determined for a number of metastatic and nonmetastatic cell lines. RESULTS: We found no evidence that selected oncogene-transfected REF transformants that were radioresistant in culture had a greater spontaneous metastatic potential than nonradioresistant REF transformants. Neither the level of expression of the p21ras protein nor that of the p53 protein was correlated with the spontaneous metastatic phenotype when tested at early passage. The metastatic phenotype appeared to be independent of p53 genotype. The majority of metastatic REF clones tested (7 out of 9 clones) expressed plasminogen activator following oncogene transfection, in contrast to nonmetastatic REF transformed cell lines. CONCLUSIONS: Our results suggest that (a) intrinsic radioresistance does not correlate with spontaneous metastatic potential in oncogene-expressing REF transformant cell lines, and (b), novel clinical strategies designed to overcome oncogene-mediated radioresistance could potentially impact on overall survival, as gains in local tumor control may not be offset by a greater risk of distant metastasis.

Animals↗
PubMed1996

The p53 gene as a modifier of intrinsic radiosensitivity: implications for radiotherapy.

BACKGROUND AND PURPOSE: Experimental studies have implicated the normal or "wild type' p53 protein (i.e. WTp53) in the cellular response to ionizing radiation and other DNA damaging agents. Whether altered WTp53 protein function can lead to changes in cellular radiosensitivity and/or clinical radiocurability remains an area of ongoing study. In this review, we describe the potential implications of altered WTp53 protein function in normal and tumour cells as it relates to clinical radiotherapy, and describe novel treatment strategies designed to re-institute WTp53 protein function as a means of sensitizing cells to ionizing radiation. METHODS AND MATERIALS: A number of experimental and clinical studies are critically reviewed with respect to the role of the p53 protein as a determinant of cellular oncogenesis, genomic stability, apoptosis, DNA repair and radioresponse in normal and transformed mammalian cells. RESULTS: In normal fibroblasts, exposure to ionizing radiation leads to a G1 cell cycle delay (i.e. a "G1 checkpoint') as a result of WTp53 mediated inhibition of G1-cyclin-kinase and retinoblastoma (pRb) protein function. The G1 checkpoint response is absent in tumour cells which express a mutant form of the p53 protein (i.e. MTp53), leading to acquired radioresistance in vitro. Depending on the cell type studied, this increase in cellular radiation survival can be mediated through decreased radiation-induced apoptosis, or altered kinetics of the radiation-induced G1 checkpoint. Recent biochemical studies support an indirect role for the p53 protein in both nucleotide excision and recombinational DNA repair pathways. However, based on clinicopathologic data, it remains unclear as to whether WTp53 protein function can predict for human tumour radiocurability and normal tissue radioresponse. CONCLUSIONS: Alterations in cell cycle control secondary to aberrant WTp53 protein function may be clinically significant if they lead to the acquisition of mutant cellular phenotypes, including the radioresistant phenotype. Pre-clinical studies suggest that these phenotypes may be reversed using adenovirus-mediated gene therapy or pharmacologic strategies designed to re-institute WTp53 protein function. Our analysis of the published data strongly argues for the use of functional assays for the determination of WTp53 protein function in studies which attempt to correlate normal and tumour tissue radioresponse with p53 genotype, or p53 protein expression.

Animals↗
PubMed1995

The p53-mediated G1 checkpoint is retained in tumorigenic rat embryo fibroblast clones transformed by the human papillomavirus type 16 E7 gene and EJ-ras.

Rat embryo fibroblast clones transformed with the human papillomavirus type 16 E7 gene and the H-ras oncogene (ER clones) fall into two groups on the basis of endogenous p53 genotype, wild type or mutant. We have compared these clones with the aim of indentifying physiological differences that could be attributed to p53 protein function. We show that all ER clones, regardless of p53 gene status, are tumorigenic and metastatic in severe combined immunodeficiency mice. We demonstrate that only the wild-type p53 protein expressed in ER clones is functional on the basis of its site-specific double-stranded DNA-binding activity and its ability to confer a G1 delay on cells following treatment with ionizing radiation. These data indicate that disruption of the p53 growth-regulatory pathway is not a prerequisite for the malignant conversion of rat embryo fibroblasts expressing the E7 gene and mutant ras. Differences in phenotype that were correlated with loss of p53 protein function included the following: serum-independent growth of ER clones in culture, decreased tumor doubling time in vivo, and increased radioresistance. In addition, we demonstrate the p53-dependent G1 checkpoint alone does not determine radiosensitivity.

Animals↗
PubMed1994

Analysis of murine antibody responses to baculovirus-expressed human immunodeficiency virus type 1 envelope glycoproteins.

An analysis of the humoral immunogenicity of a candidate AIDS vaccine (VaxSyn) in a murine model system is presented. Sera taken from a panel of mice immunized with the immunogen were analysed for their ability to bind a panel of gp120-representing peptides and limited reactivity to known sites of immunological interest was observed. Monoclonal antibodies (MAbs) were characterized as binding to a more restricted variety of regions on gp120 including C1, V2, V4 and the C terminus. A tetrazolium-based cytocidicity assay was used and shown to be an effective and objective method for the screening of human immunodeficiency virus (HIV)-neutralizing activity in large numbers of samples. None of the MAbs characterized in this study neutralize HIV-1 reference strains. The significance of these findings in view of previous publications is discussed.

AIDS Vaccines↗
PubMed1994

Mutant p53 increases radioresistance in rat embryo fibroblasts simultaneously transfected with HPV16-E7 and/or activated H-ras.

Recently, it has been suggested that abrogation of the wild type p53 protein function may alter the cellular response to DNA damaging agents, including ionizing radiation. This study was designed to compre the relative radiosensitivity and tumorigenicity of rat embryo fibroblast (REF) cell lines transfected with a mutant form of the p53 gene (plasmid MTp53pro193), alone, or in combination, with the H-ras (plasmid pEJ6.6) and HPV16-E7 (plasmid pJ4 omega 16.E7) oncogenes. Transfection of the mutant p53pro193 gene alone resulted in selected clones having increased radioresistance in culture which correlated with increased mutant p53 expression in these clones. However, the co-transfection of mutant p53 and H-ras genes or triple transfection of mutant p53, H-ras and E7 genes resulted in clones with high mutant p53 expression, significantly increased radioresistance and uniform tumorigenicity. There was no correlation between intrinsic radioresistance and spontaneous metastasis in the tumorigenic REF transfectant clones. Stepwise acquisition of radioresistance and an aggressive tumor cell phenotype is observed when the mutant p53 gene and HPV E7 co-operate with the ras oncogene in transfection assays, and can be correlated to increases in mutant p53 expression.

Animals↗
PubMed1991

Role of transfection and clonal selection in mediating radioresistance.

Transfected oncogenes have been reported to increase the radioresistance of rodent cells. Whether transfected nononcogenic DNA sequences and subsequent clonal selection can result in radioresistant cell populations is unknown. The present set of experiments describe the in vitro radiosensitivity and tumorigenicity of selected clones of primary rat embryo cells and human glioblastoma cells, after transfection with a neomycin-resistance marker (pSV2neo or pCMVneo) and clonal selection. Radiobiological data comparing the surviving fraction at 2 Gy (SF2) and the mean inactivation dose show the induction of radioresistance in two rat embryo cell clones and one glioblastoma clone, as compared to untransfected cells. Wild-type and transfectant clones were injected into three strains of immune-deficient mice (scid, NIH, and nu/nu) to assay for tumorigenicity and metastatic potential. Only the glioblastoma parent line and its transfectant clones were tumorigenic. None of the cells produced spontaneous or experimentally induced metastases. Flow cytometric analyses indicated that the induction of radioresistance could not be attributed to changes in cell kinetics at the time of irradiation. Our results show that transfection of a neomycin-resistance marker and clonal selection can impart radioresistance on both normal and tumor cells. The work also indicates that altered radiation sensitivity does not necessarily correlate with changes in cell-cycle kinetics at the time of irradiation, tumorigenicity, or altered metastatic potential. Our findings have critical implications for transfection studies investigating determinants of cellular radiosensitivity.

Animals↗
PubMed1990

Comparison between in vitro radiosensitivity and in vivo radioresponse in murine tumor cell lines. II: In vivo radioresponse following fractionated treatment and in vitro/in vivo correlations.

Survival in the low-dose region of in vitro radiation survival curves for human tumor cell lines may be correlated with the expected clinical radiocurability of tumors of similar histopathological type. The present investigation examined this hypothesis using a series of transplantable murine solid tumors. The in vivo radioresponse of the tumors following fractionated dose (10 fractions of 2 Gy given at 4 hr intervals) and single dose (20 Gy) radiation treatment was measured by growth delay and tumor cell survival assays. The measurements of tumor cell survival were initiated either immediately or 8 hr after the end of radiation treatment. There was no evidence for repair of potentially lethal damage in vivo in any of the tumors. The measurements of in vivo response were compared to parameters of in vitro radiation survival curves for the same tumor cell lines, which were measured concurrently. The tumor cell survival following 10 fractions of 2 Gy correlated best with the measured in vitro survival at 2 Gy, although good correlations were also observed with two parameters calculated from the in vitro data; the value of alpha from fitting the linear-quadratic (LQ) model and the mean inactivation dose (MID). Correlations were also observed between specific growth delay measured in vivo following 10 fractions of 2 Gy and these in vitro parameters. Despite the correlations observed, the measured survival values following 10 fractions of 2 Gy in vivo did not agree quantitatively with the theoretical values predicted from the in vitro survival data assuming equal effect for each fraction. This discrepancy indicates that other factors also contribute to the overall response of a tumor to fractionated irradiation. Nevertheless, these findings support the idea that intrinsic radiosensitivity plays a significant role in determining the overall response of a tumor to fractionated irradiation and provides strong support for the concept of testing the in vitro radiation sensitivity of biopsy specimens as a predictive assay of clinical radiocurability.

Animals↗
PubMed1990

Comparison between in vitro radiosensitivity and in vivo radioresponse of murine tumor cell lines. I: Parameters of in vitro radiosensitivity and endogenous cellular glutathione levels.

Recent studies have suggested that differences in the initial low-dose region of the radiation survival curves for human tumor cells might explain the differences in clinical response of tumors to fractionated radiation treatment. In this study, which is described in two companion papers, we investigated this hypothesis directly using animal model systems. In the present paper we determined in vitro radiation survival curves for eight murine tumor cell lines of varying histopathological type and: (a) measured survival at the 2 Gy and 8 Gy dose levels, (b) fitted parameters to the linear quadratic and two component multi-target equation models of cellular survival and (c) calculated mean inactivation doses. We found that the choice of the data fitting procedure affected the absolute value, relative ranking, and power to discriminate between the cell lines of these calculated parameters. A detailed statistical study indicated that the measured surviving fraction at 2 Gy (SF2) was the best discriminant of intrinsic radiosensitivity between the eight tumor cell lines. When these same cell lines were assayed for intracellular glutathione (GSH) levels, no correlation was found between levels of GSH and the SF2 value. Determining the SF2 value may be the method of choice to describe the low-dose region of the radiation survival curve, as it precludes the necessity of choosing a model to fit the survival data, it has excellent discriminatory powers, and it represents the survival in the radiotherapeutically relevant region of the in vitro radiation survival curve. Furthermore, as demonstrated in the companion paper, it correlates with cell survival in the tumors following 10 fractions of 2 Gy given in vivo.

Animals↗
PubMed1989

Thyroid dose distribution in dental radiography.

The anatomic position and proven radiosensitivity of the thyroid gland make it an organ of concern in dental radiography. A calibrated thermoluminescent dosimetry system was used to investigate the absorbed dose (microGy) to the thyroid gland resultant from a minimum irradiated volume, intraoral full-mouth radiography technique with the use of rectangular collimation with a lead-backed image receptor, and conventional panoramic radiography performed with front and rear lead aprons. Use of the minimum irradiated volume technique resulted in a significantly decreased absorbed dose over the entire thyroid region ranging from 100% to 350% (p less than 0.05). Because this intraoral technique results in radiographs with greater image quality and also exposes the thyroid gland to less radiation than the panoramic, this technique may be an alternative to the panoramic procedure.

Equipment Design↗
PubMed1989

Technique-dependent decrease in thyroid absorbed dose for dental radiography.

A LiF thermoluminescent dosimetry (TLD) system, calibrated in the tissue of interest with the beam used for experimentation, was employed to investigate dosages (muGy) to the thyroid region of an anthropomorphic phantom resultant from two dental complete-mouth radiographic procedures. Both techniques were compared in terms of dosages associated with combinations of lead apron and thyroid collar shielding while using a 70-kVp or 90-kVp x-ray beam for a 20-film complete-mouth series. Lead shielding significantly decreased the dose to the thyroid using both techniques (p less than 0.05). The use of the 90-kVp beam resulted in a significant reduction in the thyroid absorbed dose when using the bisecting angle technique (p less than 0.05) but caused a significant increase in the thyroid absorbed dose when the paralleling technique was used (p less than 0.05). The implementation of higher kilovoltage techniques in dental offices must therefore be dependent on the radiographic technique employed.

Humans↗