Biomedical subjects

Dennis Johnston

Publications and source records attributed to Dennis Johnston.

14 recordsLinked to original sources

PubMed2006

Comparison of full-field digital mammography and screen-film mammography for detection and characterization of simulated small masses.

OBJECTIVE: The two objectives of this study were to create an ex vivo phantom model that closely mimics human breast cancer for detection tasks and to compare the performance of full-field digital mammography with screen-film mammography in detecting and characterizing small breast masses in a phantom with a spectrum of complex tissue backgrounds. MATERIALS AND METHODS: Sixteen phantom breast masses of varying sizes (0.3-1.2 cm), shapes (round and irregular), and densities (high and low) were created from shaved tumor specimens and imaged using both full-field digital and screen-film mammography techniques. We created 408 detection tasks that were captured on 68 films. On each radiograph, six detection tasks were partially obscured by areas of varying breast-pattern complexity, including low (predominantly fatty), mixed (scattered fibroglandular densities and heterogeneously dense), and high (extremely dense) density patterns. Each detection task was scored using a five-point confidence scale by three mammographers. Receiver operating characteristic (ROC) curve analysis was performed to analyze differences in detection of masses between the two imaging systems, and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were computed. RESULTS: Full-field digital mammography showed higher area under the ROC curve than screen-film mammography for detecting masses in each breast background and performed significantly better than screen-film mammography in mixed (p = 0.010), dense (p = 0.029), and all breast backgrounds combined (p = 0.004). Full-field digital mammography was superior to screen-film mammography for characterizing round and irregular masses and low- and high-density masses. CONCLUSION: Full-field digital mammography was significantly superior to screen-film technique for detecting and characterizing small masses in mixed and dense breast backgrounds in a phantom model.

Artifacts↗

PubMed2005

Expression of interleukin-8 gene in radical prostatectomy specimens is associated with advanced pathologic stage.

BACKGROUND: We previously reported that relative expression of E-cadherin, matrix metalloproteinases (MMPs)-2 and -9, and vascular endothelial growth factor (VEGF)/vascular permeability factor in radical prostatectomy specimens (RP) can distinguish organ-confined cancers from advanced prostate cancers. Here, we evaluate the expression of interleukin-8 (IL-8) and basic fibroblast growth factor (bFGF), two other genes involved in angiogenesis and metastasis, in RP specimens. METHODS: The expression level of IL-8 and bFGF mRNA in the invasive edge of 41 prostate cancers of different stages was determined using a rapid colorimetric in situ hybridization (ISH) technique. Gene expression levels of IL-8 and bFGF were correlated with the Gleason score and pathologic stage to ascertain their relationship to prostate cancer progression. RESULTS: The expression of IL-8 and bFGF genes was detected by ISH in histologically normal prostate gland epithelium as well as in glands with foci of cancer. Increased mRNA expression of IL-8 was associated with both the Gleason score and pathologic stage of tumors and distinguished organ-confined from non-confined tumors (P = 0.002). In contrast, the expression of bFGF mRNA did not correlate with the Gleason score or pathologic stage. CONCLUSIONS: Overexpression of Il-8 mRNA, but not bFGF mRNA, in RP specimens is directly associated with progression of prostate cancer.

Biomarkers, Tumor↗

PubMed2005

Racial-ethnic differences in genetic amniocentesis uptake.

The objective of this study was to determine the role of health beliefs in genetic amniocentesis acceptance in a diverse racial-ethnic population. Participants completed a previously-validated questionnaire consisting of three sections: (1) demographics, (2) amniocentesis knowledge, and (3) health beliefs, which assessed perceived susceptibility, seriousness of potential impact, benefits of testing, and barriers to testing. The results showed that Hispanic women were less likely to accept amniocentesis (51.5% vs. Caucasian 82.8%, African American 82.9%, Asian 82.8%). Education level was the only demographic factor higher among acceptors. Women who accepted amniocentesis had higher perceived seriousness, susceptibility, and benefits HBM scores and higher knowledge scores than women who declined. HBM scores and knowledge predicted the amniocentesis decision correctly 91.5% of the time. Individual health beliefs and knowledge play a greater role in genetic amniocentesis acceptance than do demographic factors such as race-ethnicity.

Amniocentesis↗

PubMed2005

High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis.

We attempted to identify deleted segments in two model tumor suppressor gene loci on chromosomes 13q14 and 17p13 that were associated with clonal expansion of in situ bladder preneoplasia using single nucleotide polymorphisms (SNPs)-based whole-organ histologic and genetic mapping. For mapping with SNPs, the sequence-based maps spanning approximately 27 and 5 Mb centered around RB1 and p53, respectively, were assembled. The integrated gene and SNP maps of the regions were used to select 661 and 960 SNPs, which were genotyped by pyrosequencing. Genotyping of SNPs was performed on DNA samples corresponding to histologic maps of the entire bladder mucosa in human cystectomy specimens with invasive urothelial carcinoma. By using this approach, we have identified deleted regions associated with clonal expansion of intraurothelial neoplasia; which ranged from 0.001 to 4.3 Mb (average 0.67 Mb) and formed clusters of discontinuous deleted segments. The high resolution of such maps is a prerequisite for future positional targeting of genes involved in early phases of bladder neoplasia. This approach also permits analysis of the overall genomic landscape of the involved region and discloses that a unique composition of noncoding DNA characterized by a high concentration of repetitive sequences may predispose to deletions.

Carcinoma in Situ↗

PubMed2004

The homeodomain protein CDP regulates mammary-specific gene transcription and tumorigenesis.

The CCAAT-displacement protein (CDP) has been implicated in developmental and cell-type-specific regulation of many cellular and viral genes. We previously have shown that CDP represses mouse mammary tumor virus (MMTV) transcription in tissue culture cells. Since CDP-binding activity for the MMTV long terminal repeat declines during mammary development, we tested whether binding mutations could alter viral expression. Infection of mice with MMTV proviruses containing CDP binding site mutations elevated viral RNA levels in virgin mammary glands and shortened mammary tumor latency. To determine if CDP has direct effects on MMTV transcription rather than viral spread, virgin mammary glands of homozygous CDP-mutant mice lacking one of three Cut repeat DNA-binding domains (DeltaCR1) were examined by reverse transcription-PCR. RNA levels of endogenous MMTV as well as alpha-lactalbumin and whey acidic protein (WAP) were elevated. Heterozygous mice with a different CDP mutation that eliminated the entire C terminus and the homeodomain (DeltaC mice) showed increased levels of MMTV, beta-casein, WAP, and alpha-lactalbumin RNA in virgin mammary glands compared to those from wild-type animals. No differences in amounts of WDNM1, epsilon-casein, or glyceraldehyde-3-phosphate dehydrogenase RNA were observed between the undifferentiated mammary tissues from wild-type and mutant mice, indicating the specificity of this effect. These data show independent contributions of different CDP domains to negative regulation of differentiation-specific genes in the mammary gland.

Animals↗

PubMed2003

Predictors of susceptibility to smoking and ever smoking: a longitudinal study in a triethnic sample of adolescents.

This report describes a longitudinal study of the natural course of smoking initiation in a school-based, ethnically diverse (42% White, 37% African American, 20% Hispanic) sample of adolescents in grades 5, 8, and 12 who were followed prospectively for 1 year. A cohort of 659 students was identified who were never smokers at baseline and who completed questionnaires both at baseline and at 1-year follow-up. From this cohort, predictor variables were used to identify ethnic-specific risk factors for (a) "susceptibility to smoking" among the 509 students who were nonsusceptible, never smokers at baseline and (b) "ever smoking" among all 659 students who were never smokers at baseline (both susceptible and nonsusceptible). Logistic regression analyses revealed that parental and household influences (parental education, marital status, household smoking) were important predictors of ever smoking, but not of susceptibility to smoking, for African Americans. Hispanic adolescents were significantly influenced by environmental influences, namely smoking by other household members (ever smoking) and by peers (susceptibility and ever smoking), although peer pro-tobacco influences (friends who smoke or friends' approval of smoking) were important predictors of susceptibility to smoking or ever smoking for all three ethnic groups. Exposure to tobacco-related advertising was a risk factor for White (susceptibility and ever smoking) and African American (susceptibility only) adolescents but not for Hispanic adolescents. Inclusion of the susceptibility to smoking variable in the model predicting ever smoking substantially reduced the importance of other predictors in the model, suggesting that susceptibility to smoking was not an independent risk factor for ever smoking but rather a potential mediating variable. The results of this study offer important insights for designing ethnic-specific strategies for preventing smoking during adolescence.

Adolescent↗

PubMed2003

A streamlined three-dimensional volume estimation method accurately classifies prostate tumors by volume.

Prostate tumor volume has been suggested to be an important pathologic variable that predicts for clinical significance and outcome. However, the determination of tumor volume using standard methods such as computerized planimetry or image analysis is labor intensive. We studied whether length (L), width (W), and height (number of cross sections x sectional thickness, CST) of a tumor focus could be used to estimate prostate tumor volume. We studied 1091 tumor foci from 365 selected serially sectioned radical prostatectomy specimens. We randomly divided the specimens into evaluation (182 specimens) and validation (183 specimens) groups. After analyzing the evaluation group, we derived the formula 0.4 (slope of the regression line) x L x W x CST to estimate volume. We then tested whether our three-dimensional volume estimation formula could accurately classify tumor volume for specimens in the validation set as insignificant (</=0.5 cm3) or significant (>0.5 cm3), and also into a five-category tumor volume scheme. Our three-dimensional estimate accurately classified tumors into insignificant and significant total volume categories in 94.0% of cases and into the five-category scheme in 85.8% cases. These accuracy rates were significantly better than rates for other methods. The three-dimensional estimate is an accurate and straightforward method for assessing prostate tumor volume.

Body Weights and Measures↗

PubMed2003

The type B leukemogenic virus truncated superantigen is dispensable for T-cell lymphomagenesis.

Type B leukemogenic virus (TBLV) is a variant of mouse mammary tumor virus (MMTV) that causes T-cell lymphomas in mice. We have constructed a TBLV-MMTV hybrid, pHYB-TBLV, in which 756 bp of the C3H MMTV long terminal repeat (LTR) was replaced with 438 bp of the TBLV LTR. Intraperitoneal injection of pHYB-TBLV transfectants consistently resulted in T-cell lymphomas in 50% of injected weanling BALB/c mice with an average latency period of 5.7 (+/- 1.5) months. Transfectants of pHYB-TBLV containing a double-frameshift mutation in the truncated superantigen gene (sag) induced T-cell lymphomas with similar incidences, latency periods, and phenotypes, suggesting that cis-acting elements in the TBLV LTR determine disease specificity.

Animals↗

PubMed2003

The relative mRNA expression levels of matrix metalloproteinase to E-cadherin in prostate biopsy specimens distinguishes organ-confined from advanced prostate cancer at radical prostatectomy.

PURPOSE: To determine whether the expression ratio of matrix metalloproteinase (MMP) to E-cadherin mRNA (MMP:E-cadherin) in biopsy (BX) samples of prostate cancer correlate with that of radical prostatectomy (RP) specimens and assists in predicting pathologic stage. EXPERIMENTAL DESIGN: The mRNA expression levels for MMP-2 and -9 and of E-cadherin were determined by a colorimetric in situ hybridization assay in 44 paired BX and RP specimens. Clinical stage, BX Gleason score (GS), total length of cancer in BX cores, and serum prostate-specific antigen levels were also assessed. RESULTS: Clinical stage was confined in 39 of 44 (89%) patients. Subsequent to RP, however, only 17 of 44 (39%) patients had proven organ-confined disease (pT2). BX GSs agreed with the RP GS in 77% of RP specimens. We found a strong correlation between BX and RP MMP:E-cadherin ratios (correlation coefficient = 0.755). The ratio increased as the GS increased and pathologic stage advanced (pT2 versus >/= pT3). Increasing clinical stage, GS, and serum prostate-specific antigen were significantly associated with advanced cancer at RP (P = 0.004-0.0001). The BX MMP:E-cadherin ratio, however, exhibited the strongest association with pathologic stage and independently predicted the status of 89% of the RP cases based on a BX ratio of <6 (predicted stage pT2 cancer at RP) versus >/=6 (predicted stage >/= pT3 at RP). CONCLUSION: The BX MMP:E-cadherin ratio represents a novel prognostic assay for predicting stage of cancer at RP. These data provide proof of principle for directly assessing the biological potential of prostate cancer using molecular strategies in patient's specimens.

Biopsy↗

PubMed2002

Amplification/overexpression of a mitotic kinase gene in human bladder cancer.

BACKGROUND: The mitotic kinase-encoding gene STK15/BTAK/ AuroraA is associated with aneuploidy and transformation when overexpressed in mammalian cells. STK15 overexpression activates an unknown oncogenic pathway that involves centrosome amplification and results in missegregation of chromosomes. Because clinical prognosis and tumor aneuploidy are tightly linked in human bladder cancer, we examined whether increased STK15 copy number and protein levels are linked to aneuploidy in bladder cancers. METHODS: STK15 protein was visualized by immunohistochemistry in 205 formalin-fixed, paraffin-embedded human bladder tumors. STK15 gene copy number was evaluated in 61 tumors by Southern blot hybridization and in 21 of these 61 tumors by fluorescence in situ hybridization (FISH). Copy numbers of chromosomes 3, 17, 20, and 21 were evaluated by FISH with chromosome-specific probes. STK15 expression levels were related to histologic grade, stage, and DNA ploidy of the tumors and to the patients' follow-up data. The chi-square test for association was used to analyze the relationship between STK15 expression and pathologic features. All statistical tests were two-sided. RESULTS: Tumors with low levels of STK15 amplification (3-4 copies) showed minimal deviation in their chromosome copy number and diploid or near-diploid total nuclear DNA content. Tumors with higher levels of STK15 amplification (>4 copies) had a major increase of chromosome copy number and of their total nuclear DNA content, i.e., exhibited pronounced aneuploidy. Elevated expression of STK15 was strongly associated with parameters of clinical aggressiveness including high histologic grade (P<.001), invasion (P<.001), increased rate of metastasis (P<.001), and decreased metastasis-free (P<.001) and overall (P<.001) survival of patients with bladder cancer. CONCLUSION: STK15 gene amplification and associated increased expression of the mitotic kinase it encodes are associated with aneuploidy and aggressive clinical behavior in human bladder cancer.

Adult↗

PubMed2002

The importance of validating the diagnosis of coronary heart disease when measuring secondary prevention: a cross-sectional study in general practice.

PURPOSE: To compare levels of recorded risk factors and drug treatment between patients with validated and non-validated diagnoses of coronary heart disease (CHD) in Northern Ireland. METHODS: Patients with a nitrate prescription in the previous year or a CHD Read code were identified from computer records of 25 practices, stratified by partnership size and area board. Computer and paper records of a random sample of 10% of these were searched for specified criteria to validate the diagnosis of CHD. The diagnosis was considered valid if the patient was found to have one or more positive investigations for CHD. Records of blood pressure, cholesterol, blood sugar, body mass index and drugs prescribed were taken into account. RESULTS: The combined practice population was 151,071; 7338 (4.86%) were identified by the computer search as meeting the defined entry criteria for CHD. Among the 10% random sample the diagnosis of CHD could not be validated for 36.5% (265/727). Significantly more patients with a validated than non-validated diagnosis had recorded cholesterol levels below 5.0 mmol/l (55.8 vs. 34.5%, p < 0.001) and were prescribed aspirin (75.3 vs. 40.8%, p < 0.001), beta-blockers (51.5 vs. 28.3%, p < 0.001), angiotensin-converting-enzyme inhibitors (29.2 vs. 15.5%, p < 0.001) and lipid-lowering drugs (50.9 vs. 23.0%, p < 0.001). A recent nitrate prescription had a higher predictive value for validated CHD than a Read code for CHD alone (71.2 vs. 53.1%, p < 0.001). No other significant differences were found between the two groups regarding the extent or levels of recorded risk factors. CONCLUSIONS: Patients with a validated diagnosis of CHD appear to be better managed than those whose diagnosis has not been confirmed. Validation of diagnosis has important implications for assessing the provision of secondary prevention and for clinical governance.

Adolescent↗

PubMed2002

Outcome of patients with Gleason score 8 or higher prostate cancer following radical prostatectomy alone.

PURPOSE: We determine the effect of clinical and pathological variables on the outcome of patients with prostate cancer of Gleason scores 8 or greater treated with radical prostatectomy alone. MATERIALS AND METHODS: Between April 1987 and October 1998, 1,199 patients underwent radical retropubic prostatectomy. We identified 188 patients assigned a Gleason score of 8 or higher in the prostatectomy specimen who did not receive any neoadjuvant or adjuvant therapy. Median followup was 60 months (range 1 to 129). Disease recurrence was defined as any detectable prostate specific antigen level 0.1 ng./ml. or greater. RESULTS: Of 188 patients 128 (68%) had no evidence of prostate cancer after a median followup of 60 months, while 60 (32%) demonstrated a detectable PSA level. There were 58 (31%) patients with disease confined to the prostate with negative surgical margins while 108 (57%) had prostate cancer confined to the surgical specimen. Positive surgical margin with extraprostatic extension was seen in 16 (9%) patients and seminal vesicle invasion was present in 40 (21%). The 5 and 7-year disease-free survival rates for the entire cohort were 71% and 55%, respectively. Patients with specimen confined disease had a significantly higher 5-year disease-free survival rate than those with nonspecimen confined disease (84% and 50%, p <0.0001). On multivariate analysis pathological status of the surgical specimen was the most significant independent predictor of disease recurrence. Age, ethnicity, clinical stage and preoperative PSA had no independent effect on disease recurrence. CONCLUSIONS: Long-term disease-free survival can be expected in those patients with high grade prostate cancer whose disease is confined to the prostate and/or the surgical specimen.

Aged↗

PubMedDate not supplied

Hereditary multiple exostosis and pain.

This study was undertaken to characterize pain in individuals with hereditary multiple exostosis (HME). Two hundred ninety-three patients with HME completed a questionnaire designed to assess pain as well as its impact on their life. Eighty-four percent of participants reported having pain, indicating that pain is a real problem in HME. Of those with pain, 55.1% had generalized pain. Two factors were found to be associated with pain outcome: HME-related complications and surgery. Individuals who had HME-related complications were five times more likely to have pain, while those who had surgery were 3.8 more likely to have pain. No differences were found between males and females with respect to pain, surgery, or HME-related complications. The results of this study indicate that the number of individuals with HME who have pain has been underestimated and that pain is a problem that must be addressed when caring for individuals with HME.

Adolescent↗

PubMedDate not supplied

Cardioactive drugs.

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Adrenergic beta-Antagonists↗