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PubMed2006

Promoter prediction and annotation of microbial genomes based on DNA sequence and structural responses to superhelical stress.

BACKGROUND: In our previous studies, we found that the sites in prokaryotic genomes which are most susceptible to duplex destabilization under the negative superhelical stresses that occur in vivo are statistically highly significantly associated with intergenic regions that are known or inferred to contain promoters. In this report we investigate how this structural property, either alone or together with other structural and sequence attributes, may be used to search prokaryotic genomes for promoters. RESULTS: We show that the propensity for stress-induced DNA duplex destabilization (SIDD) is closely associated with specific promoter regions. The extent of destabilization in promoter-containing regions is found to be bimodally distributed. When compared with DNA curvature, deformability, thermostability or sequence motif scores within the -10 region, SIDD is found to be the most informative DNA property regarding promoter locations in the E. coli K12 genome. SIDD properties alone perform better at detecting promoter regions than other programs trained on this genome. Because this approach has a very low false positive rate, it can be used to predict with high confidence the subset of promoters that are strongly destabilized. When SIDD properties are combined with -10 motif scores in a linear classification function, they predict promoter regions with better than 80% accuracy. When these methods were tested with promoter and non-promoter sequences from Bacillus subtilis, they achieved similar or higher accuracies. We also present a strictly SIDD-based predictor for annotating promoter sequences in complete microbial genomes. CONCLUSION: In this report we show that the propensity to undergo stress-induced duplex destabilization (SIDD) is a distinctive structural attribute of many prokaryotic promoter sequences. We have developed methods to identify promoter sequences in prokaryotic genomes that use SIDD either as a sole predictor or in combination with other DNA structural and sequence properties. Although these methods cannot predict all the promoter-containing regions in a genome, they do find large sets of potential regions that have high probabilities of being true positives. This approach could be especially valuable for annotating those genomes about which there is limited experimental data.

Bacillus subtilis↗

PubMed2004

Stair performance in people aged 75 and older.

OBJECTIVES: To examine specific behaviors used by older adults while ascending and descending stairs and to assess the relationships between confidence and stair performance. DESIGN: Cross-sectional. SETTING: Center for Locomotion Studies, The Pennsylvania State University. PARTICIPANTS: Sixteen male (mean age=82.7, range= 77-89) and 16 female (mean age=82.2, range=77-87) community-dwelling adults. MEASUREMENTS: A stair self-efficacy (SSE) test was created to assess individuals' confidence in their safety on stairs. Observational stair performance measures, measures of walking speed on stairs, and the total SSE score were examined for differences due to sex, and the relationships between SSE and specific stair behaviors were assessed. RESULTS: There was a significant relationship between SSE and the safety precautions taken during stair negotiation. Those with lower SSE were more likely to ascend and descend the stairs at a slower speed, use the handrail to a greater extent, and position themselves closer to the rail. The women had lower domain-specific SSE and tended to use the handrail to a greater extent than men even though there were no sex differences in self-reported functional ability or general falls and mobility confidence. A small group of subjects exhibited characteristics of instability, particularly during stair descent, yet most of this group had high SSE scores and failed to use the handrail. CONCLUSION: It appears that confidence related to stair negotiation plays a major role in determining risk-taking propensity during stair use in older adults.

Activities of Daily Living↗

PubMedDate not supplied

Machine learning approaches for prediction of linear B-cell epitopes on proteins.

Identification and characterization of antigenic determinants on proteins has received considerable attention utilizing both, experimental as well as computational methods. For computational routines mostly structural as well as physicochemical parameters have been utilized for predicting the antigenic propensity of protein sites. However, the performance of computational routines has been low when compared to experimental alternatives. Here we describe the construction of machine learning based classifiers to enhance the prediction quality for identifying linear B-cell epitopes on proteins. Our approach combines several parameters previously associated with antigenicity, and includes novel parameters based on frequencies of amino acids and amino acid neighborhood propensities. We utilized machine learning algorithms for deriving antigenicity classification functions assigning antigenic propensities to each amino acid of a given protein sequence. We compared the prediction quality of the novel classifiers with respect to established routines for epitope scoring, and tested prediction accuracy on experimental data available for HIV proteins. The major finding is that machine learning classifiers clearly outperform the reference classification systems on the HIV epitope validation set.

Algorithms↗

PubMed2000

Dimensions of maternal behaviour characteristics in domestic and wildxdomestic crossbred sows.

We examined the maternal behaviour of seven domestic and seven wildxdomestic primiparous sows during 10 days post partum to investigate two questions: (1) Did maternal behaviour change during domestication? (2) Can the interindividual variability of maternal behaviour be subsumed into a few dimensions of maternal temperament? We recorded: (a) willingness to leave the nest for food on Day 2; (b) reaction to a playback of squeezed piglet distress vocalisation on Day 2; (c) spontaneous nursing behaviour and spontaneous lying-down behaviour on Day 5 (from an overnight video recording); (d) reactions to playbacks of various piglet distress vocalisations on Day 6 and (e) reactions to a human in the 'nest' with piglets on Day 9. Moreover, data on baseline cortisol saliva concentration and its increase during a brief transportation period and novel environment challenge at the age of 5 months were available. Crossbred sows did not differ from domestic ones in any aspect of maternal behaviour except for a higher tendency to terminate final massage during nursings and a higher frequency of changing posture from lying to standing and back during the night. Factor analysis (based on correlation matrix of 11 behaviour and cortisol variables calculated for all 14 sows after removing the effect of breed) indicated that 82% of the variability in the data could be explained by three factors: first, 'calmness' on which low night time frequency of major posture changes, carefulness of lying-down behaviour and high propensity to remain in nursing position after milk ejection loaded positively while cortisol concentrations during challenge loaded negatively; second, 'protectiveness' with high loadings of the reaction scores to the playbacks of piglet distress calls and the human presence near the piglets; and third, 'nursing activity' which was strongly positively associated with nursing frequency, and negatively with the proportion of nutritive nursings and baseline cortisol values. The results indicate that most aspects of pig maternal behaviour have not been significantly changed by domestication and that substantial variability in maternal behaviour exists between sows, perhaps in the form of several behaviour characteristics which encompass both behaviour and endocrine profiles of the sows.

Journal Article↗

PubMed1995

Violence, sensation seeking, and impulsivity in schizophrenics found unfit to stand trial.

Many studies have confirmed an association between violent behavior, impulsivity, and sensation seeking in nonpsychotic subjects. Schizophrenic patients (n = 49) who had been found unfit to stand trial were investigated for violence, according to index offenses and longitudinal histories (before and after admission) for violence. Those charged with violent offenses were significantly more often married with children, and were equally likely to direct their assaultiveness to strangers, acquaintances, and family members. The nature of the index offense seemed to be a good indicator of general violent propensity. No significant differences were found on Barratt's Impulsivity Scale and Zuckerman's Sensation Seeking Scale, except that schizophrenic patients with negative histories of violence scored higher on the thrill and adventure subscale. No pattern of substance abuse differentiated the groups. Patients charged with violent offenses more often presented with persecutory delusions, but this did not extend to those whose histories were positive for repetitive violence. Although impulsivity and sensation seeking do not seem to cause violent behavior in this group, psychopathology can also only be regarded as a necessary but not sufficient determinant.

Adolescent↗

PubMed1990

Development and validation of an index for scoring baseline respiratory disease in the very low birth weight neonate. Severity Index Development and Validation Panels and Newborn Lung Project.

An accurate description of the population at risk for neonatal chronic lung disease is clearly of prime importance for comparative studies and the planning of interventions. Attempts to explain variations in chronic lung disease rates in such studies have been compromised by lack of a way of estimating the severity of the initial pulmonary disease as a risk factor. Therefore, a severity index was developed for use in very low birth weight (less than 1501 g) neonates. Special emphasis was placed on applicability of the index in the multicenter observational setting. Development followed a clinician panel approach, with the resulting index designed to capture clinical judgment of severity. The index was validated prospectively on neonates in a neonatal intensive care unit, and retrospectively using charts from nine hospitals nationwide. Correlations of the index with clinical judgment in the two samples were .95 and .93, respectively. In an additional validation the index combined with birth weight correctly predicted oxygen dependence status at 30 days in 36 of 42 neonates consecutively admitted to five neonatal intensive care units (P = .002). Birth weight and the severity index contributed about equally to the prediction, and therefore they seem to represent partly independent components of baseline propensity for prolonged oxygen dependence.

Apgar Score↗

PubMed2001

Protein threading by learning.

By using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems.

Amino Acid Sequence↗

PubMedDate not supplied

Psychological well-being in patients with primary Sjögren's syndrome.

OBJECTIVES: To evaluate quality of life and psychological symptoms in patients with primary Sjögren's syndrome and to compare this with patients with rheumatoid arthritis. METHODS: A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine the quality of life and psychological symptoms in patients with primary Sjögren's syndrome (pSS; n = 34). Patients with rheumatoid arthritis (RA; n = 32) were used as patient controls. RESULTS: The total mean score +/- SD for PGWB was 84.9 +/- 16.2 in pSS patients and significantly lower (p = 0.001) than in RA patients (97.7 +/- 17.5). Patients with pSS had an increased propensity for depressed mood (p = 0.0009), and suffered from reduced well-being (p = 0.002) and impaired vitality (p = 0.003). CONCLUSION: The results suggest that patients with pSS have a reduced quality of life, a higher degree of distress and a lower sense of well-being than patients with RA.

Adult↗

PubMed2005

Gastric helicobacter infection induces a Th2 phenotype but does not elevate serum cholesterol in mice lacking inducible nitric oxide synthase.

Persistent Helicobacter felis infection in (C57BL/6 x 129SvEv)F1 mice induces chronic gastritis. Expression of inducible nitric oxide synthase (iNOS) is upregulated in response to Helicobacter infection. In this study, 20 10-week-old iNOS-/- mice and 20 wild-type [(C57BL/6 x 129SvEv)F1] mice were infected with H. felis by oral gavage and were assessed histologically and serologically at 32 weeks postinfection. Equal numbers of uninfected controls were sham inoculated. The mice were scored for severity of gastric inflammation, hyperplasia, glandular atrophy, and mucous metaplasia in the corpus and for the level of helicobacter colonization. The immunoglobulin G1 (IgG1), IgG2a, and IgG2c antibody responses to H. felis were determined. As a secondary measure, serum cholesterol levels were assessed. iNOS-/- mice have a propensity for increased serum cholesterol, and although controversial, several human epidemiologic studies have demonstrated an association between Helicobacter infection and several risk factors for cardiovascular disease, including elevated serum cholesterol. Nevertheless, no differences in serum cholesterol levels were observed between the H. felis-infected and -uninfected iNOS-/- mice in this study. The uninfected animals had minimal to no gastric pathology. The gastric pathology scores for the infected animals were reduced significantly in the iNOS-deficient mice relative to those for the wild-type mice (all P <0.01). Helicobacter-infected iNOS-/- mice had chronic lymphoid infiltration and negligible to mild glandular atrophy and mucous metaplasia in the fundic mucosa, while H. felis-infected wild-type mice had severe atrophic and metaplastic mucosal changes. The atrophic gastritis in the infected wild-type mice, particularly the female mice, was also accompanied by greater granulocytic infiltration, antral hyperplasia, and diminished antral colonization, unlike that in the infected iNOS-/- mice. iNOS-/- mice developed significantly lower Th1-associated IgG2c antibody responses to H. felis (P <0.0003); the Th2-associated IgG1 responses were similar (P=0.09), suggesting a greater effect of the iNOS defect on Th1 responses. H. felis colonization was significantly greater in the iNOS-deficient mice. These findings are indicative of an impaired Th1 component of the H. felis-induced inflammatory response when the influence of iNOS is removed.

Animals↗

PubMed2006

Protein disorder prediction by condensed PSSM considering propensity for order or disorder.

BACKGROUND: More and more disordered regions have been discovered in protein sequences, and many of them are found to be functionally significant. Previous studies reveal that disordered regions of a protein can be predicted by its primary structure, the amino acid sequence. One observation that has been widely accepted is that ordered regions usually have compositional bias toward hydrophobic amino acids, and disordered regions are toward charged amino acids. Recent studies further show that employing evolutionary information such as position specific scoring matrices (PSSMs) improves the prediction accuracy of protein disorder. As more and more machine learning techniques have been introduced to protein disorder detection, extracting more useful features with biological insights attracts more attention. RESULTS: This paper first studies the effect of a condensed position specific scoring matrix with respect to physicochemical properties (PSSMP) on the prediction accuracy, where the PSSMP is derived by merging several amino acid columns of a PSSM belonging to a certain property into a single column. Next, we decompose each conventional physicochemical property of amino acids into two disjoint groups which have a propensity for order and disorder respectively, and show by experiments that some of the new properties perform better than their parent properties in predicting protein disorder. In order to get an effective and compact feature set on this problem, we propose a hybrid feature selection method that inherits the efficiency of uni-variant analysis and the effectiveness of the stepwise feature selection that explores combinations of multiple features. The experimental results show that the selected feature set improves the performance of a classifier built with Radial Basis Function Networks (RBFN) in comparison with the feature set constructed with PSSMs or PSSMPs that adopt simply the conventional physicochemical properties. CONCLUSION: Distinguishing disordered regions from ordered regions in protein sequences facilitates the exploration of protein structures and functions. Results based on independent testing data reveal that the proposed predicting model DisPSSMP performs the best among several of the existing packages doing similar tasks, without either under-predicting or over-predicting the disordered regions. Furthermore, the selected properties are demonstrated to be useful in finding discriminating patterns for order/disorder classification.

Amino Acid Sequence↗

PubMed1986

Stimulus-induced vulnerability in the early and late postinfarction phase.

In 45 survivors of myocardial infarction, cardiac catheterization was performed one and six months after the acute event. After completion of the angiographic investigation, ventricular vulnerability was assessed, using programmed right ventricular stimulation (rates 120 and 140 min-1, single and double premature impulses). In 27/45 patients the results of programmed electrical stimulation were comparable at one and six months. The overall incidence of repetitive ventricular response did not change. There was no correlation between the change of repetitive ventricular response and the change of effective right ventricular refractory period and the change of angiographic parameters (Gensini score, left ventricular ejection fraction and volume indices). It is concluded that between the first and the sixth month after infarction there is no relevant alteration in the propensity to repetitive ventricular response.

Adult↗

PubMed2006

The nonsaphenous vein of the popliteal fossa: prevalence, patterns of reflux, hemodynamic quantification, and clinical significance.

BACKGROUND: A large tortuous vein coursing over the posterior aspect of the knee and the upper calf may give rise to a constellation of varicose veins unrelated to the great (GSV) or small (SSV) saphenous veins. Designated the popliteal fossa vein (PFV), it perforates the deep popliteal fascia and empties into the deep system. We examined the prevalence, anatomic reflux patterns, hemodynamic role, and clinical significance of the PFV. METHODS: We examined 543 patients (818 limbs) with venous disease, aged 14 to 94 years (median, 55 years). The study consisted of group A, comprising limbs with a PFV, and group B, formed by the remaining limbs. The history, clinical examination, and venous duplex scan findings were analyzed retrospectively. Venous clinical severity and venous segmental disease scores of group A were compared with those of an equal number of CEAP-, sex-, and age-matched control limbs. In situ venous hemodynamics of the PFV obtained with duplex scan are reported. RESULTS: A PFV was found in 24 (2.93%) of 818 limbs (95% confidence interval [CI], 1.8%-4.1%); 24 (4.4%) of 543 subjects (95% CI, 2.7%-6.2%), 12 men and 12 women aged 23 to 82 years (median, 54 years) had a PFV. CEAP clinical classes in limbs with a PFV were as follows: C2, 15 limbs; C3, 5 limbs; C4, 2 limbs; C5, 1 limb; and C6, 1 limb. Proximal and distal (92%), superficial (100%), perforator (87.5%), and complex-pattern (41.7%) reflux occurred more often in group A (P < .01). Incompetence in the GSV (75%), posterior arch, and posteromedial and saphenous tributaries was also more frequent in group A (P < .05). SSV reflux in group A (29%) matched that in group B. The PFV terminated at the deep system (96% in the popliteal vein) above the SSV (median distance, 1.5 cm; 95% CI, 0.5-2 cm). The odds ratio for a PFV in limbs with prior SSV disconnection was 5.68. Deep reflux was evenly distributed in group A (41.7%) and group B (27%). The prevalence of incompetent perforators was 283% (95% CI, 194%-373%) in group A and 96% (95% CI, 95%-98%) in group B (P < .001). PFV tributaries were distributed at the popliteal area (100%); the posterior (87.5%), medial (62.5%), and lateral (37.5%) upper calf; and the posterior distal thigh (17%), often projecting to the posterior GSV arch (50%). The (median) peak velocity of reflux in the PFV was 82.6 cm/s, the mean velocity was 17.7 cm/s, the duration was 2.4 seconds, the volume flow was 231.5 mL/min, and the expelled volume was 9.3 mL. The median diameter of the PFV at the crossing of the fascia was 0.527 cm. Venous clinical severity (range, 2-17; median, 5.5) and venous segmental disease (range, 0.5-8; median, 2.75) scores in limbs with a PFV exceeded (P <or= .04) those of the control limbs. CONCLUSIONS: With a prevalence of 4.4%, the PFV presents in limbs featuring complex reflux patterns involving all three venous systems proximally and distally. Limbs with a PFV have a higher propensity for GSV and superficial tributary reflux and have perforator vein incompetence three times more often than limbs without this vein. The PFV perforates the deep popliteal fascia terminating at the deep system (ie, the popliteal vein in 96%) distinctly above the SSV. In light of its reflux dynamics, nearing or exceeding those of severely impaired perforator veins, and the complex patterns of reflux (venous segmental disease) and venous clinical severity (high venous clinical severity scores) of the affected limbs, clinical and investigational awareness of the PFV is warranted.

Adult↗

PubMed2006

Assessing risk propensity in American soldiers: preliminary reliability and validity of the Evaluation of Risks (EVAR) scale--English version.

Risk-taking propensity is a critical component of judgment and decision-making in military operations. The Evaluation of Risks scale (EVAR) was recently developed to measure state and trait aspects of risk proneness. The scale, however, was psychometrically normed in French and no data are available for the English translation. We administered the English version of the EVAR to 165 U.S. soldiers to obtain reliability, validity, and normative data for English-speaking respondents. Confirmatory factor analysis suggested that the factor structure of the English EVAR differs from that obtained in the French studies. Instead, a three-factor solution, including recklessness/impulsivity, self-confidence, and need for control, emerged. Internal consistency was comparable to the French version. EVAR scores correlated with age, military rank, and years of service, and discriminated soldiers with histories of high-risk behavior. The data support the reliability and validity of the English version of the EVAR for evaluating risk propensity in U.S. soldiers.

Adolescent↗

PubMed1999

Propensities towards absorption are related to lapses in the monitoring of reasoning or discourse during the adult attachment interview. A preliminary investigation.

Unresolved/disorganized (U) states of mind are identified in the Adult Attachment Interview (AAI) through brief lapses in the monitoring of reasoning or discourse during the discussion of potentially traumatic experiences such as loss or abuse. These lapses have been hypothesized to indicate temporary alterations in normal states of consciousness. In parents, U attachment status predicts a pattern of infant behaviour that is associated with relatively unfavourable outcomes and has been found to be a risk factor for psychopathology in middle childhood and adolescence. In the present study (N = 140), unresolved subjects were found to be significantly elevated on Tellegens' Absorption Scale (TAS) when compared with subjects classified into the remaining adult attachment categories (secure; dismissing; preoccupied; and cannot classify). Additionally, the TAS was significantly correlated with AAI scale scores for lapses in monitoring of reasoning and/or discourse during the discussion of traumatic events. This study appears to provide the first behaviorally anchored correlate of the absorption construct outside of the domain of hypnosis. Some possible developmental origins of propensities towards absorption are discussed, including early abuse experiences and infant disorganized attachment.

Adolescent↗

PubMed2003

Long-term statin use and psychological well-being.

OBJECTIVES: We sought to study the effect of long-term statin use on psychometric measures in an adult population with underlying coronary artery disease (CAD). BACKGROUND: Previous studies have suggested associations between cholesterol lowering and psychological well-being. METHODS: Study subjects were recruited from an outpatient cardiology clinic. Psychological well-being was assessed at baseline and annually during follow-up. The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility. We estimated the odds ratios (ORs) and 95% confidence intervals (CI) that represented the strength of association between statin use (vs. no use of any cholesterol-lowering drug) and the risk of having abnormal depression, anxiety, and hostility scores. RESULTS: Study subjects had an average follow-up of four years and maximum of seven years. Comparing the 140 patients who had continuous use of statins with the 231 patients who did not use any cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR 0.63, 95% CI 0.43 to 0.93), anxiety (OR 0.69, 95% CI 0.47 to 0.99), and hostility (OR 0.77, 95% CI 0.58 to 0.93) after adjustment for the propensity for statin use and potential confounders. The beneficial psychological effects of the statins appeared to be independent of the drugs' cholesterol-lowering effects. CONCLUSIONS: Long-term use of statins among patients with CAD appeared to be associated with reduced risk of anxiety, depression, and hostility.

Adaptation, Physiological↗

PubMed1997

Differences in free-choice ethanol acceptance between taste aversion-prone and taste aversion-resistant rats.

Taste aversion (TA)-prone (TAP) and TA-resistant (TAR) rats were tested for naive, nonforced acceptance of ethanol. Ethanol acceptance had played no role in line development. Rather, the lines had been developed via bidirectional, nonsibling matings based on susceptibility to develop cyclophosphamide-induced conditioned TAs to a 0.1% saccharin solution (at cyclophosphamide doses of 12.5 mg/kg for males and 15.0 mg/kg for females, i.p.). Rats from the 23rd selectively bred generations, with no prior exposure to ethanol, were given 24-hr access to a two-bottle choice between plain tap water and a solution of ethanol in water. Rats were initially given access to 1% ethanol in water, and the ethanol concentration was increased by 1% every 3 days to a maximum of 10%. Ethanol consumption (g ethanol consumed/kg body weight) and preference scores (volume ethanol solution consumed/total fluid intake) were determined by daily bottle weighings. At 1% ethanol concentration, there were no differences between the rat lines in terms of ethanol consumption or preference. At concentrations of 2 to 10%, TAP rats consumed less ethanol and showed a decreased preference for the ethanol solutions than TAR rats. Maximum ethanol consumption was reached at the 6% concentration for both lines. The mean (+/- SE) values of consumption at 6% ethanol were 1.8 (+/- 0.8) and 5.6 (+/- 0.5) g of ethanol/kg body weight for TAP and TAR rats, respectively. Mean (+/- SE) preference scores at 6% ethanol were 26 (+/- 12) and 76 (+/- 6) for TAP and TAR rats, respectively. These findings indicate that differences in TA conditionability may be associated with the propensity of rats to be high or low consumers of ethanol. Based on these data, it is hypothesized that high susceptibility for TA conditionability may deter many individuals from consuming the high levels of ethanol that usually precede alcohol tolerance and dependence.

Alcohol Drinking↗

PubMed2004

EASED: Extended Alternatively Spliced EST Database.

We established a database of alternative splice forms (ASforms) for nine eukaryotic organisms. ASforms are defined by comparing high-scoring ESTs with mRNA sequences using BLAST, taking known exon-intron information (from the Ensembl database). Filtering programs compare the ends of each aligned sequence pair for deletions or insertions in the EST sequence, which indicate the existence of alternative splice forms with respect to the exon-intron boundaries. Moreover, we defined the alternative splice profile of each human sequence. It indicates the number of alternatively spliced ESTs (NAE), the number of constitutively spliced ESTs (NCE) as well as the number of alternative splice sites (NSS) per mRNA. NAE and NCE correspond to the EST coverage and can be used as a quality indicator for the predicted alternative splice variants. The NSS value specifies the splice propensity of a gene. Additionally, the tissue type information of all ESTs was included. This allows (i) restriction of the search to certain tissues and (ii) calculation of the tissue-NAEs, tissue-NCEs and tissue-NSS. These scores are suitable for the estimation of tissue specificity of certain ASforms. Furthermore, the developmental stage and disease information of the ESTs is available. EASED is accessible at http://eased.bioinf.mdc-berlin.de/.

Algorithms↗

PubMed1994

Prediction of pathologic stage and postprostatectomy disease recurrence by DNA ploidy analysis of initial needle biopsy specimens of prostate cancer.

BACKGROUND: DNA ploidy determination of carcinomas in radical prostatectomy specimens has shown significant correlation with patient outcome, but the predictive value of ploidy status of cancers obtained by transrectal ultrasound-guided needle biopsies has not been studied extensively. METHODS: Eighty-nine paired needle biopsy specimens (NBX) and radical prostatectomy (RPX) specimens from patients with early clinical stage (A2-B2) prostate cancer were evaluated for DNA content by image analysis of Feulgen stained tissue sections. Findings were compared with Gleason grading on the same specimens by univariate and multivariate analyses for prediction of local tumor invasion, metastasis, disease recurrence, and serum prostate specific antigen concentration during a 0.9-6.0 year clinical follow-up period. RESULTS: There was excellent correlation of ploidy status between NBX and RPX specimens (P < 0.0001); NBX and RPX grades did not correlate. On RPX specimens, aneuploid status correlated with high tumor grade (P < 0.0005). Aneuploidy in NBX specimens was associated with a twofold higher rate of extracapsular spread (ECS) (P = 0.04). Aneuploid NBX tumors featured a tenfold greater frequency of metastasis than did diploid NBX tumors (P < 0.005). Radical prostatectomy grade correlated with ECS (P < 0.001) and presence of metastatic disease (P = 0.04). On multivariate logistic regression analysis, aneuploidy in both NBX and RPX specimens was the most significant variable and independently predicted the presence of metastasis (P = 0.006 for NBX; P = 0.028 for RPX). Tumor grade of NBX and RPX specimens did not independently predict metastatic disease or disease recurrence, but RPX grade was associated independently with ECS (P = 0.005). Aneuploid NBX tumors recurred after RPX three times more often than did diploid cases, which was significant on univariate (P < 0.001) and multivariate (P = 0.018) analyses using the Cox proportional hazards model. There was no correlation with NBX or RPX Gleason score and disease recurrence. Preoperative serum PSA concentration did not correlate with tumor grade or ploidy status, but on multivariate analysis, when paired with ploidy status, independently contributed to the propensity for ECS, metastasis, and disease recurrence. CONCLUSIONS: DNA content analysis of early clinical stage prostate carcinoma needle biopsy specimens by image analysis directly correlates with radical prostatectomy specimen ploidy status and is associated independently, with the presence of metastasis, postprostatectomy disease recurrence, and ECS. Needle biopsy tumor grading did not correlate with prostatectomy grade and did not predict disease outcome accurately.

Aged↗