Search PubMed⌕ Search

Biomedical subjects

J A Mobley

Publications and source records attributed to J A Mobley.

12 recordsLinked to original sources
PubMed2004

Monitoring the serological proteome: the latest modality in prostate cancer detection.

PURPOSE: Various strategies have recently emerged to improve the diagnostic prediction of prostate cancer (CaP). One such strategy includes the mass profiling of serum protein fractions selectively adsorbed onto chemically modified probes. In the current study we further validated this approach, while offering a more versatile, less expensive and yet equally predictive alternative to existing technologies. MATERIALS AND METHODS: A solid core lipophilic C-18 resin was used to extract and enrich the low molecular weight protein fraction from patient serum for further analysis by mass spectrometry. Mass spectra generated from a 48 patient training set were data mined using multivariate analysis to identify diagnostically significant protein peaks. These peaks were then used to test a blinded study set comprising 168 patients with common statistical algorithms and commercially available software packages. RESULTS: A total of 36 peaks generated from the training set were used to test the combined set of 168 serum samples obtained from 98 healthy individuals and 70 patients with CaP. We report a sensitivity of 94.1% and a specificity of 99.0% with 1 false-positive, 4 false-negative and 5 nondiagnosed cases. CONCLUSIONS: Our results further indicate that mass profiling of serological proteins provides a means for the accurate detection of CaP. In addition, our approach was found to be superior to chip based protocols, generating rich, sharp, highly reproducible spectra attainable in a high throughput manner and at minimal cost. This technique is also scaleable for subsequent protein characterization using multidimensional protein identification technologies. Finally, analyses of mass spectra with commercially available statistical applications was found to be highly effective in generating highly discriminatory m/z values for CaP diagnosis.

Biomarkers, Tumor↗
PubMed2004

A novel diagnostic test for prostate cancer emerges from the determination of alpha-methylacyl-coenzyme a racemase in prostatic secretions.

PURPOSE: With the recent discovery that alpha-methlyacly-coenzyme A racemase (AMACR) is over expressed in a majority of prostate cancer (CaP) specimens we developed a novel polymerase chain reaction (PCR) based approach that would predict the presence of CaP from prostatic secretions. MATERIALS AND METHODS: A total of 21 patients were enlisted in this study, including 10 with CaP, 2 with high grade PIN and 9 cancer-free individuals (7 healthy men and 2 with benign hyperplasia). Total cellular RNA was extracted from prostatic secretions obtained from post-massage urine specimens. Levels of AMCAR transcripts and prostate specific antigen (PSA) transcripts in these samples were determined by quantitative reverse transcriptase-PCR analyses. Relative AMACR value scores (RAVSs) were calculated by normalizing the AMACR transcript level to that of PSA for each sample and multiplying by 100. An experimentally defined diagnostic cutoff RAVS value was determined in the cancer-free control group. RESULTS: Neither AMACR nor PSA mRNA levels were predictive of CaP when used alone. However, using RAVS values and imposing a diagnostic cutoff value of 2 SDs above the mean RAVS in the cancer-free control group all 9 (100%) cancer-free individuals, including those with benign prostatic hyperplasia, were below the cutoff and 7 of 10 (70%) with CaP had RAVS above the cutoff. Furthermore, 2 of the 3 false-negative cases showed clinically insignificant disease. The 2 patients with high grade PIN were above the cutoff in this test. CONCLUSIONS: In this study the quantification of AMACR transcripts normalized to PSA transcripts in prostatic secretions was shown to be predictive of CaP. Therefore, our novel approach using quantitative reverse transcriptase-PCR to detect the AMACR-to-PSA transcript ratio shows promise as a noninvasive screening test for CaP. Furthermore, early results demonstrate a trend toward excluding patients with clinically insignificant disease that may not yet require aggressive treatment due to a low cancer burden.

Biomarkers, Tumor↗
PubMed2001

Effects of phytoestrogens and synthetic combinatorial libraries on aromatase, estrogen biosynthesis, and metabolism.

Approximately 60% of breast cancer patients have hormone-dependent breast cancer containing estrogen receptors and requiring estrogen for tumor growth. The extent of estrogen biosynthesis and metabolism in the breast cancer tissue microenvironment influences breast-tumor development and growth, and endogenous and exogenous agents may alter the levels of hormonally active estrogens and their metabolites. Isoflavonoid phytoestrogens such as genistein exhibit numerous biochemical activities; however, their effects on estrogen biosynthesis and metabolism in breast cancer cells have not been fully examined. MCF-7 cells (hormone-dependent) and MBA-MB-231 cells (hormone-independent) were treated with genistein (100 nM) for five days and then incubated with radiolabeled estradiol (100 nM, 2.5 microCi) for 0 to 48 h. Media were extracted with ethyl acetate, and the organic residues analyzed by reverse-phase HPLC with a radioactivity flow detector. The major metabolite formed in all cases is estrone, although differences were observed between the cell lines and the various drug treatments. The formation of estrone in untreated MCF-7 cells (approximately 9.3% of radioactivity at 24 h) is relatively limited, in contrast to untreated MDA-MB-231 cells (approximately 32.0% of radioactivity at 24 h). Treatment of MCF-7 cells with 100 nM genistein increased the conversion of estradiol to estrone up to 19.5% in 24 h. The effect of genistein on estrone formation in MDA-MB-231 cells resulted in 37.7% of the radioactivity being estrone. Thus, genistein treatment of breast cancer cells resulted in increased 17-betahydroxysteroid dehydrogenase activity and elevated formation of estrone. Increased levels of oxidative 17-betahydroxysteroid dehydrogenase activity (Type II) were confirmed by Western blots. Therefore, exposure of breast cancer cells to genistein results in elevated conversion of estradiol to estrogenically weaker or inactive metabolites. The regulation of breast-tissue aromatase by exogenous agents such as drugs and environmental agents is being investigated. The benzopyranone-ring system is a molecular scaffold of considerable interest, and this scaffold is found in flavonoid natural products that have weak aromatase inhibitory activity. Medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aro- matase inhibitors. Several compounds in the initial libraries have demonstrated moderate aromatase inhibitory activity in screening assays.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Cesarean delivery for suspected fetal distress among preterm parturients.

OBJECTIVE: Among preterm parturients (< 37 weeks) who underwent cesarean delivery for suspected fetal distress, to determine the factors associated with decision-incision time (DIT) of < or = 30 minutes and to assess if umbilical arterial pH < 7.10 is more common with DIT < or = 30 or > 30 minutes. STUDY DESIGN: The peripartum course of all patients who had cesareans for suspected fetal distress over three years was reviewed. The inclusion criteria were reliable gestational age < 37 weeks and a single indication for cesarean delivery, suspected fetal distress. Twenty antepartum and intrapartum factors were used in a univariate analysis. RESULTS: The mean DIT among the 84 parturients was 30.5 +/- 21.2 minutes, and 63% of patients had surgery started within 30 minutes. The incidence of pH < 7.10 was 20%. Multivariate analysis indicated that the two factors significantly associated with prolonged time to surgery were tachycardia with decreased variability (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.6-21.6) and use of spinal anesthesia (OR 6.2, 95% CI 1.1-35.0). Though none of the 20 variables had significant univariate associations with neonatal acidosis at alpha = .05, those with P < .20 were considered in multiple logistic regression analysis. None of the 20 factors were associated with pH < 7.10, including DIT of > or = 30 minutes (OR 0.26, 95% CI 0.06-1.03). CONCLUSION: DIT is likely to be > 30 minutes if cesarean delivery is due to decreased fetal heart variability or if spinal anesthesia is utilized; neonatal acidosis, however, is not significantly associated with a prolonged interval.

Acidosis↗
PubMed1999

Risk factors for secondary arrest of labor among women >41 weeks' gestation with an unfavorable cervix undergoing membrane sweeping for cervical ripening.

OBJECTIVE: To identify the risk factor(s) for secondary arrest of labor among women with an unfavorable cervix at > 41 weeks' gestation. METHODS: Prospectively all gravid women with a Bishop score of < or = 4 and no contraindication to a vaginal delivery were candidates for this study. Univariate analysis followed by logistic regression modeling were used to identify variables with a significant association. RESULTS: Over a 9-month period, 115 women entered into the study. In univariate analysis, variables with a significant association with cesarean delivery: (1) non-Caucasian race (P = 0.007), Bishop score < 7 at hospitalization; P = 0.001, and reason for admission (P = 0.017). Logistic regression analysis yielded OR 4.7 (1.6, 15) non-Caucasian race and 9.5 (3.2, 30.8) Bishop < 7 on admission. CONCLUSION: Pregnancies > 41 weeks with an unfavorable cervix, non-Caucasian race and a failure to achieve a Bishop score of > or = 7 prior to hospitalization were significant risk factors for abdominal delivery.

Cervical Ripening↗
PubMed1999

Measurement of oxidative DNA damage by catechol estrogens and analogues in vitro.

The growth-promoting effects of estrogens in hormone-dependent tumor tissues involve receptor-mediated pathways that are well-recognized; however, the role of estrogens in tumor initiation remains controversial. Estrogen metabolites, primarily the catechol estrogens (CE's), have been implicated in tumor initiation via a redox cycling mechanism. We have developed metabolically stable CE analogues for the study of receptor versus redox cycling effects on DNA damage. Comparisons between hydroxy estradiols (HE2's), methoxy estradiols (ME2's), and hydroxymethyl estradiols (HME2) in potentiometric and DNA damaging studies were made. DNA damage was assessed in calf thymus DNA using 8-oxo-2'-deoxyguanosine (8-oxo-dG) as a genotoxic marker for oxidative stress. Increases in the number of 8-oxo-dG/10(5) dG were significant for each 2-HE2 and 4-HE2. Cu(II)SO4, a transition metal known to catalyze the redox cycling of o-quinones, substantially increased the amount of DNA damage caused by both CE's. However, DNA damage was only observed at concentrations of 10 microM or higher, much greater than what is found under physiologic conditions. Furthermore, the presence of endogenous antioxidants such as glutathione, SOD, and catalase drastically reduced the amount of DNA damage induced by high concentrations of 2-HE2. There was no DNA damage observed for the non-redox cycling HME2's, making these compounds useful probes in the study of receptor-mediated carcinogenesis. Thus, both 2-HE2 and 4-HE2 are capable of producing oxidative DNA damage at micromolar concentrations in vitro. However, since the amount of CE's has not been shown to surpass nanomolar levels in vivo, it is unlikely that free radical production via redox cycling of CE's is a causative factor in human tumorigenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Risk factors for congenital syphilis in infants of women with syphilis in South Carolina.

OBJECTIVES: This study examined risk factors for congenital syphilis in South Carolina. METHODS: Case infants with presumptive and confirmed congenital syphilis were compared with control infants born to women with reactive serologies during pregnancy, allowing investigation of risk factors for congenital rather than acquired transmission of syphilis. Data were collected from congenital syphilis report forms and birth certificates for 186 case infants and 487 controls born from 1991 to 1993. Odds ratios were calculated for maternal risk factors. RESULTS: Significant statistical trends were found for timing of first prenatal visit and number of visits. Other significant factors included rural residence (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.4, 2.9) and previous pregnancy loss (OR = 0.3, 95% CI = 0.2, 0.6). CONCLUSIONS: Prevention of congenital syphilis may be less effective among pregnant women with syphilis in South Carolina who have fewer prenatal care visits. Health care providers need further education on maternal/child syphilis management and techniques for motivating and educating patients.

Abortion, Spontaneous↗
PubMed1998

Unengaged vertex in nulliparous women in active labor. A risk factor for cesarean delivery.

OBJECTIVE: To compare the route of delivery among nulliparous parturients with and without an engaged vertex in the early, active phase of labor. METHODS: Prospectively, the position of the fetal head was ascertained among nulliparous women at 37 weeks' gestation or more in early, active labor (cervical dilation > or = 4 cm with adequate contractions). Sixteen variables, including maternal demographics, obstetric complications and intrapartum course, were examined using chi 2 and logistic regression analysis. RESULTS: Among the 77 patients, 33 (42.8%) had an unengaged vertex and 44 (57.2%) had an engaged vertex in active labor. Of the 22 cesarean deliveries for arrest disorder, 2 were in the engaged and 20 in the unengaged group (P < .001). The mean birth weight was similar among those who had vaginal (3,211 +/- 416 g) and cesarean delivery (3,400 +/- 489 g, P = .08). Univariate analysis indicated that chorioamnionitis (relative risk [RR] 2.6, 95% confidence interval [CI] 1.4-4.9) and unengaged vertex (RR 13.3, CI 3.3-53.0) were associated with cesarean delivery for arrest disorders. When entered into a multiple logistic model, only unengagement was a risk factor for cesarean delivery. The following were not associated with cesarean delivery: maternal demographics, gestational age, estimate of fetal weight, presence or absence of meconium, preeclampsia, diabetes mellitus, private obstetric care or use of epidural anesthesia. CONCLUSION: Among nulliparous parturients, an unengaged vertex is a significant risk factor for cesarean delivery for arrest disorders.

Adolescent↗
PubMed1995

Biological warfare in the twentieth century: lessons from the past, challenges for the future.

Biological warfare and fear of biological warfare have affected our wars, our peace, and our research throughout this century. During World War I, animals were deliberately infected with glanders. During World War II, biowarfare research was carried out by Japan, Germany, England, and the United States. Japan carried out biological warfare attacks in China. England used biological warfare for the assassination of Reinhard Heydrich. In the 1950s and 1960s, Army researchers released bacteria over U.S. cities in biological warfare tests. The most frequent biological warfare terrorist episodes have been contamination of food and water. Although biological warfare can be very low tech, genetic engineering is capable of making biowarfare agents available in vast quantities. Biowarfare research should continue, but the National Institutes of Health should oversee human biological warfare research.

Biological Warfare↗
PubMed1982

Nuclear accidents.

A nuclear accident with radioactive contamination can happen anywhere in the world. Because expert nuclear emergency teams may take several hours to arrive at the scene, local authorities must have a plan of action for the hours immediately following an accident. The site should be left untouched except to remove casualties. Treatment of victims includes decontamination and meticulous wound debridement. Acute radiation syndrome may be an overwhelming sequela.

Accidents↗