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M C Miller

Publications and source records attributed to M C Miller.

At least 55 records · Page 3Linked to original sources
PubMed1998

Relationship between amine-carboxyboranes and TNF alpha for the regulation of cell growth in different tumor cell lines.

The amine-carboxyboranes were shown to be synergistic with tumor necrosis factor alpha (TNF alpha) in cytotoxicity and inhibition of DNA synthesis in select types of cancer cells depending on the presence of a TNF alpha high affinity receptor on the membrane of the cell. Initially both TNF alpha and the amine-carboxyboranes reduce the influx of calcium but later cause a significant increase intracellularly. This influx is not linked with the amine-carboxyborane activating the calcitonin receptor in the tumor cells. Neither the agents nor TNF alpha directly inhibits DNA topoisomerase II activity but both did cause decreased phosphorylation of the enzyme by protein kinase C (PKC). The two agents caused synergistic inhibition. This event correlated with increased DNA protein linked breaks, DNA fragmentation and cell death. These protein linked breaks are additive with etoposide's effects but the latter agent's mechanism is different than phosphorylation of topoisomerase II. There was no evidence that the DNA fragmentation was caused by a calcium induced endonuclease enzyme in these cancer cells. The low-molecular weight amine-carboxyboranes appear to play an identical function as TNF alpha in its role to cause DNA breaks and fragmentation to cause apoptosis.

Animals↗
PubMed1998

Value of computer-assisted quantitative nuclear grading in differentiation of normal urothelial cells from low and high grade transitional cell carcinoma.

OBJECTIVE: To evaluate the ability of computer-assisted quantitative nuclear grading (QNG) using a microspectrophotometer and morphometry software to differentiate Feulgen-stained nuclei captured from normal urothelium, low grade transitional cell carcinoma (LG-TCC) and high grade transitional cell carcinoma (HG-TCC) cytology specimens. STUDY DESIGN: Feulgen-stained nuclei from a series of normal volunteers (urologic disease-free history) and from biopsy-confirmed cases of LG-TCC and HG-TCC were evaluated using a CAS-200 image analysis system. Thirty-eight nuclear morphometric descriptors (NMDs) were measured for each nucleus using a software conversion system. Backwards stepwise logistic regression analysis was applied to assess which of the NMDs contributed to QNG statistical models that could differentiate between nuclei from normals vs. LG-TCC, normals vs. HG-TCC, and LG-TCC vs. HG-TCC. Receiver operating characteristic curves and areas under the curve (AUC), as well as cell classification accuracy, were used to assess these differences. RESULTS: Statistically significant differences (P < .0001) were observed between all three categories. In the LG-TCC vs. normals, the QNG solution model required 16/38 features, with an AUC = 93%, a sensitivity = 85%, specificity = 86%, positive predictive value (PPV) = 87% and negative predictive value (NPV) = 84%. The QNG solution model for normals vs. HG-TCC required 12/38 nuclear features yielding an AUC = 99%, sensitivity = 99%, specificity = 98%, PPV = 98% and NPV = 99%. The QNG solution model for LG-TCC vs. HG-TCC required 17/38 nuclear features, with an AUC = 99%, sensitivity = 96%, specificity = 97%, PPV = 97% and NPV = 96%. CONCLUSION: Computer-assisted QNG cell classifiers based upon the measurement of 38 nuclear features, including size, shape and chromatin organization, are capable of differentiating normal urothelial nuclei from LG-TCC and HG-TCC nuclei as well as LG-TCC from HG-TCC nuclei. The QNG cell classifier has shown conclusively that there are morphometric differences between normal urothelial and LG-TCC nuclei that may not be apparent to the naked eye and that it may be useful in helping the pathologist determine the presence or absence of LG-TCC in bladder cytology specimens.

Carcinoma, Transitional Cell↗
PubMed1998

The role of biopsy pathology, quantitative nuclear morphometry, and biomarkers in the preoperative prediction of prostate cancer staging and prognosis.

The focus of this review is to survey pretreatment biopsy and patient-derived information applicable to predicting pathological stage and prognosis of men with a diagnosis of prostate cancer. Various sources of clinical and pathological information that may contribute to building decision support tools (DSTs) for application by the urologist to manage prostate cancer patients are presented. These DSTs use serum biomarkers and objective, well-established, pathology information extracted by experienced pathologists from needle-core tissue samples that describe tumor size, grade, and location. Other valuable data can be derived from the biopsy tissue, such as computer-assisted image cytometry-derived DNA ploidy and nuclear morphometry informatics, as well as select tissue biomarker results that may provide supplemental prognostic information. Also discussed are the technical and clinical limitations of these DSTs with respect to the prediction accuracy. A commercially available pretreatment prediction algorithm (UroScore, Oklahoma City, OK) was applied to predict the disease organ confinement status of the prostate cancer test case. Finally, the authors present existing and future applications of computer-derived computational solutions for incorporating all patient history, clinical laboratory, and pathology information into algorithms that can generate patient-specific predictive probability estimates of stage, recurrence, and progression.

Biomarkers, Tumor↗
PubMed1997

Correlation of antepartum uterine activity and cervical change in twin gestation.

OBJECTIVE: To determine the correlation between quantitative measurements of antepartum uterine activity and cervical change twin gestations. METHODS: Forty women from our Twin Clinic constituted the study group. Participants had a cervical examination each week between 20 and 37 weeks gestation and a cervical score (CS) was calculated as follows: CS = cervical length (cms)-cervical dilation (cms) at the internal os. The women also performed blinded home uterine activity monitoring (HUAM) for a mean of 7.0 + 3.0 hrs/wk (+SD). Uterine activity was expressed as mean number of contractions/hour/week gestation based on the average of three independent reviewers. CS was determined by a single clinician unaware of the HUAM recordings. A significant change in the CS was defined as a reduction of at least 0.5 from the preceding week. Correlation coefficients were used to determine the association between uterine activity and change in the cervical score. RESULTS: Twin pregnancy was characterized by a rise from 0.2 + .03 contractions/hr at 20 weeks to 3.2 + 2.4 contractions/hr at 37 weeks gestation. CS fell from a mean of 2.6 + 0.2 at 20 weeks to -2.1 + 0.9 at 37 weeks gestation. There was a significant negative correlation (-0.317, p < .0001) between increasing uterine activity and decreasing CS. There were significantly more (p < .002) contractions during the 7 days preceding a significant reduction in CS (3.3 + 3.5 contractions/hr) than when the CS was unchanged (1.6 +/- 1.5 contractions/hr). CONCLUSIONS: In twin gestations, an increasing frequency of uterine contractions is strongly correlated with quantifiable cervical change between 20-37 weeks gestation. Persistent daytime contraction frequencies of > 3/hr represent a risk factor for cervical dilation and/or effacement.

Adult↗
PubMed1997

Update on the appropriate staging evaluation for newly diagnosed prostate cancer.

PURPOSE: Prostate cancer clinical staging methods and decision support tools were reviewed to assess their accuracy to predict pathological staging results and determine what comprises an appropriate clinical staging evaluation. MATERIALS AND METHODS: The MEDLINE data base was searched and 238 abstracts were obtained. Data were extracted from 142 articles that evaluated the preoperative accuracy of digital rectal examination, prostate specific antigen, prostatic acid phosphatase, systematic biopsy parameters (including Gleason scoring), seminal vesicle biopsy, various imaging studies and pelvic lymphadenectomy versus pathological staging results. The sensitivity, specificity and accuracy rates were calculated and tabulated from the reported data on each method or decision support tools for organ confined, nonorgan confined and lymph node metastatic tumor. RESULTS: Decision support tools based on logistic regression analysis, which combine several statistically independent staging parameters, had greater accuracy than any single clinical staging method alone. The most accurate decision support tools for clinical staging combined digital rectal examination (T stage), systematic biopsy parameters (including Gleason scoring) and prostate specific antigen. CONCLUSIONS: The components that comprise the most accurate decision support tools for clinical staging represent an appropriate staging evaluation for the newly diagnosed prostate cancer patient in 1997. Limited use of radiographic imaging and seminal vesicle biopsy may be indicated in select patients to detect bone metastases, and plan pelvic lymphadenectomy and surgical therapy.

Biopsy↗
PubMed1997

The effect of sudden inversion stress on EMG activity of the peroneal and tibialis anterior muscles in the chronically unstable ankle.

Residual symptoms resulting from recurrent episodes of inversion-type ankle sprains may be attributed to a decreased neuromuscular response of the peroneal or tibialis anterior muscles, thereby increasing the probability for reinjury. The purpose of this study was to examine the electromyographic (EMG) response time of the peroneal and tibialis anterior muscles in response to sudden plantar flexion/inversion stress in the chronically functional unstable and normal ankle. Subjects for this study consisted of 13 athletically active individuals (five males and eight females, mean age = 19.2 +/- 1.51 years) with a previous history of a unilateral inversion-type ankle sprain. A specially designed platform that allows each foot to drop into plantar flexion/inversion from a standing neutral position was used. Reaction time in milliseconds for the peroneal and tibialis anterior muscles to sudden plantar flexion/inversion was measured via surface EMG. A paired t test was performed with the Bonferroni-Dunn correction factor to determine differences between the peroneal and tibialis anterior as well as between the chronically unstable and contralateral normal ankle. The results indicated no significant differences between the stable and unstable ankles for the peroneal or the tibialis anterior muscles. The results also indicated no significant differences existed between the tibialis anterior and peroneal muscles in either the stable or unstable ankles. The findings from the present study suggest that self-reported functional ankle instability may not result in a diminished reflex response time of the peroneal and tibialis anterior muscles to sudden plantar flexion/inversion stress.

Adult↗
PubMed1997

Comparative analysis of DNA content in polyomavirus-infected urothelial cells, urothelial dysplasia and high grade transitional cell carcinoma.

OBJECTIVE: To characterize the DNA content pattern in cytologically confirmed polyomavirus (PV)-infected urothelial cells and to compare it with DNA ploidy changes in cytologically diagnosed urothelial dysplasia and high grade transitional cell carcinoma. STUDY DESIGN: We selected 200 bladder cytology specimens consisting of four groups with 50 patients each in the following cytologic categories: (1) no evidence of malignancy or dysplasia (controls), (2) PV, (3) urothelial dysplasia (UD), and (4) high grade transitional cell carcinoma (TCC-HG). For each case, two slides with 25-mm filter imprints were stained, one using the Papanicolaou method and the other using the Feulgen staining method. The DNA index (DI), proliferative activity (S + G2M) and degree of hyperploidy (> 5C) were evaluated using an image analysis system. RESULTS: Using the Wilcoxon rank-sum test, statistically significant differences in the DI were found between the PV and UD groups (P = .008) and between the PV and TCC-HG groups (P < .0001). There was no significant difference in the DI between the PV and control groups. The S + G2M fraction for the PV group significantly differed from the control, UD and TCC-HG groups (all P < .0001). Between all four groups, the degrees of hyperploidy were significantly different as well (all P < .0001). CONCLUSION: Cytologically confirmed PV-infected urothelial cells demonstrated a unique DNA content pattern with mildly elevated proliferative activity and a significantly dispersed hyperploid DNA content pattern. DNA analysis can help to differentiate PV infection from dysplasia and high grade carcinoma.

Adult↗
PubMed1997

5-Fluorouracil interferes with paclitaxel cytotoxicity against human solid tumor cells.

Paclitaxel, a naturally occurring antimitotic agent, has shown efficacy in the treatment of certain solid tumors, particularly metastatic breast carcinoma and drug-refractory ovarian cancers. Recent studies have demonstrated that paclitaxel, in addition to its effects on microtubules and cell cycle arrest, possesses significant cell-killing activity in solid tumor cells by the induction of apoptosis. However, the mechanism by which paclitaxel leads to cell death and its relationship with paclitaxel-induced mitotic arrest is presently unclear. In this study, we attempted to determine whether pre-arresting tumor cells at other phases of the cell cycle could affect paclitaxel-induced apoptosis. We found that 5-fluorouracil (5-FU), another antineoplastic agent that usually arrests tumor cells at the G1-S phase of the cell cycle, could significantly repress the cell-killing activity of paclitaxel in solid tumor cells, even when it was added simultaneously with paclitaxel. Further studies indicated that 5-FU actually inhibits the cytotoxic effects of paclitaxel on both mitotic arrest and apoptotic cell death, suggesting that 5-FU might interfere with paclitaxel cytotoxicity at an early stage, probably by preventing tumor cells from entering G2-M phase. Because recent clinical trials have used a combination of paclitaxel and 5-FU in the treatment of metastatic breast cancers, our results also suggest that the combination of these two drugs might not be as valuable in clinical chemotherapy.

Antimetabolites, Antineoplastic↗
PubMed1996

The bacillus subtilis dinR gene codes for the analogue of Escherichia coli LexA. Purification and characterization of the DinR protein.

The Bacillus subtilis dinR gene encodes a 23-kDa protein that shares about 34% homology with the Escherichia coli LexA protein. We have purified the dinR gene product to near homogeneity, and we describe its activities. The purified DinR protein binds specifically to the promoter regions of three B. subtilis SOS genes: dinB, dinC, and recA. Electrophoretic mobility of DinR-promoter complexes in each case is identical to that of promoters bound by the B. subtilis SOS repressor (Lovett, et al., (1993) J. Bacteriol. 175, 6842-6849). Analysis of hydroxyl radical footprints of DinR bound to the dinC promoter indicates that DinR interacts with one side of the DNA providing access to the consensus operator site (5'-GAACN4GTTC-3') within two adjacent major grooves. Consistent with its proposed role as a transcriptional repressor, purified DinR displaces B. subtilis RNA polymerase from the recA promoter and represses transcription of the recA gene in vitro. We also show that purified DinR protein undergoes general base-catalyzed autodigestion as well as RecA-mediated cleavage at the peptide bond between Ala-91 and Gly-92. Corresponding to its cleavage by activated RecA following DNA damage, the level of DinR is significantly reduced in RecA+ B. subtilis cells following exposure to mitomycin C. Thus, the DinR protein is structurally and functionally analogous to the E. coli LexA protein, and accordingly, we propose renaming the protein B. subtilis LexA.

Bacillus subtilis↗
PubMed1996

A Novel X-ray Diffractometer to Study the Texture of Materials.

An X-ray energy-dispersive diffraction technique to study the texture of materials using synchrotron radiation has been developed. The design and commissioning of the diffraction instrument are described. The technique was first applied to study a drawn-wire aluminum sample which has a well known deformation texture. To demonstrate its capability further, results obtained from an erbium evaporated thin film are also presented.

Journal Article↗
PubMed1996

Ability to predict biochemical progression using Gleason score and a computer-generated quantitative nuclear grade derived from cancer cell nuclei.

OBJECTIVES: To determine the ability to predict prostate cancer progression using shape, size, and chromatin texture nuclear grading features preselected by logistic regression analyses based on expert-selected prostate cancer cell nuclei captured using a computer-assisted image analysis system. METHODS: One hundred fifteen patients with clinically localized prostate cancer were identified at the Johns Hopkins medical institutions. The mean follow-up period was 10.4 +/- 1.7 years in 70 patients without disease progression, whereas the mean time to progression for the entire group was 3.8 +/- 2.5 years. Using 5-microns Feulgen-stained tissue sections, approximately 150 cancer cell nuclei were selected and captured for each case using a CAS-200 Image Analysis System. Thirty-eight different nuclear morphometric descriptors (NMDs) were calculated for each cell nucleus. The variance of the NMDs for each tumor was examined by univariate and multivariate logistic regression analyses and by Cox survival analyses to assess their ability to predict prostate cancer progression. RESULTS: Postoperative Gleason scoring was significantly correlated with disease progression (P < 0.00001; sensitivity, 73%; specificity, 84%; receiver operating characteristic curve area under the curve (ROC-AUC), 83%). Using backward stepwise logistic regression at a stringency of P < 0.05, the variances of 11 of the NMDs were found to be multivariately significant for progression prediction (P < 0.00001; sensitivity, 78%; specificity, 83%; ROC-AUC, 86%). A single value, termed the quantitative nuclear grade (QNG), was created from the variances of these, 11 multivariately significant NMDs using the logistic regression function. The QNG and the postoperative Gleason score were combined to create a model for the prediction of progression having a sensitivity of 89%, specificity of 84%, and ROC-AUC of 92%. These two parameters (QNG and Gleason score) clearly separated the patient sample into three statistically distinct risk groups and predicted the time to progression on the basis of Kaplan-Meier survival probability analysis. CONCLUSIONS: The QNG, combined with the postoperative Gleason score, may assist in the more accurate stratification of patients undergoing radical prostatectomy into low-, moderate-, and high-risk groups for cancer recurrence and may permit the early initiation of adjuvant therapy.

Adult↗
PubMed1996

Free and complexed prostate-specific antigen serum ratios to predict probability of primary prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Ratios of free to total prostate-specific antigen (f/t PSA ratio) improved differentiation of benign prostatic hyperplasia (BPH) from prostate cancer (CaP). Using sera obtained at least 1 month prior to biopsy-confirmed diagnosis and logistic regression adjusted for disease prevalence, probability curves are constructed to predict the presence of CaP. METHODS: The patient population included 122 (44%) BPH sera and 155 (56%) prostate carcinoma sera collected prior to any therapy. The total PSA range = 2.0-20.0 ng/mL; median age = 69 years. External reference standards for both free and total PSA assays were used to standardize the assays and correct the ratio. Probability curves and tables for cancer incidence were formulated for a subset of the total test population (total PSA range = 2.0-10.0 ng/mL; 98 BPH, 118 CaP patients) by using logistic regression and prior cancer prevalence statistics derived from a published patient screening study. RESULTS: Median f/t PSA ratios were 0.18 and 0.12 in the overall sample and 0.19 and 0.12 in the subset for BPH and CaP, respectively (P = 0.0001). The median total PSA concentrations for BPH and CaP were 5.8 and 6.7 ng/mL when total PSA range = 2.0-20.0 ng/mL and were 4.9 and 5.9 ng/mL when total PSA range = 2.0-10.0, respectively. CONCLUSIONS: Cancer probability curves were constructed to help guide decisions concerning biopsy and other aspects of prostate cancer disease management. Further validation of this approach in another series of patients is necessary and is planned.

Adult↗
PubMed1996

The role of high technology in maintaining esthetic restorations.

Computer technology has revolutionized the way the world does business, allowing us to work faster, smarter, and more efficiently than ever before. Within dentistry, that translates to x-rays that use significantly smaller amounts of ionizing radiation, automated periodontal charting and storage devices, and imaging systems. Perhaps the greatest bottom-line benefit, especially in esthetic dentistry, is that these state-of-the-art developments enable dentists and hygienists to more effectively communicate with patients. The future of any restoration is based on the patient's motivation and ability to maintain an efficient oral hygiene routine. Esthetic restorations demand more vigorous home care programs to maximize their esthetic and functional life expectancy. With computerized images on screen, patients can better visualize the treatment that has been done and come to a realization that the restoration's success rests squarely on their shoulders.

Computer Graphics↗
PubMed1996

Physical modelling of hip joint forces in stair climbing.

A test device has been developed and validated to simulate physiologic loading of the hip during stair climbing. Forces about the hip joint were measured in static simulations of stair climbing using simulated extensor, abductor and adductor muscle groups to support the joint. Femoral flexion angle (to model step length and height) and applied hip flexion moment (to model trunk lean) were varied to examine the effects of different loading conditions on the hip. In stair climbing the maximum total joint force was six times body weight at 34 degrees of femoral flexion and 60 N m of hip flexion moment. Joint forces increased with hip flexion moment and varied little with femoral flexion angle, except for the posteriorly directed force. This component, which twists implants about the femoral shaft, increased with femoral flexion angle but changed little with hip flexion moment.

Biomechanical Phenomena↗
PubMed1996

Development of secondary structure, growth characteristics and cytogenetic analysis of human transitional cell carcinoma xenografts in scid/scid mice.

PURPOSE: The growth of human bladder transitional cell carcinoma (TCC) in scid/scid mice was examined. MATERIALS AND METHODS: Cystocopically obtained TCC biopsies were implanted in scid/scid mice, and successful xenografts were compared with original tumors for growth and genetic characteristics. RESULTS: Low grade papillary tumors formed fluid-filled pseudobladders lined with malignant urothelium and papillary fronds containing fibrovascular cores recruited from the murine host. High grade xenografts grew without these secondary structures. When compared with the patient tumors, xenograft growth fractures, as measured by proliferating cell nuclear antigen, p53 expression and ploidy, were similar in each. CONCLUSIONS: The scid/scid xenografts maintain phenotype and architecture. This model may be useful for studying factors determining tumor grade, angiogenesis and tissue organization.

Animals↗
PubMed1996

An algorithm for predicting nonorgan confined prostate cancer using the results obtained from sextant core biopsies with prostate specific antigen level.

PURPOSE: We determined the enhanced ability to predict nonorgan confined prostate cancer using several histopathological and quantitative nuclear imaging parameters combined with serum prostate specific antigen (PSA). MATERIALS AND METHODS: Several independent pathological and quantitative image analysis variables obtained from sextant biopsy specimens, as well as preoperative PSA were used. The study population included 210 patients with pathologically staged disease (192 with PSA). All variables were examined by univariate and multivariate logistic regression analyses to assess ability to predict disease organ confinement status. RESULTS: Univariate logistic regression analysis demonstrated that, in decreasing order, quantitative nuclear grade, preoperative PSA, total percent tumor involvement, number of positive sextant cores, preoperative Gleason score and involvement of more than 5% of a base and/or apex biopsy were significant (p < or = 0.006) for prediction of disease organ confinement status. Backward stepwise logistic regression was applied to these univariately significant variables, including deoxyribonucleic acid ploidy, to calculate a multivariate model for prediction of disease organ confinement status. This algorithm had a sensitivity of 85.7%, specificity 71.3%, positive predictive value 72.9%, negative predictive value 84.7% and area under the receiver operating characteristic curve 85.9%. CONCLUSIONS: Information from pathological study of sextant prostate biopsies, preoperative PSA blood test and a new image analysis variable termed quantitative nuclear grade can be combined to create a multivariate algorithm that can predict more accurately nonorgan confined prostate cancer compared to previously reported methods.

Aged↗
PubMed1995

The disposition, tissue distribution, and cellular transport of N-[[(trimethylamino)boryl]carbonyl]-L-phenylalanine methyl ester in CF1 mice.

The disposition and tissue distribution of 14C-labeled N-[[(trimethylamino)boryl]carbonyl]-L-phenylalanine methyl esther (1) determined in CF1 mice following i.v., p.o., and i.p. administration. Compound 1 was found to undergo rapid and extensive metabolism, and the majority of the radioactivity was found in the skin and carcass regardless of the route of administration. Approximately 55% of the radioactivity was recovered in urine and feces after 78 h; however, excretion via these routes was not complete. Degradation of compound 1 occurred at the amide bond at low pH (0.8) but at the ester bond a physiological pH. This difference in degradation was reflected in elevation of the blood radioactivity levels after p.o. administration compared to i.p. and i.v. administration.

Administration, Oral↗