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D S Coffey

Publications and source records attributed to D S Coffey.

At least 73 records · Page 4Linked to original sources
PubMed1990

Characterization of the subtypes of cell motility in ageing human skin fibroblasts.

Previous studies have noted alterations in cell migration during wound healing with age. Both intracellular and extracellular factors alter cell migration. In an effort to clarify the relationship between ageing and cell motility we have utilized time-lapse videomicroscopy to quantitatively and qualitatively study the various subtypes of cell motility including membrane ruffling, lamellapodal extension and cell translocation of ageing human fibroblasts in culture. We demonstrate a global decline in all types of cell motility of human fibroblasts with increasing donor age. Furthermore, we demonstrate that this decrease in cell motility with ageing is independent of chemotactic gradients.

Adult↗
PubMed1990

Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.

The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.

Androgen-Binding Protein↗
PubMed1990

Clinical and experimental studies of benign prostatic hyperplasia.

The canine prostate appears to be a suitable model for investigating many aspects of abnormal prostate growth related to BPH. This model has indicated that BPH is a complex pathologic process that varies with age and produces a gland that is composed of a mixture of glandular, cystic, and stromal hyperplasia juxtapositioned with foci of atrophy. Canine BPH first occurs very early in life as a glandular hyperplasia before the onset of more complex BPH. As the prostate increases in size with age, the tissue dihydrotestosterone content falls, as does the secretory capacity of the gland. The fall in glandular dihydrotestosterone content is counterbalanced by a concomitant increase in the metabolism of androgens toward dihydrotestosterone and an increase in nuclear androgen receptors. As the prostate ages, it thus becomes more sensitive to androgens, which are required for maintaining the abnormal size of the gland. Established BPH can be maintained in the absence of the testes in the presence of normal testosterone levels, and it appears that the abnormal growth is primarily attributable to an inherent change that has occurred in the aged prostate. In the dog and man, both the normal prostate and BPH are rich in growth factors and dihydrotestosterone receptor in the nucleus, yet mitotic cells are rare. Established BPH is not growing rapidly; the abnormal size of the aged prostate is maintained, not by an increase in the rate of cell replication, but rather by an apparent decrease in the rate of cell death. It appears that a combination of estrogens and 5 alpha-reduced androgens can cause this decrease in the rate of cell death and replication and that this imbalance can produce abnormal cell accumulation and an experimental prostatic hyperplasia. Besides affecting cell death and replication, estradiol has a marked effect in stimulating the stroma and collagen synthesis. Current investigations are focusing on determining the distribution of stem cells for both the epithelial and the stromal elements of the prostate, how these stem cells are recruited to form transiently proliferating cells, and how they mature and subsequently are programmed for cell death. It is believed that steroid imprinting in the neonatal and prepubertal period may be of great importance in determining the ultimate growth of the prostate. Preliminary attempts to control abnormal canine prostate growth by forcing maturation with retinoic acid, or by interfering with growth factors through the use of suramin, have not proved effective; only androgen ablation is. Important leads in the search for the etiology and control of BPH can be studied in the canine model. These concepts must ultimately be tested and confirmed for human BPH in well-controlled clinical investigations.

Aging↗
PubMed1989

Determination of canine prostatic size in situ: comparison of direct caliper measurement with radiologic and transrectal ultrasonographic measurements.

The use of transrectal ultrasonography to estimate canine prostatic size in situ was evaluated and compared to that of direct measurement via calipers and an in situ radiologic procedure. The length, width, and depth of prostates were measured by transrectal ultrasound in both the transverse and sagittal planes from which prostatic volume was calculated. Prostatic volumes were subsequently transformed into prostatic weights using the following nomogram: prostatic Weight (g) = 0.602 x prostatic Volume (cm3) + 1.16. Prostatic weights estimated by ultrasound as well as by direct measurement with caliper were similar (P greater than 0.10) to the true gravimetric weight; however, prostate weights estimated by the radiological X-ray procedure were significantly (P less than 0.01) lower. The relationship between true gravimetric prostate weight and that estimated by ultrasound was described by the following regression equation: estimated weight (g) = 1.127 gravimetric weight (g) - 1.665; r = 0.900; P less than 0.001; n = 23. In summary, the results of this study demonstrate that transrectal ultrasonography can be used to accurately predict canine prostatic weight.

Animals↗
PubMed1989

Etiology and disease process of benign prostatic hyperplasia.

The natural history of benign prostatic hyperplasia (BPH) involves two phases. The first, or pathological phase of BPH, involves two stages, termed microscopic and macroscopic BPH, neither of which produces symptomatic clinical dysuria. Nearly all men throughout the world will eventually develop microscopic BPH if they live long enough. In only about one-half of the men with microscopic BPH, however, will microscopic BPH grow to produce a macroscopic enlargement of the gland (i.e., macroscopic BPH), suggesting that additional factors are required for the progression of microscopic to macroscopic BPH. Several theories have been proposed to explain the etiology of the pathological phase of BPH. The major theories include the hypotheses that pathological BPH is due to 1) a shift in prostatic androgen metabolism that occurs with aging, which leads to an abnormal accumulation of dihydrotestosterone, thus producing the enlarged prostate (i.e., DHT hypothesis), 2) a change in the prostatic stromal-epithelial interact that occurs with aging, which leads to an inductive effect on prostatic growth (i.e., embryonic reawakening theory), or 3) an increase in the total prostatic stem cell number and/or an increase in the clonal expanding of the stem cells into amplifying and transit cells that occurs with aging (i.e., stem cell theory). The second, or clinical phase of BPH, involves the progression of pathologic BPH to clinical BPH in which the patient develops symptomatic dysuria. Only about one-half the men with macroscopic BPH progress to clinical BPH. Although the macroscopic enlargement of the prostate is a necessary condition for the development of clinical BPH, this enlargement is usually not sufficient by itself for the progression of pathologic BPH to clinical BPH. The etiology of the progression of pathological BPH to clinical BPH requires additional factors (e.g., prostatitis, vascular infarct, tensile strength of the glandular capsule, etc.). A successful treatment for clinical BPH, therefore, does not necessarily require either the prevention or elimination of all degrees of pathologic BPH. Instead, what is needed is a therapy to prevent or reverse the progression of pathologic BPH to the clinical disease.

Adult↗
PubMed1989

DNA loop domains in mammalian spermatozoa.

The highly condensed and tightly packaged DNA of hamster spermatozoa was found to be organized into topologically constrained DNA loop domains attached at their bases to a nuclear matrix. The loop domains of the sperm nuclei differed from somatic cell loop domains from the same animal in two aspects. Sperm loop domains were 60% smaller than somatic cell loop domains, with an average DNA length of 46 +/- 7 kb in sperm as compared with 76 +/- 11 kb in brain. Secondly, unlike virtually all somatic cell DNA known which is negatively supercoiled, sperm DNA was devoid of detectable supercoiling. The presence of the loop domain structure in the highly condensed DNA of mammalian spermatozoa suggests that this motif is a fundamental aspect of eukaryotic DNA organization.

Animals↗
PubMed1989

A comparison of nuclear morphometry and Gleason grade as a predictor of prognosis in stage A2 prostate cancer: a critical analysis.

The natural history of stage A2 prostate cancer is unknown. Previous studies from this institution have shown that, without treatment, a third of the men with clinically localized stage A2 prostatic adenocarcinoma will have disease progression within 4 years. Presently, most patients who present with stage A2 prostate cancer receive surgical or radiation therapy. The degree of differentiation of the tumor (Gleason score) presently is used to predict the prognosis among patients with clinically localized prostate cancer. The Gleason score does well to predict the prognosis for patients with scores of 2 to 4 and 8 to 10. Unfortunately, the majority of patients fall within the range of Gleason scores of 5 to 7. Better methods are needed to predict which patients diagnosed with stage A2 prostate cancer have a high probability of disease progression. Several studies have reported that morphometrically determined nuclear shape descriptors provided accurate separation of these patients that was superior to Gleason grading methods. To evaluate critically the usefulness of nuclear morphometry for prediction of prognosis we developed a system. The Hopkins Morphometry System, that calculated and compared 15 different shape descriptors that were analyzed by 17 different statistical tests. We tested this system on 18 untreated patients with stage A2 prostate cancer with an average followup of 10.5 years (range 5 to 18 years). For each patient 17 statistical analyses of the 15 shape descriptors (255 total) were evaluated and 50 analyses (50 of 255, 19.6%), including average nuclear roundness factor, provided significant separation (p less than 0.01) of the patients on the basis of outcome, whereas the Gleason score (p equals 0.076) did not. The best separation (p less than 0.01) was provided by the lower quartile analysis of the ellipticity shape descriptor.

Adenocarcinoma↗
PubMed1989

Prediction of metastatic potential in an animal model of prostate cancer: flow cytometric quantification of cell surface charge.

The natural history of clinically localized prostate cancer in individual patients is difficult to predict using currently available techniques. The majority of these patients will undergo treatment without knowledge of whether the tumor would have progressed during their lifetime. Because more patients are being diagnosed yearly with early stage prostate cancers it is becoming increasingly important to delineate factors that will clarify which patients have tumors with invasive potential. Using the Dunning R-3327 rat prostate animal tumor model we have previously shown that an increase in cell surface charge, as measured by individual cell electrophoresis, is associated with an increase in metastatic ability. This electrophoretic technique is limited by the small number of cells that can be analyzed during each assay. Therefore, we adapted a flow cytometric method for measurement of cell surface change, utilizing a large molecule (cationized ferritin) that binds quantitatively to the negative charges at the cell surface. With a fluorescent tag attached to the ferritin molecule, flow cytometric quantification of surface charge was possible, and this method was successful in identifying tumors with high metastatic ability in the Dunning prostate tumor model.

Animals↗
PubMed1989

Fourier analysis of cell motility: correlation of motility with metastatic potential.

We report the development of a computerized, mathematical system for quantitating the various types of cell motility. This Fourier analysis method simultaneously quantifies for individual cells (i) temporal changes in cell shape represented by cell ruffling, undulation, and pseudopodal extension, (ii) cell translation, and (iii) average cell size and shape. This spatial-temporal Fourier analysis was tested on a series of well-characterized animal tumor cell lines of rat prostatic cancer to study in a quantitative manner the correlation of cell motility with increasing in vivo metastatic potential. Fourier motility coefficients measuring pseudopodal extension correlated best with metastatic potential in the cell lines studied. This study demonstrated that Fourier analysis provides quantitative measurement of cell motility that may be applied to the study of biological processes. This analysis should aid in the study of the motility of individual cells in various areas of cellular and tumor biology.

Adenocarcinoma↗
PubMed1989

Identification of a sperm nuclear annulus: a sperm DNA anchor.

We report the isolation and characterization of a new nuclear structure from spermatozoa of the golden Syrian hamster which we term the nuclear annulus. The nuclear annulus was located at the implantation fossa, the point at which the tail is joined to the sperm head, inside the nucleus adjacent to the inner nuclear envelope. Extraction of sperm nuclei with 2 M NaCl and 10 mM dithiothreitol caused the solubilization of the protamines and DNA decondensation. This released the DNA from its structural constraints except that the DNA remained anchored to the nuclear annulus, which survived the extraction procedure. Nuclear annuli were isolated and examined by scanning electron microscopy. The nuclear annulus was a double-crescent, ring-shaped structure, 2.10 +/- 0.16 micron long and 1.36 +/- 0.13 micron wide. We believe that the nuclear annulus may play an important role in the organization of sperm DNA.

Animals↗
PubMed1988

Early cell motility changes associated with an increase in metastatic ability in rat prostatic cancer cells transfected with the v-Harvey-ras oncogene.

The development of metastatic ability by cancer cells is a multifactorial process whose temporal events are complex and poorly understood. One step in the metastatic process may involve cell motility. Previous studies reported correlations between motility and metastatic ability. Whether this correlation, seen in cancer cells maintained for long periods of time, is an epiphenomenon developing late in the growth of the cancer as a selection artifact of continuous passage, or is critically required for the acquisition of metastatic ability is unknown. To investigate the relationship between cell motility and the acquisition of metastatic ability, advantage was taken of recently developed DNA transfection methods for inducing high metastatic ability in initially low metastatic cancer cells. The Dunning AT2.1 cell line, a clonal rat prostatic cancer cell line with low metastatic ability, was transfected with a plasmid containing the neomycin resistance gene alone or in combination with the v-Harvey-ras oncogene. A series of the transfected cells was isolated by limiting dilution. After the first in vitro passage following transfection, cells were inoculated into rats to characterize their metastatic ability. The same transfectants were simultaneously studied using our visual grading system of cell motility to study the early motility changes associated with newly acquired metastatic ability. The data demonstrate increased membrane ruffling, pseudopodal extension, and cell translation (translocation) in the v-H-ras-transfected cell lines with high metastatic potential.

Animals↗
PubMed1988

Metastatic potential prediction by a visual grading system of cell motility: prospective validation in the Dunning R-3327 prostatic adenocarcinoma model.

A method for accurate prediction of prognosis in individual patients with prostatic carcinoma does not exist. The limitations of pathological grading systems may result from the failure of standard pathological examination of fixed dead tissue to accurately assess the biological and metastatic behavior of live tumor cells. Many of the sublines of the Dunning R-3327 rat prostatic adenocarcinoma are histologically similar yet differ in metastatic potential. Cells from the Dunning model were grown in culture and filmed by time-lapse videomicroscopy. These cells exhibited characteristic membrane ruffling, pseudopodal extension, and cellular translation that could be graded with 80% reproducibility. Individual cells from sublines with high metastatic potential were separated from cells from sublines of low metastatic potential in 96% of cases. We have applied our cell motility grading system to prospectively classify the metastatic potential of neoplastic cells. The mean motility grades of sublines of high and low metastatic potential differed significantly (Mann-Whitney-Wilcoxon, P less than 0.0005). Among seven sublines in which the grading system was developed, individual cells were correctly classified as high or low metastatic in 71% of cases by ruffling or pseudopodal extension, 73% of cases by translation, and 75% of cases by motility index, an average of the three parameters of motility. Among four newly tested sublines, cells from a low metastatic and high metastatic sublines were perfectly classified. Cells from two other low metastatic sublines were misclassified. When all 88 cells from the 11 sublines were classified, high metastatic cells were detected with 94% sensitivity and 50% specificity. The predictive value of a determination of low metastatic was 93%, whereas the predictive value of an assignment of high metastatic was 52%. The ability to detect and accurately classify most highly metastatic cells while rarely erring in a classification of low metastatic potential suggests that a grading system of cancer cell motility should be evaluated in human prostatic carcinoma. The motility of live prostatic carcinoma cells may predict patient prognosis better than standard pathological grading systems.

Adenocarcinoma↗
PubMed1988

National crop loss assessment network: quality assurance program.

A quality assurance program was incorporated into the National Crop Loss Assessment Network (NCLAN) program, designed to assess the economic impacts of gaseous air pollutants on major agricultural crops in the United States. To satisfy US EPA requirements that all environmental data collected be of known and documented quality, adequate for the intended use, the quality assurance program developed standardized research and monitoring protocols among sites, and included a range of audit and review procedures. The goal of the quality assurance program was to quantitatively describe the overall quality of data collected in terms of precision, accuracy, completeness, representativeness, and comparability. From this program, it can be concluded that (1) project data quality objectives were valuable for determining the acceptability of data from diverse sites, (2) standardized protocols ensured data comparability among research sites, (3) independent on-site audits served to evaluate protocol adherence, and (4) precision and accuracy measurements provided a way to assess data quality, determine data acceptability, and indicate the need for instrument adjustment or repair.

Journal Article↗
PubMed1988

Cell surface charge in predicting metastatic potential of aspirated cells from the Dunning rat prostatic adenocarcinoma model.

The transplantable Dunning R-3327 rat prostatic adenocarcinoma model has provided a series of tumor variants with broad ranges of metastatic potential. We tested whether cell surface charge might be related to metastatic potential by measuring the electrophoretic mobility of live tumor cells obtained by needle aspiration. Cells were aspirated from tumors with low metastatic potential (following subcutaneous inoculation of 10(6) tumor cells the H, G and AT-1 variants had less than 5% metastases; AT-2 had 5-20%) and were compared to the electrophoretic mobility of cells aspirated from highly metastatic tumors (MAT-LyLu, MAT-Lu, AT-3 had greater than 90% metastases). Electrophoretic mobility expressed in mu/sec/volt/cm. was measured on 100 cells from each tumor subline, and the cell surface charge expressed as a zeta potential was calculated from electrophoretic mobility using the Helmholtz-Smoluchowski equation. The average zeta potential (+/- S.E.M.) for the four sublines with low metastatic potential was (-17.4 +/- 0.4 mV) compared to the three sublines with high metastatic potential (-26.5 +/- 0.7 mV), and the differences were significant (p less than .01) using the Mann-Whitney Wilcoxon test. Using a zeta potential of -20.5 mV as the cutoff between high and low metastatic potential, the sensitivity and specificity of zeta potential in predicting metastatic potential in 140 determinations on seven tumor lines were 92% and 82.5%, respectively. The predictive value of a positive test (value greater than -20.5 mV) was 80% and the predictive value of a negative test (value less than -20.5 mV) was 93%. The results support a difference in the cell surface charge between these metastatic and nonmetastatic tumors with increasing negativity at the cell surface correlating with increased metastatic potential, but not with tumor growth rates.

Adenocarcinoma↗
PubMed1988

The role of androgens and estrogens in the pathogenesis of experimental nonbacterial prostatitis.

The etiology and pathogenesis of nonbacterial prostatitis remains unclear. This study provides evidence that genetic background, advancing age, and hormonal imbalance are important etiologic factors for prostatitis in rats. It also demonstrates that Lewis and Wistar rats develop a spontaneous nonbacterial prostatitis with advancing age, making them good animal models for the laboratory investigation of this disease. Spontaneous nonbacterial prostatitis is much more common in Lewis rats (72%) than in Wistar rats (27%, p less than .05), and does not occur in Sprague-Dawley rats. The incidence of spontaneous prostatitis is significantly higher in older animals than in younger animals (72% old adult Lewis rats vs. 30% young adult Lewis rats, p less than .05). Administration of exogenous 17 beta-estradiol increases the incidence and severity of prostatitis in old Wistar rats (100% treated vs. 27% control, p less than .01). Castration has a similar effect. Testosterone can block the effect of estradiol on prostatitis, however treatment with an anti-estrogen or an aromatase inhibitor to block estrogen action does not improve prostatitis in the rat. The major finding of this study is the demonstration that severe prostatitis can be induced in young adult Wistar rats by neonatal treatment with 17 beta-estradiol followed several months later in adulthood by testosterone administration. The results of this study suggest that genetic background, advancing age, and hormonal imbalance contribute to the pathogenesis of nonbacterial prostatitis in rats.

Aging↗