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Biomedical subjects

D J Merchant

Publications and source records attributed to D J Merchant.

At least 19 recordsLinked to original sources

Scheduled brief admissions: patient "tuneups".

1. Incorporating brief, planned admissions into the treatment plan of chronically mentally disabled patients has demonstrated positive outcomes related to health care services, as well as to the patients' perceptions of their own health status. 2. A comparison of the "Tuneup" program before and since its inception showed that, while the number of patient hospitalizations increased, the patients' length of stay, amount of unplanned hospitalizations, and cost decreased significantly during this period. 3. The chronically mentally ill are a population at risk for a variety of hardships, including rehospitalization, social isolation, homelessness, and even death. Psychiatric nurses who understand the needs of these persons can serve as a vital force in mental health care reform.

Adult↗

Primary explant culture of human prostate tissue: a model for the study of prostate physiology and pathology.

An explant of human prostate tissue containing viable acini will give rise in vitro to an outgrowth of epithelial cells of presumed basal cell origin. These cells can be passaged by trypsinization, undergo numerous population doublings (up to 50-60), and attempt a normal pattern of differentiation, which may succeed, to varying degrees, depending on conditions of culture. The system can serve as a useful model for analysis of the role of hormones, growth factors, cytoskeletal elements, cell-cell interactions, and of the basement membrane both in normal physiology and in pathology of the prostate. The system also should prove useful in the evaluation of the possible roles of chemical carcinogens, radiation, and viral or cellular oncogenes in carcinogenesis. Moreover, the model system should be useful in the evaluation of chemical, physical, or biological agents for treatment or prevention of prostate cancers.

Animals↗

Terminally differentiating epithelial tissues in primary explant culture: a model of growth and development.

Many epithelial tissues are characterized by the presence of basal cells which serve the dual roles of self-renewal and of progression through terminal differentiation, to a functional state. Such tissues, when grown in vitro as primary explants, exhibit a characteristic pattern of outgrowth and development which includes both renewal and efforts toward normal differentiation. The degree of differentiation achieved depends upon conditions of culture and may be modulated in a variety of ways. The human prostate constitutes such a system and offers numerous possibilities for investigating basic control mechanisms in growth and development. Information on a variety of epithelial tissues is reviewed and experimental results using human prostate tissue are presented.

Cell Differentiation↗

Phenotypic and cytogenetic characterization of a cell line derived from primary prostatic carcinoma.

A new cell line, PPC-I, has been established from a specimen obtained from a patient with a poorly differentiated adenocarcinoma of the prostate. This is the first line of its type derived from a primary prostatic tumor site. PPC-I cells have become immortalized in culture, exhibit transformation parameters including relaxed growth factor requirements and anchorage-independent growth, and are highly tumorigenic in nude mice. Cytogenetic studies by G-banding revealed a grossly abnormal karyotype, with a modal chromosome number of 84, multiple marker chromosomes including both homogeneously staining regions and double minutes and clonal loss of chromosomes 3, 5, 10, 15 and Y.

Aged↗

Cytogenetic analysis of four primary prostatic cultures.

Primary cell cultures were established from tissue specimens obtained from patients undergoing transurethral resection of the prostate. Cytogenetic analysis of these cultures revealed a normal male chromosomal complement from one and a 45,X karyotype from another patient with benign prostatic hyperplasia. In addition, a normal male chromosomal complement was observed from a moderately differentiated prostatic carcinoma, and a grossly abnormal karyotype was observed from a poorly differentiated adenocarcinoma of the prostate. This latter specimen contained a modal chromosome number of 84 with several consistent marker chromosomes including homogeneous staining regions and double minutes, and no normal chromosomes 3, 5, 10, 15 or Y. Primary prostatic cell cultures exhibit epithelial-specific keratin intermediate filament proteins, and, in conjunction with cytogenetic analysis, provide a model for the study of human prostate cancer.

Chromosome Aberrations↗

Primary explant culture: an in vitro model of the human prostate.

Human prostate tissue gave rise to essentially pure cultures of basal cells in vitro. Careful analysis by phase-contrast microscopy and photography suggested that these cells attempt to differentiate into secretory acinar cells. This was confirmed by immunocytochemical analysis for prekeratin which is present only in basal cells in situ and for prostatic acid phosphatase, prostate-specific antigen, and prostate fluid antigen, which are present only in secretory acinar cells in situ.

Acid Phosphatase↗

Monoclonal antibodies against a soluble cytoplasmic antigen in human prostatic epithelial cells.

Antibodies against a soluble cytoplasmic protein contained in prostate epithelial cells were developed using the hybridoma technique. This was done to provide markers for these cells that can be used to identify acinar cells in culture and to follow their development and/or differentiation over long periods of time. The antibodies do not recognize prostatic acid phosphatase nor the prostate antigen. They do recognize prostate acinar cells in formalin fixed tissue sections. The basal cells underlying the prostate epithelial acinar cells do not appear to contain the antigen. The antigen detected is believed to be a product of differentiated prostatic acinar cells.

Animals↗

Primary cultures of human prostatic epithelial cell from transurethral resection specimens.

The objective of this work was to design a simple and reproducible method of culturing human prostatic epithelial cells from attainable tissue. This type of system is essential for in vitro studies of prostatic cancer and benign prostatic hyperplasia (BPH). The most readily available source of prostatic tissue is the transurethral prostatic resection (TURP). This tissue can be obtained at surgery and processed immediately in the laboratory using standard cell culture techniques. By detailed sectioning and careful histologic examination of the tissue which represented the mirror image of each explant that was cultured, we found that tissue containing viable glandular structure yielded epithelial outgrowths. Pieces of tissue that did not yield epithelial outgrowth were composed only of fibromuscular stroma or contained acini which were damaged (usually cauterized). We concluded that this type of system can be used routinely to study prostatic disease on an individual basis.

Cells, Cultured↗

Virology studies and cell lines for prostate cancer.

Immunological and biochemical probes for viral genomes and products, growth in cell culture, co-culture methods to activate latent genomes, use of activating agents, and electron microscopy have been used in efforts to demonstrate RNA viruses in prostate cancer. Despite findings of C-type particles and p30 antigens, the role of RNA viruses appears to be secondary, with activation of the virogene being a relatively uncommon occurrence. No compelling evidence for Herpes II or cytomegalovirus as etiologic agents has emerged, despite their common presence in the urogenital tract. Though the search for integration of fragments of viral genome into host DNA is still in progress, it appears unlikely that these viruses would account for a significant number of prostate carcinomas. Progress has been achieved in developing simple, reliable, primary culture methods for human prostatic tissue, using explants or dispersed cells. Three cell lines, all from metastatic foci, have been established, are characterized, and are available for distribution. One neonatal cell strain retains many properties of normal prostate.

Cell Line, Tumor↗

Characterization of prostate cells.

It is obvious from this brief review that the weakest link in the successful application of in vitro models to answer questions related to prostatic cancer is the lack of adequate markers to permit characterization of the cells with regard to organ and tissue origin and their neoplastic status. In our opinion there is little to be gained in defining markers for other purposes until we can manage these basic areas of recognition.

Cell Differentiation↗

Requirements of in vitro model systems.

In summary I would encourage the continued development of a variety of model systems with maximum characterization and with careful definition of questions to be asked. At the same time it is imperative that the biology of the prostate, and of BPH and prostatic carcinoma in particular, be kept clearly in mind so that appropriate questions can be asked and valid conclusions drawn.

Animals↗

Model systems for the study of prostatic cancer.

Application of suitable in vivo and in vitro model systems are necessary to further investigations in prostatic adenocarcinoma. Model systems are defined, and discussed in terms of their potential application to the study of the neoplastic process.

Adenocarcinoma↗

Prostatic tissue cell growth and assessment.

The potential for use of cell and organ culture systems in the study of prostatic tumors is high. The nature of this organ and our lack of basic information about it limit the usefulness of in vitro techniques at present but these shortcomings can be overcome by concerted effort of interested investigators. At the present time organ culture methods are available which can yield valuable information. To achieve notable success requires considerable understanding of the method in terms of principles, detail of technique, and interpretation. Several important questions must be resolved in order for cell culture methods to achieve their potential: (1) effect of disaggregation procedures on prostatic tissue, (2) appropriate selection of specimens, particularly with regard to controls, (3) ability to clearly identify and select cell types, and (4) how to overcome the variable of serum as a source of hormones. Considering the fact that less work has been done on the prostate than most tissues, recent developments in the area of cell and organ culture seem most encouraging and the future looks bright indeed. Two continuously propagated cell lines of pupative prostatic origin have been described. One of these developed in culture apparently as the result of a spontaneous transformation while the other was propagated from an adenocarcinoma. If these cell lines can be conclusively proved to be representative of the tissues of origin we already are well on the way to the application of in vitro systems to study of the prostate.

Adenocarcinoma↗

Survey of interferon production and sensitivity human cell lines.

Seven presumed diploid and 11 established cell lines were studied for their ability to produce free interferon in response to a standardized Newcastle disease virus challenge. Interferon production was evaluated in both serum-containing and serum-free medium. The ability of these cell lines to respond to the application of a standard interferon preparation by becoming resistant to virus was also examined. The diploid lines were distinctly more efficient producers of interferon than were the established lines. They also evidenced a greater requirement for serum to produce their maximum titers, but some were able to produce good titers in serum-free medium. The diploid lines were uniformly more sensitive to the application of exogenous interferon than were the established cell lines and attained greater degrees of virus resistance, but all lines tested displayed measurable sensitivity to interferon.

Animals↗