Biomedical subjects

D D Mickey

Publications and source records attributed to D D Mickey.

12 recordsLinked to original sources

PubMed1979

C-type virus particles in human urogenital tumours after heterotransplantation into nude mice.

C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been serially transferred in nude mice of NIH(S) background. Except for one case in which C-type particles were present in the epithelial cells as well as the connective tissue, the viruses were only found within the stroma of the heterotransplanted tumours. Peroxidase labelling with anti-mouse serum demonstrated that the connective tissue supporting the transplanted human tumours was of mouse origin. Competition radioimmunoassays demonstrated that MuLV interspecies viral protein was present in high titre in the transplanted tumour extracts and also in extracts of 2 spontaneous mouse-tumour extracts. These data suggest that endogenous viruses of the nude mice are activated by the graft, and only subsequently infect the human tumour cells and form particles.

Animals↗

PubMed1978

Isolation of a human prostate carcinoma cell line (DU 145).

A long-term tissue culture cell line has been derived from a human prostate adenocarcinoma metastatic to the brain. The cell line, DU 145, has been passaged 90 times in vitro over a period of 2 years. The cells are epithelial, grow in isolated islands on plastic Petri dishes, and form colonies in soft agar suspension culture. Karyotypic analysis demonstrates an aneuploid human karyotype with a modal chromosome number of 64. Distinctive marker chromosomes (a translocation Y chromosome, metacentric minute chromosomes and three large acrocentic chromosomes) have been identified. Electron microscopy of the original tumor tissue and of the tissue culture cell line show a remarkable similarity in cell organelle structure.

Acid Phosphatase↗

PubMed1978

Prostate and transitional cell carcinoma: radioimmunoassay of viral tumor-associated antigens.

Partially purified extracts from human urothelial tumors were utilized as competing antigens in competition radioimmunoassays in conjunction with purified RNA viral interspecies proteins and the respective antibodies to these viral proteins in efforts to detect the presence of one of the structural components of type C RNA viruses, the p30 core protein. Some antigen present in extracts of 25% of the bladder and 22% of the prostate tissues assayed demonstrated cross-reactivity with the viral p30 protein used in the radioimmunoassay system. These findings suggest that some human urothelial tissues contain a protein similar to the p30 core protein of the C-type RNA viruses and that this protein might prove useful in clinical surveys of patients with urogenital tumors.

Antigens, Neoplasm↗

PubMed1977

Scanning and transmission electron microscopy of human prostatic acinar cells.

Benign hyperplastic and neoplastic human prostate tissue samples were obtained by needle biopsy, transurethral resection or open prostatectomy. Acinar cells of both types of tissues were examined in the scanning electron microscope. It had been reported previously that adenocarcinoma acinar cells were more heterogeneous in size and shape than BPH acinar cells; the purpose of this study was to determine if there were surface morphology differences between the two types of tissues. Acinar cells were found to be extremely heterogeneous in their surface morphologies; three major types of surface morphologies were present - microvillous, ruffled, and bare. Within each class of surface morphology there was heterogeneity, both in size and density, of surface structures present. Microvillous, ruffled, and bare cells appeared to be present in normal, BPH, and neoplastic acini with no significant qualitative or quantitative differences in surface morphologies. Infrequently, it was possible to distinguish between well-differentiated and poorly-differentiated carcinomas because cells of the latter tissues were present in sheets rather than acini and appeared flat and totally devoid of surface detail. The SEM studies also sought to determine a marker to establish the origin of prostate tissue culture cells as normal, BPH or cancerous. Surface morphologies from tissues could be traced into the tissue cultures; again, three types of cells are present - bare, microvillous, and ruffled. However, since surface morphology does not appear to be a distinguishin feature of the pathology of the tissue it cannot provide a distinguishing marker for the origin of tissue culture cells. Scanning electron microscopy also provided an opportunity to observe possible secretory mechanisms and products in the prostate acinar cells.

Adenocarcinoma↗

PubMed1977

Correlation of apparent molecular weight and antigenicity of viral proteins: an SDS-page separation followed by acrylamide-agarose electrophoresis and immunoprecipitation.

A simple method is described which combines a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SOS-PAGE) in the first demension with a second electrophoresis, at right angles to the first, into an agarose matrix. The proteins, separated by SDS-PAGE, are exposed to appropriate antisera after the second stage electrophoresis and immunoprecipitates form in the agarose corresponding to the relative electrophoretic mobilities of proteins in the first stage SDS-PAGE separation. The method thus provides a simple, reproducible means for correlating antigenicity with apparent molecular weight of proteins. The technique is qualtitative, but requires smaller quantities of antisera than more conventional immunoelectrophoretic methods such as rocket electrophoresis.

Antigens, Viral↗

PubMed1977

Development and application of basic research techniques in bladder cancer research.

The growth of transitional epithelial cells with different growth media and growth supports was examined. Sephadex G-10, Bio-Gel P-20, Bio-Glas-1000, DEAE-Sephadex A-50, DEAE-cellulose, CM-Sephadex C-50, acid-soluble collagen, and immobilized collagen fibers were used to enhance plating efficiency. Acid-soluble collagen layers optimally increased the plating efficiency of primary cultures of bladder carcinoma. Media alterations with serial combinations of fetal calf, newborn calf, calf, bovine, and bull serum with minimum essential medium, Roswell Park Memorial Institute Tissue Culture Medium 1640, Connaught Medical Research Laboratories Medium 1066, Medium 199, Grand Island Biological, National Cancer Tissue Culture 135, 1415, McCoy's 5A, and National Cancer Institute medium were established. No promotion of cell division was noted with any one of these basic medium formulations.

Animals↗

PubMed1977

Heterotransplantation of a human prostatic adenocarcinoma cell line in nude mice.

Nude mice of NIH/Swiss background were utilized for the heterotransplantation of a tissue culture cell line derived from a human prostate adenocarcinoma metastatic to the brain. These cells, which had been grown in vitro for 13 passages, formed solid tumors when injected s.c. into nude mice. The cell line DU 145 has been passaged 60 times in vitro over a period of 18 months. Tumors removed from the mice were serially transplanted to additional mice and reestablished in vitro. Light-microscopic analysis of the tumor grown in nude mice revealed a strong similarity to the patient's metastatic tumor. The ultrastructure of the tumor cells propagated in nude mice was compared to that of the original human tumor cells and to the tissue culture cells, both before and after passage in nude mouse. No major differences were detected. Karyotypic analysis of the tumor cells grown in vitro before mouse passage, grown in nude mouse, and grown in vitro after mouse passage indicated chromosomal identity and consistent marker chromosomes: three large acrocentric chromosomes and metacentric minute chromosomes.

Adenocarcinoma↗

PubMed1976

Oncornavirus-like protein expression in human prostatic tissue.

A sensitive competition radioimmunoassay using 125 I-labelled p 30 interspecies antigen, antiserum specific to the interspecies antigen of the feline leukaemia virus, and aqueous tissue extracts from prostate was used to examine benign hyperplastic prostates for the presence of protein components able to complete with the interspecies viral antigens. Six of 20 prostatic nodular hyperplastic tissues were competitive in radioimmunoassay with the 125 I-labelled viral antigen for binding sites on the antiviral antibodies. These findings suggest the presence of oncornavirus-like proteins in prostatic nodular hyperplasia. No correlation could be made between the presence of competing protein and histological features of acute or chronic prostatitis and squamous metaplasia.

Antibodies, Viral↗

PubMed1976

Serial carcinoembryonic antigen assays in patients with metastatic carcinoma of prostate being treated with chemotherapy.

Serial carcinoembryonic antigen (CEA) assays were conducted in patients with endocrine-unresponsive prostatic adenocarcinoma who were being treated with multidrug chemotherapy. Changes in CEA correlated with the clinical status of the patient in 70 per cent of the determinations and were more accurate than acid phosphatase in monitoring the response to treatment.

Acid Phosphatase↗

PubMed1976

Antigenic activity of human urothelial tissue.

Partially purified extracts from 71 human urothelial tumors and from 75 human urothelial non-tumor tissues were used as competing antigens in competition radioimmunoassay in an effort to detect the presence of 1 of the structural components of type C-ribonucleic and viruses, the p30 core protein. Testing of the tissue extracts was carried out by homologous and heterologous assay systems using 125I-labeled murine (Friend) and feline (Rickard) p30 antigens and anti-feline and anti-murine p30 antisera. The homologous assays were designed to detect the presence of p30 antigens in the human tissue extracts having similar characteristics to the p30 antigens of either the feline or murine type C viruses. The heterologous assay system was designed to detect interspecies antigenic determinants common to murine and feline viruses and also primate viruses. A competing antigen present in 28 per cent of the tissue extracts assayed demonstrated an antigenic protein that competed with the viral p30 protein used in the heterologous radioimmunoassay system and to a lesser extent in the homologous feline radioimmunoassay system. Antigenic competitor proteins were found in tumor and non-tumor tissue. These data suggest that some human urothelial tissues contain at least part of the genome of 1 or more type C viruses. Those tissues that are positive only in the heterologous assay system behave like viral p30 antigens already identified in tissues of several other primates. Those tissues that are positive in the heterologous assay system and the homologous system indicate that the p30 antigenic activity is closely related to that p30 present in feline C-type viruses. Further purification and more detailed characterization of those competing proteins are now under study.

Antigens, Viral↗

PubMed1975

Detection of oncornavirus antigenic activity in human urothelial tissues.

Our studies indicate that certain urologic tissues demonstrate evidence of proteins which compete with the interspecies antigens of C-type ribonucleic acid viruses for binding sites of the feline and murine oncornavirus antiglobulins. This fact indicates either the association of viral antigens within these tissues or the presence of a protein so similar to the interspecies antigen that it cross reacts. Studies are now underway to localize reacting antigens within these urologic cells, to correlate the immunologic properties with enzymatic properties known to be specific for oncornaviruses and to assay the activity of patient sera with isolated interspecies antigens. Sera from patients with urologic malignancies will be tested to determine whether the sera can effectively absorb reactivity from tissue extracts or compete with reagent rabbit antisera raised against the interspecies component of the viruses. Should either activity be detected in patient sera, clinical screening will be undertaken to determine if this approach is applicable to early detection of urologic malignancies.

Animals↗

PubMedDate not supplied

Morphologic and immunologic studies of human prostatic carcinoma.

Benign and malignant prostatic tissue was removed in surgery and partitioned for (a) ultrastructural study, (b) tissue culture, and (c) (c) immunochemical study. Fourteen malignant and 18 benign prostatic cancer specimens were examined by transmission electron microscopy (TEM) for the presence of viruses or virus-like particles. Viruses could not be identified with assurity in thin sections. Acinar cells of normal, benign prostatic hypertrophy (BPH), and neoplastic prostate tissue were examined in the scanning electron microscope and TEM and found to be extremely heterogenous in their surface morphologies. Three major types of surface morphologies were present: microvillous, ruffled, and bare. All three types of cells were present in normal, BPH, and neoplastic acini. A collagenase procedure was utilized to remove the stromal cells from glandular structures prior to in vitro cultivation. Partially purified extracts from 71 human urothelial tumors and 75 human urothelial nontumor tissues were used as competing antigens in competition radioimmunoassay in an effort to detect the presence of one of the structural components of type-C ribonucleic acid viruses, the p30 core protein. The urothelial tumors tested included 42 BPH specimens and 18 prostatic carcinoma specimens. Thirty-eight percent of the prostatic carcinoma tissues and 48% of the BPH tissues demonstrated the presence of a protein antigenically similar to the p30 core protein of an oncogenic RNA virus.

Adenocarcinoma↗