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Biomedical subjects

S D Voss

Publications and source records attributed to S D Voss.

28 records · Page 2Linked to original sources
PubMed1989

Serum levels of the low-affinity interleukin-2 receptor molecule (TAC) during IL-2 therapy reflect systemic lymphoid mass activation.

Expression of the low-affinity interleukin-2 (IL-2) receptor molecule (TAC) has been associated with lymphocyte activation, in vitro and in vivo [Greene WC (1987) Clin Res 35:439]. We have used an enzyme-linked immunosorbent assay (ELISA) to quantify the role of released and cell-bound IL-2 receptor following in vitro or in vivo activation of human lymphocytes with IL-2. In vitro experiments, culturing fresh peripheral blood lymphocytes in 30 U/ml IL-2 (corresponding to the steady-state IL-2 concentration achieved in patients receiving IL-2 in our clinical trials), showed that the levels of IL-2 receptor released into the culture media exceeded the levels of cell-associated receptor, with both rising in parallel to the cytotoxic activity of the peripheral blood lymphocytes (PBL) against cultured tumor cells. In 12 patients receiving high-dose IL-2 for the treatment of various malignant neoplasms, the levels of IL-2 receptor released into the serum rose dramatically during the IL-2 infusion, and then fell following cessation of the IL-2 infusion. This heightened release of IL-2 receptor into the serum occurred during the episodes of profound lymphopenia that developed within hours after patients began an IL-2 infusion. Following each 4-day infusion of IL-2, a rebound lymphocytosis was observed, as has been previously reported. Serum IL-2 receptor levels do not rebound in parallel; rather, they reach a plateau near the end of the 4-day infusion and then decrease upon cessation of IL-2. These changes in serum IL-2 receptor levels accompany changes in lytic activity of circulating PBL on Daudi target cells. These results suggest that lymphocyte populations exposed to IL-2 in vivo are activated to become cytotoxic, release TAC, and relocate in non-peripheral blood compartments. Following cessation of the IL-2 infusion these activated lymphocytes return to the peripheral circulation and do not secrete TAC as vigorously as while influenced directly by the IL-2 infusion.

Carcinoma, Renal Cell↗
PubMed1987

Post-transcriptional regulation of a murine homeobox gene transcript in F9 embryonal carcinoma cells.

A 2.4 kb RNA encoded by the murine Hox 1.1 (m6) homeobox gene is induced when F9 stem cells are differentiated with retinoic acid and dibutyryl cyclic AMP. The regulation of Hox 1.1 expression was probed by using cycloheximide, an inhibitor of protein synthesis. Production of the Hox 1.1 RNA in differentiating F9 cells was not blocked by treatment with cycloheximide, indicating that new protein synthesis is not required for its induction. On the contrary, this transcript was detected in F9 stem cells treated with cycloheximide, anisomycin, or emetine alone. Nuclear transcription assays indicated that the Hox 1.1 gene was transcribed in F9 stem cells and that the rate of transcription did not change early in the differentiation of F9 cells. These observations indicate that the induction of Hox 1.1 transcripts in F9 stem cells during differentiation is not regulated at the level of transcription initiation but results from stabilization of the transcript.

Animals↗
PubMed1985

Clustered homeo boxes are differentially expressed during murine development.

A murine homeo box (m6-12) known to be expressed during differentiation of embryonal carcinoma cells lies within a cluster of homeo boxes located in 30 kilobase pairs of genomic DNA. We have established the organization of the boxes within this complex, as well as the nucleotide sequence of a second box, m5-4. Similar to the m6-12 box, expression of novel m5-4 transcripts is induced upon differentiation of embryonal carcinoma cells. Transcripts of genes containing m6-12 were found in embryonic tissue during almost all stages of prenatal development studied, whereas expression of m5-4 was detected only in 12 day embryonic tissue. Finally, we have described the differential expression of these homeo-box-containing regions in various adult tissues.

Amino Acid Sequence↗
PubMed1982

Effects of dietary aroclor 1254 and cyclopropene fatty acids on hepatic enzymes in rainbow trout.

Diets containing Aroclor 1254 (PCB); cyclopropene fatty acids (CPFA), and PCB plus CPFA were fed to rainbow trout (Salmo gairdneri) for 15 weeks to determine the effects on hepatic microsomal activities of ethoxyresorufin-O-deethylase, ethoxycoumarin-O-deethylase, and benzo(a)pyrene monooxygenase. Ethoxyresorufin-O-deethylase activity continued to increase to a level 77-fold higher than control at week 15. Ethoxycoumarin O-deethylase and benzo(a)pyrene monooxygenase activities increased to 7.1-fold and 47-fold over control at week 9, respectively. Cytochrome P-450 values remained approximately 2-fold above controls from week 5 through week 15. At weeks 1 and 3, cytochrome P-450 levels were not significantly different from control. Dietary CPFA significantly depressed ethoresorufin-O-deethylase and ethoxycoumarin-O-deethylase activities, but had no effect on benzo(a)pyrene monooxygenase activity. Ethoxyresorufin-O-deethylase, ethoxycoumarin-O-deethylase, nd benzo(a)pyrene monooxygenase activities in the combined PCB-CPFA-fed trout were significantly higher than in control- or CPFA-fed trout, and significantly lower than in PCB-fed trout. This is the first time dietary PCBs have been shown to induce the MFO system in rainbow trout. These results provide a possible explanation for the effects of dietary PCBs on the metabolism and expression of other chemical carcinogens.

7-Alkoxycoumarin O-Dealkylase↗
PubMedDate not supplied

Structural analysis of murine genes containing homoeo box sequences and their expression in embryonal carcinoma cells.

The presence of homoeo box sequences in the genomes of vertebrates has suggested that these metazoans possess the equivalent of the homoeotic genes that have a key role in regulating the development of the fruitfly Drosophila melanogaster. We report here that a novel murine homoeo box-containing gene is expressed in embryonal carcinoma stem cells. Transcripts of the sequences that flank the homoeo box of this gene are found in these cells before and after induced differentiation, whereas a specific transcript that seems to contain the homoeo sequence is only present after differentiation.

Animals↗
PubMedDate not supplied

Gene therapy: a primer for radiologists.

Gene therapy is one of the most rapidly evolving areas in medicine. Radiologists should have an understanding of basic techniques used to identify and clone a gene and insert it into a vector capable of directing expression in mammalian tissues. DNA delivery systems include retroviral vectors (RNA viruses), adenoviral vectors (DNA viruses), and cationic liposomes, along with strategies that involve ultrasound-directed gene transfer, computed tomography-guided gene transfer, and transcatheter gene delivery, in particular via the hepatic artery. Genes being evaluated in preclinical and clinical trials include oncogenes, antioncogenes (tumor suppressor genes), suicide genes, conventional antimetabolites, antiangiogenesis factors, secreted immunostimulatory cytokines such as interleukins and interferons, and immunomodulatory cell surface proteins, including foreign HLA proteins and costimulatory molecules. A foundation in molecular biology is needed for the practicing radiologist interested in but unfamiliar with current gene therapy terminology and experimental strategies. Such a foundation will encourage the dissemination of basic biologic, diagnostic imaging, and interventional oncoradiologic developments and should facilitate integration of the radiologist into the gene therapy team.

Cystic Fibrosis↗
PubMedDate not supplied

Costimulation of human natural killer cell proliferation: role of accessory cytokines and cell contact-dependent signals.

Despite the importance of natural killer (NK) cells in the immune response, the regulation of human NK cell growth has not been well characterized. We have hypothesized that, similar to the proliferation of T and B lymphocytes, optimal proliferation of NK cells requires costimulatory signals as well as a primary mitogenic stimulus. Evidence for costimulation by both soluble cytokines and cell contact-dependent factors is presented. Soluble IL-1 and TNF were found to augment NK cell proliferation in response to primary mitogenic cytokines, including IL-2, IL-4, IL-7, and IL-12. The costimulatory effect of IL-1 and TNF is strongly enhanced by the calcium ionophore ionomycin. Coculture of NK cells with irradiated K562 cells can largely substitute for the costimulatory signal provided by ionomycin. Costimulation by K562 requires intimate cell contact and is not reconstituted by cell-free supernatants. Activated T lymphocytes can also mediate contact-dependent costimulation of NK cells; resting PBMC, several NK-sensitive cell lines, and all NK-resistant cell lines tested were not found to be costimulatory. Engagement of CD16 did not augment NK cell proliferation. Thus, triggering of natural killing or antibody-dependent cell-mediated cytotoxicity (ADCC) does not consistently provide a costimulatory signal for NK cell proliferation. Cell contact-dependent costimulation of NK cells does not appear to involve known receptors that can costimulate T cells, including CD2, CD27, CD28, CD29, or LFA-1. The molecular nature of the putative NK cell costimulatory receptor remains to be elucidated. Nevertheless, human NK cells could be expanded in vitro using leukocyte-conditioned medium (LCM) as a source of IL-2 and accessory cytokines and ionomycin to bypass the putative receptor for cell contact-dependent costimulation. NK cells expanded in LCM and ionomycin express typical NK cell antigens and mediate natural killing and ADCC. Further characterization of the costimulatory signals for NK cell proliferation may elucidate the physiologic regulation of NK cell growth and may ultimately allow more effective manipulation of these lymphocytes in the immunotherapy of human diseases.

Antibody-Dependent Cell Cytotoxicity↗