Expression of human prostate-specific antigen (PSA) in a mouse tumor cell line reduces tumorigenicity and elicits PSA-specific cytotoxic T lymphocytes

 Human prostate-specific antigen (PSA) has a highly restricted tissue distribution. Its expression is essentially limited to the epithelial cells of the prostate gland. Moreover, it continues to be synthesized by prostate carcinoma cells. This makes PSA an attractive candidate for use as a target antigen in the immunotherapy of prostate cancer. As a first step in characterizing the specific immune response to PSA and its potential use as a tumor-rejection antigen, we have incorporated PSA into a well-established mouse tumor model. Line 1, a mouse lung carcinoma, and P815, a mouse mastocytoma, have been transfected with the cDNA for human PSA. Immunization with a PSA-expressing tumor cell line demonstrated a memory response to PSA which protected against subsequent challenge with PSA-expressing, but not wild-type, tumors. Tumor-infiltrating lymphocytes could be isolated from PSA-expressing tumors grown in naive hosts and were specifically cytotoxic against a syngeneic cell line that expressed PSA. Immunization with tumor cells resulted in the generation of primary and memory cytotoxic T lymphocytes (CTL) specific for PSA. The isolation of PSA-specific CTL clones from immunized animals further demonstrated that PSA can serve as a target antigen for antitumor CTL. The immunogenicity studies carried out in this mouse tumor model provide a rationale for the design of methods to elicit PSA-specific cell-mediated immunity in humans. Received: 4 April 1996 / Accepted: 31 May 1996     

Dysbindin-1, a Schizophrenia-Related Protein,Functionally Interacts with the DNA- Dependent Protein Kinase Complex in an Isoform-Dependent Manner

DTNBP1 has been recognized as a schizophrenia susceptible gene, and its protein product, dysbindin-1, is down-regulated in the brains of schizophrenic patients. However, little is known about the physiological role of dysbindin-1 in the central nervous system. We hypothesized that disruption of dysbindin-1 with unidentified proteins could contribute to pathogenesis and the symptoms of schizophrenia. GST pull-down from human neuroblastoma lysates showed an association of dysbindin-1 with the DNA-dependent protein kinase (DNA-PK) complex. The DNA-PK complex interacts only with splice isoforms A and B, but not with C. We found that isoforms A and B localized in nucleus, where the kinase complex exist, whereas the isoform C was found exclusively in cytosol. Furthermore, results of phosphorylation assay suggest that the DNA-PK complex phosphorylated dysbindin-1 isoforms A and B in cells. These observations suggest that DNA-PK regulates the dysbindin-1 isoforms A and B by phosphorylation in nucleus. Isoform C does not contain exons from 1 to 6. Since schizophrenia-related single nucleotide polymorphisms (SNPs) occur in these introns between exon 1 and exon 6, we suggest that these SNPs might affect splicing of DTNBP1, which leads to impairment of the functional interaction between dysbindin-1 and DNA-PK in schizophrenic patients.     

Energy Return on Investment (EROI) for Forty Global Oilfields Using a Detailed Engineering-Based Model of Oil Production

Studies of the energy return on investment (EROI) for oil production generally rely on aggregated statistics for large regions or countries. In order to better understand the drivers of the energy productivity of oil production, we use a novel approach that applies a detailed field-level engineering model of oil and gas production to estimate energy requirements of drilling, producing, processing, and transporting crude oil. We examine 40 global oilfields, utilizing detailed data for each field from hundreds of technical and scientific data sources. Resulting net energy return (NER) ratios for studied oil fields range from ≈2 to ≈100 MJ crude oil produced per MJ of total fuels consumed. External energy return (EER) ratios, which compare energy produced to energy consumed from external sources, exceed 1000:1 for fields that are largely self-sufficient. The lowest energy returns are found to come from thermally-enhanced oil recovery technologies. Results are generally insensitive to reasonable ranges of assumptions explored in sensitivity analysis. Fields with very large associated gas production are sensitive to assumptions about surface fluids processing due to the shifts in energy consumed under different gas treatment configurations. This model does not currently include energy invested in building oilfield capital equipment (e.g., drilling rigs), nor does it include other indirect energy uses such as labor or services.     

POLLEN ENERGETICS AND POLLINATION MODES

The caloric content of pollen for several different species was determined by using a semimicro oxygen bomb calorimeter. The species studied were divided into subsets for statistical comparisons. The subsets considered were wind-pollinated dicots, monocots and gymnosperms; insect-pollinated dicots; and taxonomic subclasses of the wind-pollinated angiosperms (Asteridae, Hamamelidae, Caryophyllidae and Commelinidae). The results indicated a statistically significant caloric content difference (0.05 or higher) between wind-pollinated dicots vs. monocots and gymnosperms. There was no statistical difference between wind-pollinated dicots and insect-pollinated dicots. All subclasses were significantly different from one another. A statistically significant difference was found between two tribes in the Asteraceae which have shifted from insect to wind pollination, providing additional evidence for an independent evolution of the two. The need for future research in this area is discussed.     

Hydrocarbon-metabolizing activity of various mammalian cells in culture

Summary Two methods for determining the hydrocarbon-metabolizing enzyme activity of cultured mammalian cells were compared. The method designed to measure benzo[a]an-thracene-induced aryl hydrocarbon hydroxylase activity could detect and quantify enzyme activities in low passage rodent cells, but could not reproducibly detect levels in intermediate or high passage mouse, rat, or human cells. The method designed to measure the ability of a cell to convert benzo[a]pyrene from an organic-soluble to an aqueous acetone-soluble form proved to be more reproducible. This technique, when modified, was demonstrated to be an effective screening test for the detection of those lines with higher levels of hydrocarbon-metabolizing enzymes. Supported by the Council for Tobacco Research and Contract NIH 70-2068 within the Virus Cancer Program, National Cancer Institute, National Institutes of Health.