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     

Genetic variation at pig plasma protein locus PLP1 and its assignment to chromosome 5

A new genetic polymorphism of an unidentified plasma protein (PLP1) in pigs was described by using a method of two-dimensional gel electrophoresis and protein staining. Two codominant alleles, with frequencies of 0.83 and 0.17, were found in the Swedish Yorkshire breed. The PLP1 marker was typed in a three-generation pedigree and tested for linkage against a set of 128 markers. The PLP1 locus showed significant LOD score values with three different microsatellite markers (S0092, DAGK and S005), previously assigned to chromosome 5.     

REPRODUCTION AND RECRUITMENT OF NUCULOMA TENUIS (BIVALVIA: NUCULOIDA) FROM LOCH ETIVE, SCOTLAND

A population of the protobranch bivalve Nuculoma tenuis at adepth of c. 54 m in Loch Etive, West Scotland, was sampled monthlyfrom September 1986 to October 1988. The density of N. tenuisin the samples, and the relative proportions of adults and postlarvae,varied markedly from month to month suggesting patchiness atthe scale of the sampling. There was evidence for spatial segregationof adults and postlarvae. A seasonal reproductive cycle occurred,with a synchronised spawnout in winter; the exact timing appearingto vary in successive years by up to 2 months. Despite markedlyseasonal spawning, no recruitment peak was evident in shell-lengthfrequencies, and benthic postlarvae were present throughoutthe year. This corroborates findings from an earlier laboratorystudy, suggesting a prolonged phase of meiobenthic developmentin this species. (Received 1 February 1995; accepted 15 March 1995)     

Evidence for K+ channel control in Vicia guard cells coupled by G-proteins to a 7TMS receptor mimetic

To explore the involvement of a class of seven-trans-membrane-span (7TMS) receptors in cellular signalling, a synthetic analogue (mas7) of the amphipathic tetradecapeptide mastoparan was used to mimic hormonal stimulus in guard cells of Vicia faba. The ability for mas7 to substitute for an activated receptor complex was assayed by the effect on guard cell ion channel activities in the absence of any hormonal stimulus. Currents carried by inward-(I_K,in) and outward-(I_K,out) rectifying potassium channels were determined under voltage clamp conditions before, during, and after exposure to mas7. The dominant effect of mas7 was to inactivate I_K,in within 30 sec of application. By contrast, I_K,out was largely unaffected under these conditions. The effect of mas7 on I_K,in was both concentration- and voltage-dependent. At any one clamp voltage, mas7 inactivation showed Michaelian behaviour, with a mean K_i of 0.05 ± 0.02 µM at ?240 mV. Increasing mas7 concentration also shifted the voltage for half-maximal activation of the current negative, with 0.5 µM mas7 effecting a ?13 ± 2 mV displacement and lengthening the halftime for activation of the current by up to threefold. By contrast, the non-amphipathic analogue of mas7, masCP, had no appreciable effect on the steady-state current or its activation kinetics; nor was the poly-cation polylysine able to substitute for mas7 in its action on the K⁺ channels. Application of the non-hydrolysable analogue of GDP, GDP-β-S, either by iontophoresis or by diffusion from the microelectrode, effectively blocked mas7-induced inactivation of I_K,in. These, and additional results provide in vivo evidence for the involvement of G-protein-linked 7TMS receptors in the regulation of membrane transport in a higher plant cell.