Editor's note: Science Scan is a roundup of recently published biotechnology-related research.
Could it be that unsafe, high-risk, high-frequency sex is itself a form of protection against HIV infection and AIDS?
This counterintuitive suggestion finds support in the the current Proceedings of the National Academy of Sciences (PNAS), dated Feb. 2, 1999. The research paper?s title is ?Lack of infection in HIV-exposed individuals is associated with a strong CD8+ cell non-cytotoxic anti-HIV response.? Its principal author is virologist Jay Levy, at the University of California, San Francisco.
?The relative risk of infection by HIV correlates directly with the number of exposures to the virus,? begins Levy?s report. Then, it adds a kicker: ?However, within any exposed uninfected (EU) population, some individuals remain uninfected despite multiple unprotected encounters with HIV-infected partners.?
To wrestle this paradox to the mat, the co-authors probed the practices and immune cells of 60 high-risk EU individuals, in their 30s and 40s, at four AIDS clinics around the country. Of this number, 16 were women who reported up to 60 vaginal-intercourse encounters during the past 12 months, and 16 men who had received up to 24 anal encounters during the year.
The remaining 28, mixed male and female, had had repeated unprotected sexual exposure. Two of them also shared narcotic needles with an infected partner. The sexual partners of all 60 subjects were HIV-positive.
The co-authors cited at least five possible explanations for this apparent, unlikely immunity: replication-defective viral strains; reduced susceptibility of target cells; lack of a viral coreceptor; HIV-specific antibodies; or T cells that can inhibit viral spread without killing its target cell.
?Based on this latter mechanism,? the paper observed, ?repeated exposures could potentially lead to enhancement of antiviral immunity, functioning much like a booster vaccination.?
The co-authors conclude, ?The discovery of this immunologic correlate to protection is encouraging for the future design of anti-HIV vaccines ?
Procyon?s Prostate Cancer Protein Curbed Tumor Growth In Mice; Human Trials Seen By Year?s End
In recent years, prostate-specific antigen (PSA) has become a diagnostic and prognostic indicator of prostate carcinoma. This is the commonest diagnosed malignancy, and the second leading cause of cancer-related death in American men.
PSA is a protein secreted into seminal fluid, and detectable by urologists in blood and urine. So is prostate secretory protein (PSP), a 94-amino-acid molecule found more recently on late-stage prostate cancer cells. It too has diagnostic/prognostic potential in patients whose tumors are androgen-independent.
New data suggest that PSP94 may be therapeutic as well.
A paper in the February 1999 issue of The Prostate bears the title: ?Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis.? Its senior author is radiation oncologist Dean Tang, of Wayne State University, of Detroit.
Prostate cancer patients with positive PSP94 expression, his article points out, ?have a much better prognosis than those with negative expression.? It reports that in vitro and in vivo, the protein checked the growth of a human prostate cancer cell line, PC3.
The co-authors purified PSP94 from human seminal fluid supplied by the fertility clinic at University Hospital, in London, Ontario. One week after implanting PC3 tumor cells under the skins of nude (immunodeficient) mice, they injected PSP94 daily into randomized animals. Controls got only saline.
By 34 days after implantation, the tumors of control mice averaged 0.30 cubic centimeters in size, versus a statistically significant 0.12 in PSP94-treated animals. ?In vivo xenograft experiments confirmed the efficacy of PSP94 in retarding tumor growth,? the article pointed out, ?which may have resulted from a combination of both reduced cell proliferation and survival.? Microscopic examination of the tumor cells revealed ?cell death reminiscent of apoptosis.?
?In light of these observations,? the paper concluded, ?our current study suggests that PSP94 may represent a novel, apoptosis-based, tumor-specific and potentially nontoxic agent applicable to the clinical treatment of prostate cancers.?
The paper?s first author is Seema Garde, a researcher at Procyon BioPharma Inc., also in London, Ontario. That firm?s president and CEO, Chandra Panchal, told BioWorld Today that the preclinical results ?provide validation of Procyon?s approach to treating hormone-refractory, or end-stage, prostate cancer, for which there is currently no effective treatment. Procyon remains on target to initiate human clinical studies using this therapeutic approach by the end of 1999.?
Swedes, Belgians Breed Lean Wild Boars, Muscled Farm Pigs, To Track Imprinted Meat Traits
Not all of a person?s genes, inherited from mother and father, are equal in clout. Some may be turned off or on in offspring, depending on which parent bequeathed them. This effect, known as genomic imprinting, has been implicated in cancer and other diseases.
One concept current among geneticists explains genomic imprinting as nature?s ploy to maximize ? in polygamous species ? one parent?s genetic bequest to its progeny at the expense of the other.
Polygamy is a way of life for domestic pigs. Breeders make a point of crossing many sows with a single blue-ribbon boar, to maximize that designated hitter?s prize-winning traits, say of muscularity versus fat deposition.
Two brief, back-to-back reports in the February 1999 issue of Nature Genetics describe pig-crossing experiments at the molecular level in Sweden and Belgium. Geneticist Leif Andersson, of the Swedish University of Agricultural Sciences, in Uppsala, reports: ?A paternally expressed QTL [quantitative trait loci] affecting skeletal and cardiac muscle mass in pigs maps to the IGF2 locus.?
Andersson and his co-authors generated an intercross between the European Wild Boar and Large White domestic porkers. They used this pedigree to map quantitative trait loci in their offsprings? chromosomes. They chose the imprinted IGF2 gene as a candidate locus on the short arm of pig chromosome 2 because of its evolutionary homology to human chromosome 11?s short arm.
They found evidence for a paternally expressed QTL at the tip of the porcine chromosome 2. It ?had large effects on lean meat content in ham,? their paper noted, ?[and] on the area of the longissimus dorsi muscle, heart weight and backfat thickness. . . .? The Large White allele, the paper said, ?was associated with larger muscle mass and reduced backfat thickness, consistent with the difference between this breed and the Wild Boar population.? This imprinting evidence indicated ?clear paternal expression.?
The IGF2 gene is well documented in prenatal development; Andersson?s result ?demonstrates a role for the IGF2 region in postnatal development as well,? said the paper. The data bear, the paper points out, ?on association between genetic polymorphisms in the insulin-IGF2 region, multi-factorial traits and diseases in humans and meat-producing farm animals.?
The Belgian paper is remarkably similar. Its heading reads: ?An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs.? It emanates from the University of Liege, with geneticist Michel Georges as senior author. n