SV40 association with human malignancies and mechanisms of tumor immunity by large tumor antigen

SV40 was discovered as a contaminate of poliovirus vaccine lots distributed to millions of individuals in the United States between 1955 and 1963 while contaminated vaccine batches were later circulated worldwide. After SV40 was observed to cause in vitro animal and human cell transformations and in vivo tumor formations in animals, the search for a connection between the virus and human malignancies has continued to the present day. Different molecular methods have been used to detect SV40 gene products in a variety of human cancers, though SV40 causality in these tumor types has yet to be established. These data, however, are not without controversial issues related to inconclusive SV40 serological and epidemiological evidence alongside tools and methodologies that may contribute to false-positive results in human specimens. This review will also explore how vaccination against SV40 protein products may be used to help prevent and treat individuals with SV40-expressing cancers. Received 19 September 2006; received after revision 8 November 2006; accepted 13 December 2006     

Effect of partition coefficient on microsegregation during solidification of aluminium alloys

In the modeling of microsegregation, the partition coefficient is usually calculated using data from the equilibrium phase diagrams. The aim of this study was to experimentally and theoretically analyze the partition coefficient in binary aluminum-copper alloys. The samples were analyzed by differential thermal analysis (DTA), which were melted and quenched from different temperatures during solidification. The mass fraction and composition of phases were measured by image processing and scanning electron microscopy (SEM) equipped with an energy-dispersive X-ray spectroscopy (EDS) unit. These data were used to calculate as the experimental partition coefficients with four different methods. The experimental and equilibrium partition coefficients were used to model the concentration profile in the primary phase. The modeling results show that the profiles calculated by the experimental partition coefficients are more consistent with the experimental profiles, compared to those calculated using the equilibrium partition coefficients.     

Antigenic peptides recognized by T lymphocytes from AIDS viral envelope-immune humans

T-lymphocyte immunity is likely to be an important component of the immune defence against the AIDS virus, because helper T cells are necessary for the antibody response as well as the cytotoxic response. We have previously predicted two antigenic sites of the viral envelope protein gp120 likely to be recognized by T lymphocytes, based on their ability to fold as amphipathic helices, and have demonstrated that these are recognized by T cells of mice immunized with gp120 (ref. 1). A peptide corresponding to one of these sites can also be induce immunity in mice to the whole gp120 protein. Because many clinically healthy seropositive blood donors have already lost their T-cell proliferative response to specific antigen, we tested the response to these synthetic peptides of lymphocytes from 14 healthy human volunteers who had been immunized with a recombinant vaccinia virus containing the AIDS viral envelope gene and boosted with a recombinant fragment. Eight of the 14 responded to one peptide, and four to the other peptide, not included in the boost. These antigenic sites recognized by human T cells may be useful components of a vaccine against AIDS. We also found a correlation between boosting with antigen-antibody complexes (compared to free antigen) and higher stimulation indices, suggesting a more effective method of immunization.     

Extent, duration and speed of the 2004 Sumatra-Andaman earthquake imaged by the Hi-Net array

The disastrous Sumatra-Andaman earthquake of 26 December 2004 was one of the largest ever recorded. The damage potential of such earthquakes depends on the extent and magnitude of fault slip. The first reliable moment magnitude estimate of 9.0 was obtained several hours after the Sumatra-Andaman earthquake, but more recent, longer-period, normal-mode analyses have indicated that it had a moment magnitude of 9.3, about 2.5 times larger. Here we introduce a method for directly imaging earthquake rupture that uses the first-arriving compressional wave and is potentially able to produce detailed images within 30 min of rupture initiation. We used the Hi-Net seismic array in Japan as an antenna to map the progression of slip by monitoring the direction of high-frequency radiation. We find that the rupture spread over the entire 1,300-km-long aftershock zone by propagating northward at roughly 2.8 km s(-1) for approximately 8 minutes. Comparisons with the aftershock areas of other great earthquakes indicate that the Sumatra-Andaman earthquake did indeed have a moment magnitude of approximately 9.3. Its rupture, in both duration and extent, is the longest ever recorded.     

Prolonged KREEP magmatism on the Moon indicated by the youngest dated lunar igneous rock

Primordial solidification of the Moon (or its uppermost layer) resulted in the formation of a variety of rock types that subsequently melted and mixed to produce the compositional diversity observed in the lunar sample suite. The initial rocks to crystallize from this Moon-wide molten layer (the magma ocean) contained olivine and pyroxene and were compositionally less evolved than the plagioclase-rich rocks that followed. The last stage of crystallization, representing the last few per cent of the magma ocean, produced materials that are strongly enriched in incompatible elements including potassium (K), the rare earth elements (REE) and phosphorus (P)--termed KREEP. The decay of radioactive elements in KREEP, such as uranium and thorium, is generally thought to provide the thermal energy necessary for more recent lunar magmatism. The ages of KREEP-rich samples are, however, confined to the earliest periods of lunar magmatism between 3.8 and 4.6 billion years (Gyr) ago, providing no physical evidence that KREEP is directly involved in more recent lunar magmatism. But here we present evidence that KREEP magmatism extended for an additional 1 Gyr, based on analyses of the youngest dated lunar sample.     

Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals

T lymphocytes from mice and healthy humans immunized against the human immunodeficiency virus (HIV) envelope have recently been shown to recognize two antigenic regions of the gp160 HIV-envelope protein which have been located on the basis of amphipathicity. In HIV-infected humans, T-cell proliferative responses are lost soon after infection. Here we demonstrate that interleukin-2 production is often retained even when proliferative activity is absent, and that it can be used to monitor T-helper cell responses by HIV-seropositive donors. We use this approach to investigate the T-helper cell response of 42 asymptomatic HIV-seropositive patients to four synthetic gp160 peptides and to influenza A virus, an antigen requiring intact CD4 T-helper cell function. As many as 67% of the HIV-seropositive donors who retain responsiveness to influenza A virus respond to a single peptide, and 85-90% responded to at least one of the peptides.     

Towards progress on DNA vaccines for cancer

Cancer immunotherapy faces many obstacles that include eliciting immune reactions to self antigens as well as overcoming tumor-derived immunosuppressive networks and evasion tactics. Within the vaccine arsenal for inhibiting cancer proliferation, plasmid DNA represents a novel immunization strategy that is capable of eliciting both humoral and cellular arms of the immune response in addition to being safely administered and easily engineered and manufactured. Unfortunately, while DNA vaccines have performed well in preventing and treating malignancies in animal models, their overall application in human clinical trials has not impacted cancer regression to date. Since the establishment of these early trials, progress has been made in terms of increasing DNA vaccine immunogenicity and subverting the suppressive properties of tumor cells. Therefore, the success of future plasmid DNA use in cancer patients will depend on combinatorial strategies that enhance and direct the DNA vaccine immune response while also targeting tumor evasion mechanisms. Received 2 April 2007; received after revision 14 May 2007; accepted 21 May 2007