Michael R. Quastel

Linkage of boronated polylysine to glycoside moieties of polyclonal antibody; boronated antibodies as potential delivery agents for neutron capture therapy

Among the ways to deliver comparatively large amounts of boron to cells in vitro for boron neutron capture studies is the linkage of a boronated macromolecule such as polylysine to an antibody. In order to reduce interference with immunoreactivity, boronated polylysine (BPL) was linked to oligosaccharide moieties on the IgG molecule distant from the antibody combining sites. The resultant bioconjugate was chromatographically separated from free BPL and unconjugated antibody using a Sephacryl S300 column. The total measured boron per BPL-IgG conjugate, determined by direct current plasma atomic emission spectroscopy, was estimated to be approximately 6 x 10(3) atoms. This, together with molecular weight estimations, indicated conjugation of about 3 polylysines to each IgG molecule. Immunoreactivity of the conjugate was found to be the same as that of the unconjugated polyclonal antibody. This was based on its concentration dependent interference with immunometric reactions for an antigen (TSH), whereas heat inactivated or non-specific antibody had no such inhibitory effects. The results support the hypothesis that the binding affinity of the conjugate for antigen was preserved after its linkage to BPL under the conditions described. The methodology described in this report may have applicability for the preparation of boronated antibodies as delivery agents for BNCT.

Low-dose environmental radiation, DNA damage, and cancer: The possible contribution of psychological factors

Radiation causes DNA damage, increases risk of cancer, and is associated with psychological stress responses. This article proposes an evidence-based integrative model in which psychological factors could interact with radiation by either augmenting or moderating the adverse effects of radiation on DNA integrity and eventual tumorigenesis. Based on a review of the literature, we demonstrate the following: (1) the effects of low-dose radiation exposures on DNA integrity and on tumorigenesis; (2) the effects of low-dose radiation exposure on psychological distress; (3) the relationship between psychological factors and DNA damage; and (4) the possibility that psychological stress augments and that psychological resource variables moderate radiation-induced DNA damage and risk of cancer. The additional contribution of psychological processes to radiation–DNA damage–cancer relationships needs further study, and if verified, has clinical implications.

Suppression of lymphocyte activation by a soluble factor released from the human placental chorionic membrane: chemical analysis and functional characterization

ABSTRACT: A heat‐resistant factor that markedly and reversibly inhibits human lymphocyte activation was discovered in culture medium of human placental chorion. The chorionic factor inhibits lymphocyte proliferation in response to polyclonal mitogens and in the mixed leukocyte response. The inhibitory action is most effective if the factor is added during the first 24 h of lymphocyte culture and is reversible. The chorionic factor is sensitive to proteinase K, pepsin and bovine pancreatic protease; its activity is completely lost after papain digestion and following treatment with trichloracetic acid (TCA). The factor prevents the expression of IL‐2 receptors and class II MHC glycoproteins (HLA‐DR) on phytohemagglutinin‐stimulated PBMC but does not affect the expression of MHC class I molecules. It inhibits the replication of IL‐2‐dependent CTLD cells but is without effect on the growth of various human or murine cell lines or acute leukemic cells. Human placental chorion is thus capable of releasing in vitro a nontoxic heat‐resistant factor with protein characteristics that reversibly inhibits processes associated with the early stages of lymphoid cell triggering. This factor may play a role in an immunoregulatory mechanism that prevents maternally mediated immune rejection of the conceptus.

Chronic diseases and mortality among immigrants to Israel from areas contaminated by the Chernobyl disaster: a follow-up study

ObjectivesTo examine six chronic diseases and all-cause mortality among immigrants to Israel from areas contaminated by the Chernobyl accident.MethodsThe medical data were obtained from the two largest HMOs in Israel. In the assessment of chronic diseases, individuals were divided into three groups: less exposed (n = 480), more exposed (n = 359), and liquidators (n = 45) and in the mortality analysis, into two groups: less exposed (n = 792) and more exposed (n = 590).ResultsCompared to the less exposed, adults from the more exposed group had increased odds of respiratory disorders (OR = 2.34, 95% CI 1.21, 4.54) and elevated odds, with borderline significance, of ischemic heart disease (OR = 2.01, 95% CI 0.97, 4.20). In addition, the liquidators had increased odds of hypertension compared to the less exposed (OR = 2.64, 95% CI 1.24, 5.64). The Cox proportional-hazards model indicated no difference in the ratio of all-cause mortality between the exposed groups during the follow up period.ConclusionsOur study, conducted approximately two decades after the accident, suggests that exposure to radionuclides may be associated with increased odds of respiratory disorders and hypertension.

Neutron Generator as a Neutron Source for BNCT

A neutron generator was investigated for a neutron source for BNCT. Neutron generators have some obvious advantages over nuclear reactors for this purpose. The neutron source is the reaction D(d,n)3He. Moderation is done with heavy water. The optimal thickness of the heavy water layer was found to be 18 cm. To reduce the number of source neutrons, the beam should be used at angular interval 400–500 to the forward neutron direction. A beryllium reflector of thickness 20 cm was found to increase the neutron fluence by a factor of 4. The beam is clean of gamma rays.