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We apply Wildeshaus's theory of motivic intermediate extensions to the motivic decomposition conjecture, formulated by Deninger–Murre and Corti–Hanamura. We first obtain a general motivic decomposition for the Chow motive of an arbitrary smooth projective family |$f:X \rightarrow S$| whose geometric fibers are Tate. Using Voevodsky's motives with rational coefficients, the formula is valid for an arbitrary regular base |$S$|⁠ , without assuming the existence of a base field or even of a prime integer |$\ell $| invertible on |$S$|⁠. This result, and some of Bondarko's ideas, lead us to a generalized formulation of Corti–Hanamura's conjecture. Secondly we establish the existence of the motivic decomposition when |$f:X \rightarrow S$| is a projective quadric bundle over a characteristic |$0$| base, which is either sufficiently general or whose discriminant locus is a normal crossing divisor. This provides a motivic lift of the Bernstein–Beilinson–Deligne decomposition in this setting. [ABSTRACT FROM AUTHOR]

The hypotheses that Swedish patients with four or more primary tumours [including at least one cutaneous malignant melanoma (CMM)] harbour an increased number of CDKN2A (formerly p16) germline mutations, and that this group of patients show a predisposition to other tumours, e.g. nonmelanoma skin cancer (NMSC), were studied descriptively. So far the mutation 113insArg explains all CDKN2A-associated CMM in ethnic Swedes. All patients with four or more primary tumours, of which at least one was a CMM, from the Southern Swedish Regional Tumour Registry , between 1958 and 1999, were included in this study. Forty-four patients were found and subdivided into three groups according to having multiple CMM (group A) or single CMM ± NMSC (groups B and C). Screening for the presence of the Swedish founder mutation 113insArg in blood or in tissue blocks was performed. Patients in group A were younger at the time of the first CMM diagnosis than patients in group B and group C. The 113insArg mutation was found in four of 44 patients (9%), three with multiple CMM. In group C ( n = 14) no founder mutation was evident, while in group B ( n = 15) one mutation carrier was found. Nonmutation carriers with multiple CMM (group A) also had a predilection for meningiomas and neurinomas (four patients) or multiple NMSC (three patients). In group B CMM were especially associated with adenocarcinomas but in group C CMM were associated with multiple NMSC. The association between meningiomas and neurinomas (no acoustic neurinoma was seen) might indicate a new syndrome. Patients in groups B and C may harbour unknown genetic defects, which could interact with different environmental risk factors. [ABSTRACT FROM AUTHOR]

A technique for detecting IgM rubella antibodies by immunofluorescence was developed. Total serum IgG was removed by prior immunoabsorption with anti- γFc. This prevents interference by rheumatoid factors in the serum. The test appeared sensitive and specific in sera of rubella convalescents and infants with congenital rubella. [ABSTRACT FROM AUTHOR]

High affinity interleukin 2 receptors (HA-IL-2R) on mitogen-or antigen-stimulated T cells have been shown to efficiently bind interleukin 2 (IL-2) and to transduce the activation signal(s) that facilitate proliferation. This study was initiated to determine whether the impaired proliferative response of T cells from elderly individuals can be attributed to the defective expression of HA-IL-2R. While cells from both young and old individuals had statistically insignificant differences in the number of HA-IL-2R per membrane IL-2R-positive cell and these receptors displayed similar binding affinities with 125-IL-2, there were consistently fewer cells and fewer cells expressing HA-IL-2R in the cell cultures from elderly individuals. The magnitude of the age-associated impairment in cell proliferation was decreased, but remained present, when Percoll fractionated lymphoblasts, as compared to peripheral blood lymphocytes (PBL), were cultured in the presence of exogenous interleukin 2 (IL-2). The results demonstrate that a significantly larger percentage of lymphocytes from elderly individuals do not respond to mitogenic stimulation and, probably due to stimulus stress, die in culture. As a consequence there are fewer functionally competent cells expressing the HA-IL-2R in cultures from elderly individuals, which in turn contributes to the age-related defect in the lymphocyte proliferative response. [ABSTRACT FROM AUTHOR]

Current models of T cell activation implicate increases in intracellular free Ca2+ concentration and activation of the Ca2+ and phospholipid dependent enzyme protein kinase C (PKC) as important early events leading to interieukin 2 (IL-2) production, interleukin 2 receptor (IL-2R) expression, and subsequent cell proliferation. The present study examined the age-related defect in T cell proliferation to determine if the signals that activate PKC and increase intracytosolic free Ca2+ concentration might be defective. Using phorbol myristate acetate (PMA), which directly activates PKC, and Ca2+ ionophore A23187, which increases intracellular cytoplasmic free Ca2+ concentration, the induction of IL-2 secretion, IL-2R expression and cell proliferation were studied. The results demonstrate that following stimulation with PMA and A23187, purified T cells from elderly subjects demonstrate low levels of IL-2 production, IL-2R expression and cell proliferation. Exogenous purified human IL-2 did not fully correct the low proliferative responses of T cells from old donors, however, did markedly boost the response. While it appears that the inability of T cells to express IL-2 Rand respond to IL- 2, along with a lower endogenous IL-2 production are limiting factors in cell proliferation, the inability of PMA and A23187 to correct this defect suggests that the early phases of signal transduction per se are probably not a primary cause of the immunodeficiency seen in ageing. [ABSTRACT FROM AUTHOR]

Human peripheral blood T lymphocytes were treated with phorbol myristate acetate (PMA), an activator of protein kinase C (PKC) activity, and with the calcium ionophore A23187. The resulting accumulation of specific mRNA for interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R), as well as IL-2 secretion and membrane IL-2R expression were examined. At low concentrations (0.1 μM), A23187 synergized maximally with PMA to induce proliferation, to increase IL-2R mRNA levels and the expression of membrane IL-2R, and to produce a low but sufficient accumulation of IL-2 mRNA and IL-2 secretion. A high concentration of A23187 (1.0 μM) did not show any synergism for the accumulation of IL-2R mRNA, membrane IL-2R expression and inhibited the proliferation of PMA co-stimulated T cells. It did, however, induce maximum accumulation of IL-2 mRNA and IL-2 secretion. [ABSTRACT FROM AUTHOR]

Sorted OKT4+ cells treated with pokeweed mitogen (PWM) and subsequently X-irradiated were used as a source of helper T cells to examine human T and B cell function. PWM-induced immunoprotein synthesis by human peripheral blood lymphocytes was the model used to study cellular interactions. PWM was shown to induce helper T cell function which caused non-PWM treated B cells to secrete immunoglobulin. PBL from certain individuals could not be induced by PWM to secrete Ig therefore allogeneic co-cultures of helper T cells and B cells were examined to define the defective cell population. Ig synthesis allogeneic cultures of T and B cells was always greater than that observed in autologous cultures when cells from responders were assayed. However, when allogenic cultures were initiated using B cells from a responder and PWM treated T cells from a non-responder and examined for Ig synthesis, the B cell responses were markedly lower than seen in the autologous responder cultures. In addition, PWM activated helper T cells from a responder induced a significantly higher Ig synthesis by B cells from a non-responder. These observations indicate that PBL from individuals who do not respond in a PWM driven Ig synthesis assay have relatively normal B cell function but are deficient in helper T cell function. [ABSTRACT FROM AUTHOR]

The effect of age on the proliferative response to 12-O-tetradecanoyl phorbol-13-acetate (TPA) was examined using peripheral blood lymphocytes from 185 adults. TPA-induced DNA synthesis measured by cellular 3H-thymidine incorporation was found, like the responses of cells activated by PHA and Con A, to markedly diminish with advancing age. The presence of indomethacin (1 μ/ml) or Ro 20-5720(10 μg/ml) in TPA activated cell cultures, unlike PHA stimulated cultures, did not result in augmentation of ³H-thymidine incorporation by cells from elderly individuals. These results demonstrate that prostaglandin synthesizing suppressor cells are not responsible for the age-related depression of cellular immune function observed in TPA activated cells and confirm the observation that decreased production and/or utilization of soluble mediators, such as IL-2, may account for the diminished mitogen responsiveness of lymphocytes from elderly individuals. [ABSTRACT FROM AUTHOR]

The effect of age on the in vitro generation of immunoglobulin-secreting cells in pokeweed mitogen-stimulated cultures was examined using a staphylococcal protein A plaque assay. Although there was no statistically significant decrease with age in the numbers of plaque-forming cells, subjects whose cells failed to produce immunoglobulin were four times more common amongst individuals over 55 years of age. Simultaneously-measured I and B lymphocyte numbers, 3H-thymidine incorporation by mitogen-stimulated cultures, and serum immunoglobulins were comparable in both the young and the aged. [ABSTRACT FROM AUTHOR]

Antibodies raised in rabbits against the bovine serum albumin conjugates of O-ethylguanosine and N-(guanosin-8-yl)-N-acetyl-2-aminofluorene have been used to develop-a high-sensitive enzyme-linked immunosorbent assay (HS-ELISA) for the quantification of adducts in DNA modified by ethylating agents and N-acetyl-2-aminofluorene. Linear dose-response relations were obtained in the non-competitive HSELISA between 0.5 fmol and 50 fmol O-ethyldeoxyguanosine per 2.8 μg DNA, and between 0.1 fmol and 20 fmol N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofhiorene per 0.8 μg DNA. The sensitivity of an ultrasensitive radio-immunoassay was in the same order of magnitude. Modification levels as low as 0.1 μmol of adduct/mol DNA-nucleotides (1: 10) can be detected by each assay. [ABSTRACT FROM PUBLISHER]

Presents a response by K. Nielsen and colleagues on their article "Melanoma and nonmelanoma skin cancer in patients with multiple tumors--evidence for new syndromes in population-based study," published in the previous issue of the "British Journal of Dermatology."