Evaluation of spatial filters to create smoothed maps of health data.

Spatial filters have been used as an easy and intuitive way to create smoothed disease maps. Birth weight data from New York State for 1994 and 1995 are used to compare the traditional filter type of fixed geographical size with a filter size of constant or nearly constant population size. The latter are more appropriate for mapping disease in geographic areas with widely varying population density, such as New York State. Issues such as the choice of population size for the filter, the scale of smoothing, the ability to detect true spatial variation and the ability to smooth over random spatial noise are evaluated and discussed.

Induction of cytotoxic cell activity by peptide fragments of beta 2-microglobulin.

A heptapeptide fragment of beta 2-microglobulin has been described by Abiko in hemodialysates of uremic patients and found to inhibit E-rosette formation by human T cells. In order to study the possible immunoregulatory effects of this heptapeptide, we investigated its effect on human cytotoxic cell activity. Low concentrations (10(-8) to 10(-7)M) of the heptapeptide enhanced cytotoxic activity of human lymphocytes against herpes simplex virus-infected cells by 50-60% whereas higher concentrations (10(-4)M) depressed cytotoxicity. When lymphocytes were incubated with the heptapeptide during an in vitro sensitization assay, an even stronger enhancement was observed. In an attempt to define possible structure-activity correlations, synthetic peptide fragments were also tested for their effect on cytotoxic cell activity. Thus, the corresponding desHis-hexapeptide (2-7) had little enhancing effect on fresh lymphocyte cytotoxicity but significantly enhanced cytotoxic activity following presensitization. In contrast, further amino acid deletions resulting in 3-7, 4-7, 5-7 or 6-7 fragments had no significant activity. Alternatively, C-terminal deletions resulting in 1-6, 1-5 or 1-4 fragments also failed to exert any effect on lymphocyte-mediated cytotoxicity. We suggest that the heptapeptide and its 2-7 hexapeptide fragment may play a role in regulating host cytotoxic responses to viruses in health and disease.

Cellular immune function in uremia: altered cytotoxic and suppressor cell responses to an immunomodulating heptapeptide.

Hemodialysates of uremic patients have been shown by T. Abiko, M. Kumikawa, and H. Sekimo (Biochem. Biophys. Res. Commun. 86, 945, 1979) to contain a heptapeptide which inhibits E-rosette formation by human T cells. This heptapeptide also corresponds to a fragment of beta 2-microglobulin and may play an immunoregulatory role in uremia. We investigated the potential for induction of cytotoxic and suppressor cells by the synthetic heptapeptide (HP) in blood lymphocytes of normal donors and uremic patients. Cytotoxic activity of normal lymphocytes was significantly enhanced by low concentrations of HP while high concentrations depressed it. Two patterns of responsiveness were observed among uremic patients: a high responder group reacted similarly to normals, whereas a low responder group showed little reactivity to HP. Removal of the NH2-terminal histidine of the heptapeptide strongly diminished its enhancing activity on normal cytotoxic cells while maintaining activity on uremic lymphocytes. When HP and des-His-HP were studied as possible inducers of suppressor cell activity, only the latter was found to be active on normal cells. Lymphocytes from uremic patients failed to respond to either HP or des-His-HP in suppressor cell generation. It is suggested that continuous interaction between lymphocytes and high concentrations of HP or des-His-HP in uremia may have altered their sensitivity to the immunomodulatory effects of the peptides and may be instrumental in the immune deficiency associated with renal failure.