Widely variable prevalences of allergic diseases have been reported in tropical populations, and this has been suggested to be due to effects of the nonspecific polyclonal stimulation of IgE synthesis caused by the helminthic infections that are endemic in these areas. Since 1980, we have been evaluating the allergic reactivity of different socioeconomic sectors of the population of tropical Venezuela (lat. 2–12°N), and in the present study analyze the overall results obtained in the laboratory evaluation of children (5–15 years of age) belonging to these groups. Children of medium-high socioeconomic level (M-HSEL), who experience occasional helminthic infections, have moderately high total serum IgE levels, and have elevated skin test positivities and specific IgE levels against environmental allergens. Persons of low socioeconomic level, in the urban, and particularly rural situation experience frequent helminthic infection, and have highly elevated total serum IgE levels. In contrast to the M-HSEL, the majority of these children have detectable specific IgE antibody against a variety of inhalant allergens, but relatively few have high levels, and their skin test positivity is also low. In these frequently parasitized persons, evidence of saturation of mast cell Fcε receptors was found by tests of passive sensitization. We propose, therefore, that helminthic parasites have a biphasic effect on allergic reactivity; occasional infections are stimulatory, via their nonspecific potentiation of IgE synthesis against environmental allergens, and frequent infections are suppressive due to the widely polyclonal stimulation that they cause, resulting in both diminished specific antibody production against any given allergen and mast cell Fcε receptor saturation.
The presence of the biologically uncommon D-aspartic acid (D-aspartate) in human brain white matter has been previously reported. The earlier study has now been expanded to include D/L-aspartate ratios from 67 normal brains. The data show that the D-aspartate content increases rapidly from 1 year to approximately 35 years of age, levels off in middle age, and then appears to decrease somewhat. The D-aspartate content in gray matter remains at a consistently low level (half of that found in white matter) throughout the human life span. Within the limitations of current analytical methods, there was no detectable difference in D/L-aspartate ratios in white and gray matter of brains with Alzheimer's disease and several other pathologies when compared with brains of normal subjects. However, the presence of a significant D-aspartate level in white matter during the adult life span may lead to changes in protein configuration related to dysfunctions associated with the aging brain.
The present studies were undertaken to examine how the substitution of racemized forms of selected amino acids in synthetic peptides of guinea pig myelin basic protein (GPMBP) would alter the host's immunological ability to recognize such molecules. Using peptides from the 69-84 sequence of GPMBP containing a D-serine at position 70 or 75 (69-84[D-ser70 or D-ser75]) or D-aspartate at position 82 (69-84[D-asp82]), the findings demonstrated that the position of the diastereomer substitution on these neuropeptides was critical with respect to the ability of the immune system to recognize the molecule. Thus substitution of D-asp at position 82 or D-ser at position 75 abrogated the ability of these peptides to induce experimental autoimmune encephalitis and proliferation of host T cells. In contrast, a peptide containing a D-ser70 residue was capable of inducing clinical disease in rats, as well as stimulating T lymphocytes from 69-84-(D-ser70)-injected animals. Moreover, although this D-peptide was shown to share at least some determinant(s) with the 69-84 peptide, the use of 69-84(D-ser70)-stimulated cell lines demonstrated that some epitope(s) unique to this molecule could stimulate CD4+ syngeneic T cells.
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