Citations

Objective.Eosinophil-associated proteins, especially eosinophil-derived neurotoxin, may be important contributors to the neurologic pathology and symptoms caused byBaylisascaris procyonis infection.Methods.Two cases of severe B procyonisencephalitis with evidence of marked eosinophil degranulation in the central nervous system are presented. Serial cerebrospinal fluid (CSF) specimens were collected from each patient during the course of their illness. Antibodies against B procyonis were measured in the patients' serum and CSF. Levels of the eosinophilopoietin interleukin-5 (IL-5) and 2 important eosinophil proteins, eosinophil-derived neurotoxin and major basic protein, were assayed in the CSF.Results.Both patients had rapidly progressive central nervous system disease with evidence of eosinophilic meningoencephalitis. Both tested positive for antibodies to B procyonis in serum and CSF and had progressively worsening deep white matter changes on magnetic resonance images of the brain. CSF levels of IL-5, eosinophil-derived neurotoxin, and major basic protein were markedly elevated over controls.Conclusions.This is the first report of the measurement of IL-5, eosinophil-derived neurotoxin, and major basic protein in human CSF. In addition to traumatic damage and necrosis caused by migrating larvae, eosinophil-derived neurotoxin from associated eosinophilic inflammation may be an important contributory factor in the pathogenesis of B procyonis encephalitis. parasite, eosinophil-derived-neurotoxin, major basic protein, eosinophilia, hypereosinophilia, interleukin-5, encephalitis, child.

Objective. Surgery for craniosynostosis has evolved rapidly over the past two decades, with increased emphasis on early, extensive operations. Older published series may not accurately reflect more recent experience. Our study was designed to analyze outcome in a large series of consecutive patients treated recently at a single center.Methods. We reviewed 250 consecutive patients who underwent surgical treatment of craniosynostosis between January 1, 1987 and December 31, 1992. They were divided into nine groups by suture involvement: sagittal, unilateral coronal, bilateral coronal, unilateral lambdoid, bilateral lambdoid, metopic, multiple suture, the Klee-blattschädel deformity (cloverleaf skull), and acquired craniosynostosis. Outcome was analyzed in terms of residual deformities and irregularities, complications, mortality, as well as the need for additional surgery.Results. There were 157 males (62.8%) and 93 females (37.2%), with most of the male preponderance accounted for by the large sagittal synostosis group, which consisted of 82 males and 25 females. Median age at first operation was 147 days. A named syndrome was present in 23 patients (9.2%) and was more common than expected with bilateral and unilateral coronal synostosis, the Kleeblattschädel deformity, and multiple suture synostosis. There were two deaths (0.8%), both with Klee-blattschädel patients, and 17 other complications (6.8%). Morbidity and mortality were significantly associated with secondary vs primary operations and syndromic vs nonsyndromic patients. Outcome analysis revealed the best surgical results with metopic synostosis and significantly less good results with the Kleeblattschädel deformity, multiple suture synostosis, and bilateral coronal synostosis.Conclusions. Using modern surgical techniques, craniosynostosis can be corrected with good outcomes and relatively low morbidity and mortality, particularly for otherwise healthy, nonsyndromic infants.

Collagen-induced arthritis (CIA) is an animal model of autoimmune inflammatory polyarthritis that has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC), H-2, and restricted to the H-2q and H-2r haplotypes. Whereas the role of the H-2A molecule in susceptibility to CIA is well established, little is known about the role of H-2E molecule in the disease. In this study, we analyzed the effect of a transgenic E beta d molecule on CIA susceptibility in a recombinant mouse B10.RQB3, which expresses the CIA susceptible Aq genes and an Eak gene, but does not produce an E molecule since Ebq is nonfunctional. In the presence of an Ebd transgene, a viable E molecule is generated. Whereas B10.RQB3 were susceptible to CIA, B10.RQB3-E beta d+ showed a dramatic reduction in the incidence of arthritis as well as a decrease in the level of anti-mouse and anti-bovine CII antibodies in their serum. No clear cut differences in the expression of T cell receptor (TCR) V beta was observed between E beta d+ and E beta d- transgenic mice. Mechanisms underlying the protective effect of E beta d transgenic molecule on CIA may shed light on how HLA-DR molecules influence human RA.

A protein immunochemically related to the eosinophil granule major basic protein (gMBP) is found in increased concentration in the plasma of pregnant women and has been localized to placental trophoblasts by immunofluorescence. Pregnancy MBP (pMBP) is indistinguishable from gMBP in its reactivity with polyclonal antisera and a panel of 14 mouse mAbs. We report the purification of pMBP from human placenta by: (a) affinity chromatography over mAb immobilized on Sepharose, (b) gel filtration in 6 M guanidine.HCl buffer, and (c) reversed-phase HPLC. Purified pMBP and gMBP are biochemically indistinguishable in that both: (a) bind to DNA, (b) polymerize and bind to carrier proteins via disulfide linkages, (c) have a molecular weight of 14,000, (d) have isoelectric points greater than 10.6, (e) comigrate in two-dimensional gels, (f) coelute during reversed-phase HPLC on C18 columns, (g) have identical peptide maps after three different digestions, and (h) have partial amino acid sequence identity. This physicochemical identity has important implications as to the role of pMBP in human placentation.

Human eosinophil peroxidase (EPO) was purified from eosinophil granules derived from the peripheral blood of patients with eosinophilia. The molecular mass of the H and L subunits was determined by gel filtration to be 57,000 and 11,000 daltons, respectively. The partial amino acid sequences of both subunits were used to construct oligonucleotides for the screening of several cDNA libraries, including one derived from human-induced umbilical cord mononuclear cells. A cDNA clone was isolated corresponding to EPO. The nucleotide sequence revealed an open reading frame of 2,106 bp, corresponding to a prosequence, L chain, and H chain, in this order. Comparison of the EPO nucleotide sequence with other peroxidases, such as myeloperoxidase, suggests the existence of a multigene family.

Eosinophil granule major basic protein (MBP), a potent toxin for helminths and various cell types, is a 13.8-kD single polypeptide rich in arginine with a calculated isoelectric point (pI) of 10.9. A cDNA for human MBP was isolated from a gamma GT10 HL-60 cDNA library. The nucleotide sequence of the MBP cDNA indicates that MBP is translated as a 25.2-kD preproprotein. The 9.9-kD pro-portion of proMBP is rich in glutamic and aspartic acids and has a calculated pI of 3.9, while proMBP itself has a calculated pI of 6.2. We suggest that MBP is translated as a nontoxic precursor that protects the eosinophil from damage while the protein is processed through the endoplasmic reticulum to its sequestered site in the granule core toxic MBP, and we present results from the literature suggesting that other cationic toxins, which damage cell membranes, may also be processed from nontoxic precursors containing distinct anionic and cationic regions.

Guinea pig eosinophil granules are characterized by the presence of a basic protein of low molecular weight which accounts for greater than 50% of granule protein. This protein, termed the major basic protein (MBP), readily aggregates and becomes insoluble, and the formation of aggregates is dependent on the establishment of disulfide bonds. Analysis of concentrated preparations of MBP often revealed a series of bands which were multiples of a monomeric unit with a mol wt of approximately 11,000. Analysis of reduced and alkylated MBP on a 10% agarose column equilibrated with 6 M guanidinium chloride revealed a single polypeptide chain with a mol wt of 10,800. Amino acid analysis of the protein revealed the presence of 13% arginine, consistent with the basic character of the molecule. Four residues of tryptophan, were present, indicating that MBP is not a histone. The MBP did not increase vascular permeability when injected into the skin of guinea pigs, nor did it antagonize the effect of histamine and bradykinin in the skin. MBP also did not contract the isolated guinea pig ileum and when mixed with histamine or bradykinin did not inhibit their activity on the gut. MBP had only weak, if any, antihistaminic activity. MBP possessed weak bactericidal activity when compared to histone and then only with one strain of E. coli. MBP precipitated DNA, neutralized heparin, and activated papain. On a molar basis MBP was more active than cysteine in activating papain. These results do not point to any unique biological activity associated with MBP other than those expected of a protein as basic as it is and one which possesses reactive sulfhydryl groups. Possible functions of eosinophils based on the properties of the MBP are discussed.