Platelet-activating factor (PAF) may be involved in the pathogenesis of Escherichia coli O157-associated hemolytic uremic syndrome (HUS). PAF is degraded to inactive products by PAF acetylhydrolase. In this study, we investigated whether a PAF acetylhydrolase gene mutation (G-->T transversion at position 994) is involved in HUS in Japanese children. A point mutation in the PAF acetylhydrolase gene (G994T) was identified using polymerase chain reaction in 50 Japanese children with E coli O157-associated HUS and 100 healthy Japanese. We then determined the relationship between the PAF acetylhydrolase G994T gene mutation and clinical features of HUS. There was no difference in genotype and allele frequencies between patients with HUS and healthy controls. The mean duration of oligoanuria was significantly longer in patients with the GT genotype than in those with the GG genotype (P = 0.012). Although 11 of 15 patients (73%) heterozygous for the mutant allele (GT) required dialysis, only 13 of the 35 wild-type homozygotes (GG; 37%) required dialysis (P = 0. 030). Mean plasma PAF acetylhydrolase activity was significantly less in patients with the GT genotype than in those with the GG genotype (P < 0.0001). In conclusion, we have shown an association between the G994T PAF acetylhydrolase gene mutation and the severity of renal damage in E coli O157-associated HUS. Our study suggests that analysis of the PAF acetylhydrolase gene mutation in Japanese children with E coli O157-associated HUS may allow the prediction of the severity of HUS.
Title: The production and coexistence of neurotransmitters in the neurons of the rat's locus coeruleus[ Iijima K Ref: Kaibogaku Zasshi, 74:591, 1999 : PubMed
The production and coexistence of neurotransmitters in the locus coeruleus is reviewed. Immunocytochemical and in situ hybridization evidence demonstrated that the LC consists mainly of a single cell population that is producing GABA and 5-HT in addition to noradrenaline (NA) simultaneously in single neurons. The coexistence of GABA, 5-HT and NA in single LC neurons was proved by identifying the same neurons in adjacent sections alternately immunostained by different antisera. In situ hybridization detected the signals of glutamic acid decarboxylase mRNA and tryptophan hydroxylase mRNA indicating the presence of GABA/GAD system and the ability to produce 5-HT in many LC neurons. Neuroanatomical studies strongly suggest that a single NA cell population produces multiple transmitters so that the LC can play a role in mechanism controlling the human's adaptation to environmental changes. The present author introduces three different recent works concerning the LC. Caff concluded that the concept of a NA-ergic cell population in all mammals is questionable. In similar cases to the domestic pig's LC, acetylcholinesterase activity, muscarinic and nicotinic receptor proteins should be checked. Tohyama et al. examined various receptor proteins in the LC and found localization of GAGAA, glutamate and glycine receptors. Maeda et al. reported that doaminergic neurons in the hypothalamus play a powerful role in mechanisms controlling the activity of NA-ergic neurons in the LC. Senile dementia of Alzheimer type causes marked atrophy and cell loss in the LC as well as the frontal lobe of the cerebrum. Molecular biology of the cell has been devoted to clarify the pathology of this fatal disease.
Platelet-activating factor (PAF) is a potent mediator of inflammatory injury in renal diseases. PAF is degraded to inactive products by PAF acetylhydrolase. Recently, a point mutation (G to T transversion) of the PAF acetylhydrolase gene was observed at position 994, and this mutation was found to contribute to the variability in plasma PAF levels, with undetectable plasma PAF acetylhydrolase activity occurring in homozygous patients (TT genotype) and reduced levels of activity in heterozygous patients (GT genotype). Therefore, we investigated the effect of the PAF acetylhydrolase gene mutation on the pathogenesis and progression of immunoglobulin A (IgA) nephropathy. Genomic DNA was obtained from 89 children with IgA nephropathy and 100 controls. We identified the PAF acetylhydrolase gene mutation (G994T) by polymerase chain reaction. There was no significant difference in genotypic frequency between patients and controls. However, urinary protein excretion at the time of biopsy was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. The percentage of glomeruli with mesangial cell proliferation was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. These results indicate the PAF acetylhydrolase gene mutation may influence the degree of proteinuria and the extent of mesangial proliferation in the early stage of childhood IgA nephropathy.
BACKGROUND: Platelet-activating factor (PAF) may be involved in the pathogenesis of steroid-responsive nephrotic syndrome (SRNS). PAF is degraded to inactive products by PAF acetylhydrolase. We have investigated whether PAF acetylhydrolase gene mutation is involved in SRNS in Japanese children. METHODS: We identified a point mutation in the PAF acetylhydrolase gene (G994T) using the polymerase chain reaction in 101 Japanese children with SRNS and 100 healthy Japanese. RESULTS: There was no difference in the genotype and allele frequencies between patients with SRNS and normal controls. The mean number of relapses during the first year after onset was significantly higher in the 26 patients who were heterozygous for the mutant allele (GT) than in 75 wild-type homozygotes (GG) (2.61 +/- 1.98 vs. 1.33 +/- 1.35; P = 0.0019). CONCLUSIONS: We conclude that analysis of the PAF acetylhydrolase gene mutation at position 994 in Japanese children with SRNS allows the identification of patients who are more likely to have a disease relapse.
Title: Histochemical studies on the cerebellum of squirrel monkey (Saimiri sciurea) Shantha TR, Iijima K, Bourne GH Ref: Acta Histochemica, 27:129, 1967 : PubMed
