Mizoi Y

Thymus of abused/neglected children

Forty-six cases of child abuse/neglect autopsied during the period of 1967 to 1990 were investigated. The weight and histological findings of the thymus were compared with those of control children. In most abused and/or neglected children, the weight of the thymus decreased conspicuously. Involution correlated well to the degree and period of maltreatment. In cases without weight loss of the thymus, i.e. spasmodic abuse by a mentally deranged parent or foster parent, a short history of maltreatment was noted. On the other hand, marked involution was observed in cases of prolonged physical abuse and/or neglect. Microscopically, a decrease in the number and pyknosis of lymphocytes were observed in the involuted thymus. Atrophy of the thymus was more conspicuous in the cortex than in medulla. Immunohistochemically, CD-1a positive cells (immature thymocytes) decreased in cases with thymic involution. This involution appears to be an important index of the degree and duration of child abuse/neglect. Furthermore, thymic involution in the early stage of childhood may also be related to insufficiency of the immune system.

Molecular basis for subtypic differences of the “a” subunit of coagulation factor XIII with description of the genesis of the subtypes

The “a” subunit of human coagulation factor XIII (F13A) exhibits genetic polymorphism defined by four common alleles, F13A*1A, *1B, *2A, and *2B. We have previously suggested on the basis of the isoelectric focusing patterns of the four allele products that point mutations at two separate sites and one intragenic crossing over might be involved in the genes of F13A polymorphism. Here, we report nucleotide substitutions associated with F13A polymorphism. A C/T transition of the second nucelotide of codon 564 in exon 12 is responsible for the difference between F13A*1A and *1B and that between F13A*2A and *2B, and a set of two base changes in codons 650 and 651 in exon 14 leads to the differences between F13A*1A and *2A and those between F13A*1B and *2B. The four combinations of the point mutations at the two exons thus correspond to the four alleles, two of which were generated by the point mutations from ancestral monomorphic gene. The results suggest strongly that intragenic crossing over must be involved in the genesis of the fourth allele. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods discriminating these base changes in exons 12 and 14 are also presented.

Endogenous formation of 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid in man as the possible causative substance of eosinophilia-myalgia syndrome associated with ingestion ofl-tryptophan

Abstract1-Methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA) is now thought to be a possible causative substance of eosinophilia-myalgia syndrome associated with ingestion ofl-tryptophan. In the present study a factor affecting endogenous formation of MTCA in 32 healthy men is studied. Urinary excretions of MTCA and 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (TCCA) were measured by high-performance liquid chromatography (HPLC) with fluorometric detection after administration of a high or low protein diet as well as peroral tryptophan (0.5 g) or ethanol (0.4 g/kg). Blood ethanol and acetaldehyde levels were determined by gas chromatography after ethanol consumption. Both, the high protein diet and tryptophan resulted in a significant rise of urinary TCCA. In contrast, ethanol intake caused increased excretion of MTCA, though a relationship between blood acetaldehyde level and urinary excretion of MTCA was not shown. We showed for the first time that an elevation of urinary excretion of MTCA following ethanol consumption in man without ingestion ofl-tryptophan tablets implicated eosinophilia-myalgia syndrome.