To date, little has been known about the extent of sequence variation in the C-terminal part of the Plasmodium vivax merozoite surface protein 1 (PvMSP1) which has been considered to be a potential vaccine candidate. Here, we examined the variation in the region encompassing interspecies conserved blocks (ICBs) 8 and 10 of PvMSP1 by DNA sequencing of 14 Thai isolates and three Brazilian isolates. Eighteen different alleles were detected. Three new sequence types had been identified in polymorphic region between ICB8 and CB9: one was possibly a result of intragenic recombination between the Belem and Salvador I alleles and the others displayed unique repeats. A striking variation was observed in a stretch of 38 codons in polymorphic block between conserved block CB9 and ICB10, resulting in eight different sequence types, probably generated by interallelic recombination at a single or multiple sites. There is no apparent linkage between these two polymorphic sites. On the other hand, a single or stretches of nucleotide substitutions are dimorphic like in Plasmodium falciparum MSP1 (PfMSP1) in the remaining parts, creating microheterogeneity of sequences. The C-terminal 19 kDa-encoding region was extremely conserved with a single dimorphic exchange at a known position. Thus, this study provides evidence of intragenic recombination occurring in the 3' portion of PvMSP1 and suggests that the 3' portion of PvMSP1 is more diverse than that in PfMSP1.

3' Untranslated Regions↗

PubMed2000

A peculiar vacuolization in the kidney transplant of a child treated with tacrolimus.

Tacrolimus (TAC) is a useful immunosuppressive agent in the prevention of rejection. However, the blood level between its therapeutic and toxic levels is narrow such that its nephrotoxicity is a problem. Moreover, its bioavailability and pharmacokinetics are highly variable. We experienced a case of acute nephrotoxicity, in which the blood level rose about 10 times above the expected level. We found a peculiar vacuolization in the transplant biopsy specimen. This change showed a marked vacuolization of the tubular cells, suggestive of acute nephrotoxicity by TAC.

Adolescent↗

PubMed2000

Super long-term surviving two renal grafts with severe arteriolosclerosis and glomerulosclerosis.

Two long-term renal transplant survivors, for about 20 yr, with unusual histological features in the allograft kidney are reported. In both cases, marked hyalinosis was observed in the arterioles of the transplanted kidney, despite never having been administered cyclosporine or tacrolimus. The cause remains unknown at the present time, but we think that the changes could be multifactorial in origin, including due to aging of the graft, hypertension, hyperlipidemia and chronic rejection. We conclude that histological analysis of the allograft kidney must be performed in long-term renal transplant survivors, in order to understand the histological changes in the chronic phase after kidney transplantation and to predict the prognosis of the graft.

Adult↗

PubMed2000

A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses.

New strategies are required to identify the most important targets of protective immunity in complex eukaryotic pathogens. Natural selection maintains allelic variation in some antigens of the malaria parasite Plasmodium falciparum. Analysis of allele frequency distributions could identify the loci under most intense selection. The merozoite surface protein 1 (Msp1) is the most-abundant surface component on the erythrocyte-invading stage of P. falciparum. Immunization with whole Msp1 has protected monkeys completely against homologous and partially against non-homologous parasite strains. The single-copy msp1 gene, of about 5 kilobases, has highly divergent alleles with stable frequencies in endemic populations. To identify the region of msp1 under strongest selection to maintain alleles within populations, we studied multiple intragenic sequence loci in populations in different regions of Africa and Southeast Asia. On both continents, the locus with the lowest inter-population variance in allele frequencies was block 2, indicating selection in this part of the gene. To test the hypothesis of immune selection, we undertook a large prospective longitudinal cohort study. This demonstrated that serum IgG antibodies against each of the two most frequent allelic types of block 2 of the protein were strongly associated with protection from P. falciparum malaria.

Africa↗

PubMed2000

Removal of anti-A/B antibodies with plasmapheresis in ABO-incompatible kidney transplantation.

Because of a shortage of cadaver donors in Japan, ABO-incompatible living kidney transplantation has been carried out. Sixty-seven ABO-incompatible living kidney transplantations (LKT) were performed between January 1989 and December 1995 at our institution. In our previous report on the long-term results of ABO-incompatible LKT, graft survival of ABO-incompatible LKT up to 3 years was significantly lower than that of ABO-compatible LKT, but no significant difference was seen from 4 to 8 years. We removed anti-A/B antibodies by immunoadsorption and/or double filtration plasmapheresis before kidney transplantation. There was a significant difference between the anti-A/B antibody titers before and after plasmapheresis. The anti-A/B antibody titers also were well suppressed over the long term after transplantation.

ABO Blood-Group System↗