First serologic evidence of human spotted fever group rickettsiosis in Korea

To investigate the prevalence of spotted fever group rickettsioses in Korea, a serosurvey of Japanese spotted fever rickettsiosis in patients with acute febrile illness was conducted with an indirect immunofluorescence assay. Overall, 19.88% of the patients were found to have polyvalent antibody against Rickettsia japonica. This study is the first documentation of spotted fever group rickettsiosis in Korea.     

Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population.

Abundant biochemical evidence links deficient activity of mitochondrial alpha-ketoglutarate dehydrogenase with neuropathologically confirmed Alzheimer's disease (AD). Reduced alpha-ketoglutarate dehydrogenase activity has also been associated with anti-mortem measures of clinical disability. One of the genes encoding this complex, namely, DLD, lies within a chromosome 7 region that is in linkage disequilibrium with AD. We therefore examined the hypothesis that variation in DLD is associated with AD risk. Denaturing HPLC was used to search for sequence variations in the coding and flanking regions of all exons of DLD, but no abundant variants that alter protein sequence were found. However, four common SNPs were identified and genotyped in a case-control series of 297 Caucasians from New York City, including 229 residents of a Jewish nursing home. Logistic regression analysis was performed for the four-locus DLD genotype, sex, and ApoE4 status to determine the association of these independent variables with AD. Significant associations with AD were observed for ApoE4 (P < 10(-6)) and sex combined with DLD genotype (P = 0.013). The association with the DLD genotypes appears only in the male population in both the Caucasian series (P = 0.0009, n = 83) and the Ashkenazi Jewish subseries (P = 0.017, n = 49). The DLD genotype appears to operate independently of APOE in conferring AD risk.     

A novel Plasmodium falciparum erythrocyte binding protein-2 (EBP2/BAEBL) involved in erythrocyte receptor binding

The 175-kDa erythrocyte binding protein (EBA-175) of Plasmodium falciparum and Duffy antigen binding proteins of P. vivax and P. knowlesi are members of a protein family. The features of this protein family include a cysteine-rich motif present in the erythrocyte receptor-binding domain. We identify here a novel 140-kDa P. falciparum erythrocyte binding protein (EBP2/BAEBL) containing the signature cysteine-rich motif by comparative analysis of gene sequence information. Polyclonal antibodies generated by immunization with an EBP2/BAEBL DNA vaccine immunoprecipitated a 140-kDa protein from P. falciparum schizont-infected erythrocyte lysates. Similar to EBA-175, the binding of EBP2/BAEBL to human erythrocytes was dependent on sialic acids because neuraminidase treatment of those erythrocytes rendered them incapable of binding, but differed from EBA-175 in that trypsin treatment decreased EBP2/BAEBL binding by only twofold compared to a 10-fold reduction in EBA-175 binding. Antibodies raised against the putative erythrocyte-binding domain of EBP2/BAEBL effectively blocked the binding of native EBP2/BAEBL to erythrocytes. These functional antibodies localize EBP2/BAEBL to the invasive apical end of the merozoite. We identify EBP2/BAEBL as a paralogue of EBA-175 and as a novel P. falciparum vaccine candidate.     

Discrimination of single-copy IS6110 DNA fingerprints of Mycobacterium tuberculosis isolates by high-resolution minisatellite-based typing

Seven isoniazid-resistant isolates with mutations in the NADH dehydrogenase (ndh) gene were molecularly typed by IS6110-based restriction fragment length polymorphism analysis. All seven isolates with the R268H mutation had identical 1.4-kb IS6110 fingerprints. High-resolution minisatellite-based typing discriminated five of these isolates; two isolates were identical.     

Utility of fine-needle aspiration in the diagnosis of primary osteosarcoma

Fine-needle aspiration (FNA) is a reliable, safe, and cost-effective procedure with a well-established role in the diagnosis of various solid tissue neoplasms. The role of FNA in the diagnosis of primary bone tumors, including osteosarcoma (OGS), is controversial and has yet to be established. We reviewed our experience with the use of FNA as a diagnostic technique over the past 8 yr at our institution. Diagnosis was conclusive in 26 (65%) of 40 patients, 18 of whom went to neoadjuvant therapy and/or resection based solely on the FNA interpretation of either "high grade sarcoma" or "osteosarcoma." Of the remaining 14 (25%) patients, 12 had inconclusive diagnosis and two (5%) were false-negatives. An inconclusive diagnosis was most likely to be an inadequate or paucicellular aspirate, seen in six (15%) patients. An additional six patients had variants of osteosarcoma (four chondroid, one "giant cell rich," one parosteal) that made definitive diagnosis impossible. The two that were incorrectly classified were diagnosed as fracture callus and plasmacytoma. FNA is an accurate and cost-effective tool for the initial diagnosis of primary osteosarcoma with a sensitivity of 65% and accuracy of 95%. Inconclusive diagnoses are likely to be due to insufficient sample cellularity or the presence of OGS variant. In our experience, FNA is sufficient to provide the diagnosis of OGS prior to definitive treatment when interpreted in conjunction with imaging studies and clinical findings. In those cases where FNA fails to yield a diagnostic sample, a traditional biopsy can be performed.     

The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status

We have recently described the association between rheumatoid arthritis and a coding single-nucleotide polymorphism in the intracellular protein tyrosine phosphatase, PTPN22. The disease-associated polymorphism, 1858 C/T (rs2476601), encodes an amino-acid change (R620W) in one of four SH3 domain binding sites in the PTPN22 molecule. We have now extended our initial studies to address three questions: (1) Is the association with rheumatoid arthritis limited to rheumatoid factor (RF) positive disease? (2) Does homozygosity for PTPN22 R620W substantially increase disease susceptibility? (3) Is there an interaction between PTPN22 and the rheumatoid arthritis (RA)-associated HLA-DRB1 shared epitope alleles? A total of 1413 Caucasian rheumatoid arthritis patients and 1401 Caucasian controls were genotyped. The results support the view that PTPN22 was strongly and preferentially associated with RF positive disease (OR=1.75, 95% CI 1.46-2.10, P=1.3 x 10(-9)). The PTPN22 risk allele was not significantly associated with RF negative disease (OR=1.19, 95% CI 0.92-1.53, P=0.18), although a very weak association cannot be completely excluded. There was a strong dose effect on disease risk; two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA (OR=4.57, 95% CI 2.35-8.89). There was no evidence of a genetic association between PTPN22 and HLA susceptibility alleles.