Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells

Immunostimulatory oligodeoxynucleotides (IS ODN) can mediate a number of immunologic effects. We previously demonstrated that treatment of B cell chronic lymphocytic leukemia (B-CLL) cells with one class of IS ODN, CpG ODN, alters their phenotype and increases their immunogenicity. Here, we demonstrate that in contrast to the classic understanding of CpG ODN as inhibitors of B cell apoptosis, IS ODN including CpG ODN induce apoptosis in B-CLL cells. It is important that these changes are seen not only with CpG ODN but with ODN that lack the classical CpG motif. B-CLL cells from 20 subjects were treated in vitro with IS ODN for up to 7 days. IS ODN treatment resulted in increased numbers of apoptotic cells in 13 out of 20 B-CLL samples. IS ODN enhanced apoptosis in samples with 13q deletion as a single aberration and had a heterogeneous effect on apoptosis in samples with other aberrations including 17p deletion, 11q deletion, or trisomy 12. Induction of apoptosis did not correlate with expression of the CpG ODN receptor Toll-like receptor 9. Apoptosis was dependent on the activation of caspases and was accompanied by up-regulation of CD95/Fas and its ligand. We conclude that IS ODN including CpG ODN can induce apoptosis of most B-CLL samples. The ability of IS ODN to induce apoptosis differs based on cytogenetic status. Up-regulation of CD95/Fas may play a role in IS ODN-induced apoptosis of B-CLL.     

Progress in Rhesus Histocompatibility Typing Resulting from the Second International Nonhuman Primate Histocompatibility Workshop (1973)

The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developd in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Efficiency of the ortho VITROS assay for detection of hepatitis C virus-specific antibodies increased by elimination of supplemental testing of samples with very low sample-to-cutoff ratios

The clinical significance of specimens with low sample-to-cutoff (S/Co) ratios in the Ortho VITROS chemiluminescence assay (CIA) for detection of antibodies to hepatitis C virus (HCV) was evaluated. In one study of 482 CIA-reactive samples, none of the 83 samples with S/Co ratios of < 5 was HCV RNA positive. In a subsequent study, 332 samples with S/Co ratios of between 1 and 20 were tested with the recombinant immunoblot assay (RIBA). None of the 163 samples with S/Co ratios of < 5 was RIBA positive, 83% were RIBA negative, and 28 samples (18%) were RIBA indeterminate. HCV RNA and/or clinical evidence of hepatitis was not found in the 27 indeterminate cases examined. These results show that over 99% of samples with very low S/Co ratios (< or = 5) have no evidence of HCV infection. Therefore, we suggest that the HCV antibody testing algorithm for the VITROS assay might be modified to eliminate supplemental testing of samples with very low S/Co ratios.     

The Gm-Pi linkage heterogeneity in view of Pi M subtypes

In this study linkage between the loci for Gm (γ-type heavy-chain immunoglobulin markers) and Pi (α₁-antitrypsin/α₁-protease inhibitor) has been shown in families segregating for the Pi M subtypes (Ml, M2, M3 and Msal) as identified by separator isoelectric focusing. The estimate for the Gm-Pi (M-type) recombination is 0-29 (95% limits 0-24-O37) at a peak lod score of 4-31 and with no sex difference. This value is not significantly different from updated recombination frequency estimates for Gm-Pi in Pi MS (0-26) and Pi MZ, SZ and FZ families (0 21). The overall Gm-Pi recombination fraction estimate of 0 26 (95 % limits O23-0-30) at a peak lod score of 20-75 must now be considered as solid. There is a significant heterogeneity within the male Pi MZ families in that the new Finnish families show a higher recombination between Gm and Pi. There is also a possible segregation distortion (Z:M = 23:8). The heterogeneity is discussed in terms of haplotypes, the behaviour of which could be determined by linked genes or chromosomal rearrangements. The possibility that the α₁-antitrypsin level influences recombination frequency has not been ruled out, but cannot explain the heterogeneity within Pi MZ families.     

Ramification of the portal vein at the porta hepatis in humans

The ramification of the portal vein at the porta hepatis was studied by anatomic dissection performed in 32 formalin fixed human livers. In all the specimens there were branches which ran towards the caudate lobe, arising from the portal vein and either from the left or the right portal branches. Tri-and quadrifurcation of the portal vein was observed. In 5 cases (16%) there were branches arising from left portal branch or portal vein and directed anteriorly to the quadrate lobe or to the region of the gall-bladder sulcus. These branches ranged from 1.0 to 6.0 mm in diameter. The portal caudate branches were divided into 3 groups.Group 1: Branches to the papillary process; 1 or 2 branches in 26 cases (82%), 3 or 5 branches in 3 cases (9%) and no branches in 3 cases (9%);