Response of tibialis anterior tendon to a chronic exposure of stretch-shortening cycles: age effects.

BACKGROUND: The purpose of the current study was to investigate the effects of aging on tendon response to repetitive exposures of stretch-shortening cycles (SSC's). METHODS: The left hind limb from young (3 mo, N = 4) and old (30 mo, N = 9) male Fisher 344 x Brown Norway rats were exposed to 80 maximal SSCs (60 deg/s, 50 deg range of motion) 3 x/week for 4.5 weeks in vivo. After the last exposure, tendons from the tibialis anterior muscle were isolated, stored at -80 degrees C, and then tested using a micro-mechanical testing machine. Deformation of each tendon was evaluated using both relative grip-to-grip displacements and reference marks via a video system. RESULTS: At failure, the young control tendons had higher strain magnitude than the young exposed (p < 0.01) and the old control tendons (p < .0001). Total load at inflection was affected by age only (p < 0.01). Old exposed and control tendons exhibited significantly higher loads at the inflection point than their young counterparts (p < 0.05 for both comparisons). At failure, the old exposed tendons carried higher loads than the young exposed tendons (p < 0.05). Stiffness was affected by age only at failure where the old tendons exhibited higher stiffness in both exposed and control tendons than their young counterparts (p < 0.05 and p < 0.01, respectively). CONCLUSION: The chronic protocol enhanced the elastic stiffness of young tendon and the loads in both the young and old tendons. The old exposed tendons were found to exhibit higher load capacity than their younger counterparts, which differed from our initial hypothesis.

Impact of negatively charged patches on the surface of MHC class II antigen-presenting proteins on risk of chronic beryllium disease.

Chronic beryllium disease (CBD) is a granulomatous lung disease that occurs primarily in workers who are exposed to beryllium dust or fumes. Although exposure to beryllium is a necessary factor in the pathobiology of CBD, alleles that code for a glutamic acid residue at the 69th position of the HLA-DPbeta1 gene have previously been found to be associated with CBD. To date, 43 HLA-DPbeta1 alleles that code for glutamic acid 69 (E69) have been described. Whether all of these E69 coding alleles convey equal risk of CBD is unknown. The present study demonstrates that, on the one hand, E69 alleloforms of major histocompatibility complex class II antigen-presenting proteins with the greatest negative surface charge convey the highest risk of CBD, and on the other hand, irrespective of allele, they convey equal risk of beryllium sensitization (BeS). In addition, the data suggest that the same alleles that cause the greatest risk of CBD are also important for the progression from BeS to CBD. Alleles convey the highest risk code for E26 in a constant region and for E69, aspartic acid 55 (D55), E56, D84 and E85 in hypervariable regions of the HLA-DPbeta1 chain. Together with the calculated high binding affinities for beryllium, these results suggest that an adverse immune response, leading to CBD, is triggered by chemically specific metal-protein interactions.

TNF-alpha polymorphisms in chronic beryllium disease and beryllium sensitization.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine involved in normal immune functions. The aim of this study was to investigate if there is an association between chronic beryllium disease or beryllium sensitization and two variants of the TNF-alpha gene located at -308 and -238 called TNF-alpha-308*02 and TNF-alpha-238*02. METHODS: TNF-alpha-308 and TNF-alpha-238 genotyping was conducted in a large, population-based cohort consisting of 886 beryllium workers (92 individuals with chronic beryllium disease, 64 who were beryllium sensitized, and 730 individuals without sensitization or disease). RESULTS: The odds of chronic beryllium disease in the presence of at least one TNF-alpha-308*02 or TNF-alpha-238*02 allele was not significant (OR=1.0; 95% CI=0.7, 1.7 and OR=0.8; 95% CI=0.4, 1.6). This was true regardless of whether a worker was homozygous or heterozygous for TNF-alpha-308*02 or TNF-alpha-238*02. Similarly, neither allele was associated with sensitization (P>0.05). CONCLUSIONS: Unlike an earlier report, there was no association between these specific TNF-alpha alleles and either chronic beryllium disease or sensitization to beryllium.

DNA-sequence determination of exon 2 of a novel HLA-DPB1 allele, HLA-DPB1*0403.

Sequence determination using HLA-DPB1 allele-specific primers for a DNA sample donated by an African-American individual revealed the presence of a novel haplotype. This new allele was found as a heterozygote together with HLA-DPB1*0402. The new allele was similar to HLA-DPB1*1601, however, it varied in two single nucleotide polymorphisms resulting in alanine residues at positions 55 and 56 of the mature protein rather than aspartic acid and glutamic acid, respectively. Allele-specific DNA-sequence determination was verified by sequence determination in forward and reverse directions after cloning in pCR2.1. This cloning strategy resulted in DNA products representing 19 clones confirming the novel allele (GenBank accession number AY823995 and is now listed in the IMGT/HLA database as HLA-DPB1*0403) and 17 clones representing HLA-DPB1*0402.

The association between HLA-DPB1Glu69 and chronic beryllium disease and beryllium sensitization.

BACKGROUND: Several case-control studies have found an association between chronic beryllium disease (CBD) and HLA-DPB1 gene variants. However, the relationship between HLA-DPB1 and beryllium sensitization, and whether the presence of one or two HLA-DPB1(Glu69) alleles is differentially associated with CBD and beryllium sensitization have not been completely resolved. METHODS: Restriction fragment length polymorphism (RFLP) analysis was used to address these questions in a large population-based cohort consisting of 884 beryllium workers (90 with CBD, 64 beryllium sensitized). RESULTS: HLA-DPB1(Glu69) was associated with both CBD (OR = 9.4; 95% CI = 5.4, 16.6) and sensitization (OR = 3.3, 95% CI = 1.9, 5.9). Further, workers with CBD and sensitization were more likely to be homozygous HLA-DPB1(Glu69) compared to workers without disease or sensitization (P < 0.001). CONCLUSIONS: Follow-up of this cohort, scrutiny of HLA-DPB1 haplotypes, and evaluation of gene-environment and gene-gene interactions will be important for fully understanding the immunogenetic nature of this occupational disease.