Citations

Abstract Environmental factors play an important role in the rise and manifestation of allergic conditions in genetically predisposed subjects. Increased exposure to indoor/outdoor allergens is a significant factor in the development of allergic sensitization and asthma. Recently, strong relationships between the immune response to several highly purified allergens and specific human leukocyte antigen (HLA)-DQ and -DR haplotypes have been reported. The major antigens from clinically important allergens have been cloned and sequenced. However, whether innate structural features of major allergens or peculiar immune recognition of these molecules contribute to the overly robust immune responses is not known. We generated and used transgenic (tg) mice expressing single HLA class II transgene(s) to characterize the allergen epitopes presented by particular HLA class II molecules. Next, we generated in vivo models for asthma in the HLA tg mice by intranasal challenge with allergenic extracts. Furthermore, we used a single epitope to induce an allergic lung inflammation. Our system offers a sophisticated technique for systematically identifying the genetic (individual human class II) and antigenic (individual allergenic epitopes) basis of asthma sensitivity and has important implications for new treatment strategies.

Scientifically, it has been questioned if the coracoacromial ligament has a significant role of serving as a pulley for the supraspinatus tendon. The purpose of this study was to examine the changes of abduction moment arms of the rotator cuff and deltoid muscle after anterior acromioplasty. In normal condition and after sectioning of the coracoacromial ligament and acromioplasty, abduction moment arms of four cuff tendons and three portions of the deltoid were obtained with four cadaver shoulders by computing the slope of the tendon excursion versus the glenohumeral abduction angle curve using a magnetic tracking device. In intact joints, the abduction moment arms of the supraspinatus increased from 20 mm to 27 mm with the arm abducted from 0° to 30°, which showed a better condition of the glenohumeral abduction. Then, they decreased to 23 mm with arm in 60° abduction. After sectioning of the coracoacromial ligament and acromioplasty less than 4 mm thick, the abduction moment arms of supraspinatus did not increase. This finding suggested that the coracoacromial ligament and acromion, anatomically, did not serve as pulleys for the supraspinatus tendon. However, the abduction moment arm of the middle deltoid decreased after an acromioplasty.

The effect of aging on long bone mechanical properties and bone formative capacity was characterized in the male Fisher 344 rat. The femurs of rats from three age groups (4 mo., 12 mo. and 28 mo.) were tested in three-point bending to determine their structural properties. The apparent material properties were then calculated by adjusting for bone geometry. Bone formation was assessed by dynamic histomorphometry of both cortical and cancellous bone as well as by Northern blot analysis for the expression of the osteoblast phenotypic proteins osteopontin (OP), osteocalcin (OC), type I collagen (COL) and alkaline phosphatase (AP). Aging resulted in a decline in the apparent material properties that was associated with a compensatory alteration of bone geometry that preserved structural strength and stiffness. Histomorphometric analysis revealed significant age-related decreases in cancellous bone volume, trabecular number and increased trabecular separation suggesting the existence of senile osteopenia in the proximal tibia of the male Fisher 344 rat. A significant decline in bone formation rate (BFR), but not mineral apposition rate, suggests that a reduction in osteoblast number, but not osteoblast activity, contributes to age-related bone loss. The decline in BFR with aging was reflected in a decreased mRNA expression for OP, OC and COL but not AP. Further, the pattern of mRNA expression was consistent with reduced osteoblast differentiation with aging. The present study indicates the age-related decline in material properties of long bones is paralleled by a decrease in osteogenesis.

Abstract This study examined the prognostic value of circulating peripheral blood plasma cells (PBPCs) in patients with primary systemic amyloidosis (AL). A sensitive slide-based immunofluorescence technique was used to assess 147 patients for circulating PBPCs. Circulating monoclonal plasma cells were quantified as a percentage of circulating cytoplasmic immunoglobulin-positive cells (PBPC%). The absolute circulating plasma cell count was also determined. When analyzed retrospectively, 24 (16%) of 147 patients were found to have detectable circulating PBPCs. Overall survival for patients with high PBPC%'s (> 1%) was poorer (median survival, 10 vs 29 months;P = .002). Similarly, overall survival for patients with high PBPC counts (> 0.5 × 106/L) was significantly poorer (median, 13 vs 31 months;P = .003). Increased percentages of bone marrow plasma cells (BMPC%; P = .0004), increased levels of serum β2-microglobulin (P = .04), and dominant cardiac amyloid involvement (P = .03) also predicted poorer survival. The combined consideration of circulating PBPCs and BMPC% identified low-, intermediate-, and high-risk groups with median survivals of 37.5, 15.5, and 10 months, respectively (P = .0003). Multivariate analysis revealed circulating PBPCs and BMPC% to be independent prognostic factors for survival. Patients with PBPC%'s of 2% or higher were significantly more likely to have a coexisting clinical diagnosis of multiple myeloma (50% vs 12%, P = .008). The prognostic value of circulating PBPCs may help select treatment for patients with AL.

Purpose: The purpose of this article is to determine the response rate and toxicity of PCV administered before radiation therapy in patients with newly diagnosed LGO/LGOA and to explore correlations between response with 1p/19q deletions and aberrant p53 expression. Background: Despite prolonged survival of patients with low-grade oligodendroglioma (LGO) and oligoastrocytoma (LGOA), the majority will succumb to progressive disease. Because procarbazine, lomustine (CCNU), and vincristine (PCV) is active in patients with recurrent LGO/LGOA, we hypothesized that it would be beneficial as primary therapy. Methods: Adult patients with residual tumor on magnetic resonance imaging scan following biopsy or subtotal resection of LGO/LGOA received up to six cycles of PCV. Radiation therapy (59.4 or 54.0 Gy) began within 10 weeks of completing chemotherapy or immediately if there was evidence of tumor progression on PCV. Tumor tissue was analyzed by fluorescent in situ hybridization for 1p and 19q deletion and by immunohistochemistry for p53 expression. Results: Eight of 28 (29%) and 13 of 25 (52%) eligible patients demonstrated tumor regression as assessed by the treating physician and a blinded central neuroradiology reviewer, respectively. Myelosuppression was the predominant toxicity. Loss of 1p and 19q were associated with LGO but not LGOA (P = .009), were inversely associated with p53 detection, and were not associated with response to PCV (possibly because of the small sample size). Conclusion: PCV produces tumor regressions in a meaningful proportion of patients with LGO/LGOA. Toxicity, especially myelosuppression, is significant. Loss of 1p and 19q seems limited to patients with pure LGO and is inversely related to p53 alterations.

ABSTRACT We investigated the effect of multiple freeze-thaw cycles on mumps, measles, and rubella virus serum antibody levels with whole-virus immunoglobulin G enzyme-linked immunoassays. Fresh serum samples from nine healthy adult volunteers were divided into six sets of five aliquots each. Samples were taken through a total of 10 freeze-thaw cycles and stored at 4°C until assayed. Each assay measurement was done in replicates of five, and the mean value was reported. After completing 10 freeze-thaw cycles, we found no clinically or statistically significant effect on measured antibody levels and found no discernible detrimental effect on the ability to measure these antibodies by enzyme-linked immunoassays.