Knee effusions, popliteal cysts, and synovial thickening: association with knee pain in osteoarthritis.

OBJECTIVE: To evaluate the association of effusions, popliteal cysts, and synovial thickening with knee symptoms in older persons with and without radiographic (XR) osteoarthritis (OA), using magnetic resonance imaging (MRI). METHODS: Subjects with and without knee symptoms were recruited from Veterans Affairs and community sources. All had weight-bearing knee radiographs. Subjects were divided into 3 groups: Knee pain/XROA group had knee symptoms and radiographic OA; No knee pain/XROA group had no knee symptoms and radiographic OA; and No knee pain/no XROA group had no knee symptoms and a normal radiograph. A single knee was imaged using a 1.5 T MR scanner using T1 and T2 weighted and proton density SE imaging sequences. MRI were read for effusion, popliteal cysts, and synovial thickening. RESULTS: The mean age of subjects was 67.0 years (66.6% male). We studied 381 subjects with Knee pain/XROA, 52 with No knee pain/XROA, and 25 with No knee pain/no XROA. The prevalence of moderate or larger effusions was: Knee pain/XROA 54.6%, No knee pain/XROA 15.6%, and No knee pain/no XROA 11.1%. Popliteal cysts were present in 33.0% of Knee pain/XROA subjects, 28.0% No knee pain/XROA, and 9.1% No knee pain/no XROA. After adjusting for the severity of radiographic OA, there was a difference between those with and without knee pain in prevalence of moderate or larger effusions (p < 0.001) and synovial thickening, independent of effusion (p < 0.001), but not in the prevalence of popliteal cysts. Further, among those in Knee pain/OA group, synovial thickening was associated with the severity of knee pain. CONCLUSION: Effusions and popliteal cysts are common in middle aged and elderly people. After adjusting for the degree of radiographic OA, moderate or large effusions and synovial thickening were more frequent among those with knee pain than those without pain, suggesting these features are associated with the pain of knee OA. In those with knee symptoms, synovial thickening is uniquely associated with the severity of knee pain.

Identification of two new Pmp22 mouse mutants using large-scale mutagenesis and a novel rapid mapping strategy.

Mouse mutants have a key role in discerning mammalian gene function and modelling human disease; however, at present mutants exist for only 1-2% of all mouse genes. In order to address this phenotype gap, we have embarked on a genome-wide, phenotype-driven, large-scale N-ethyl-N--nitrosourea (ENU) mutagenesis screen for dominant mutations of clinical and pharmacological interest in the mouse. Here we describe the identification of two similar neurological phenotypes and determination of the underlying mutations using a novel rapid mapping strategy incorporating speed back-crosses and high throughput genotyping. Two mutant mice were identified with marked resting tremor and further characterized using the SHIRPA behavioural and functional assessment protocol. Back-cross animals were generated using in vitro fertilization and genome scans performed utilizing DNA pools derived from multiple mutant mice. Both mutants were mapped to a region on chromosome 11 containing the peripheral myelin protein 22 gene (Pmp22). Sequence analysis revealed novel point mutations in Pmp22 in both lines. The first mutation, H12R, alters the same amino acid as in the severe human peripheral neuropathy Dejerine Sottas syndrome and Y153TER in the other mutant truncates the Pmp22 protein by seven amino acids. Histological analysis of both lines revealed hypo-myelination of peripheral nerves. This is the first report of the generation of a clinically relevant neurological mutant and its rapid genetic characterization from a large-scale mutagenesis screen for dominant phenotypes in the mouse, and validates the use of large-scale screens to generate desired clinical phenotypes in mice.

Cytotoxic antibody in acute myeloblastic leukaemia during immunotherapy: lack of tumour specificity.

Cytotoxic antibodies to antigens specific for leukaemic myeloblasts have been sought in the serum of patients with acute myeloblastic leukaemia treated by immunotherapy with irradiated allogeneic myeloblasts and BCG. Assays of complement- and K-cell-mediated activity were used. Cytotoxicity to allogeneic myeloblasts was detected in both assays. When sera from 15 patients, taken at various times during immunotherapy, were systematically tested against a panel of 5 myeloblasts, the following patterns emerged: 1. No antibody was cytotoxic against all myeloblasts of the panel in either the K-cell or complement-dependent assay. However, all myeloblasts of the panel were lysed by a number of sera. 2. Cytotoxic antibody was detected as often against a panel of lymphocytes from healthy donors as against the panel of allogeneic myeloblasts. 3. Fresh and cryopreserved myeloblasts were equally susceptible to lysis in both assays. 4. Experiments failed to demonstrate any deterioration of cytotoxic antibody on storage. 5. The number of K-cell-revealed cytotoxic antisera increased with length of immunotherapy. This pattern was not apparent for antibodies revealed by complement. 6. No instance of cytotoxicity in either assay was seen when serum was tested against 12 autologous myeloblasts. It is considered that cytotoxic antibody detected with allogeneic myeloblasts is probably directed against HLA antigens common to immunizing and test target myeloblasts and target lymphocytes.

Resistance of certain leukaemic myeloblasts to immunological attack.

Leukaemic cells from four out of 19 patients with acute myeloblastic leukaemia are shown to be resistant to lysis by rat anti-muman-myeloblast antibody in the presence of complement. To a lesser degree this is reflected in lack of immunogenicity of these myeloblasts. It is suggested that these findings may be relevant in planning immunotherapy in this disease and evaluating the benefit of this type of treatment. Finally data are presented to show that loss of immunogenicity of myeloblasts after irradiation with 10,000 R, as is practised in certain immunotherapy schedules, is small compared with differences in immunogenicity between non-irradiated myeloblasts from different individuals.