Musculoskeletal disorders associated with type-IV hyperlipoproteinaemia.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J H Herman.
Explore the source record for details and available documents.
The secondary immune response to tetanus toxoid in 14 patients with rheumatoid arthritis (RA) has been studied in suspension cultures of peripheral blood lymphocytes (PBL) and synovial membrane obtained at synovectomy. Sequential cultures of PBL from three normal subjects established the optimal time of antibody response at 5 days. At this time, the antitetanus antibody produced was predominantly IgG, comprising half of this immunoglobulin fraction. Rheumatoid synovium synthesized 5-9 times more IgG than PBL, expressed as per cent of total protein synthesis, but only negligible amounts of tetanus antibody. The same results were observed in synovial cultures following repeated immunization and after the additional intra-articular injection of tetanus antigen. This marked limitation of the synovium to respond to exogenous antigen in spite of its large immunoglobulin production was considered consistent with a prior commitment of the synovial lymphoid infiltrate to other antigen.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The authors identified persistent Th activation in five of seven children (71.4%) diagnosed as having Fanconi's anemia or Diamond-Blackfan syndrome. Th reactivity was no longer present in one patient after bone marrow transplantation. Tests on family members and other patients with bone marrow dysfunctions of childhood showed no Th activation. Less than 1 percent of healthy children or blood donors had Th activation. Patients with a variety of hemolytic and hypoplastic conditions also had a low incidence of Th activation. However, 13.5 percent of cord blood specimens demonstrated Th reactivity. This study indicates that Th activation may be a red cell developmental marker present in congenital hypoplastic anemias and also expressed on newborn red cells.
Explore the source record for details and available documents.
Neonatal alloimmune thrombocytopenia (NAIT) most commonly involves antibodies directed against the PlA1 antigen, but other platelet specific alloantigens have been associated with it. We describe the case of a mother whose first three infants developed NAIT secondary to anti-Bak(a) antibodies, while her fourth infant did not. The three affected infants were treated postnatally with platelet transfusions. The fourth infant was treated antenatally with one dose of intravenous immunoglobulin (IVIg) given to the mother. Postpartum analysis revealed the infant's platelets to be Bak(a)-positive but negative for elevated IgG. Maternal serum reacted with neonatal platelets in vitro, but cord serum was negative for antiplatelet antibodies. These clinical observations do not prove the efficacy of IVIg; however, they raise several questions: Why wasn't this infant thrombocytopenic? Why didn't the umbilical cord contain maternal antibody? Was the single dose of IVIg responsible for preventing NAIT? IVIg is currently under investigation in a clinical trial evaluating its effectiveness in preventing NAIT in mothers with anti-PlA1 antibodies, where it has shown some success. There have been no reports of the use against anti-Bak(a) antibodies. We suggest that a weekly dose schedule may not be necessary for all affected pregnancies, and antibodies with specificity other than anti-PlA1 may require less vigorous therapy.
In studies designed to establish the safety and efficacy of laser treatment of arthritis, the in vitro effect of Nd:YAG laser radiation on normal, osteoarthritic and rheumatoid synovial tissue and synovial fibroblast metabolism has been addressed. Defined energy levels of normal pulsed radiation (TEMoo mode) consistently up-regulated synovial tissue explant culture hyaluronic acid and protein synthesis. In contrast, high intensity Q-switched delivery down-regulated the response. The application of normal pulsed radiation had a variable effect on synovial fibroblast synthesis but the response of any given cell isolate was consistent. DNA synthesis and cell viability were not affected.
Previous investigations of ribonucleotide binding activity in the sera of patients with connective tissue diseases unexpectedly identified binding to the single stranded nucleotide polyadenylic acid (Poly [A]) in osteoarthritic patients serving as control subjects. The basis for this response and the nature of the binding factor(s) were not evaluated. Hypothesizing that such activity may originate from diseased joint tissue and that its measurement would provide a valuable parameter to assess active cartilage catabolism, the present study examined the Poly (A) binding affinity of cartilage isolates. It was shown that low buoyant density associative cesium chloride gradient fractions of guanidine extracts of cartilage could bind to Poly (A). Activity appeared to be largely masked in native proteoglycan aggregates but could be identified in low buoyant density dissociative cesium chloride gradient fractions of aggregates. Chondroitin sulfate, hyaluronic acid and native and denatured cartilage collagen had a minimal binding affinity. By nucleotide absorption, a purine ring specificity was shown for the active binding factor. Using polyacrylamide slab gel elution and Poly (A) affinity chromatography, activity was localized to a 57 KDa protein.
Previous investigations assessing ribonucleotide binding in the sera of patients with diverse forms of connective tissue disease unexpectedly identified positive responses in control osteoarthritic subjects. The current study, using a radiolabelled assay, confirms the presence of a polyadenylic acid (Poly [A] binding factor(s) in the sera of a group of 50 well-characterized patients having primary or secondary forms of this disease process as contrasted with matched control subjects. The significance of such binding activity is unknown. No significantly meaningful correlation could be established between serum Poly (A) binding levels and clinical or x-ray parameters of disease.
The lysosomal endopeptidase cathepsin D is the most abundant proteinase in chondrocytes. Its significance in the pathogenesis of cartilage matrix proteoglycan (PG) degradation in osteoarthritis (OA) is unclear. The extracellular localization of cathepsin D and its potential spatial relationship to areas of PG depletion has been studied in human femoral head OA cartilage. Enzyme was identified by indirect immunofluorescence using rabbit antisera developed against a highly purified cathepsin D preparation. PG distribution was assessed in parallel sections by safranin O staining. Specimens were selected to include regions of cartilage having minimal structural and cellular alterations, severe reduction in thickness, hypocellularity, multicellular chondrocyte clusters and varying degrees of PG loss. Cathepsin D was identified in chondrocytes. When overlying fibrous connective tissue pannus was present, extracellular enzyme was predominantly localized to the cartilage-pannus interface. Cathepsin D could not be demonstrated extracellularly in areas of cartilage that were partially or totally devoid of PG. Chondrocytes in damaged regions, particularly in the superficial and upper transitional zones showing diffuse hypercellularity and/or "brood" clusters, contained increased enzyme staining. Results fail to support a role for cathepsin D in extracellular matrix PG degradation. The potential significance of this enzyme in the pathogenesis of OA would appear relegated to intracellular catabolism. Its intracellular increase at pathologic sites is consistent with enhanced catabolic activity in such regions.
Investigations were performed to determine the potential of an immunologically-mediated basis underlying development of severe bilateral knee chondrolysis arising over a 2-yr period in a 29-yr-old man. Humoral and cell-mediated immune responses to autologous and homologous articular cartilage proteoglycan and collagen rich fractions were identified in sequential studies. Employing gradient derived peripheral blood mononuclear cells there was demonstration of spontaneous, T cell mitogen augmented and autologous cartilage antigen-induced release of factors capable of degrading articular cartilage proteoglycans and inhibiting chondrocyte glycosaminoglycan synthesis. Evidence has thus been provided incriminating immunologic events, likely functioning in a perpetuant manner, in the pathogenesis of this chondrolytic process.