Immunogenicity of xenogeneic cartilage matrix components in a rabbit model

Purified xenogeneic cartilage matrix components, including proteoglycan subunits, chondroitin 4 sulfate, and chondroitin 6 sulfate, were inoculated into the knee joint of rabbits, and local as well as systemic responses were evaluated. proteoglycan was associated with synovial hyperplasia and infiltrates of eosinophils and lymphocytes and with rising titers of antiproteoglycan antibodies in a tanned sheep rbc hemagglutination assay over a six-week period of weekly intra-articular injections and observations. Chondroitin sulfates failed to evoke detectable changes in the joint or serum. Immunogenicity of cartilage matrix components may play a role in allogeneic and xenogeneic osteochondral grafts, and it is also possible that autogenous matrix immunogens exist and contribute to progression of degenerative joint disease. The immunogenicity of allogeneic and autogenous cartilage matrix components remains undefined.     

Biofeedback treatment of atopic dermatitis

To investigate the feasibility of a behaviorally oriented intervention program with atopic dermatitis, 12 patients were exposed to a fixed sequence of treatment phases including a no-treatment baseline phase, a phase incorporating nonspecific treatment factors, and a phase involving frontal electromyographic (EMG) feedback and relaxation instructions. Photographic analyses of involved skin areas revealed significant remission of dermatological problems across the entire program, although significant changes could not be attributable to any specific phase. Ratings of itching level decreased within but not across treatment sessions, and variable correlations across subjects were found between frontal EMG and itching level. MMPI results from the dermatitis subjects were within normal limits. Overall, the results provided mixed support for the hypothesis that atopic dermatitis may be amenable to intervention through behaviorally oriented treatment procedures.     

X-Y chromosome univalency in the testes of hyperthermic mice: II. Light and electron microscopic analysis of synaptonemal complexes

Hyperthermia-induced X-Y dissociation has been observed in diakinesis-metaphase I sper-matocytes but not in pachytene spermatocytes, which have been implicated as highly susceptible to heat stress. To determine X-Y dissociation in pachytene spermatocytes and to compare levels of dissociation between pachytene and diakinesis-metaphase I spermatocytes male ICR mice were exposed to 35°C ± 0.07°C and 65% ± 0.14% relative humidity for 2 or 4 days. Control mice were housed at 24°C ± 0.04°C and 43% ± 0.58% relative humidity. Mice were killed 0, 3, 5, 8, or 10 days after stress and the testes processed for meiotic chromosome display at diakinesis-metaphase I and synaptonemal complex display at pachynema. Twenty-five to thirty cells per mouse at both stages of meiosis were observed with light microscopy, and pachytene spreads with transmission electron microscopy to determine heat-stress effects on synaptonemal complex structure. Statistical analyses revealed significant linear increases in X-Y dissociation with prolonged exposure to heat at pachynema and diakinesis-metaphase I. Levels of pachytene dissociation were one-half the levels of dissociation at diakinesis-metaphase I. The resolvable structure of the lateral elements of the synaptonemal complex was not affected by heat stress.     

The health seeking process: An approach to the natural history of illness

Culture, Medicine, and Psychiatry - Anthropological research on health-related behaviors in the United States has tended to emphasize folk illnesses among particular subcultural groups, obscuring...     

Formation of pyrophosphate by soluble guanylate cyclase from rat lung.

The guanylate cyclase reaction was studied to determine the identity of the product(s) formed other than guanosine-3′,5′-monophosphate (cyclic GMP). Partially purified guanylate cyclase preparations from rat lung catalyzed the formation of nearly equal amounts of PP₁ and of cyclic GMP from GTP. Column chromatography of the enzyme preparation on DEAE-Sephadex or Bio-Gel A-5m failed to separate the enzyme(s) involved in formation of cyclic GMP and of PP₁. Nucleotide inhibitors of cyclic GMP formation also inhibited PP₁ formation, and Ca²⁺, a stimulant of cyclic GMP formation in the presence of Mn²⁺, also stimulated PP₁ formation. Detectable PP₁ formation was not observed when ATP was present instead of GTP.The results show that guanylate cyclase, in vitro, catalyzes the formation of pyrophosphate from GTP concomitant with the synthesis of cyclic GMP.     

Impaired synthesis of prostaglandin E2 by lung fibroblasts and alveolar epithelial cells from GM-CSF-/- mice: implications for fibroproliferation

Prostaglandin E(2) (PGE(2)) is a potent suppressor of fibroblast activity. We previously reported that bleomycin-induced pulmonary fibrosis was exaggerated in granulocyte-macrophage colony-stimulating factor knockout (GM-CSF(-/-)) mice compared with wild-type (GM-CSF(+/+)) mice and that increased fibrosis was associated with decreased PGE(2) levels in lung homogenates and alveolar macrophage cultures. Pulmonary fibroblasts and alveolar epithelial cells (AECs) represent additional cellular sources of PGE(2) within the lung. Therefore, we examined fibroblasts and AECs from GM-CSF(-/-) mice, and we found that they elaborated significantly less PGE(2) than did cells from GM-CSF(+/+) mice. This defect was associated with reduced expression of cyclooxygenase-1 and -2 (COX-1 and COX-2), key enzymes in the biosynthesis of PGE(2). Additionally, proliferation of GM-CSF(-/-) fibroblasts was greater than that of GM-CSF(+/+) fibroblasts, and GM-CSF(-/-) AECs were impaired in their ability to inhibit fibroblast proliferation in coculture. The addition of GM-CSF to fibroblasts from GM-CSF(-/-) mice increased PGE(2) production and decreased proliferation. Similarly, AECs isolated from GM-CSF(-/-) mice with transgenic expression of GM-CSF under the surfactant protein C promoter (SpC-GM mice) produced more PGE(2) than did AEC from control mice. Finally, SpC-GM mice were protected from fluorescein isothiocyanate-induced pulmonary fibrosis. In conclusion, these data demonstrate that GM-CSF regulates PGE(2) production in pulmonary fibroblasts and AECs and thus plays an important role in limiting fibroproliferation.