Nitric oxide production during adjuvant-induced and collagen-induced arthritis.

OBJECTIVE: To investigate the role of nitric oxide (NO) production and NO synthase (NOS) induction during adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) in Dark Agouti rats. METHODS: Urinary nitrate excretion and immune NOS (INOS) messenger RNA (mRNA) expression were measured in the joint, lymph node, spleen, and liver tissues following the induction of either AIA or CIA. RESULTS: Urinary nitrate excretion and iNOS mRNA expression increased substantially during joint inflammation in both models of arthritis. However, the increases in urinary nitrate excretion and iNOS mRNA expression observed in the joint, liver, and spleen tissues during AIA were greater than those observed during CIA, although iNOS induction in the lymph nodes was similar for both models. A prior injection with Mycobacterium bovis heat-shock protein resulted in suppression of arthritis and NO production in AIA, but not in CIA. CONCLUSION: Differences in NO production during AIA versus CIA are a reflection of the fundamental pathophysiologic differences between these 2 models of arthritis. Thus, NO production in these 2 models could not be merely a nonspecific reaction to the adjuvant injection, nor simply a byproduct of local inflammation in the joint.

Molecular cloning, tissue expression of human xanthine dehydrogenase.

Xanthine dehydrogenase (XDH, EC 1.1.1.204) is a molybdenum iron-sulphur flavin hydroxylase which oxidizes a variety of purines, pterins and other heterogenic nitrogen compounds, serving as a rate-limiting enzyme in nucleic acid degradation. In this work, we have isolated and sequenced cDNA clones of human liver XDH. The obtained cDNA covers 4577 bases of human liver XDH mRNA with a 63 bp 5'-end untranslated region and a 515 bp 3'-end untranslated region. A termination codon TGA and a polyadenylation signal AATAAA were identified. An open reading frame encodes 1333 amino acid residues. The assignment of the N-terminal was confirmed by directly sequencing that region of purified human milk XDH. Northern blot analysis shows that the human XDH gene is widely expressed in human tissues.

Alveolar hemorrhage syndromes: diffuse microvascular lung hemorrhage in immune and idiopathic disorders.

We have reviewed the alveolar hemorrhage (AH) syndromes, defined as immune or idiopathic disorders associated with diffuse microvascular hemorrhage into the acinar portion of the lung. The disorders that are most often associated with AH include antibasement membrane antibodies (ABMA) disease, idiopathic pulmonary hemosiderosis, systemic lupus erythematosus, systemic vasculitides, and idiopathic rapidly progressive glomerulonephritis. An approach to the recognition, diagnosis, and treatment of the AH syndromes has been outlined and several illustrative case studies have been presented. Recognition of AH is not usually difficult, but does require a high index of suspicion, since many disease processes may give rise to hemoptysis with infiltrates on chest roentgenogram. Recognition of AH is aided by careful clinical and laboratory assessment for evidence of extrapulmonary disease; simple hematologic studies such as sequential hemoglobins and iron studies; and measurement of carbon monoxide uptake by the lungs. Early recognition of AH may decrease the likelihood of respiratory failure and end-stage renal disease. The specific etiology of AH is usually determined by clinical examination, serologic assay for ABMA, and percutaneous renal biopsy by immunofluorescence. Open-lung biopsy is required in a minority of cases. High-dose pulse methylprednisolone appears to effectively control AH of diverse etiology. Combined plasma exchange and immunosuppression controls AH in ABMA disease and is the treatment of choice in this disorder. Cyclophosphamide is used for Wegener's granulomatosis, and sometimes in systemic necrotizing vasculitis, in an attempt to prevent irreversible damage to the kidneys.

Selenium and vitamin E deficiencies do not enhance lung inflammation from cigarette smoke in the hamster.

The early lung inflammatory response to cigarette smoke may be oxidant-mediated. We fed Syrian hamsters a diet deficient in selenium and vitamin E to determine whether impairment of the lung's antioxidant defenses might worsen inflammation induced by cigarette smoke. After 8 wk, cigarette-smoke-exposed animals had characteristic inflammatory lesions in the distal airways. Increased numbers of phagocytes, predominantly macrophages, were recovered by lavage and these cells exhibited enhanced oxidative metabolism. Animals fed the deficient diet had profound depletions of selenium and vitamin E, but no alterations in the histologic appearance of smoke-induced inflammatory lesions, in the numbers of phagocytes recruited, or in the oxidative metabolism of these phagocytes. These results suggest that selenium and vitamin E are unimportant in protecting against cigarette-smoke-induced lung injury.