Pulmonary sarcoidosis: could mycoplasma-like organisms be a cause?

The etiology of sarcoidosis is unknown but an unusual bacterial agent is possible. Mycoplasma-Like Organisms [MLO] are obligate intracellular cell wall deficient bacteria with a distinctive ultrastructural appearance. MLO are a common cause of various transmissible plant diseases. Despite over 25 years of effort MLO remain uncultivated. Molecular biologic studies indicate MLO are only distantly related to extracellular cultivable mycoplasma. Diagnosis of MLO diseases is based chiefly on detection of the organisms in infected cells by electron microscopy. Recently MLO have been detected by electron microscopy within leucocytes in sterile inflamed aqueous and vitreous humor from patients with idiopathic chronic uveitis including sarcoidosis uveitis. Preliminary molecular biologic studies suggest that human MLO are quite closely related phylogenetically to plant MLO. Inoculation of human uveitis MLO into mouse eyelids produced chronic uveitis and lethal systemic granulomatous disease with MLO within leucocytes and endothelial cells in the disease sites. The MLO induced animal pulmonary disease resembled sarcoidosis. This report describes abnormal intracellular bodies consistent with MLO within leucocytes and endothelial cells adjacent to the granulomas in transbronchial biopsies from 9 corticosteroid untreated sarcoidosis patients versus none in 4 control lungs.

Colloquium on scientific authorship: rights and responsibilities.

The Colloquium on Scientific Authorship was held at the National Institutes of Health (NIH) at a time of extraordinary scrutiny by the public of the ethics of scientists, as represented by intense interest of the press and the Congress of the United States. Indeed, several regulations dealing with scientific misconduct have been proposed during the last year in the Federal Register, and new legislation has been proposed in the Congress. As a result of these concerns, conferences have been organized by the Institute of Medicine, the American Association for the Advancement of Science/American Bar Association, the Council of Biology Editors, and other groups. The colloquium at NIH, which was held May 31, 1988, and sponsored by the Intramural Scientists, focused on publication practices, especially multiple authorship, as contributing to perceived difficulties. The participants suggested various changes in conventions related to authorship that might help prevent future problems.

Addisonian crisis while taking high-dose glucocorticoids. An unusual presentation of primary adrenal failure in two patients with underlying inflammatory diseases.

The diagnosis of acute hypoadrenalism seldom is considered in patients without known adrenal insufficiency who are taking supraphysiologic amounts of glucocorticoids. We report two patients who presented in acute addisonian crisis on more than one occasion while taking high doses of glucocorticoids (30 to 40 mg of prednisone daily) for underlying inflammatory disease (recurrent pleuropericarditis and sarcoidosis). Evidence of severe mineralocorticoid deficiency was present in each patient, and the conditions of both improved remarkably when mineralocorticoid was added to their regimens. The cause of primary adrenal failure and its acute presentation was unclear in both patients but is presumed to be related to the underlying inflammatory disease.

Linkage between ligand binding and the dimer-tetramer equilibrium in the Monod-Wyman-Changeux model of hemoglobin.

G. Weber [(1984) Proc. Natl. Acad. Sci. USA 81, 7098-7102] has inferred that the Monod-Wyman-Changeux (MWC) model for ligand binding by hemoglobin would require (contrary to experimental evidence) that increased ligand binding must promote stabilization of alpha 2 beta 2 tetramers with respect to dissociation into alpha beta dimers. Reexamination of the MWC model, however, in the light of general linkage principles and the specific analysis by G. K. Ackers and M. L. Johnson [(1981) J. Mol. Biol. 147, 559-582] shows that the opposite relation must hold, in agreement with experiment. The T form of the tetramer, with low ligand affinity, must be destabilized and progressively dissociates into the high-affinity dimers, designated D, as ligand binding increases. Each ligand molecule bound shifts the standard Gibbs free energy delta G2T for the D-T equilibrium by approximately 3 kcal/mol in favor of the dimer. Thus, T must exist in (at least) five delta G levels of cooperative free energy as it becomes progressively destabilized by successive binding of ligand molecules. Dissociation of the R tetramer to dimers, in contrast, is independent of the amount of ligand bound, so long as dimers and R-state tetramers possess the same (high) affinity for ligand. While the intrinsic ligand-binding constants of the T and R states (KT and KR) remain unchanged throughout by the postulates of the model, the model should not be regarded as a strictly two-state system in view of the multiple free-energy levels indicated above. The present analysis gives approximate, though not precise, agreement with experimental findings on the dimer-tetramer equilibrium considered by Weber and provides a rationale for interpreting other recent experiments concerning this equilibrium.