Lewis Johnson

Chronic orbital inflammatory disease: parasitisation of orbital leucocytes by mollicute-like organisms.

Chronic orbital inflammatory disease (COID) is usually considered non-infectious and idiopathic. Treatment is empirical, palliative, and may not prevent disease progression. COID occurs in isolation or in association with various systemic diseases. Exophthalmos may be an important presenting sign. Vasculitis, lymphoid infiltrates, and granulomas are common. Mollicute-like organisms (MLO) parasitising and destroying vitreous leucocytes are often found to cause human chronic uveitis when an appropriate search is made. Inoculation of these MLO into mouse eyelids produced chronic uveitis and exophthalmic orbital inflammatory disease. Mollicutes are cell wall deficient bacteria. Extracellular mollicutes cause human and animal diseases characterised by lymphoid infiltrates, immunosuppression, and autoantibody production. Intracellular morphologically similar bacteria are non-cultivable pathogens termed MLO. Identification is based on direct detection in diseased cells by transmission electron microscopy. MLO are cytopathogenic and detection is aided by the alterations they produce. MLO replace the cytoplasm, destroy the organelles, and alter the nucleus. This results in cell proliferation, destruction, and dysfunction. MLO parasitise lymphocytes, monocytes, and polymorphonuclear leucocytes. This report describes orbital leucocytes parasitised by MLO in three patients with isolated COID. Rifampicin treatment of MLO disease is discussed.

Sarcoidosis associated uveitis. Parasitization of vitreous leucocytes by mollicute-like organisms.

Abstract. Mollicute‐Like Organisms (MLO) have been reported to be a cause of uveal tract and orbital chronic inflammatory disease. MLO are intracellular cytopathogenic cell wall deficient bacteria. No culture system exists for MLO. MLO disease diagnosis is based chiefly on direct detection of the organisms within diseased cells using a transmission electron microscope. Uveitis producing MLO are detectable within vitreous leucocytes as 0.005–0.01 micron filaments and undulating pleomorphic 0.01–1.0 micron tubulo‐spherical bodies. Human uveitis producing MLO can be passed to laboratory animals. Inoculation into mouse eyelids produced intraocular, orbital, and lethal systemic chronic progressive inflammatory disease. MLO parsitised lesional leucocytes were found in all the disease sites. The MLO induced mouse chronic interstitial pneumonitis displayed ‘sar‐coid‐like’ granulomas. This report describes MLO parasitised vitreous leucocytes in the chronic uveitis of four sarcoidosis patients. The results indicate that MLO caused the uveitis. The implications of the results and Rifampin treatment of MLO disease are discussed.

Murine chronic tubulointerstitial nephritis: induction by human uveitis mycoplasma-like organisms

&NA; Mycoplasma‐like organisms (MLO) are non‐cultivated intracellular cell wall deficient pathogenic bacteria with a distinctive ultrastructural appearance. Diagnosis of MLO disease rests on finding the organisms in parasitized cells using a transmission electron microscope. MLO are a well studied cause of transmissible chronic plant vascular disease responsive to antibiotics. MLO have recently been found to cause human chronic progressive ophthalmic disease including uveitis. In human uveitis MLO are readily found within parasitized intraocular fluid leucocytes. Inoculation of human uveitis MLO into mouse eyelids produced a high incidence of chronic progressive ophthalmic disease including uveitis. MLO also disseminated to produce randomly distributed lethal systemic inflammatory disease. MLO parasitized leucocytes and microvascular alterations were found in the disease sites by electron microscopy. This report describes the chronic progressive tubulointerstitial nephritis in 12 of 100 human uveitis MLO eyelid inoculated mice versus 0 in 200 control mice (p<0.0001). MLO parasitized leucocytes accompanied by tubular and microvascular alterations were found by electron microscopy in all 12 inflamed kidneys versus 0 of 4 control kidneys. Pathobiology of the MLO‐induced murine nephritis, resemblance of this nephritis to human idiopathic chronic tubulointerstitial nephritis, bacterial molecular biology, and antibiotic therapy of MLO disease are discussed.

Postinflammatory cataracts in the mouse: induction by human mycoplasma-like organisms.

Cataracts often occur in humans secondary to uveitis. Uveitis may be caused by various infectious agents, but rarely is the agent detected in the cataract. Mycoplasma-like organisms (MLO) were recently reported to cause human uveitis and retinitis. Cataracts were often present in those inflamed eyes. MLO are intracellular cell wall deficient pathogenic bacteria. They are pleomorphic tubulospherical and filamentous organisms with a characteristic ultrastructural appearance. No MLO culture system has been found despite 20 years of effort. The diagnosis of MLO disease rests on detection of the organisms in parasitised cells by a transmission electron microscope and response to antibiotics. In human intraocular inflammatory disease MLO are detectable in parasitised leucocytes and retinal pigment epithelial cells at the disease sites. Inoculation of MLO from a human source into mouse eyelids produced intraocular, chronic, progressive, inflammatory disease, with intraocular leucocytes parasitised by MLO in 15 of 100 mice versus 0 in 200 controls (p less than 0.05). This report describes the cataracts with MLO-parasitised intralenticular leucocytes in the inflamed eyes of 14 of those 15 mice versus 0 in 200 control mice (p less than 0.05). The results indicate that MLO penetrated the lens capsules to produce the cataracts, and they suggest that MLO could cause human cataracts. Alternative methods for detection of MLO and rifampin treatment of MLO intraocular disease are discussed.

Mouse exophthalmic chronic orbital inflammatory disease. Induction by human leucocyte intracellular Mollicutes.

Mollicutes are cell wall deficient bacteria which may be overlooked or confused with viruses because of indistinct light microscopic morphology, poor staining, difficulty in cultivation, and the ability to pass 0.450 micron filters. As they have a distinctive ultrastructural appearance they can be identified using transmission electron microscopy [TEM]. Using TEM vitreous leucocytes from chronic endogenous uveitis patients may demonstrate non-cultivable intracellular 0.005–1.0 micron mollicute-like organisms [MLO], some of which develop into distinctive cell walled cocci, 0.5–0.7 micron in diameter. Inoculation of those MLO containing human vitreous into mouse eyelids produces chronic cardiac and uveal vasculitis with orbital inflammation. Similar MLO are found within the mouse lesional leucocytes. This report describes the chronic orbital inflammation with vasculitis in 67 of 100 of those MLO inoculated mice versus 0 of 200 controls (P<0.05). Exophthalmos with inflammation also occurred in 12 of those 67 mice (P<0.05). MLO were found within orbital lesional leucocytes of 10 of 10 of those mice using a TEM versus 0 of 10 controls. The results indicate that vasculitis and exophthalmos were important features of this MLO induced mouse orbital inflammation. The implication of these results for human idiopathic chronic orbital inflammatory disease is discussed.

Mycoplasma-like organism induced murine cardiac microvasculopathy. A transmission electron microscopic study.

Mycoplasma-Like Organisms [MLO] are intracellular cell wall deficient bacteria that cause ocular chronic vasculitis in man and chronic vascular disease in plants. Since MLO do not grow in culture, diagnosis of MLO-induced disease requires identification of the organisms by electron microscopy. Ultrastructurally, MLO appear as pleomorphic tubulo-spherical and filamentous organisms. In human ocular disease MLO have been detected in parasitised leucocytes and retinal pigment epithelial cells. We have previously reported the results of injecting MLO infected human vitreous into mouse eyelids. Two thirds of the mice developed chronic disease at the inoculation site, but, more importantly, the mice also developed lethal systemic MLO disease. Carditis with histologic features similar to those of various types of human carditis occurred in 18% of the mice. This report describes the ultrastructural features of the cardiac microvascular MLO disease in those 18 mice that died of carditis after inoculation with human MLO-infected vitreous. MLO were identified in leucocytes and endothelial cells of the murine vascular lesions. The vascular lesions were characterized by destruction of vessel walls as well as proliferation of endothelial cells. Electron dense deposits were seen in basement membranes and pericytial tissues. Similar features have been described in other bacterial vascular infections and in human idiopathic carditis. We suggest that MLO could be a cause of human cardiovascular disease and should be looked for in such cases.