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A patient is presented who had therapy-resistant epileptic seizures from the 7th day of life. Examination at the age of 17 months revealed a mentally retarded boy with epileptic seizures, generalised myoclonic contractions, and abnormal ocular movements. A cerebral CT scan showed central and cortical atrophy. Lactate levels in serum, cerebrospinal fluid and urine were elevated, the pyruvate level was raised in serum. A quadriceps muscle biopsy revealed aspecific morphologic signs of a myopathy. Biochemical analysis showed decreased substrate oxidation rates in the mitochondria associated with low rates of ATP production. Total and free carnitine levels were decreased. Investigation of the respiratory chain revealed a defect in the proximal part of respiratory chain involving the region of coenzyme Q. Based on clinical and chemical data it is likely that the patient is suffering from a multi-system disorder.

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Overaccumulation of abnormally organized mitochondria in so-called "ragged-red" skeletal muscle fibers Is a morphological hallmark of mitochondrial myopathies, in particular of mitochondrial encephalomyopathies. Characteristic for the abnormal mitochondria is the occurrence of highly ordered crystallineImmuno-electron microscopy revealed that these inclusions react heavily with specific antibodies against mitochondrial creatine kinase (Mi-CK). Image processing of selected crystalline inclusions, sectioned along the crystallographic b, c planes, resulted in an averaged picture displaying an arrangement of regular, square-shaped particles with a central cavity. The overall appearance, dimensions, and symmetry of these bullding blocks are very reminiscent of single isolated Mi-CK octamers. Taking these findins together, it is concluded that Mi-CK oiamers indeed represent the major, if not the only, component of these mitochondrial inclusions.The mitochondrial myopathies in which a defect in mitochondrial metabolism is thought to be the primary cause of the disease are clinically, biochemically, and genetically a heterogeneous group of disorders (1-3). For example, biochemical analysis reveals that respiratory chain deficiencies can be absent or vary from isolated defects to combined defects of several complexes of the chain (4, 5). To a varying degree, respiratory chain defects have also been reported in the so-called "encephalomyopathies"-i.e., in chronic progressive external ophthalmoplegia (CPEO), in Kearns-Sayre syndrome, in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), and in MERRF [myoclonus epilepsy with ragged-red fibers (RR fibers)] syndrome. All of these diseases are characterized by the presence of RR fibers in muscle biopsy specimens (1, 2).Characteristic aspects of the pathology in the RR fibers are an accumulation of abnormal and enlarged mitochondria and the occurrence in these mitochondria of highly ordered crystal-like inclusions, often referred to as "railway-track" or "parking lot" inclusions, within their intermembrane spaces (6, 7).Using optical diffraction techniques on thin muscle biopsy sections, the mitochondrial inclusions were shown to be true crystals (8). Two distinct types of crystals, type I (Fig. 1A) and type II (Fig. 1B), can be distinguished on the basis of shape, size, pattern, unit cell dimension, specific location of the crystals in the mitochondrial intermembrane space, and occurrence in different muscle fiber types. Understanding the role of the crystals in relation to the patient's pathology, either in terms of causative dysfunction or of mitochondrial response to a disease, requires a detailed knowledge of their chemical composition. Therefore, the biochemical and immunological nature ofthese inclusions has been studied using proteolytic digestion, enzyme cytochemistry, and immunogold labeling techniques. In addition, image processing of selected areas of these crystalline inclusions was performed to obtain more detailed s...

In this paper we present, based on elaborate ultrastructural studies, data on the existence of both intracellular and extracellular stages of Pneumocystis carinii, which result in a proposal of a new life cycle of the parasite. Up to now the formation of daughter cells in thick-walled pneumocysts is supposed to be the only way of multiplication. The present study shows that in rats treated with cortisone acetate the formation of daughter cells also takes place within thin-walled pneumocysts. In our opinion this way of multiplication is important for the understanding of the rapid increase in number of the parasites in an infected lung. The presence of pneumocysts inside the alveolar epithelial cells suggests that intracellular development of the parasites can occur, but the method of cell penetration, intracellular multiplication and parasite liberation is still unknown. Moreover our observations for the first time indicate a direct pathogenicity of the parasites in host cells.