Biomedical subjects
Publications and source records attributed to M Elleder.
A survey is presented of adult type neurometabolic disorders with dominant psychiatric and/or neurological and myopathic symptomatology. Also mentioned are the manifest clinical symptomatology in heterozygous state and asymptomatic or oligosymptomatic clinical pictures in homozygotes.
Phagocytosis of native allogenic red blood cells was observed in cultures of skin fibroblasts obtained from patients with neuronal ceroid-lipofuscinosis, Niemann-Pick disease type C and morbus Fabry. Occasional phagocytizing cells were observed in 9 other syndromes. Cells from three normal donors did not phagocytize.
We describe here a male infant with a rare form of glycogenosis caused by deficiency of heart specific phosphorylase b kinase. The disease phenotype was characterized by severe glycogenosis restricted to the heart muscle with secondary rapidly progressive hypertrophic cardiomyopathy causing death at the age of 47 days.
Clinicopathological studies of a series of nine children with a new subform of Jansky-Bielschowsky disease or late infantile neuronal ceroid lipofuscinosis (LINCL) is presented. The onset of this subform is between 2.5-3.5 years of age with initial neurological symptoms of abnormal motor skills caused by cerebellar and extrapyramidal signs. Soon after dementia, myoclonic seizures are followed. Visual impairment is more clearly seen after the age of 5 or 6 years. The ultrastructural studies of the skin and/or buffy coat showed abundant lysosomal storage of curvilinear profiles, rarely intermixed with fingerprint profiles. The MRI of the head performed in seven cases, showed initially enlargement of the ventricles that is secondary to basal ganglia atrophy and presence of cerebellar and cerebral atrophy. In 4 of 7 cases (Cases 1, 5, 6, 8) abnormalities in the deep white matter showing increased signals of T2-weighted imaging in the periventricular areas of the fronto-parietal region, internal capsule, tracks of the brainstem, and white matter of cerebellum were seen. These abnormalities were also observed by post-mortem neuropathological studies in three cases (nos. 7-9). The MRI in Cases 7 and 9 was not performed. The electrophysiological abnormalities (EEG, ERG, VER) are similar as described in the classical LINCL. Neuropathological studies done in 3 of 9 cases showed generalized brain atrophy and unique type of neuronal cytoplasmic inclusion body in the basal ganglia, brainstem, dentate nuclei, and rarely, cerebral cortex. These large, round neuronal cytoplasmic inclusions were pink in hematoxylin (HE), violet in cresyl violet, and dark blue with Klüver-Barrera method.(ABSTRACT TRUNCATED AT 250 WORDS)
The test is based on the reaction of unesterified cholesterol with fluorescent antibiotic filipin giving a strongly fluorescent, stable cholesterol-filipin complex suitable for in situ detection. The test is useful for the evaluation of impaired cholesterol esterification in cultured cells (fibroblasts or others) in Niemann-Pick disease type C.
The first case of infantile sialic acid storage disease in Czech Republic is presented in a four-and-half year-old girl. The clinical phenotype consisted of moderate hepatosplenomegaly and skin hypopigmentation, early psychomotoric and developmental arrest, associated with truncal ataxia and lower extremities spasticity, extinguished acoustic and visual perception (optic atrophy without macular alteration) and remarkable automutilation phenomena. The appearance was normosomatic and there were minimal dysostotic changes. Skin and liver biopsy displayed moderate amount of lucent storage lysosomes in epithelial, mesenchymal, and neural elements. Alder-Reily granules were found in the bone marrow and peripheral blood cells. The urinary excretion of mucopolysaccharides and oligosaccharides was not increased. The autopsy showed heterogenous neuronal and glial brain storage (lucent lysosomes, lipopigment, membranous cytoplasmic bodies), severe hypomyelination and severe storage in the splenic sinus endothelium. Diagnosis was made by proving thirteen fold increase of free sialic acid in the fibroblast culture. It is pointed out that in the case of a mucopolysaccharidosis-like storage disease unexplainable by a hydrolytic enzyme deficiency, it is the enzyme product storage which must be suspected. At present, the only candidate is the sialic acid storage disease.
Explore the source record for details and available documents.
Severe graft-versus-host disease (GVHD) developed following intravenous administration of parental BN.lx lymphoid cells into (SHR x BN.lx)F1 animals. Clinical symptoms, including foot-pad hyperemia, slobbering, melaena, progressive weight loss leading to death within 3 to 4 weeks, can be completely abrogated by 8 injections of PMEA starting 1 h after cell administration. Practically normal histological findings in PMEA-treated animals contrasted with nearly complete damage of bone marrow, lymphoid infiltration of salivary glands and even ulceration with hemorrhage of the epidermoid part of the stomach in untreated control GVHD animals.
New clinicopathological phenotypes are described in this report. A subclinical form of cholesterol ester storage disease was diagnosed in two adult female patients with hyperlipoproteinaemia type IIb. Both were profoundly deficient in acid lipase activity. Fabry's disease was described with intensive storage of globotriaosyl ceramide restricted solely to the heart muscle which was enormously hypertrophic. The clinical course resembled that of idiopathic hypertrophic cardiomyopathy. The variants of sphingomyelinase deficiency type A described previously are reviewed and their clinical course revised. Two of the three patients with the minimal neurological lesion still display, after a four year interval, a stable course (ages 7 and 14 years) while the neurological status of the third one (aged 8 years) deteriorated profoundly. The clinical condition of the two cases with protracted neurovisceral symptomatology (aged now 29 and half, and 30 years) is unchanged.
The aim of the present work was to develop a chromatographic system for the separation of individual fluorophores extracted from neuronal ceroid lipofuscinosis (NCL) brain and isolated storage bodies. Extracts from gray matter were best resolved on silica-gel HPTLC plates using a mixture of chloroform/methanol/water (55:45:10 by vol.). Two other chromatographic systems were tested which gave poorer separation. Corrected fluorescence spectra were obtained on the original extract and fluorescence intensity, especially at longer wavelengths was increased in both samples. Yellow and blue fluorophores were detected on HPTLC plates using a primary violet and secondary yellow filter with cut-off levels of 400 and 520 nm, respectively. Plates were photographed at 20 min, 2 h and 1 week after chromatography. With this filter system, up to 12 yellow bands of differing intensity were observed at 20 min but with time, some of these changed to blue as a result of autoxidation. NCL tissues emit yellow fluorescence when viewed under light microscopy, however extracted material did not demonstrate a distinct peak in this region of the spectrum which should be around 575 nm. HPTLC confirmed this observation and time studies revealed that autoxidation changes occur and must be carefully controlled to reduce artifacts. The discrepancy between extracted and non-extracted observations may be the result of superposition of multiple fluorophores with differing maxima and/or a self-absorption phenomenon. The combination of chromatographic separation and spectral analysis as described in this study, may be a valuable technique to further clarify the characteristics of compound fluorescent lipopigments. It is suggested that NCL fluorophores of human brain differ in their properties from other models.
Lysosomal storage inclusions were observed in skin eccrine gland secretory and myoepithelial cells in three cases of Krabbe's disease. In addition to storage there were numerous degenerative changes, occasionally resulting in cell necrosis. These findings suggest a generalized nature of the storage process in this lysosomal enzymopathy and point to high galactocerebroside turnover in eccrine gland epithelium. This knowledge may be of value in the biopsy diagnosis of Krabbe's disease.
Two cases of Gaucher's disease (Types I and III) are described with a substantial part of the storage cell population in several organs (liver, adrenal cortex) intensively vacuolized and transformed into non-specific foam cells. The transformation process encompassed massive three-dimensional distension of the lysosomal system filled with typical lipid tubules as well as severe reduction of the intervening cytoplasm and decrease or disappearance of histochemically detectable enzyme activities, high in typical Gaucher cell (GC). Such an extensive GC foamy transformation may cause diagnostic embarrassment in microscopic interpretation especially of liver biopsies.
An extracellular ceroid-type (ECC) lipopigment which appears histologically as wavy hyaline membranes or, less frequently, as an amorphous solid or broadly reticulated mass is described. Its ultrastructure is either amorphous or membranous and consists either of simple linear membrane-like aggregates or elaborated trilaminar membranes. The histochemical profile is, as in histiocytic intracellular ceroid, dominated by autofluorescence, strong hydrophobicity, acid and extraction resistance. Staining for aromatic acid residues and periodic acid-Schiff positivity are strong but variable. Lectin receptors are either absent or sparse. The pigment is found solely within the lipid rich tissue debris, bound to processes marked by necrosis of adipose or steatosed tissues and interpreted as originating de novo extracellularly from liquid unsaturated lipids under the influence of local enzymatic and nonenzymatic lipid oxidation catalysts. A hitherto unknown form of extracellular ceroid is the so-called membranocystic lesion found in Nasu-Hakola's disease, in several other conditions and in annular ceroid in human atheromas.
Three cases of congenital histiocytic disorders--generalized Langerhans cell histiocytosis, generalized juvenile xanthogranuloma and so-called congenital self-healing histiocytosis are compared using histiochemical, immunohistochemical and ultrastructural methods. The results showed a typical morphological pattern of Langerhans cell histiocytosis (S 100+, CD 1+, alpha-mannosidase +) with an unusual self-healing cutaneous phenomenon. The congenital self-healing histiocytosis showed a non-Langerhans cell immunophenotype (CD 14+, CD 1-, S 100-) and morphological appearance resembling the evolutive "early" stage of juvenile xanthogranuloma. A diffuse cellular positivity of alpha-mannosidase in juvenile xanthogranuloma and congenital self-healing histiocytosis differed from a typical perinuclear globular positivity of this enzyme in Langerhans cell histiocytosis. It is concluded that congenital self-healing histiocytosis may in some cases be of non-Langerhans cell type and under this term a clinically characteristic syndrome of histiocytic proliferation of Langerhans cells or tissue histiocytes may be included.
Explore the source record for details and available documents.
Diagnosis of GM2 gangliosidosis and other most frequent thesaurismoses of the central nervous system was exposed on a case of a 2-year-old boy. Diagnostic process which exploited routine methods commonly used in every department of pathology enabled to choose chemical and enzymological investigation of brain tissue.
The first diagnostic phase of Gaucher's disease is based on correct evaluation of clinical history as well as on finding of typical striated Gaucher's cells in bone marrow. Nevertheless, there can occur surprising diagnostic faults in spite of believed easy identification of this classic storage disease. They can be caused by a primary atypical or secondary modified clinical phenotype. Another source of diagnostic error or hesitation can be in an atypical appearance of Gaucher's cells because of poorly distinct cytoplasmic striation (solid voluminous cytoplasm) or classical vacuolized pattern.
A case is presented of Fabry's disease manifesting in an adult (aged 64) as hypertrophic nonobstructive cardiomyopathy caused by massive ceramidtrihexoside storage confined exclusively to the cardiocytes. There was no storage detectable in capillaries or in any other structure of the organs examined (liver, pancreas, brain, aorta, pulmonary artery, coronary arteries, heart valves). The clinical picture was dominated by heart failure slowly progressing during the last fifteen years of the patient's life terminated by pulmonary thromboembolism. There were no clinical signs of ocular, renal or skin affection. Since no unfixed tissues were available for enzyme analysis diagnosis had to be done using formaldehyde fixed tissues. The isolated stored lipid was characterized by TLC and by proton magnetic resonance analysis as globotriaosyl ceramide (Gal alpha 1-4 Gal beta 1-4 Glc beta 1-1' Cer) and was proved to be cleaved by control cell homogenates but left intact by those prepared from Fabry mutant cells (leukocytes, cultured fibroblasts). alpha galactosidase activity in each of his four daughters was in heterozygous range (peripheral leukocytes were used for analysis). The existing variants of cardiological syndromes in Fabry's disease are reviewed together with problems of diagnosis of atypical cases.