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Biomedical subjects

W Schlote

Publications and source records attributed to W Schlote.

At least 55 records · Page 3Linked to original sources
PubMed1991

Sphingolipid activator protein 1 deficiency in metachromatic leucodystrophy with normal arylsulphatase A activity. A clinical, morphological, biochemical, and immunological study.

A 7-year-old boy had clinical features of metachromatic leucodystrophy (MLD), however, an increased urinary sulphatide excretion was found in the presence of normal arylsulphatase A (and alpha-galactosidase A) activity. A rectal biopsy showed metachromatically staining storage macrophages as well as nonmetachromatic, but PAS-positive, submucosal neurons filled with membranous cytoplasmic bodies. These two types of storage material led to testing for a sphingolipid activator protein (SAP) deficiency. Loading tests with sulphatide and globotriaosylceramide showed deficient turnover of both sphingolipids in cultured fibroblasts. Using the Ouchterlony method, there was no reactivity between a described anti-SAP 1 antiserum and the patient's fibroblast extracts. This new case of SAP-1 deficient MLD was compared with the four cases of this variant known from the literature. Our results indicate that rectal biopsy morphology and lipid loading biochemistry should prove useful for the screening of SAP defects.

Biopsy↗
PubMed1991

[HIV encephalopathy].

The early manifestation of HIV infection of the brain, HIV encephalitis, is due to the invasion of HIV infected mono- and multinuclear macrophages into the brain tissue and cerebrospinal fluid. These cells are intensely PAS reactive, auto-fluorescent and express the macrophage antigen CD68. They clearly prefer the white matter of cerebral hemispheres, corpus callosum and internal capsule. Lymphocytic infiltrates and microglial nodules are additional, unspecific changes. HIV encephalopathy following HIV encephalitis is patho-anatomically characterized by brain tissue damage. Its clinical correlate is so-called AIDS dementia complex. It presumably is caused by neurocytotoxic and myelinotoxic factors released by activated macrophages and/or by shedding HIV retrovirus proteins. HIV encephalopathy includes leukoencephalopathy, diffuse poliodystrophy, disseminated basal ganglia damage and brain atrophy. In some cases, granulomatous angiitis may occur.

AIDS Dementia Complex↗
PubMed1989

Neuronal autophagy in experimental Creutzfeldt-Jakob's disease.

We report an experimental model of Creutzfeldt-Jakob's disease (CJD) in mice leading to the formation of giant autophagic vacuoles (AV) in neurons of the cerebral cortex. These AV appear at the end of the incubation period (4-6 months postinoculation), together with spongy changes and clinical symptoms. Autophagy, a process of intracellular digestion of cell constituents by the lysosomal compartment, is known in many cell types, where it plays a role both in the physiological turnover and in pathological processes and is involved in protein metabolism. The same also occurs in neurons. Here autophagy is known to occur in the normal state and leads to residual bodies called lipofuscin granules. An increase in lipofuscin is known to occur in human and experimental CJD. Therefore, an increase in autophagy and in AV can be expected. In our experimental model, the activation of neuronal autophagy may be related to an alteration in neuronal protein metabolism.

Animals↗
PubMed1988

Lymphoma-specific T- and B-cell responses suggest the involvement of HTLV-I in virus-non-productive lymphomas of a married couple.

In a married couple, a T-cell and a B-cell lymphoma occurred at the same time in the husband (FR) and wife (FE), respectively. Serum antibodies of patient FE with less advanced tumor progression specifically recognized HTLV-I-related envelope precursor molecules of 66-68 kDa molecular mass on HTLV-I-infected T- and B-cell lines, but not on HTLV-II or HIV-infected cells. In addition, in vivo-activated CD8+ T-cell lines (TCL) from this patient specifically lysed autologous B-lymphoma cells, T-lymphoma cells from the husband (FR), as well as the HTLV-I-transformed MT2 T-cell line. All positive target cells shared an HLA-class-I cross-reactive determinant identified by the alloantiserum WER127. On a clonal level, the specificity of the cytotoxic T-cell response was unequivocally distinguishable from classical natural-killer-like cytotoxicity. Results imply the involvement of a common inductive agent in the manifestation of malignant lymphoma in both patients (FR and FE). Since antibodies from cases with classical HTLV-I-induced adult T-cell leukemias (ATLL) did not bind antigens on cells of either lymphoma (FR or FE) and active virus production was not demonstrable under various different conditions, these results argue against HTLV-1 itself being the transforming agent. However, humoral and cellular immune responses of one patient (FE), in addition to de novo HLA-class-1 antigen expression of both patients, are nonetheless consistent with the involvement of viral infections(s). These were responsble for the expression of HTLV-1-characteristic envelope determinants of the malignant progeny of respective T- and B-cell origin.

Aged↗
PubMed1988

T and B cell specific immune responses to purified protein derivative in the cerebrospinal cavity may be maintained and regulated independently of systemic immune control.

In vivo activated T cells could be isolated from cerebrospinal fluid (CSF) of a patient suffering from chronic meningitis of unclear origin. Although the patient's skin reactivity to purified protein derivative (PPD) was negative, and peripheral T cells did not proliferate to this antigen in vitro, the majority of T cell clones from CSF specifically recognized PPD on either autologous or allogeneic HLA class II compatible macrophages. Remarkably, peripheral blood mononuclear cells potently suppressed the PPD-specific proliferative responses of healthy donors. The selective enrichment of oligoclonal IgG in the CSF but not in the patient's serum further indicated T and B cell responses lacking systemic feedback control. Analyses of a persisting immune stimulation in the CSF provide a potent diagnostic tool and may explain neurological complications as observed in a number of autoimmune diseases and chronic infections.

Adult↗
PubMed1987

Autopsy findings in AIDS--a histopathological analysis of fifty cases.

Fifty consecutive AIDS autopsy cases were evaluated. All subjects showed one or more opportunistic infections and malignancies included in the AIDS case definition with cytomegalovirus and Kaposi's sarcoma being most prevalent. Mycobacterial and cryptococcal infections occurred only infrequently. Most patients of our series after successful treatment of Pneumocystis carinii pneumonia or cerebral toxoplasmosis later succumbed to less treatable conditions like disseminated cytomegalovirus or fungal infections or malignant lymphoma. In the absence of specific treatment for the HIV infection leading to these lethal complications special emphasis must be put on the prevention of HIV transmission and spread.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Adrenoleukodystrophy in an adult female. A clinical, morphological, and neurochemical study.

A 43-year-old female with adrenoleukodystrophy (ALD) is described, who developed spastic tetraparesis, suffered grand mal seizures, and became stuporous and demented during the last 5 years of her life. Computed tomography revealed symmetrical hypodense lesions in the peritrigonal regions. Adrenal insufficiency was not evident except for skin pigmentation. The ultrastructure of a rectal biopsy specimen showed inclusions with lamellae and interspersed clefts in macrophages of the submucosal layer. At autopsy, the adrenals were found to contain large foam cells filled with similar inclusions. The brain cortex and the spinal cord were histologically normal. However, cerebral white matter exhibited widespread demyelination which spared only the arcuate fibres. In regions of less severe demyelination scattered inflammatory cells were seen. On electron microscopy, aggregates of typical paired leaflets with distinct intermediate lines were demonstrated in perivascular macrophages. Histochemical study showed these cells to contain free as well as esterified cholesterol. Gas chromatographic analysis of very long chain fatty acids (VLFA) from the demyelinated cerebral white matter showed a marked increase of C26:0 fatty acid in cholesterol esters and above-normal values for C24:0 and C24:1 in gangliosides. It is suggested that the condition was a heterozygote form of X-linked ALD. Patients with neurodegenerative symptoms with or without adrenal insufficiency can easily be screened for X-linked ALD by VLFA analysis in blood or cultured fibroblasts.

Adrenal Glands↗
PubMed1987

Intracellular lucifer yellow staining and electron microscopy of neurones in slices of fixed epitumourous human cortical tissue.

To examine the complete morphology and ultrastructure of lipofuscin-containing human pyramidal cells, epitumourous biopsy tissue was lightly fixed in paraformaldehyde. Cortical slice preparations were immersed in an injection chamber which was transferred to a fixed stage microscope. Electrodes were filled with an aqueous solution of the fluorescent dye Lucifer Yellow and attached to a micromanipulator. Epifluorescence illumination was used to visualize and guide the tip of the Lucifer pipette towards lipofuscin-containing, autofluorescent pyramidal cell somata. After impaling, the neuron was intracellularly stained by iontophoretic injection of Lucifer Yellow. Subsequent graphical reconstructions of injected pyramidal cells revealed complete filling of their dendritic arborizations. Comparison with published Golgi-material prepared for light microscopy revealed no patho-morphological changes in the tissue. Eventually, dye-filled cells were photooxidized in the presence of diaminobenzidine, which resulted in the formation of a homogeneously brown reaction product. Bleached cells were then osmicated and embedded in plastic. Electron microscopy revealed fine electron-opaque label distributed throughout the karyo- and cytoplasm and there were no apparent gross ultrastructural changes. Cytological details, such as organelles and membranes were not obscured by the reaction product. Due to its autofluorescence, the pigment part of the lipofuscin also underwent photoconversion, resulting in a highly enhanced electron-dense matrix. Due to its high selectivity and relative methodological simplicity, the approach presented is considered to be a promising alternative to the gold-toning modification of the Golgi-electron microscope technique.

Brain Neoplasms↗
PubMed1986

[Form variants of globular hyaline microthrombi. Light microscopy, immunohistochemical and scanning and transmission electron microscopy observations].

Globular hyaline microthrombi are characterized by their diameter (2-30 micron), globular form, and positive PAS and PTAH reaction. They are a morphologic indicator of disturbed microcirculation and hemostasis, such as that occurring in shock. In two of our cases, we observed large globular hyaline microthrombi, some with central webbed degradation progressing to the formation of closed or open hollow globules. The electron microscopic findings were similar to those observed by other investigators in typical shock bodies. On the basis of the morphologic findings, the authors conclude that degradation phenomena start at the center of globular hyaline microthrombi and can progress to the surface where accelerated fibrinolysis is possible. The cellular elements that other investigators have described as a possible condensation center for fibrin precipitate proved to be structurally intact cells that are apparently located in niches of open hollow globules or in the center of circular hyaline microthrombi. The diagnostic relevance, vitality, and temporal classification are discussed.

Adult↗
PubMed1986

Normomorphic sialidosis in two female adults with severe neurologic disease and without sialyl oligosacchariduria.

Two female patients of German origin, aged 38 and 21 years, with myoclonus epilepsy and cerebellar ataxia, but without dysmorphic signs and dementia, were found to excrete normal amounts of sialyl oligosaccharides in their urine. The younger patient showed cherry red spots in her ocular fundi. The older patient had a brother with an autopsy-proven neuronal storage disease compatible with sialidosis, and in her rectal biopsy lamellar inclusion bodies were detected. Enzyme assays in cultured fibroblasts of both patients revealed a profound but incomplete deficiency of oligosaccharide sialidase activity and normal beta-galactosidase activity. Adult sialidosis was diagnosed in both patients. In their fibroblasts, moderate elevations of bound sialic acid could also be measured. The small residual sialidase activity, which in the older patient had a normal KM value, is considered responsible for the late onset and slow clinical course of the disease. It is concluded that in adult sialidosis the extraneural storage process can be difficult to demonstrate in terms of metabolite accumulation or excretion during the course of intraneuronal storage.

Adult↗
PubMed1986

Ultrastructural heterogeneity of neuronal lipofuscin in the normal human cerebral cortex.

The ultrastructure of the age pigment in neurons of the normal human isocortex was investigated in seven autopsies and two biopsies. In the autopsies four cortical areas of Brodmann, viz. 6, 7, 11 and 17 were studied. The lipofuscin granules appear as complexes composed of lipid and pigment. These are characterized by their shape, frequency per neuron, the relative amount of pigment and lipid in the complexes, and the structure of the matrix. The neurons contain numerous varieties of lipopigment, six of which occur with great frequency and are designated as varieties 1-6. Variety 1 is found in pyramidal neurons and seems to be characteristic of long loop projectory neuronal systems. 2 is found in large non-pyramidal neurons. 3 is found in pyramidal and non-pyramidal neurons. 4, 5 and 6 are found in non-pyramidal neurons. The pigment matrix is linear in all six varieties of lipopigment. Short linear elements are present in varieties 1, 2 and 5. Long linear elements are found in varieties 3, 4, and 6. Circular whorled arrangements are found in 4. We think that these varieties of lipofuscin may signify metabolic and/or functional differences of the different types of neurons and may contribute to the biochemical classification of cortical neurons.

Aged↗
PubMed1985

Familial occurrence of dermatomyositis and progressive scleroderma after injection of a local anaesthetic for dental treatment.

In an 11-year-old boy severe dermatomyositis occurred a few days after injection in the jaw of a local anaesthetic of the amide type for tooth extraction. The patient's grandmother was affected by progressive scleroderma at the age of 34 years, also after injection of a local anaesthetic for dental treatment. Both cases are discussed with special reference to the immuno-genetic aspects of the origin of dermatomyositis.

Adult↗
PubMed1985

Familial lysosomal storage disease with generalized vacuolization and sialic aciduria. Sporadic Salla disease.

Two eight- and sixteen-year-old children with severe progressive neurologic disease revealed an ultrastructural finding of lysosomal vacuolization in mesenchymal or parenchymal cells of different organ biopsies (skin, muscle, nerve and liver), which may be very suggestive of mucolipidosis. However, in our patients biochemical tests available for these diseases yielded negative results, except for increased excretion of free sialic acid in urine and sialic acid storage in cultured fibroblasts. The clinical picture and the ultrastructural and biochemical findings were compatible with Salla disease, a rare lysosomal storage disease originally observed in Finland.

Adolescent↗
PubMed1985

Comparison of isolated cells from liver, colon, and kidney of guinea pig.

Liver cells, colon epithelial cells, and kidney tubule fragments were isolated from guinea pig using methods previously employed in the rat. All three cell preparations exhibited well-preserved structure. Respiration was highest in kidney tubule fragments (25 nmol O2/mg protein X min) and was well coupled in all preparations. When cells were incubated at 37 degrees C, they accumulated K+ in a ouabain-sensitive manner. Incorporation of [3H]phenylalanine and [3H]uridine into acid-precipitable material proceeded linearly over at least 40 min. The cytochrome P-450 content (175 pmol/mg cell protein) and activity (aminopyrine demethylation) of liver cells exceeded that of the other two preparations 15- to 20-fold. The results indicate good maintenance of function in all three preparations. Because guinea pig epithelial cells exhibit some advantages over isolated cells from other species, the present preparations are well suited for comparing the cell physiology of the respective organs.

Aminopyrine↗