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At least 217 records · Page 12Linked to original sources
PubMed1991

Lectin histochemistry of feline sphingomyelinosis.

The brain from a Siamese cat with sphingomyelinosis was examined with lectin histochemistry. Swollen neurons were stained with Canavalia ensiformis agglutinin (Con A). Some of them were also stained with Ricinus communis agglutinin-I (RCA-I) and Ulex europaeus agglutinin-I (UEA-I). A small number of axonal spheroids and glia cells were positive for Con A, RCA-I, UEA-I and wheat germ agglutinin. Control tissues were weakly stained with Con A, but not with any of the other lectins. These results indicate that affected neurons contain mannose and glucose residues in addition to sphingomyelin. This study points to the possibility that the characteristics of lectin histochemical study might be helpful for the diagnosis of sphingomyelinosis.

Animals↗
PubMedDate not supplied

Sea-blue histiocyte syndrome with bone anomalies.

Two sisters, now 29 and 24 years old, are described. They presented a congenital storage of, most probably, phospholipids in the histiocytes of the sea-blue type or blue pigmentophages. The granules of these cells showed a PAS positivity and strong positivity for acid phosphatase, but there were negative also for non-specific esterase, naphthol-AS-D-chloracetate esterase and iron acid also for urine mucopolysaccharide. The two cases differed from all the described cases in the absence of hepatosplenomegaly and in the presence of bone changes resembling late spondyloepiphyseal dysplasia or atypical dysostosis multiplex.

Acid Phosphatase↗
PubMed1976

[Sphingomyelin lipoidosis (author's transl)].

The case of a girl is described who was 3 1/4 years of age and was admitted of the hospital because of hepato-splenomegaly. In addition to this, there were peculiar alterations in the lungs, an increase of lipoids in the blood, a characteristic alteration of the retina, and bone marrow and liver cells storing lipoid. The diagnosis of sphingomyelin lipoidosis (Niemann-Pick) was confirmed by electronmicroscopic and biochemical investigation of a percutaneous liver biopsy specimen.

Bone Marrow↗
PubMed1992

Niemann-Pick type II fibroblasts exhibit impaired cholesterol esterification in response to sphingomyelin hydrolysis.

Fibroblasts from patients with Niemann-Pick Type II disease, including the panethnic type C (NPC) and Nova Scotia Acadian type D (NPD) forms, exhibit reduced or delayed stimulation of cholesterol esterification by low density lipoprotein (LDL). Based on recent evidence that cholesterol esterification can also be stimulated by cell surface sphingomyelin hydrolysis, we have compared the response of normal, NPC and NPD fibroblasts to treatment with exogenous sphingomyelinase (SMase). Staphylococcus aureus SMase (greater than 0.05 U/ml) hydrolyzed over 90% of endogenous sphingomyelin within 1 h and increased incorporation of [3H]oleic acid into cholesterol-[3H]oleate after an initial lag in all three cell types. However, normal levels of cholesterol esterification were not observed for NP Type II fibroblasts: four NPD cell lines exhibited an average of 32% of normal response while cholesterol esterification was only 20% in two well-characterized NPC lines. A third NPC line exhibited normal response to SMase despite greater than 90% impairment of LDL-stimulated cholesterol esterification. Incubation of fibroblasts with LDL followed by SMase produced a synergistic response, particularly in NPC cells where there was little response to either treatment alone. Chloroquine abolished LDL-stimulated cholesterol esterification in normal fibroblasts but had no effect on the response to SMase, indicating that lysosomal enzymes may not be involved in SMase-mediated cholesterol esterification. These results suggest that intracellular processing of cholesterol derived from either LDL or release from the plasma membrane (by sphingomyelin hydrolysis) is affected in Niemann-Pick Type II cells and that these pathways can complement one another in the stimulation of cholesterol esterification.

Cell Line↗
PubMed2026

Activation of pro-survival autophagy by a small molecule promoting p62 oligomerization.

Autophagy is a critical mechanism of cellular quality control, orchestrated by selective autophagy receptor (SAR) proteins. Pharmacologically enhancing the cargo-targeting capacity of SARs presents an attractive but underexplored strategy for the precise therapeutic activation of autophagy. Here, we characterize SQ-1, a small-molecule activator of autophagy that engages the prototypical SAR protein p62/sequestosome-1 (SQSTM1). We show that SQ-1 sensitizes p62 to oxidation and promotes its disulfide-mediated oligomerization in response to mitochondrial reactive oxygen species (ROS). This ROS-dependent activation of p62-mediated selective autophagy enhances the clearance of ROS-generating mitochondria and restores cell viability in models of Niemann-Pick type C1 disease, which is marked by impaired autophagic flux. In summary, the unique mode of action of SQ-1 enables self-regulated autophagy activation, offering a potential therapeutic strategy for lysosomal storage disorders and a broader spectrum of age-related diseases characterized by defective autophagy.

Niemann-Pick type C1 disease↗
PubMed1978

An unusual case of phospholipidosis.

We present the results of a structural, histochemical and lipid-chromatographic study of tissues obtained at postmortem from an unusual case of phospholipidosis. A previous biopsy of the appendix and liver (Elleder et al., 1975a) had revealed a predominance of phosphoglyceride storage, principally of lysobisphosphatidic acid (LBPA) postmortem material showed that this lipid was stored exclusively in central neurons. In the spleen and the lymph node, however, sphingomyelin (SP) was shown, histochemically and chromatographically, to be the main lipid stored. Total sphingomyelinase (SPase) activity in the appendix was reduced to about 50% of normal. Neuroaxonal dystrophy (NAD) and a conspicuous discrepancy between the degree of distension of some neurons and their lipid content deserve special mention. The case is contrasted with classical sphingomyelinosis; the complexity of the Niemann-Pick group of diseases is discussed as an indication of the difficulties of classification of any atypical case.

Appendix↗
PubMed1975

[Phosphoglyceridosis].

On the basis of a bioptic examination of the appendix, skin and a liver specimen, the diagnosis of phospholipidosis was made in a girl aged 27 months. In contrast to the Niemann-Pick's complex of sphingomyelinoses, phosphoglycerides were stored in larger amounts than spingomyelin. The disease should be undoubtedly included under one heading with the so-called "kephalinosis" [11] and with the cases described by Wiedemann et al. [10]. The terms "Type II phospholipidosis [Baar-Wiedemann's disease]" or, briefly, phosphoglyceridosis, appear to be most adequeate for designating the diseases in question. The disorder can be diagnosed on the basis of iron hematoxylin staining, visualizing all phospholipids. In Niemann-Pick's sfingomyelinosis, alkaline hydrolysis does not alter the colour, whereas in the phosphoglyceridosis under discussion the colour is substantially reduced or even desappears after alkaline hydrolysis.

Child, Preschool↗
PubMed1991

Lectin histochemistry of foamy cells in non-nervous tissues of feline sphingomyelinosis.

Foamy cells in non-nervous tissues from a female Siamese cat with sphingomyelinosis were examined by lectin histochemistry. Many foamy cells, so-called Niemann-Pick cells, were found in the non-nervous tissues, such as liver, spleen, lung, kidney, adrenal gland, lymph node and tonsil. These cells were positive for Concanavalia ensiformis agglutinin, Ricinus communis agglutinin-I and wheat germ agglutinin. Storage materials in the foamy cells were different from those in affected cells of the nervous tissues. This study suggests that lectin histochemistry might be helpful in the diagnosis of sphingomyelinosis.

Animals↗
PubMed1992

Morphometric studies of pancreatic acinar granule formation in NCTR-Balb/c mice.

NCTR-Balb/c mice are afflicted with a cholesterol lysosomal storage disorder stemming from a defect in intracellular cholesterol processing. The clinical and biochemical abnormalities expressed in the mice resemble Niemann-Pick type C and D disorders in humans. One of the proposed mechanisms to explain the pathophysiology of the disorder implies a defect in the process of membrane transport that normally takes place in the vesicular movement of cholesterol to specific target sites in the cell. Secretory granule formation in pancreatic acinar cells is one of the biological processes known to involve massive membrane flow. Thus, we have undertaken a morphometric study of the regranulation mechanism in the pancreatic acinar cells of the mutant mice, as a way of studying cellular membrane movement. Electron micrographs of pancreatic acinar cells from mutant and normal mice were taken at several time points after extensive degranulation induced by pilocarpine injection. Two hours after stimulation the pancreatic cells demonstrated a complete loss of granules, and at later time points newly formed granules appeared. Identical unit granule volumes were observed in both groups, indicating that the progranules were of normal size. However, the rate of granule formation and maturation was reduced in the mutant mice, which might be the result of a defect in membrane function.

Animals↗
PubMed1976

Accumulation of glyceryl ether lipids in Wolman's disease.

We have shown that ether-linked glycerolipids accumulated in the adrenal, liver, and spleen of a male Chinese infant with Wolman's disease; the increases were mainly in the alkyl and alk-1-enyl glycerolipids that did not contain phosphorus. Alkyldiacylglycerol accounted for a portion of the rise in the neutral alkylglycerols. The spleen also contained increased amounts of ether-linked phosphoglycerides of the alkyl and alk-1-enyl types. Organs from a Niemann-Pick patient were also included in this study; they did not show comparable rises in the content of ether-linked glycerolipids, suggesting the possibility that storage of these compounds may be characteristic of Wolman's disease, or a variant form thereof.

Adrenal Glands↗
PubMed1975

Lipidosis with a predominant storage of phosphoglycerides (phospholipidosis type II--Baar, Wiedemann).

A case of a 27 month old girl suffering from a rare form of lipidosis is described. Clinical symtoms consisted of a moderate hepatosplenomegaly and a progressive psychomotor retardation. Bioptical examination of the liver, appendix and skin revealed a pronounced lipid storage in histiocytes, hepatocytes, vascular endothelium and in peripheral nervous system. Histochemically, a generalized storage of phosphoglycerides and cholesterol was found. It was accompanied with a moderate amount of sphingomyelin and a variable amount of glycolipids (predominantly glycosphingolipids), the latter being stored mainly in the peripheral nervous system and in the vascular endothelium. Chromatographically, an increased concentration of lysobisphosphatidic acid and cholesterol could be detected. The ultrastructure of storage cytosomes was rather pleomorphic often with concentrically lamellar appearance. Further details of the investigation are described and the relation of this case to those described by Baar and Hickmans (1956) and Wiedemann et al. (1972) is stressed. Due to a strong evidence that this group of diseases represents a new type of phospholipid storage disease the name "Phospholipidosis Type II" (Baar-Wiedemann) or "Phosphoglyceridosis" is proposed, whereas "Phospholipidosis Type I" or "Sphingomyelinosis" should be reserved for the classical Niemann-Pick complex.

Appendix↗
PubMed2025

Discovery of novel diagnostic biomarkers of hepatocellular carcinoma associated with immune infiltration.

OBJECTIVE: Diagnosis of hepatocellular carcinoma (HCC) remains challenging for clinicians. Machine learning approaches and big data analyses are viable strategies for identifying HCC diagnostic markers. MATERIALS AND METHODS: In this study, we downloaded mRNA expression profiles of HCC from the GEO database and used random forest and machine learning algorithms, such as least absolute shrinkage and selection operator, to screen for reliable diagnostic genes. Disease Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis enrichment analyses were performed to explore differential gene functions and disease pathways. CIBERSORT was performed to calculate the immune cell infiltration of HCC and the correlation between diagnostic genes and immune cells. Cell experiments were performed to evaluate the function of R-spondin 3 (RSPO3) in HCC cells. Immunohistochemical staining was used to evaluate the protein expression of CD138, CD206 and iNOS. RESULTS: The results indicated that extracellular matrix protein 1 (ECM1), Niemann-Pick C1-Like 1 (NPC1L1) and RSPO3 were down-regulated in HCC compared with the normal group (p&#x2009;<&#x2009;0.05), which was validated in clinical tissue samples. Moreover, ECM1, NPC1L1 and RSPO3 had high diagnostic values (AUC > 0.75) for HCC in both training and test groups. Immuno-infiltration analysis revealed that ECM1 and RSPO3 were highly positively correlated with neutrophil and macrophage M2 levels, whereas they were negatively correlated with Tregs. RSPO3-si affected cell proliferation and apoptosis in HCC. Furthermore, RSPO3 exhibited a positive correlation with tumour progression, the proportion of plasma cells and M2 macrophages in mice, while showing a negative association with M1 macrophages. CONCLUSION: The present study identified ECM1, NPC1L1 and RSPO3 as new diagnostic biomarkers for HCC based on normal and diseased samples from HCC, meanwhile the pro-oncogenic function of RSPO3 and its regulation on immune infiltration have been confirmed.

Carcinoma, Hepatocellular↗
PubMed1992

Storage material from urine and tissues in the nephropathic phenotype of infantile sialic acid storage disease.

We analysed urine and tissue specimens from two nephrotic infantile sialic acid storage disease patients (nISSD) for free and bound sialic acids in comparison to non-nephrotic ISSD patients (ISSD), patients with minimal change nephrosis (nControl) and normal controls (Control). No differences in the excretion of urinary free sialic acid could be detected between ISSD and nISSD urines. Sialyloligosaccharide fractions were only slightly elevated and of apparently normal composition. Owing to glomerular dysfunction, measurable quantities of protein-bound sialic acids were present in nISSD and nControl. In nISSD tissues, free sialic acid was elevated 18-100-fold above control and 3-12-fold above Niemann-Pick A (NPA) samples. The storage of membrane-bound sialic acid was slightly increased compared to control tissues, but equal to those from NPA, thus reflecting an unspecific increase of membranes due to lysosomal storage. According to these results no major biochemical differences were detectable between ISSD and nISSD. The nephrotic syndrome in nISSD could not be related to a general deficit in the sialylation of glycoproteins. Nevertheless, a cell membrane-specific alteration in sialoglycoproteins of glomerular cells might still be possible.

Glycosaminoglycans↗