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Biomedical subjects

P Fredman

Publications and source records attributed to P Fredman.

At least 145 records · Page 8Linked to original sources
PubMed1983

Colorectal carcinomas have a characteristic ganglioside pattern.

The gangliosides in six colorectal and two pancreatic carcinomas were examined. Their concentration in the primary tumour and the metastases was 5-10 fold higher than in normal colon mucosa. This increase involved the simple gangliosides, GM3 and GD3, as well as complex mono- and disialogangliosides. Some complex monosialogangliosides were detected in all the colorectal and pancreatic carcinomas but neither in normal colon mucosa and pancreas nor in kidney and lung carcinomas.

Aged↗
PubMed1982

Lipid accumulation in liver, spleen, lungs and kidneys of miniature-pigs after chloroquine treatment.

Chronic chloroquine treatment of type-Göttingen miniature-pigs induced lipid accumulation in the liver, spleen, lungs and kidneys. The lipid analyses showed marked quantitative and qualitative differences between the organs. In the liver the lipids affected most were cholesteryl esters and glucosylceramides, which were increased at the most 20 times. Cholesterol and ganglioside concentrations were also increased, though less markedly. The concentration of acidic phospholipids was slightly increased but that of the neutral phospholipids was unaffected. There was a considerable inter-individual variation in the lipid changes. Spleen and lung showed significant increases of all the major lipids. Glucosylceramide was increased more than the other lipids, namely 6-fold in the spleen and 10-fold in the lung. The concentration of acidic phospholipids as well as that of gangliosides was increased by 50% in the spleen and by 100% in the lung. The organ affected least was the kidney, in which only the glycolipids, both acidic and neutral, were significantly increased. Common to all the organs of the chloroquine-treated pigs was the large increase of glucosylceramide, ganglioside CM2 and bis(monoacylglyceryl)phosphate. The ganglioside increase affected all the individual gangliosides and, except for the increased proportion of ganglioside GM2, there were not remarkable changes in the ganglioside pattern in any of the organs.

Animals↗
PubMed1982

Rabbit intestinal glycoprotein receptor for Escherichia coli heat-labile enterotoxin lacking affinity for cholera toxin.

The receptors for cholera toxin and Escherichia coli heat-labile toxin (LT) in rabbit small intestinal epithelium were characterized and compared. (i) In vivo studies in ligated intestinal loops showed that whereas LT B subunits could block the fluid secretogenic action of purified LT as well as cholera toxin, cholera toxin B subunits did not inhibit the LT response even when tested in a concentration 100-fold higher than one which gave complete blocking of cholera toxin action. (ii) In vitro studies indicated that isolated intestinal epithelial cells or brush-border membranes could bind about 10-fold more of E. coli LT than of cholera toxin. (iii) All binding sites for cholera toxin in duodenal, jejunal, or ileal mucosal cells or brush-border membranes were extracted by chloroform-methanol-water (4:8:3), which removed lipids quantitatively but did not extract glycoproteins. The extracted cholera toxin binding sites were to greater than 95% recovered in a monosialoganglioside fraction; quantitatively these sites closely corresponded to the concentration of chromatographically identified mucosal GM1 ganglioside (1 nmol of cholera toxin was bound per 1 to 2 nmol of GM1). In contrast, a substantial fraction of mucosal binding sites for E. coli LT remained in the delipidized tissue residue, and these sites had properties consistent with a glycoprotein nature. Thus, whereas cholera toxin appeared to bind highly selectively to GM1 ganglioside receptor sites of rabbit small intestine, E. coli LT bound both to GM1 ganglioside and to a main glycoprotein receptor for which cholera toxin lacks affinity.

Animals↗
PubMed1981

Chemical structures of three fucogangliosides isolated from nervous tissue of mini-pig.

In the nervous tissue of miniature pig, type Göttingen, three fucosyl-containing gangliosides are major gangliosides. All three were found in dorsal-root ganglia and spinal cord, but only two of them in the forebrain. The concentrations of these gangliosides were increased in chloroquine intoxication. Their chemical structures were determined by component analysis, partial acid and enzymatic degradation and assay of the partially methylated sugars after hydrolysis, reduction and acetylation. Mass spectrometric analysis of the intact gangliosides as permethylated, permethylated-reduced and permethylated-reduced-silylated derivatives confirmed the following structures of the three gangliosides. (See Formula in text).

Animals↗
PubMed1981

Chloroquine-induced accumulation of gangliosides and phospholipids in skeletal muscles. Quantitative determination and characterization of stored lipids.

High doses of the lysosomotropic drug chloroquine result in lipid storage in many organs in animals. We used miniature pigs, type Göttingen, to study the lipid accumulation in skeletal muscle after chloroquine intoxication for more than 200 days. The lipids of the quadriceps muscle in intoxicated and in age-matched control pigs were characterized and determined. The lipid storage was larger in skeletal muscle than in any other organ of the intoxicated pigs. The concentration of phospholipids was increased threefold, acidic phospholipids relatively more than neutral ones. The lysosome-specific acidic phospholipid bis(monoacylglyceryl)phosphate content was almost 50-fold larger in the intoxicated pigs than in the controls. Cholesterol was increased slightly more than the phospholipids, but there was no particular accumulation of cholesteryl esters, which has been shown to occur in the liver. For the first time a storage of gangliosides, relatively more pronounced than of other lipids, was demonstrated in skeletal muscle in the drug-induced lipidosis. The concentration of total gangliosides was increased 10--15-fold, and the pattern of gangliosides showed some distinct changes resulting in at least a 100-fold increase in the concentration of ganglioside GM2 (II3NeuAc-GgOse4Cer).

Animals↗
PubMed1981

Chloroquine intoxication induces ganglioside storage in nervous tissue: a chemical and histopathological study of brain, spinal cord, dorsal root ganglia, and retinal in the miniature pig.

The effect of chronic chloroquine intoxication on lipid composition, particularly the gangliosides, was studied in the nervous system of miniature pigs, type Göttingen. The tissues examined were cerebrum, spinal cord, dorsal root ganglia and retina. Chloroquine was given in the diet in doses of 2.0-3.5 g/kg good. The intoxication of the pigs was started at the age of 100-240 days and continued for 177-219 days. The control pigs received the same diet without chloroquine. The ganglioside concentration was increased in all the tissues examined. Dorsal root ganglia and retinal were the tissues affected most and showed a twofold increase. This corresponded to the light and electron microscopically demonstrated extensive storage process in the perikarya of dorsal root ganglion cells and inner ganglion cells of the retinal. Under light microscopy the storage material was granular, intensely PAS-positive and dissolved by paraffin embedding. The electron microscopical equivalent consisted of conglomerates of membranous lysosomal residual bodies. In cerebrum the ganglioside concentration was increased by 12%. Storage in the brain varied widely between different systems and types of cells. The allocortex was much more affected than the isocortex. Certain inhibitory ganglion cell types, such as the basket cells, exhibited the most massive storage of all. The spinal medulla was morphologically less involved but showed approximately the same ganglioside increase, though not statistically significant. With the exception of cerebrum the increase in the tissues examined involved all the individual gangliosides, most severely ganglioside GM2 and three fucogangliosides. In cerebrum only the ganglioside GM2 was increased more than the other gangliosides. Chloroquine intoxication did not affect the concentration of phospholipids or cholesterol in the cerebrum, spinal cord or dorsal root ganglia, but in retina the acidic phospholipids were significantly increased.

Animals↗
PubMed1980

Binding of intraluminal toxin in cholera: trial of GM1 ganglioside charcoal.

A study was undertaken to investigate whether toxin produced in the gut lumen contributes significantly to clinical illness and whether binding such toxin by GM1 ganglioside adsorbed onto charcoal could alter the clinical course of disease. 46 patients with severe cholera receiving standard intravenous therapy were randomly assigned to one of three groups: GM1 ganglioside-charcoal (16), charcoal alone (16), or water (14). The results demonstrated that patients were given sufficient GM1 ganglioside-charcoal to bind all luminal toxin produced by Vibrio cholerae in their intestines. Patients treated with GM1 ganglioside tended to have a greater reduction in purging than patients treated with either charcoal alone or water. This difference was statistically significant soon after beginning medication (8-15 h) and the reduction in fluid-loss was especially pronounced in patients with very severe initial purging who had been ill only for a short time before admission. These results suggest that toxin produced in the gut lumen increases fluid-loss early in cholera, but that later in the course of disease, toxin which is inaccessible to luminal binding agents in the major stimulus of purging.

Adolescent↗
PubMed1980

Separation of gangliosides on a new type of anion-exchange resin.

A new anion exchange resin, Spherosil-DEAE-Dextran, consisting of porous glass beads covered with cross-linked DEAE-Dextran, was used in the separation of gangliosides. The gangliosides were eluted from the resin with a discontinuous gradient of potassium acetate in methanol, separating the gangliosides quantitatively into mono-, di, tri-, tetra- and pentasialoganglioside fractions. The new resin was found to have higher binding capacity, to show less unspecific adsorption and to give a better separation of the higher oligosialogangliosides than did DEA-Spherosil, QAE-Sephadex, DEAE-Sephadex and DEAE-Sepharose. Anion exchange chromatography improved discrimination between closely allied gangliosides as well as quantification and identification of individual gangliosides, especially the minor ones. The new procedure was used in the separation of the gangliosides in human infant forebrain and cerebellum.

Adult↗
PubMed1980

A procedure for the quantitative isolation of brain gangliosides.

In a systematic study of the optimal conditions for the quantitative isolation of gangliosides from brain tissue and their further purification the yield of gangliosides obtained by extraction of the tissue twice with twenty volumes of chloroform/methanol/water (4 : 8 : 3, v/v) was larger than that obtained with all other solvents tested, including tetrahydrofuran/phosphate buffer. The gangliosides were separated from other lipids by phase partition, water was added to the total lipid extract to give a final chloroform/methanol/water volume ratio of 4 : 8 : 5.6. Isolation of gangliosides from the total lipid extract with the aid of anion-exchange resins was not practical as a routine procedure on a large scale. The crude gangliosides extract was freed from low molecular weight contaminants by dialysis against water. This method was superior to the purification on gel filtration media or on anion-exchange resins, which required large columns with selective losses of gangliosides as a result. The present method has been applied to human brain, and the concentration and distribution of gangliosides in the human forebrain in infancy and old age are given.

Aged↗
PubMed1980

Sendai virus receptor: proposed recognition structure based on binding to plastic-adsorbed gangliosides.

The binding of Sendai virus to polystyrene petri dishes to which various gangliosides of defined structures had been adsorbed was determined. The ganglioside-bound virus was visualized either by a water vapor condensation method or by a hemadsorption method. By either assay, specific virus binding of high affinity was demonstrated to the gangliosides GT1a, GQ1b, and GPlc which have a common end sequence in the oligosaccharide moiety: NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc leads to. Binding also occurred to the GD1a and GT1b gangliosides, which have the same end carbohydrate sequence except for the terminal N-acetylneuraminic acid, but the affinity was only 1-9% of that of the gangliosides with a terminal disialosyl linkage. It is proposed that the structure NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc is the recognition-specific structure of the receptor for Sendai virus that is present on cell membrane gangliosides and possibly also glycoproteins. Binding tests to plastic-adsorbed glycolipids are suggested to be a useful tool for identification of the receptor recognition structure.

Adsorption↗