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Biomedical subjects

O Nilsson

Publications and source records attributed to O Nilsson.

At least 271 records · Page 15Linked to original sources

Monoclonal antibodies against gastrointestinal tumour-associated antigens isolated as monosialogangliosides.

Monoclonal antibodies were produced after immunization of mice with a colorectal adenocarcinoma cell line or liver metastasis membranes from a patient with colon adenocarcinoma. Many monoclonal antibodies were found to react with colorectal adenocarcinoma cells but not with normal colon mucosa, blood lymphocytes, myeloma cells or lung epithelial carcinoma cells. Three of these 'colorectal tumour-specific' antibodies appear to define different antigens that were found in the complex monosialoganglioside fraction from 60 to 90% of the colorectal and pancreatic adenocarcinoma tumours or metastases examined but essentially lacking in normal colon mucosa and other normal or tumour tissues tested.

Adenocarcinoma↗

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↗

Studies on the strongyle egg output of horses after treatment with oxfendazole (Synanthic vet. Syntex).

The effect of oxfendazole (Synanthic vet. Syntex) on the strongyle egg output of naturally infected horses was evaluated. It was demonstrated that the compound, administered orally as an 18,5% paste or as 6,48% pellets mixed in feed (46.3 grams per 300 kg bodyweight) at a dose-rate of 10 mg per kg bodyweight, markedly reduced the strongyle egg output over a 10 week period. As this period to egg reappearance is considerably longer than for most other anthelmintics at recommended dose levels, oxfendazole may be considered a valuable compound for the control of strongylosis in horses.

Animals↗

The occurrence of psychosine and other glycolipids in spleen and liver from the three major types of Gaucher's disease.

Glycolipid changes in spleen autopsy specimens were determined in four cases of Gaucher's disease type I, three cases of type II, and twelve cases of type III. These changes were also determined in liver autopsy specimens from three cases of type II and in nine cases of type III. The concentration of glucosylceramide in spleen was of the same magnitude in all three types, 36.3 +/- 11.7 mmol/kg in type I, 32.7 +/- 8.5 mmol/kg in type II, and 32.6 +/- 6.9 mmol/kg in type III. In liver there were large differences in the glucosylceramide concentration between splenectomized and non-splenectomized cases. Thus, in the non-splenectomized type III cases it was 9.9 +/- 3.0 mmol/kg, while in the splenectomized type III cases it was 24.1 +/- 6.1 mmol/kg. The accelerated deposition of glucosylceramide in liver after splenectomy was also demonstrated by analyses of liver biopsy specimens. A 2-6-fold increase of gangliosides was found in liver and spleen from the three types, with no significant differences between the types. The increase of gangliosides was limited almost exclusively to GM3. Glucosylsphingosine, never detected in normal tissue, was demonstrated in all samples from Gaucher's livers and spleens. The concentration in spleen was in type II, 0.16 +/- 0.05 mmol/kg, in type III, 0.19 +/- 0.05 mmol/kg, while in type I it was significantly lower, 0.07 +/- 0.03 mmol/kg. In liver, the highest concentrations occurred in the splenectomized type III subjects, 0.16 +/- 0.08 mmol/kg, while in the non-splenectomized type III cases it was 0.06 +/- 0.02 mmol/kg and in type II 0.09 +/- 0.02 mmol/kg. The demonstration of high concentrations of the cytotoxic compound glycosylsphingosine may be a contributing factor behind the tissue necrosis and fibrosis commonly seen in spleens and livers from Gaucher's patients.

Adolescent↗

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↗

Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: significant differences between type I and type III.

A method was developed for the determination of cerebrosides in 1 ml of plasma or 1 ml of packed erythrocytes. At least 90% of the cerebroside fraction consisted of glucosylceramide. In the erythrocytes, nothing but glucosylceramide was identified. The method was applied to plasma samples from 25 controls, 34 Gaucher Type III obligate carriers, 16 Gaucher Type III patients, 7 Gaucher Type I patients and 7 patients with myelogenous or lymphatic leukemia, as well as to erythrocyte samples from 20 controls, 6 Gaucher Type III obligate carriers, 16 Gaucher Type III patients and 6 Gaucher Type I patients. The concentration of plasma cerebroside was 11.4 +/- 4.2 (S.D.) in controls, 11.8 +/- 2.6 in Gaucher Type III carriers, 30.4 +/- 7.7 in Gaucher Type III patients and 21.8 +/- 6.7 mumol/l in Gaucher Type I patients. The Gaucher patients had significantly increased (p less than 0.001) plasma cerebroside values, while the plasma cerebroside concentration of the leukemic patients was only slightly increased, 14.7 +/- 5.7 mumol/l. In the packed erythrocyte pellet the corresponding values were: Controls 2.9 +/- 0.7, Gaucher Type III carriers 2.9 +/- 0.7, Gaucher Type III patients 9.2 +/- 2.4 and Gaucher Type I patients 6.5 +/- 2.7 mumol/l. The phospholipid concentration was the same in all the three Gaucher groups and was not significantly different from that in the controls.

Adolescent↗

Accumulation of glucosylceramide and glucosylsphingosine (psychosine) in cerebrum and cerebellum in infantile and juvenile Gaucher disease.

Three major clinical variants of Gaucher disease have been defined: Type I, chronic nonneuronopathic; Type II, acute neuronopathic; and Type III, subacute neuronopathic. In a search for the underlying molecular basis of the neurological manifestations, the concentration and composition of cholesterol, phospholipids, neutral glycosphingolipids, and gangliosides were examined in cerebral and cerebellar cortices of five cases of Type II, eight cases of Type III, and one case of presumed Type I/III. In Type II the concentration of glucosylceramide was 140-530 mumol/kg in cerebral cortex and 51-450 mumol/kg in cerebellar cortex, the highest values found in the most fulminant cases. These concentrations were 20-80 times greater than normal in cerebral cortex and 5-40 times normal in cerebellar cortex. In type III the concentration of glucosylceramide was 37-65 and 59-1750 mumol/kg in cerebral and cerebellar cortex, respectively. The highest concentrations were found in the cerebellum of patients who had survived splenectomy for several years. The ceramide composition of the accumulated glucosylceramide suggested that brain gangliosides were the major precursors of the glucosylceramide in brains of Type II but in cerebellar cortex in Type III was partly of extracerebral origin. The levels of lactosylceramide and oligohexaosylceramides were slightly raised in all brain specimens from the Gaucher cases. The ganglioside concentration was normal, whereas there was a certain increase in the proportion of GM2 and GM3 gangliosides. The brain glycosphingolipid changes in the Type I/III case were similar but slightly less than those in Type III cases of corresponding age. Glucosylsphingosine (psychosine), never detected in normal human brain, was demonstrated in brains from all the Gaucher cases. The psychosine concentration was highest in Type II cases, 3.8-8.8 and 3.9-12.3 mumol/kg in cerebral and cerebellar cortex, respectively, with the highest values found in the most fulminant cases. In type III the psychosine concentration varied more widely, 0.8-4.6 and 1.4-6.3 mumol/kg in cerebral and cerebellar cortex, respectively. The lowest value, 0.7 mumol/kg, was found in the Type I/III case. Our method detected psychosine down to 0.01 mumol/kg, which means that the concentration of psychosine was increased at least 100- to 1000-fold in Gaucher grey matter. We suggest that the accumulation of the cell-toxic substance psychosine is the basis for the extensive neuronal cell loss in Gaucher disease, which is most striking in Type II disease.

Adolescent↗

Distribution of some non-physiological amino acids (AIB, DAB, MeAIB) in mice.

The distribution of labelled 2-aminoisobutyric acid (AIB), 2,4-diaminobutyric acid (DAB) and 2-(methylamino)-isobutyric acid (MeAIB) was studied by whole body autoradiography in mice. All the amino acids were rapidly cleared from the blood and were taken up in most of the organs in the body. The results suggest the presence of operating transport systems for these amino acids into the majority of different cell types in mice. In the central nervous system, small amounts could be registered and in the pancreas there was a marked difference between DAB, which was not taken up, and the other two amino acids which were heavily accumulated. In an early embryo only MeAIB was observed in a high concentration.

Aminobutyrates↗

Characterization and quantitative determination of gangliosides and neutral glycosphingolipids in human liver.

The neutral and acidic glycolipids from the liver of an 11-year-old male were quantitatively isolated and characterized. The total concentration of gangliosides was also determined in sampled from five other human livers. Lipid-bound sialic acid varied between 190-248 nmol/g with a mean value of 212 nmol/g. The major ganglioside was GM3, which represented 91.6% of the sialic acid. Besides GM3 and GM1, a wide variety of other minor monosialogangliosides were isolated. Gangliosides of the gangliotetraose series with up to four sialic acids were demonstrated in human liver for the first time. The composition of the ceramide portion of the gangliotetraose gangliosides was considerably different from that of the "visceral" gangliosides, GM3, GD3, and LM1 (sialosyl-lactoneotetraosylceramide), which suggests that these two groups of gangliosides are biosynthesized in two different pools. The concentration of the neutral glycolipids was approximately the same as that of the gangliosides. Lactosylceramide was the largest fraction, closely followed by galactosylceramide, glucosylceramide, and globotriaosylceramide. The ceramide composition of the neutral glycolipids resembled that of the "visceral" gangliosides, suggesting that they are metabolically related. 2-Hydroxy fatty acids were found in glucosyl-, galactosyl-, and lactosylceramides as well as in ganglioside GM3.

Adolescent↗

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↗

Cleavage rate and morphology of early human embryos obtained after artificial fertilization and culture.

Ovarian follicles were aspirated at midcycle from 193 women admitted to the hospital because of infertility or for legal sterilization. Eighteen women had not received prior hormone stimulation and 175 had been stimulated either with Clomiphene citrate and hCG with hCG alone. Preovulatory oocytes could not be obtained from any of the women in the non-stimulated group, but were obtained from 86 (49%) in the stimulated group. Of these 86, oocytes from 63 women were cultured successfully and from 47 (75%) cleavage occurred. The most advanced stages observed were about 10-cell embryos, but no attempts were made to culture them further. Almost all the oocytes which cleaved were obtained from women in whom the progesterone level started to rise from the basal level within 24 hours of the operation. Eight cleaved oocytes were taken for transmission electron microscopy (TEM). Early cleavage stages showed spheroidal mitochondria with a few peripheral cristae, while the number of elongated mitochondria with transverse cristae increased in later stages. Mitochondria-vesicle complexes, consisting of a vesicle filled with a dense substance and surrounded by 5-15 mitochondria, were observed in early (but not in more advanced) embryos. The complex is probably part of a transport system from the nucleus to the mitochondria. In the later stages, a type of granulated vesicle appeared. Thus, some changes occurred in tact with the degree of development, while no differences could be seen between oocytes with differing cleavage rates.

Adult↗