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Biomedical subjects

E Jellum

Publications and source records attributed to E Jellum.

At least 73 records · Page 4Linked to original sources

Marker polypeptides distinguishing between cancer cell clones with high and low potential for spontaneous metastasis in murine fibrosarcoma cells.

Consistent differences in expression of specific proteins were observed between numerous cancer cell clones with high and low potential for spontaneous metastasis. Seventeen clones from two unrelated murine fibrosarcomas were examined concomitantly for spontaneous formation of lung metastases and for occurrence of individual polypeptide differences by high resolution two-dimensional gel electrophoresis. One of the identified marker polypeptides, designated Hi:2, was very strongly expressed by all 10 strongly metastatic clones, but was absent from 6 and only weakly expressed by one of the 7 weakly metastatic clones. Another marker polypeptide, designated Lo:6, was consistently most strongly expressed by the weakly metastatic clones. Among the approximately 2000 individually separated cellular polypeptides, only these two marker polypeptides consistently distinguished between the strongly and weakly metastatic clones from both fibrosarcomas. Five other polypeptides also distinguished between highly and weakly metastatic clones, but not as stringently.

Animals↗

Mass spectrometry in diagnosis of metabolic disorders.

Mass spectrometry is an important part of multicomponent analytical systems designed for diagnosis of metabolic disorders. In our laboratory capillary gas chromatography/mass spectrometry (GC/MS) with computerized library search is used primarily to separate and identify urinary organic acids. About 50 different diseases with increased excretion of organic acids are recognized today. Other techniques, including thin-layer chromatography, high-performance liquid chromatography with diode array detector, automatic amino acid analysis and two-dimensional electrophoresis are used to detect other compounds of diagnostic significance. The diagnostic use of GC/MS is exemplified by studies on two siblings. One died of his disease at approximately 1 year old. Both excreted 3-hydroxydicarboxylic acids (C8-C12) as identified by mass spectrometry. These metabolites are secondary to systemic carnitine deficiency. Low-fat diet normalized the clinical condition of the surviving sibling. GC/MS is now used to monitor the efficacy of dietary treatment by analysing the dicarboxylic acid excretion in this patient. Modern DNA technology is rapidly becoming increasingly important for diagnosis, particularly prenatal diagnosis, of metabolic diseases. It is suggested, however, that mass spectrometry will continue to be an important diagnostic tool for many years ahead.

Female↗

Mapping of synovial fibroblast proteins by high resolution two-dimensional polyacrylamide electrophoresis.

The highly sensitive protein separation technique two-dimensional polyacrylamide gel electrophoresis was used to study the cellular protein synthesis in 1) cultured human rheumatoid and 2) normal synovial fibroblasts and 3) normal skin fibroblasts. No reproducible differences were found that could be ascribed to cellular origin, the disease or in vitro cellular aging. The reasons for that probably were related to the cell cultures and not to failure of protein detection.

Arthritis, Rheumatoid↗

N-acetylaspartic aciduria in a child with a progressive cerebral atrophy.

Excessive excretion of N-acetylaspartic acid in urine is reported in a 6-yr-old child with extensive and progressive cerebral atrophy. The concentration in urine was 947-1,433 mumol/mmol creatinine (controls, n = 10, 5-21 mumol/mmol creatinine) and the daily excretion approximately 3-4 mmol. In cerebrospinal fluid from the patient the concentration was 611 mumol/l (controls, n = 10, not detectable, detection limit 2.3 mumol/l). The concentration of N-acetylaspartic acid in serum was 7 mumol/l. The low level in serum compared to the high urinary excretion of NAA suggests the possibility that NAA is synthesized in the kidneys in addition to the brain. This patient may cast new light on the functional role of N-acetylaspartic acid in humans.

Amino Acid Metabolism, Inborn Errors↗

Liver transplantation in a 23-year-old tyrosinaemia patient: effects on the renal tubular dysfunction.

Orthotopic liver transplantation was performed on a 23-year-old female with hereditary tyrosinaemia. The disorder was diagnosed at 7 years of age due to severe rickets, and the patient was treated with a diet restricted in phenylalanine and tyrosine. Nineteen months before the transplantation she had an acute episode of diffuse gastrointestinal bleeding due to portal hypertension. Three subsequent bleeding episodes with accompanying ascites and signs of encephalopathy were considered life-threatening. Nine months after the liver transplantation the patient is well, but serum transaminases are slightly elevated. Without dietary restrictions serum tyrosine and inorganic phosphate are normalized, no succinylacetone can be detected in serum, and urinary excretion of p-hydroxyphenyllactate and p-hydroxyphenylpyruvate is normal. Excretion of amino acids, glucose and beta 2-microglobulin decreased significantly after the transplantation but is still elevated. The succinylacetone concentration in urine is about 20% of the preoperative level. After an oral tyrosine load, succinylacetone excretion increased sevenfold but no deterioration of the renal tubular function was observed and no tyrosine metabolites were detectable in serum. The findings indicate that the defective tyrosine metabolism occurs in the kidneys, but does not produce tubular dysfunction. The residual tubular dysfunction of the patient is probably due to irreversible damage of the tubular epithelium.

Adult↗

Trace elements and rheumatoid arthritis (RA)--pathogenetic and therapeutic aspects.

Rheumatoid arthritis is characterized by increased activity of macrophages which produce toxic forms of oxygen. Such oxygen has been suggested as mediator also of rheumatoid inflammation. Gold accumulates in lysosomes of the macrophages and stabilizes lysosomal and other cell membranes leading to reduced liberation of toxic oxygen. Intracellular production of metallothionein can be induced. Zinc in high doses parenterally can immobilize macrophages and also induce metallothionein-like proteins. Copper and zinc are components of SOD which detoxifies oxygen, and copper-thiolate complexes are reported to be anti-inflammatory. The therapeutic effect of penicillamine and other thiols like aurothiomalate may also be related to an anti-oxidative action. Therapeutic induction of increased intracellular levels of glutathione or administration of selenium in such a form that it incorporates into glutathione-peroxidase and increases the efficacy of the enzyme may lead to accelerated metabolism of toxic oxygen.

Arthritis, Rheumatoid↗

Isoelectric focusing and two-dimensional gel electrophoresis in plasma and cerebrospinal fluid from patients with dementia.

IgG profiles of cerebrospinal fluid (CSF) and plasma from patients with Alzheimer's disease/senile dementia of Alzheimer type, multi-infarct dementia and aged nondemented individuals were analyzed using isoelectric focusing (IEF) followed by immunofixation and high resolution two-dimensional polyacrylamide gel electrophoresis (PAGE). The IEF profiles of plasma and CSF in patients with dementia were diffuse and lacked oligoclonal bands and were identical to those of nondemented individuals. The investigation of plasma and CSF by two-dimensional PAGE did not reveal any specific protein pattern in the demented individuals compared to the controls.

Adult↗

High resolution two-dimensional protein electrophoresis in clinical chemistry.

High resolution two-dimensional (2D)-electrophoresis has been developed to the stage that it is possible to resolve several thousand proteins in cells and tissue, and over six-hundred proteins are separated in human serum. The 2D-technique has been applied to analyses of serum from patients with multiple myeloma, macroglobulinemia and other gammopathies, and to separate apolipoproteins and study abnormalities and polymorphism of these proteins. Cerebrospinal fluid from patients with various neurological diseases has been studied by 2D-electrophoresis and seems to yield information on multiple sclerosis. The 2D-technique has been applied to normal and malignant cells and biopsies, and offers a possibility to detect disease-related proteins. Protein spots from 2D-gels may be used to raise monoclonal antibodies which subsequently can be used to develop simple clinical chemical tests for disease markers. The 2D-electrophoretic method is, however, not yet suitable as a typical routine analysis in the clinical chemistry laboratory, but is primarily a research tool of considerable potential.

Blood Proteins↗

Systematic laboratory diagnosis of human metabolic disorders.

A multicomponent analytical system for diagnosis of human metabolic disorders is overviewed. After preliminary analysis of the urine with simple chemical tests and standard clinical chemistry methods, the samples undergo a variety of chromatographic separations. Paper chromatography and thin-layer chromatography determine carbohydrates and mucopolysaccharides. Amino acids are analysed by automatic ionexchange chromatography. Gas chromatography - mass spectrometry with computerized library search is used to separate and identify organic acids, and high performance liquid chromatography with computerized diodearray detector is used to analyse metabolites of nucleic acids and other non-volatile or labile constituents. The system, gradually developed during the past two decades, is routinely used to diagnose, via its detection of pathological metabolites, around 100 different metabolic disorders. The methods may also be used to monitor the efficacy of therapeutic treatment in some of the cases where this is possible.

Chromatography, High Pressure Liquid↗

Urinary excretion of N-acetyl amino acids in patients with some inborn errors of amino acid metabolism.

Urinary organic acid profiles of patients with Maple Syrup Urine Disease (MSUD), hereditary tyrosinemia and phenylketonuria (PKU) have been studied by means of capillary GC-MS-computer technique. In addition to the characteristic metabolites of these disorders, increased amounts of N-acetylleucine, N-acetylisoleucine and N-acetylvaline were found in MSUD-urine. Increased excretion of N-acetylphenylalanine occurred in PKU, and in tyrosinemia both the latter compound and increased N-acetyltyrosine excretion were observed. These results together with literature reports of similar studies on patients with other aminoacidopathies may indicate that most disorders which result in accumulation of one or more specific amino acids, will convert a small fraction of them into their corresponding N-acetyl derivative.

Acetylation↗

Analysis of cellular and membrane extracts of human leukocytes from rheumatoid arthritis patients using two-dimensional electrophoresis.

Peripheral blood leukocytes from 30 patients with classic or definite rheumatoid arthritis (RA) and 18 healthy controls were separated into lymphocytes, monocytes and granulocytes and labelled with 35S-methionine. The integral membrane proteins with an amphiphilic nature were separated from hydrophilic proteins by use of the nonionic detergent Triton X-114. Both whole cells and membrane proteins were isotope labelled and separated by high resolution two-dimensional electrophoresis under denaturing conditions. Polypeptide spots were visualised by autoradiography. No consistent differences were found when leukocytes from RA patients were compared to the controls.

Arthritis, Rheumatoid↗

Mapping of proteins from cultured fibroblasts of synovial and subcutaneous origin by high resolution two-dimensional polyacrylamide gel electrophoresis.

Nine different cell lines of human (A) rheumatoid and (B) normal synovial fibroblasts and of (C) normal skin fibroblasts were obtained from tissue explants and grown as monolayers. The cellular protein synthesis was studied by high resolution two-dimensional polyacrylamide gel electrophoresis. Between the fourth and 10th passage of the cells in culture apparently no consistent differences were found which could be ascribed to the origin of the cells, to the rheumatoid state of the synovial tissue, or to the increasing age of the cultured fibroblasts.

Adult↗

Enzyme activity and protein patterns as premalignant markers in mucosal biopsy specimens from the large intestine.

Total enzyme activity of glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LD) was measured in homogenates of resected biopsy specimens and in endoscopic biopsy specimens. LD isoenzyme patterns were scanned by a laser technique after agarose gel electrophoresis. Examinations were performed in homogenates of premalignant lesions such as ulcerative colitis and adenomas of the colon, with normal mucosa and carcinomas as control material. Additionally, two-dimensional electrophoretic protein patterns were compared for normal mucosa, adenomas, and carcinomas of the large intestine. The mean activity of both G6PD and LD was highest in the presence of dysplasia; however, only G6PD activity seemed independent of inflammatory changes. The percentage of LD isoenzyme M monomers was significantly higher in homogenates of specimens with dysplastic changes than in specimens with only inflammatory changes. A positive correlation was found between total LD isoenzyme M monomers and LD 5 monomers for the whole material and for each of the histological subgroups of ulcerative colitis. A positive correlation between total LD activity and the percentage of LD 5 monomers was seen only for dysplastic, adenomatous, and malignant tissues. The several hundred protein spots seen on two-dimensional protein maps showed that most of the spots were common for normal mucosa, adenomas, and carcinomas, but differences were also seen. Polyps and carcinomas had strikingly similar protein patterns, different from that of normal mucosa. The results of the two-dimensional protein electrophoresis lend further support to the hypothesis that polyps are precursors of carcinomas of the large intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗