Combined hepatic and renal transplantation in primary hyperoxaluria type 1 (PH1): long-term results.
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Adult↗
Biomedical subjects
E Jellum
Publications and source records attributed to E Jellum.
The JANUS serum bank.
The on-going JANUS project was initiated by the Norwegian Cancer Society in 1973. The serum bank comprises close to 0.5 million serum samples collected from 170,000 donors. From 2-16 consecutive samples are available from each donor. The sera are stored at -25 degrees C. At regular intervals the JANUS-collection is matched against the files of the Norwegian Cancer Registry. From 1973 to 1991 almost 5000 of the donors have developed some form of cancer. Frozen serum samples collected from a few months to 18 years prior to clinical recognition of their disease are consequently available for research purposes. The aim of the JANUS-project is to search in these premorbid sera for chemical, biochemical, immunological or other changes that might be indicative of cancer development at early stages. Gas chromatography-mass spectrometry and two-dimensional protein electrophoresis have been used to evaluate the stability of the frozen sera. Some recent findings are: CA125 is elevated several months prior to diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumour marker in subgroups of thyroid cancer; low level of selenium in serum reflects increased risk of thyroid cancer; and raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkin's disease. On-going research includes trace elements and cancer, and studies on lipid-profiles, diet and cancer. The serum bank may in principle be used for other purposes, e.g. in environmental studies. Analysis of sequential sera may determine chemical substances in the sera that might reflect differences in exposure to environmental pollutants in the period 1973-1991.
Antigens, Tumor-Associated, Carbohydrate↗
Slow replenishment of carnitine deficiency after cessation of long-term treatment with pivaloyl-containing antibiotics.
Long-term treatment with pivampicillin and pivmecillinam for 6-24 months in five adults and one child reduced the total serum carnitine concentration to 3.7-14 mumol/l (reference value: 25-66 mumol/l). Muscle carnitine was reduced to 0.3-0.7 mumol/g wet weight (reference value: 3-5 mumol/g) in two cases. All patients had muscle symptoms with weakness, asthenia and pains. One showed signs of carnitine depletion in the liver with increased secretion of dicarboxylic acids (C6, C8, C10) in urine and limited ketone body formation during prolonged fasting. Serum carnitine increased slowly after cessation of therapy and reached normal concentrations after 6-12 months. All symptoms caused by carnitine depletion disappeared. This was achieved on a normal diet without carnitine supplementation.
Adult↗
Polyunsaturated fatty acids in serum phospholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway.
We have tested the hypothesis that specific polyunsaturated fatty acids (PUFA) of the n-3 and n-6 families, as measured in serum phospholipids, are negatively associated with the risk of breast cancer. The study is based on serum samples from women who have donated blood to the Janus serum bank at the University Hospital in Oslo, Norway. It consists of sera from 87 women who developed breast cancer (cases) subsequent to blood donation and 235 women who were free of any diagnosed cancer (controls), but were of similar age and had similar blood storage time as the cases. We measured fatty acids (monounsaturated, polyunsaturated and saturated) in serum phospholipids, and made comparisons between cases and controls. The results showed that there was an inverse relation between the n-6 PUFA linoleic acid (18:2n-6) and risk of breast cancer, but this association was restricted to women who were 55 years and younger. In this age group, the relative risk (odds ratio) of women in the highest quartile of linoleic acid was 0.4 (95% confidence limits, 0.2 and 1.0) compared with women in the lowest quartile, and there was a negative trend over quartiles of linoleic acid (Mantel's chi for trend = -2.49, P < 0.02). No association was noted between the n-3 PUFA of marine oil origin and breast cancer risk. If the measured concentration of linoleic acid in serum phospholipids reliably reflects dietary intake, these data suggest that linoleic acid in the diet may decrease breast cancer risk among women at premenopausal and perimenopausal age. No similar association with n-3 unsaturated fatty acids was observed. It is noteworthy that none of the measured fatty acids (saturated or unsaturated) showed a positive association with breast cancer risk.
Breast Neoplasms↗
[Glutaric aciduria type I].
Glutaric aciduria type I is a congenital metabolic disease caused by an enzymatic defect in the degradation of the amino acids lysine and tryptophane. This article presents five Norwegian patients with this condition. Early clinical features may be similar to those of encephalitis. The further clinical course is dominated by choreoathetosis, hyperkinesis and spasticity. The diagnosis is made by tracing enhanced glutaric acid in the urine. The treatment is a low protein diet containing only small quantities of lysine and tryptophane. Four of our patients underwent a neuropsychological examination. Despite the fact that such patients are difficult to test, our examination indicates that the condition has a greater effect on motor than on cognitive functions.
Adolescent↗
Branched-chain amino acids increase the seizure threshold to picrotoxin in rats.
During infusion of branched-chain amino acids (BCAAs) in humans, changes in ventilatory drive, appetite, and sleep have been reported. The mechanism by which BCAAs exert their effects on CNS remains unclear. Picrotoxin is a proconvulsant drug, acting as an antagonist on the GABA-benzodiazepine receptor complex. Twenty rats were randomized to receive either an IP injection with 4% BCAAs (300 mg/kg; 8 ml/kg) (n = 10) or placebo (saline 8 ml/kg) (n = 10). The mean latency time from injection to onset of seizures was recorded as an indication of the seizure threshold. Latency time was significantly longer for BCAAs than for placebo, 11.2 (+/- 1.9) vs. 8.3 (+/- 1.8) min. Thus, a BCAA injection increased the seizure threshold to picrotoxin (p < 0.03). This suggests that BCAA infusion may exert effects on the GABA-benzodiazepine receptor complex.
Amino Acids, Branched-Chain↗
Capillary electrophoresis for diagnosis and studies of human disease, particularly metabolic disorders.
High-performance capillary electrophoresis (HPCE) has been used in a multicomponent analytical system designed to diagnose and study human diseases, particularly metabolic disorders. Comparative analyses, using HPCE, high-performance liquid chromatography (HPLC) and an automated amino acid analyser, were carried out on urine and blood samples from patients with homocystinuria, cystinuria, glutathione synthetase deficiency and adenylosuccinase deficiency. HPCE of the sulphur-containing amino compounds, derivatized with monobromobimane and detected by fluorescence spectroscopy, was a quick and simple alternative to classical amino acid analysis. The detection of the characteristic succinylpurines associated with adenylosuccinase defect was equally well achieved with HPLC and HPCE (absorbance detector). Owing to the possible connection between deficiency of taurine (2-amino-1-ethanesulphonic acid) in the heart and the development of cardiomyopathy and heart failure, a simple HPCE method was developed for the determination of taurine in sub-milligram samples of biopsies of the myocardium. The homologue 3-amino-1-propanesulphonic acid was the internal standard, and derivatives of 9-fluorenylmethyl chloroformate and fluorescence detection were used. It is suggested that the potential of HPCE to analyse small volumes should be exploited in biomedicine and clinical diagnosis to analyse sub-milligram samples of tissue biopsies and cells.
Biopsy↗
Epstein-Barr virus antibody patterns preceding the diagnosis of non-Hodgkin's lymphoma.
Immunosuppressed patients who develop non-Hodgkin's lymphoma (NHL) have abnormal antibody responses against the Epstein-Barr virus (EBV) prior to the diagnosis of malignancy. To see if this is also true of "spontaneous" cases in the general population, we undertook a collaborative serologic case-control study. From 4 serum banks containing specimens from over 240,000 persons, 104 subjects were identified for whom a blood specimen had been stored an average of 63 months before diagnosis of NHL, and 259 controls matched for age, sex, ethnic group and date of serum collection. The relative risks (RR) for subsequent development of NHL associated with elevated levels of IgG and IgM antibodies against viral capsid antigen were 2.5 (95% confidence interval = 1.1-5.7) and 3.2 (1.3-7.5), respectively; these associations increased with age at diagnosis. For the nuclear antigen, the distribution of titers for cases was more restricted than that of controls, with fewer cases having either elevated or low titers, RR = 0.5 (0.2-1.4) and 0.5 (0.2-1.2), respectively. Cases had significantly lower antibody titers against the cytomegalovirus, RR = 0.4 (0.2-0.9). These findings suggest that, at least for some patients, NHL is preceded by an enhanced level of endogenous immunosuppression with resultant EBV activation. This observation supports the role of EBV either directly in the development of NHL or as a primary marker of immune dysfunction.
Adult↗
Epstein-Barr virus antibody patterns preceding the diagnosis of nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) patients have elevated IgG and IgA antibody titers against the Epstein-Barr viral capsid antigen (VCA) and the diffuse component of the early antigen complex (EA-D) at diagnosis. Several studies have implied that the presence of anti-VCA-IgA can be used as a screening marker for early NPC. To evaluate this further, we undertook a serologic case-control study based on four serum banks which together had specimens from over 240,000 persons. Seven cases of undifferentiated or poorly differentiated NPC were diagnosed in the period after serum collection ranging from 26 months to 154 months. Two controls per case matched on serum bank, age, sex, race, and date of serum collection were selected by a predetermined random process. For anti-VCA-IgG, the geometric mean titer for cases (88.3) was significantly higher than that for controls (75.5, P less than 0.05). The difference was greatest among the Asian patients. No significant differences were found for anti-VCA-IgA, anti-EA-D, and anti-EA-R or anti-EBNA. No time effects were evident when titers were plotted against time of blood collection preceding diagnosis. Our results do not suggest EBV activation in the period preceding NPC diagnosis, nor that detectable IgA antibody against VCA is a marker for early disease.
Adult↗
Interpreting complicated chromatographic patterns.
GC-MS, HPLC, automatic amino acid analysis, high-resolution two-dimensional electrophoresis and capillary electrophoresis are suitable for the multicomponent analysis of body fluids and tissues. Manual interpretation of the complex metabolite and protein profiles thereby obtained is usually difficult, except in the case of metabolic disorders, where major deviations from the normal profiles often are observed. Implementation of multivariate data analysis makes it possible to retrieve diagnostic information that otherwise may be overlooked, as shown in this report where patients with leprosy have been examined. Urine samples were analysed by ion-exchange chromatography and by GC-MS to obtain profiles of amino acids and organic acids. Qualitative and quantitative information on 68 metabolites were then analysed by principal components analysis (PCA) and by partial least square models (PLS). Three different PLS dimensions were found (cross-validation) corresponding to controls (persons without leprosy), paucibacillary and multibacillary leprosy.
Amino Acids↗
Polymorphism of a platelet polypeptide.
Polymorphism of a platelet protein is described. The gene products are represented by two peptides of MW around 30 kD. The allele frequency was estimated to 0.85 and 0.15, the common variant being of slightly higher MW and about 2 charge units more acidic than the other. The peptides were neither released nor phosphorylated, and subcelluar fractionation indicated localization to the cytosol. Attempts to raise antibodies failed, and further characterization could not be done, but the peptides seem to differ from all reasonably well characterized platelet proteins so far.
Alleles↗
Advances in the use of computerized gas chromatography-mass spectrometry and high-performance liquid chromatography with rapid scanning detection for clinical diagnosis.
A multi-component analytical system designed for the diagnosis of metabolic disorders is described. The urinary components are separated by a variety of chromatographic techniques, including automated amino acid analysis, high-performance liquid chromatography with diode-array detection and gas chromatography-mass spectrometry with a computerized mass spectral library search for identification of organic acids. The complete system can be used to diagnose over 100 different metabolic diseases. The usefulness of the chromatographic system is exemplified by the pre- and postnatal diagnosis of glutaric aciduria type I, the diagnosis of lysinuric protein intolerance and of alkaptonuria. Drugs and diet may cause interfering metabolites, as exemplified by glycofurol, used as a solvent for intravenous drugs, and saccharin. It is predicted that chromatography and mass spectrometry will continue to be important diagnostic tools for many years ahead.
Acids↗
Profiling cells and body fluids--chromatography and two-dimensional electrophoresis as complementary techniques.
Recent results on the use of gas chromatography-mass spectrometry, high-performance liquid chromatography with diode array detector, amino acid analysis and high-resolution two-dimensional (2-D) electrophoresis to study body fluids and cells in health and disease are surveyed. The chromatography profiling techniques are particularly suitable for the diagnosis of inborn errors of metabolism, with DNA technology as a complementary tool for prenatal diagnosis. Both chromatography and electrophoresis were utilized to study pre-diagnostic sera from the JANUS serum bank and to classify certain bacteria. Protein profiling by 2-D electrophoresis was employed to identify marker proteins associated with the metastatic properties of cloned cancer cells. The electrophoretic technique is also appropriate as a preparative tool for isolating sufficient amounts of marker proteins for microsequencing of amino acids. Chromatography and protein profiling were complementary tools for evaluating the toxicity and mutagenicity of environmental samples in a new test utilizing living human leukocytes and fibroblasts.
Amino Acids↗
Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis.
In patients with Hodgkin's disease, titers of IgG antibody against viral capsid antigen of Epstein-Barr virus and the prevalence of antibodies against early antigen are higher than expected. To evaluate whether this condition antedates diagnosis, we identified 43 persons with Hodgkin's disease, from whom blood had been drawn and stored for an average of 50.5 months before diagnosis, and 96 controls from the same populations, from whom blood had been drawn at the same time. The relative risks of Hodgkin's disease associated with elevated levels of IgG and IgA antibodies against capsid antigen were 2.6 (90 percent confidence interval, 1.1 to 6.1) and 3.7 (1.4 to 9.3), respectively. For Epstein-Barr nuclear antigen, the relative risk was 4.0 (1.4 to 11.4), and for early antigen D it was 2.6 (1.1 to 6.1). However, the prevalence of IgM antibody against capsid antigen was substantially lower in patients with Hodgkin's disease (0.22 [0.04 to 1.3]). These associations were stronger in serum samples obtained at least three years before diagnosis than in serum samples obtained closer to diagnosis. We conclude that the development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein-Barr virus. Whether Epstein-Barr virus has a direct role in the pathogenesis of the disease or is simply a marker for a more fundamental factor affecting the immune control of latent infections is unknown.
Antibodies, Viral↗
Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: relevance for early detection of ovarian cancer.
To investigate the sensitivity of the CA 125 immunoradiometric assay for occult ovarian neoplasia, serum CA 125 levels were retrospectively determined "blind" in specimens collected from 105 women who subsequently developed ovarian neoplasia, and from 323 matched controls. The distribution of CA 125 levels was very different between the case and control populations (p = 0.0001) over the entire collection-to-diagnosis interval (range 1-143 months). Median CA 125 levels for all cases, and for those collected more than 24, 36 or even 60 months prior to diagnosis, were always 18 U/ml or greater, compared with a median of 10.9 U/ml for controls. Half of the cases collected within the 18 months preceding diagnosis had CA 125 levels of more than 30 U/ml and one-third had levels greater than 65 U/ml. About one-fourth of those collected prior to 60 months before diagnosis had levels above 30 U/ml. In contrast, approximately 7% and 0.9% of controls had levels in excess of 30 or 65 U/ml, respectively. Elevations occurred in cases eventually diagnosed with localized or advanced cancer, and with borderline or obviously malignant disease. These results provide an insight into the preclinical biology of ovarian neoplasia that may help in designing methods for early detection of this disease, and demonstrate the usefulness of the JANUS serum bank as a resource in evaluating serum tests.
Adult↗
Chromatography for diagnosis of metabolic diseases.
Chromatographic techniques, including computerized capillary gas chromatography-mass spectrometry and high-performance liquid chromatography with rapid scanning detection are important parts of a multicomponent analytical system designed for the diagnosis of human metabolic disorders. The usefulness of such a system is exemplified by the finding of a new case with the very rare disease hypersarcosinuria and the detection of unusual metabolites in a case of phenylketonuria.
Amino Acids↗
Leukocyte L1 protein and the cystic fibrosis antigen.
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Antigens, Surface↗
Marker polypeptide differences between spontaneous strongly and weakly metastatic cancer cells identified by 2-dimensional gel electrophoresis.
A recent 2-dimensional gel electrophoresis study revealed several polypeptide differences between a strongly metastatic and a weakly metastatic clone from a single chemically induced murine fibrosarcoma (Jellum et al., 1984). To exclude the possibility that this was merely coincidental, the study is extended here to 2 other fibrosarcomas recently and similarly induced in mice of the same inbred strain. Metastatic potential was defined by the number of lung metastases spontaneously formed from a transplanted primary footpad tumor. One strongly (or moderately) metastatic cell line and I weakly metastatic line from each of the 3 fibrosarcomas were examined in the same experiments. In confirmation of our previous results, the same polypeptides consistently occurred in considerably greater amounts in the weakly metastatic than in the strongly metastatic cells. One of these marker polypeptides was absent from the strongly metastatic cell lines. In comparison with 2 of the 3 most metastatic lines, the third line was only moderately metastatic, and differed least strongly from the 3 weakly metastatic cell lines with regard to expression of th marker polypeptides. Marker polypeptide expression showed no consistent correlation with tumorigenicity. No other consistent polypeptide differences between strongly metastatic and weakly metastatic cells could be identified among the approximately 2,000 cellular polypeptides separated on the gels.
Animals↗