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S Thunell

Publications and source records attributed to S Thunell.

At least 19 recordsLinked to original sources

Free amino acids in plasma and muscle during 24 hours post-operatively--a descriptive study.

Intracellular amino acids in skeletal muscle show a specific concentration pattern on the third post-operative day. The temporal development of these changes has not been clarified. Here the amino acid concentrations in skeletal muscle were studied during the first post-operative day in fourteen patients undergoing elective abdominal surgery. Muscle amino acids were determined pre-operatively, as well as at 12 and 24 h post-operatively. In muscle the concentrations of glutamine and the basic amino acids decreased gradually during the first 24 h after surgery to 79% (P less than 0.001) and 67% (P less than .001) respectively. The sum of the essential amino acids decreased to 73% (P less than 0.001) at 12 h, but thereafter rose to 91% (P less than 0.05) at 24 h. The sum of the BCAA decreased to 84% (P less than 0.05) at 12 h but then increased to 116% (P less than 0.05) at 24 h. The alanine concentration increased to 122% (P less than 0.001) during the first post-operative day. In plasma the alanine concentration increased at 12 h while most other amino acids declined. At 24 h post-operatively the plasma concentrations of all amino acids had returned to normal or showed a tendency towards normalization except for phenylalanine, which increased. At the end of the first post-operative day the concentrations of amino acids in muscle were consistent with the alterations previously observed three days after surgery. The changes in plasma amino acid concentrations only partly reflected those in muscle.

Amino Acids

Liver transplantation in a boy with acute porphyria due to aminolaevulinate dehydratase deficiency.

The clinical and biochemical outcome of a liver transplantation in a seven-year-old boy with acute porphyria due to aminolaevulinate dehydratase deficiency is described. Before transplantation standard liver function tests were normal and the rationale for transplantation was that the new liver would reduce the metabolic disturbance and thus avert the porphyric symptoms. During the year after the transplantation, the functioning of the new liver has been excellent. Basal excretion of porphyrin and porphyrin precursors has remained unchanged but, with the new liver transplant the patient has been able to withstand several porphyrinogenic challenges without increasing the excretion. Episodes of neurological and respiratory crises may have been due to persistent porphyric vulnerability. Alternatively, two early attacks may have been caused by neurotoxic effects of cyclosporin in combination with the existing damage to nervous tissue.

Acute Disease

Alcoholic beverages in acute porphyria.

Alcohol consumption habits and the clinical consequences of intake of alcoholic beverages were examined in 254 individuals with a diagnosis of acute intermittent porphyria or variegate porphyria, using a questionnaire. The study failed to demonstrate a connection between the amount of ethanol consumed, or the frequency of ingestion, and the development of symptoms of acute porphyria, other than in extreme consumption patterns. It was concluded that agents in alcoholic beverages other than ethanol play important roles in precipitating the porphyric symptoms. A majority of the individuals were able to identify alcoholic beverages that were less well tolerated and those that were better tolerated. The results suggest that polyphenolic compounds and 3 to 5 carbon chain hydrophobic alcohols may be responsible for the induction of clinical symptoms in acute porphyria by some alcoholic beverages. On the basis of these findings advice is proposed on alcohol counseling in inducible porphyria.

Acute Disease

Growth hormone improves muscle protein metabolism and whole body nitrogen economy in man during a hyponitrogenous diet.

Healthy male volunteers (n = 12) were given a normocaloric hyponitrogenous diet for a conditioning period of 7 days. Thereafter they were blindly randomized to receive daily injections of methionyl recombinant human growth hormone (met-hGH) 0.06 IU/kg or saline during a second week of hyponitrogenous nutrition. The met-hGH group showed a lower urinary urea excretion and a lower serum concentration of urea as compared with the control group. In skeletal muscle, the polyribosome concentration, indicative of muscle protein synthesis, as well as the concentrations of glutamine, alanine, aspartate, serine, and threonine, decreased in the control group, whereas no such changes were seen in the met-hGH-treated group. Since provision of met-hGH prevented protein catabolism in muscle and improved whole body nitrogen economy, investigations of the possible beneficial effects of met-hGH to prevent skeletal muscle vast after surgical trauma are advocated.

Amino Acids

delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote.

delta-Aminolevulinate dehydratase deficient porphyria, a recently recognized inborn error of heme biosynthesis, results from the markedly deficient activity of the heme biosynthetic enzyme, delta-aminolevulinate dehydratase (ALA-D). The four homozygotes described to date with this disorder have remarkably distinct phenotypes, ranging from a severely affected infant with failure to thrive to an essentially asymptomatic 68-year-old male. To investigate the molecular nature of the lesions causing the severe infantile-onset form, total RNA was isolated from cultured lymphoblasts of the affected homozygote, RNA was reverse-transcribed to cDNA, and the 990-bp ALA-D-coding region was amplified by the PCR. Heterozygosity for an RsaI RFLP within the ALA-dehydratase-coding region permitted identification of the paternal and maternal mutant alleles prior to sequencing. The maternal mutation (designated G133R), a G-to-A transition of nucleotide 397, predicted a glycine-to-arginine substitution at residue 133 at the carboxyl end of the highly conserved zinc-binding site in the enzyme subunit. The G133R mutation created a PstI site and permitted the confirmation and rapid detection of this lesion in amplified genomic DNA from maternal relatives. The paternal mutation, a G-to-A transition of nucleotide 823, predicted a valine-to-methionine substitution of residue 275 (designated V275M). This mutation was confirmed in genomic DNA from family members by the competitive PCR technique. Both missense mutations, which occurred at CpG dinucleotides, resulted in the synthesis of enzyme subunits such that the activity of the homooctameric enzyme was markedly reduced, thereby causing the severe infantile-onset phenotype in the affected homozygote.

Aminolevulinic Acid

Relationship between haemoglobin A1C in early type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformation in Sweden.

This prospective nationwide study examined the relationship between diabetic control in early pregnancy as assessed by HbA1C and the incidence of spontaneous abortion and fetal malformation. HbA1C and plasma C-peptide were determined in 532 women with Type 1 (insulin-dependent) diabetes mellitus, corresponding to approximately 80% of all the diabetic pregnancies in the country during the study period 1982-1985, and 222 non-diabetic control women. Median gestational week for sampling was 9.0 in the Type 1 diabetic and 10.0 in the control group. The median value of HbA1C was 7.7% in the diabetic and 5.3% in the control group (p less than 0.001). The rates of spontaneous abortion, 7.7% vs 7.2%, and malformation, 4.3% (major 2.0%) and 2.4% (major 1.0%), were not significantly different between the diabetic and control group, respectively. These rates of malformation were not significantly different from the national figures of 4.55% (major 1.75%). Much elevated HbA1C, i.e., greater than 10.1% equal to 8 SD above the normal mean control value, was significantly associated with the occurrence of spontaneous abortion (p less than 0.001) and malformation (p less than 0.01). Discriminant analysis revealed that after correction had been made for the significant value of HbA1C to predict the occurrence of spontaneous abortion and malformation, no further predictive power was displayed by measurable plasma C-peptide, maternal age or duration of diabetes or presence of diabetic microangiopathy. We conclude that poor metabolic control in early pregnancy contributes to an increased risk of both spontaneous abortion and fetal malformation.

Abortion, Spontaneous

ELISA for measuring porphobilinogen deaminase in human erythrocytes.

An ELISA method has been developed to quantitate human porphobilinogen deaminase in erythrocyte lysate. The antiserum used in the assay was raised against the erythropoietic form of human porphobilinogen deaminase. The IgG fraction was characterized by use of immunoblotting technique, rocket immunoelectrophoresis and immunotitration and shown to be monospecific. The measuring range of the method was from 4 ng to 50 pg. Intra- and inter-assay coefficients of variation were 6% and 7%, respectively. Erythrocyte lysates from 97 apparently healthy individuals were assayed giving a mean erythrocyte porphobilinogen deaminase protein concentration of 150 +/- 28 SD (micrograms/g Hb) and a specific enzyme activity of 750 +/- 140 SD (nkat/g). Eight patients with acute intermittent porphyria were also investigated. A decreased concentration of enzyme protein, i.e. 84 +/- 13 SD (micrograms/g Hb) with a normal specific activity, was found.

Ammonia-Lyases

Stress hormones given to healthy volunteers alter the concentration and configuration of ribosomes in skeletal muscle, reflecting changes in protein synthesis.

1. The influence of elevated concentrations of stress hormones on the concentration of ribosomes and the relative proportion of polyribosomes, reflecting protein synthesis in vivo, in human skeletal muscle was investigated. Healthy volunteers were given a 6 h infusion of adrenaline (n = 8), cortisol (n = 8), a triple-hormone combination of adrenaline, cortisol and glucagon (n = 8), or saline (n = 8). 2. The total ribosome concentration declined by 30.4 +/- 7.2% in the triple-hormone group (P less than 0.01), by 26.9 +/- 8.6% in the cortisol group (P less than 0.05) and by 24.8 +/- 11.2% in the adrenaline group (P less than 0.05). The proportion of polyribosomes to total ribosomes decreased by 8.5 +/- 2.2% in the triple-hormone group (P less than 0.05). 3. During hormone infusion the serum glucose levels were enhanced. The insulin concentrations in serum were elevated in the adrenaline group and the triple-hormone group, but not in the cortisol group. Serum insulin decreased in the control group. 4. The results indicate an effect of the combined stress hormone infusion on the total ribosome concentration as well as on the relative abundance of polyribosomes. The single hormones influenced the total ribosome concentration only. The results suggest a critical role for stress hormones in producing the decline in muscle protein synthesis seen after trauma.

Adult

Mutations in acute intermittent porphyria detected by ELISA measurement of porphobilinogen deaminase.

To study the existence of different mutations in acute intermittent porphyria, erythrocyte porphobilinogen deaminase activity and enzyme protein concentration were investigated in 125 porphyria gene carriers from 31 families, and in 121 apparently healthy controls. Porphobilinogen deaminase concentration (micrograms/gHb) was quantified using a recently developed double-sandwich ELISA. The ratio of enzyme catalytic activity to the concentration of enzyme protein was expressed as the porphobilinogen specific activity (nkat/g). The controls had a mean porphobilinogen deaminase concentration of 160 +/- 35 micrograms/gHb and a specific activity of 762 +/- 127 nkat/g. Two different types of mutation causing acute intermittent porphyria were detected. The majority (91%) of gene carriers, from 25 families, had a diminished porphobilinogen deaminase concentration of 102 +/- 18 micrograms/gHb, with a slightly lowered specific activity of 634 +/- 105 nkat/g. In 9% of the gene carriers, representing six different families, an increase in porphobilinogen deaminase concentration to 269 +/- 46 micrograms/gHb, and a highly significant reduction in specific activity to 234 +/- 48 nkat/g, were found, which indicates the presence of a different mutation.

Ammonia-Lyases

Porphobilinogen deaminase in human erythrocytes: purification of two forms with apparent molecular weights of 40 kDa and 42 kDa.

Porphobilinogen deaminase was purified from human erythrocytes by ion-exchange chromatography, gel filtration and hydrophobic interaction chromatography. Two forms of the enzyme were isolated, with apparent molecular weights of 40 kDa and 42 kDa, and in relative amounts of 85% and 15%, respectively. Both forms were found to have an N-terminal amino acid sequence identical to that published for the erythropoietic form of porphobilinogen deaminase, as deduced from a cDNA clone. The two forms present could each be separated into three differently charged subforms by Mono Q chromatography.

Amino Acid Sequence

Bacteriuria diagnosis and antibiotic susceptibility testing in a group practice by dipslide techniques.

In group practice, screening for bacteriuria and antibacterial susceptibility testing of bacteria in urine specimens were performed by dipslide methods (Uricult and Sensicult, Orion Diagnostica) and the results were evaluated with respect to conventional cultivation of urine specimens and standardized susceptibility testing by the disc diffusion method at a bacteriological laboratory. Bacteriuria diagnosis by screening by the Uricult method seemed to be satisfactorily performed except for some streptococcal strains. In the case of direct susceptibility testing by the Sensicult dipslide method, however, the results obtained by personnel at the surgeries and by trained bacteriologists displayed unacceptable disparities, despite the fact that a continuously running training programme was established.

Anti-Bacterial Agents

A gel filament as an analytical tool: the testing of an affinity chromatographic, product-immobilizing linear gel for determination of enzymatic activity.

A new technique for quantitative analysis is proposed. An underfined volume of the test solution is exposed to a reagent in the form of a gel filament of capillary dimensions. The linear progress in the gel of the compound in question is followed with the aid of the coloured reaction products deposited along its path. With the use of the enzyme gamma-glutamyl transpeptidase it is shown that the velocity in the system of the component to be analysed, as determined by measurement of its coloured track, is related to its activity in the test solution.

Aniline Compounds

Thin-layer chromatographic procedure for the detection, isolation and identification of basic psychotropic drugs in urine.

A procedure is described for the detection and identification of basic psychoactive drugs in urine. In the analytical system proposed, detection is dependent on thin-layer chromatography and chromophoric spraying of the resulting chromatogram. Identification is based on the extractability of the compound at the pH applied, on RF values in two solvents, on colour characteristics after exposure to a sequence of reagents, on fluorescence and UV-absorption characteristics, on retention times in different gas-liquid chromatographic systems and on the behaviour in ion-pair extraction with methyl orange. The procedure has been applied to some narcotic alkaloids and amines which exhibit central stimulant action.

Alkaloids

Antibacterial susceptibility testing by the dip-slide technique: a methodological evaluation.

Antibacterial susceptibility testing of urine specimens by the dip-slide method was compared to the standardized disc diffusion method. A boarder line of 12 mm inhibition zone on the slide could be used to select strains resistant to sulphisadimidine, ampicillin, nitrofurantoin or nalidixic acid. In the case of the sulphonamide, the results were grewtly influenced by composition of the medium. Susceptibility testing with the dip-slide method seems to be a useful test to differentiate strains likely to respond to therapy from resistant strains.

Ampicillin