Biomedical subjects

S Bak

Publications and source records attributed to S Bak.

At least 19 recordsLinked to original sources

PubMed2000

[Mortality in epilepsy. A review].

The overall risk of premature death in patients with epilepsy is two to three times that of the general population. The mortality risk is highest in patients with symptomatic epilepsy, but the mortality rate is also increased in patients with idiopathic epilepsy, indicating that epilepsy itself carries an increased risk of premature death. Cerebrovascular disease and primary brain tumours are common causes of death in patients with symptomatic epilepsy, while sudden unexplained death (SUDEP), accidents, suicide and status epilepticus are important causes of epilepsy related deaths. Prevention of accidents and suicide in patients with epilepsy and further knowledge on SUDEP is essential in order to reduce the mortality rate of epilepsy.

Accidents↗

PubMed2000

Intron-exon organization and phylogeny in a large superfamily, the paralogous cytochrome P450 genes of Arabidopsis thaliana.

The cytochrome P450 gene superfamily is represented by 80 genes in animal genomes and perhaps more than 300 genes in plant genomes. We analyzed about half of all Arabidopsis P450 genes, a very large dataset of truly paralogous genes. Sequence alignments were used to draw phylogenetic trees, and this information was compared with the intron-exon organization of each P450 gene. We found 60 unique intron positions, of which 37 were phase 0 introns. Our results confirm the polyphyletic origin of plant P450 genes. One group of these genes, the A-type P450s, are plant specific and characterized by a simple organization, with one highly conserved intron. Closely related A-type P450 genes are often clustered in the genome with as many as a dozen genes (e.g., of the CYP71 subfamily) on a short stretch of chromosome. The other P450 genes (non-A-type) form several distinct clades and are characterized by numerous introns. One such clade contains the two CYP51 genes, which are thought to encode obtusifoliol 14a demethylase. The two CYP51 genes have a single intron that is not shared with CYP51 genes from vertebrates or fungi, or with any other Arabidopsis P450 gene. Only a few of the Arabidopsis P450 genes are intronless (e.g., the CYP710A and CYP96A subfamilies). There was a relatively good correlation between intron conservation and phylogenetic relationships between members of the P450 subfamilies. Gene organization appears to be a useful tool in establishing the evolutionary relatedness of P450 genes, which may help in predictions of P450 function.

Amino Acid Sequence↗

PubMed2000

Transgenic tobacco and Arabidopsis plants expressing the two multifunctional sorghum cytochrome P450 enzymes, CYP79A1 and CYP71E1, are cyanogenic and accumulate metabolites derived from intermediates in Dhurrin biosynthesis.

Novel cyanogenic plants have been generated by the simultaneous expression of the two multifunctional sorghum (Sorghum bicolor [L.] Moench) cytochrome P450 enzymes CYP79A1 and CYP71E1 in tobacco (Nicotiana tabacum cv Xanthi) and Arabidopsis under the regulation of the constitutive 35S promoter. CYP79A1 and CYP71E1 catalyze the conversion of the parent amino acid tyrosine to p-hydroxymandelonitrile, the aglycone of the cyanogenic glucoside dhurrin. CYP79A1 catalyzes the conversion of tyrosine to p-hydroxyphenylacetaldoxime and CYP71E1, the subsequent conversion to p-hydroxymandelonitrile. p-Hydroxymandelonitrile is labile and dissociates into p-hydroxybenzaldehyde and hydrogen cyanide, the same products released from dhurrin upon cell disruption as a result of pest or herbivore attack. In transgenic plants expressing CYP79A1 as well as CYP71E1, the activity of CYP79A1 is higher than that of CYP71E1, resulting in the accumulation of several p-hydroxyphenylacetaldoxime-derived products in the addition to those derived from p-hydroxymandelonitrile. Transgenic tobacco and Arabidopsis plants expressing only CYP79A1 accumulate the same p-hydroxyphenylacetaldoxime-derived products as transgenic plants expressing both sorghum cytochrome P450 enzymes. In addition, the transgenic CYP79A1 Arabidopsis plants accumulate large amounts of p-hydroxybenzylglucosinolate. In transgenic Arabidopsis expressing CYP71E1, this enzyme and the enzymes of the pre-existing glucosinolate pathway compete for the p-hydroxyphenylacetaldoxime as substrate, resulting in the formation of small amounts of p-hydroxybenzylglucosinolate. Cyanogenic glucosides are phytoanticipins, and the present study demonstrates the feasibility of expressing cyanogenic compounds in new plant species by gene transfer technology to improve pest and disease resistance.

Arabidopsis↗

PubMed1999

Metabolic engineering of p-hydroxybenzylglucosinolate in Arabidopsis by expression of the cyanogenic CYP79A1 from Sorghum bicolor.

Glucosinolates are natural products in cruciferous plants, including Arabidopsis thaliana. CYP79A1 is the cytochrome P450 catalysing the conversion of tyrosine to p-hydroxyphenylacetaldoxime in the biosynthesis of the cyanogenic glucoside dhurrin in sorghum. Both glucosinolates and cyanogenic glucosides have oximes as intermediates. Expression of CYP79A1 in A. thaliana results in the production of high levels of the tyrosine-derived glucosinolate p-hydroxybenzylglucosinolate, which is not a natural constituent of A. thaliana. This provides further evidence that the enzymes have low substrate specificity with respect to the side chain. The ability of the cyanogenic CYP79A1 to integrate itself into the glucosinolate pathway has important implications for an evolutionary relationship between cyanogenic glucosides and glucosinolates, and for the possibility of genetic engineering of novel glucosinolates.

Arabidopsis↗

PubMed1999

Optimized expression and catalytic properties of a wheat obtusifoliol 14alpha-demethylase (CYP51) expressed in yeast. Complementation of erg11Delta yeast mutants by plant CYP51.

CYP51s form the only family of P450 proteins conserved in evolution from prokaryotes to fungi, plants and mammals. In all eukaryotes, CYP51s catalyse 14alpha-demethylation of sterols. We have recently isolated two CYP51 cDNAs from sorghum [Bak, S., Kahn, R.A., Olsen, C. E. & Halkier, B.A. (1997) Plant J. 11, 191-201] and wheat [Cabello-Hurtado, F., Zimmerlin, A., Rahier, A., Taton, M., DeRose, R., Nedelkina, S., Batard, Y., Durst, F., Pallett, K.E. & Werck-Reichhart, D. (1997) Biophys. Biochem. Res. Commun. 230, 381-385]. Wheat and sorghum CYP51 proteins show a high identity (92%) compared with their identity with their fungal and mammalian orthologues (32-39%). Data obtained with plant microsomes have previously suggested that differences in primary sequences reflect differences in sterol pathways and CYP51 substrate specificities between animals, fungi and plants. To investigate more thoroughly the properties of the plant CYP51, the wheat enzyme was expressed in yeast strains overexpressing different P450 reductases as a fusion with either yeast or plant (sorghum) membrane targeting sequences. The endogenous sterol demethylase gene (ERG11) was then disrupted. A sorghum-wheat fusion protein expressed with the Arabidopsis thaliana reductase ATR1 showed the highest level of expression and activity. The expression induced a marked proliferation of microsomal membranes so as to obtain 70 nmol P450.(L culture)-1, with CYP51 representing 1.5% of microsomal protein. Without disruption of the ERG11 gene, the expression level was fivefold reduced. CYP51 from wheat complemented the ERG11 disruption, as the modified yeasts did not need supplementation with exogenous ergosterol and grew normally under aerobic conditions. The fusion plant enzyme catalysed 14alpha-demethylation of obtusifoliol very actively (Km,app = 197 microm, kcat = 1.2 min-1) and with very strict substrate specificity. No metabolism of lanosterol and eburicol, the substrates of the fungal and mammalian CYP51s, nor metabolism of herbicides and fatty acids was detected in the recombinant yeast microsomes. Surprisingly lanosterol (Ks = 2.2 microM) and eburicol (Ks = 2.5 microm) were found to bind the active site of the plant enzyme with affinities higher than that for obtusifoliol (Ks = 289 microM), giving typical type-I spectra. The amplitudes of these spectra, however, suggested that lanosterol and eburicol were less favourably positioned to be metabolized than obtusifoliol. The recombinant enzyme was also used to test the relative binding constants of two azole compounds, LAB170250F and gamma-ketotriazole, which were previously reported to be potent inhibitors of the plant enzyme. The Ks of plant CYP51 for LAB170250F (0.29 microM) and gamma-ketotriazole (0.40 microM) calculated from the type-II sp2 nitrogen-binding spectra were in better agreement with their reported effects as plant CYP51 inhibitors than values previously determined with plant microsomes. This optimized expression system thus provides an excellent tool for detailed enzymological and mechanistic studies, and for improving the selectivity of inhibitory molecules.

Amino Acid Sequence↗

PubMed1998

Cloning of three A-type cytochromes P450, CYP71E1, CYP98, and CYP99 from Sorghum bicolor (L.) Moench by a PCR approach and identification by expression in Escherichia coli of CYP71E1 as a multifunctional cytochrome P450 in the biosynthesis of the cyanogenic glucoside dhurrin.

A cDNA encoding the multifunctional cytochrome P450, CYP71E1, involved in the biosynthesis of the cyanogenic glucoside dhurrin from Sorghum bicolor (L.) Moench was isolated. A PCR approach based on three consensus sequences of A-type cytochromes P450- (V/I)KEX(L/F)R, FXPERF, and PFGXGRRXCXG-was applied. Three novel cytochromes P450 (CYP71E1, CYP98, and CYP99) in addition to a PCR fragment encoding sorghum cinnamic acid 4-hydroxylase were obtained. Reconstitution experiments with recombinant CYP71E1 heterologously expressed in Escherichia coli and sorghum NADPH-cytochrome P450-reductase in L-alpha-dilaurylphosphatidyl choline micelles identified CYP71E1 as the cytochrome P450 that catalyses the conversion of p-hydroxyphenylacetaldoxime to p-hydroxymandelonitrile in dhurrin biosynthesis. In accordance to the proposed pathway for dhurrin biosynthesis CYP71E1 catalyses the dehydration of the oxime to the corresponding nitrile, followed by a C-hydroxylation of the nitrile to produce p-hydroxymandelonitrile. In vivo administration of oxime to E. coli cells results in the accumulation of the nitrile, which indicates that the flavodoxin/flavodoxin reductase system in E. coli is only able to support CYP71E1 in the dehydration reaction, and not in the subsequent C-hydroxylation reaction. CYP79 catalyses the conversion of tyrosine to p-hydroxyphenylacetaldoxime, the first committed step in the biosynthesis of the cyanogenic glucoside dhurrin. Reconstitution of both CYP79 and CYP71E1 in combination with sorghum NADPH-cytochrome P450-reductase resulted in the conversion of tyrosine to p-hydroxymandelonitrile, i.e. the membranous part of the biosynthetic pathway of the cyanogenic glucoside dhurrin. Isolation of the cDNA for CYP71E1 together with the previously isolated cDNA for CYP79 provide important tools necessary for tissue-specific regulation of cyanogenic glucoside levels in plants to optimize food safety and pest resistance.

Amino Acid Sequence↗

PubMed1998

The presence of CYP79 homologues in glucosinolate-producing plants shows evolutionary conservation of the enzymes in the conversion of amino acid to aldoxime in the biosynthesis of cyanogenic glucosides and glucosinolates.

A cDNA encoding CYP79B1 has been isolated from Sinapis alba. CYP79B1 from S. alba shows 54% sequence identity and 73% similarity to sorghum CYP79A1 and 95% sequence identity to the Arabidopsis T42902, assigned CYP79B2. The high identity and similarity to sorghum CYP79A1, which catalyses the conversion of tyrosine to p-hydroxyphenylacetaldoxime in the biosynthesis of the cyanogenic glucoside dhurrin, suggests that CYP79B1 similarly catalyses the conversion of amino acid(s) to aldoxime(s) in the biosynthesis of glucosinolates. Within the highly conserved 'PERF' and the heme-binding region of A-type cytochromes, the CYP79 family has unique substitutions that define the family-specific consensus sequences of FXP(E/D)RH and SFSTG(K/R)RGC(A/I)A, respectively. Sequence analysis of PCR products generated with CYP79B subfamily-specific primers identified CYP79B homologues in Tropaeolum majus, Carica papaya, Arabidopsis, Brassica napus and S. alba. The five glucosinolate-producing plants identified a CYP79B amino acid consensus sequence KPERHLNECSEVTLTENDLRFISFSTGKRGC. The unique substitutions in the 'PERF' and the heme-binding domain and the high sequence identity and similarity of CYP79B1, CYP79B2 and CYP79A1, together with the isolation of CYP79B homologues in the distantly related Tropaeolaceae, Caricaceae and Brassicaceae within the Capparales order, show that the initial part of the biosynthetic pathway of glucosinolates and cyanogenic glucosides is catalysed by evolutionarily conserved cytochromes P450. This confirms that the appearance of glucosinolates in Capparales is based on a cyanogen 'predisposition'. Identification of CYP79 homologues in glucosinolate-producing plants provides an important tool for tissue-specific regulation of the level of glucosinolates to improve nutritional value and pest resistance.

Amino Acid Sequence↗

PubMed1997

Cloning and expression in Escherichia coli of the obtusifoliol 14 alpha-demethylase of Sorghum bicolor (L.) Moench, a cytochrome P450 orthologous to the sterol 14 alpha-demethylases (CYP51) from fungi and mammals.

Obtusifoliol 14 alpha-demethylase from Sorghum bicolor (L.) Moench has been cloned using a gene-specific probe generated using PCR primers designed from an internal 14 amino acid sequence. The sequence identifies sorghum obtusifoliol 14 alpha-demethylase as a cytochrome P450 and it is assigned to the CYP51 family together with the sterol 14 alpha-demethylases from fungi and mammals. The presence of highly conserved regions in the amino acid sequences, analogous substrates and the same metabolic role demonstrate that the sterol 14 alpha-demethylases are orthologous enzymes. The sterol 14 alpha-demethylases catalyse an essential step in sterol biosynthesis as evidenced by the absence of a 14 alpha-methyl group in all known functional sterols. A functional sorghum obtusifoliol 14 alpha-demethylase was expressed at high levels in Escherichia coli and purified using an efficient method based on temperature-induced Triton X-114 phase partitioning. The recombinant purified enzyme produced a type I spectrum with obtusifoliol as substrate. Reconstitution of purified recombinant enzyme with sorghum NADPH-cytochrome P450 reductase in dilaurylphosphatidylcholine micelles confirms that obtusifoliol 14 alpha-demethylase catalyses the 14 alpha-demethylation of obtusifoliol to 4 alpha-methyl-5 alpha-ergosta-8, 14,24(28)-trien-3 beta-ol as evidenced by GC-MS. The isolation of a cDNA clone encoding the plant sterol 14 alpha-demethylase, combined with the previously isolated cDNA clones for fungal and mammalian sterol 14 alpha-demethylases, provides an important tool in the rational design of specific inhibitors towards the individual sterol 14 alpha-demethylases.

Amino Acid Sequence↗

PubMed1997

MR imaging of the wrist in carpal tunnel syndrome.

PURPOSE: To determine whether specific parameters measured on MR images correlated to electrophysiological changes in carpal tunnel syndrome (CTS). MATERIAL AND METHODS: Prospective clinical examinations were made of 20 patients with suspected CTS. We performed bilateral electrophysiological examinations of the median nerve and bilateral MR imaging of the wrists. RESULTS: The electrophysiological examination suggested median nerve entrapment in 18 wrists. These wrists were compared to the remaining 22 electrophysiologically normal wrists. In addition, we compared both wrists in 12 patients with unilateral symptoms of CTS without reference to the electrophysiological findings. We found no difference in specific MR parameters between the 2 groups. CONCLUSION: Neither symptoms nor electrophysiological findings in CTS were related to specific MR parameters.

Carpal Bones↗

PubMed1997

Isolation and reconstitution of cytochrome P450ox and in vitro reconstitution of the entire biosynthetic pathway of the cyanogenic glucoside dhurrin from sorghum.

A cytochrome P450, designated P450ox, that catalyzes the conversion of (Z)-p-hydroxyphenylacetaldoxime (oxime) to p-hydroxymandelonitrile in the biosynthesis of the cyanogenic glucoside beta-D-glucopyranosyloxy-(S)-p-hydroxymandelonitrile (dhurrin), has been isolated from microsomes prepared from etiolated seedlings of sorghum (Sorghum bicolor L. Moench). P450ox was solubilized using nonionic detergents, and isolated by ion-exchange chromatography, Triton X-114 phase partitioning, and dye-column chromatography. P450ox has an apparent molecular mass of 55 kD, its N-terminal amino acid sequence is -ATTATPQLLGGSVP, and it contains the internal sequence MDRLVADLDRAAA. Reconstitution of P450ox with NADPH-P450 oxidoreductase in micelles of L-alpha-dilauroyl phosphatidylcholine identified P450ox as a multifunctional P450 catalyzing dehydration of (Z)-oxime to p-hydroxyphenylaceto-nitrile (nitrile) and C-hydroxylation of p-hydroxyphenylacetonitrile to nitrile. P450ox is extremely labile compared with the P450s previously isolated from sorghum. When P450ox is reconstituted in the presence of a soluble uridine diphosphate glucose glucosyltransferase, oxime is converted to dhurrin. In vitro reconstitution of the entire dhurrin biosynthetic pathway from tyrosine was accomplished by the insertion of CYP79 (tyrosine N-hydroxylase), P450ox, and NADPH-P450 oxidoreductase in lipid micelles in the presence of uridine diphosphate glucose glucosyltransferase. The catalysis of the conversion of Tyr into nitrile by two multifunctional P450s explains why all intermediates in this pathway except (Z)-oxime are channeled.

Amino Acid Sequence↗

PubMed1997

A clinical trial of dextromethorphan in amyotrophic lateral sclerosis.

INTRODUCTION: Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, excitotoxicity mediated by glutamate has been implicated. Dextromethorphan is a NMDA-glutamate receptor antagonist with neuroprotective properties. MATERIAL AND METHODS: The effect of treatment with dextromethorphan (150 mg daily) in ALS patients was evaluated in a randomized, double-blind, placebo-controlled study. Forty-five patients were included in the analysis. RESULTS: At the end of the treatment period, 12 months after randomization, 15 patients (65%) in the placebo group and 12 patients (55 %) in the dextromethorphan group were still alive (log rank test, P=0.49). Rates of disease progression, as expressed by rates of decline in pulmonary function and in functional disability, were similar in both groups except for a significantly less pronounced rate of decline in the ability scores for the lower extremities in the dextromethorphan group. CONCLUSION: Treatment with a relatively low dose of dextromethorphan did not result in an improvement in 12-month survival in ALS.

Adult↗

PubMed1997

Development of an ostomy competency.

Staff educators and staff nurses developed an ostomy competency, with the guidance and expertise of the advanced practitioner and enterostomal nurse at a large teaching hospital. The competency improved the quality of care for surgical ostomy patients. Care was standardized and staff nurses' clinical knowledge was enhanced. Following the sessions, staff nurses verbalized increased confidence in working with patients with ostomies and demonstrated increased autonomy and problem-solving abilities. No variances in educational aspects of care were noted on clinical pathways.

Clinical Competence↗

PubMed1996

Isolation and reconstitution of the heme-thiolate protein obtusifoliol 14alpha-demethylase from Sorghum bicolor (L.) Moench.

The heme-thiolate (cytochrome P450) enzyme which catalyzes the 14alpha-demethylation of obtusifoliol has been isolated from microsomes prepared from etiolated seedlings of Sorghum bicolor (L.) Moench. The obtusifoliol 14alpha-demethylase is a key enzyme in plant sterol biosynthesis and a target for the design of phyla-specific sterol 14alpha-demethylase inhibitors. Microsomal cytochrome P450s were solubilized by using the detergents Renex 690 and reduced Triton X-100, and the obtusifoliol 14alpha-demethylase was isolated by DEAE ion exchange and dye affinity column chromatography. The isolated enzyme has an absorption spectrum characteristic for low spin cytochrome P450s and produces a Type I binding spectrum with obtusifoliol as substrate. Binding spectra were not obtained with lanosterol, campesterol, sitosterol, or stigmasterol. Obtusifoliol 14alpha-demethylase has an apparent molecular mass of 53 kDa and is estimated to constitute approximately 20% of the total cytochrome P450 content of the microsomal membranes and about 0.2% of the total microsomal protein. Gas chromatography-mass spectrometry analysis of reconstitution experiments with dilauroylphosphatidylcholine micelles containing isolated obtusifoliol 14alpha-demethylase and sorghum NADPHcytochrome P450 oxidoreductase demonstrated the conversion of obtusifoliol (4alpha,14alpha-dimethyl-5alpha-ergosta-8, 24(28)-dien-3beta-ol) to 4alpha-methyl-5alpha-ergosta-8,14, 24(28)-trien3beta-ol, the 14alpha-demethylated product of obtusifoliol with a double bond introduced at the Delta14 position. The N-terminal amino acid sequence of the protein is MDLADIPQ/KQQRLMAGXALVV. Five internal sequences were obtained after endoproteinase Lys-C and Glu-C digestion. The fragment AAGAFSYISFGGGRH aligns with the unique heme binding domain of mammalian and yeast sterol 14alpha-demethylases which belong to the CYP51 family. Therefore it is conceivable that the obtusifoliol 14alpha-demethylase from plants also belongs to the CYP51 family, the only P450 family so far known to be conserved across the phyla.

Carbon Monoxide↗

PubMed1996

Why are most drowning victims men? Sex differences in aquatic skills and behaviors.

Men have higher drowning rates than women for most age groups. Data from a 1991 national household survey (n = 3042) on aquatic activities were used to examine hypotheses about differential drowning rates by sex. Men and women were compared by (1) exposure to aquatic environments; (2) frequency of aquatic activities involving or potentially involving, submersion; (3) swimming training and ability; (4) aquatic risk-taking behaviors; and (5) alcohol use on or near the water. Men had elevated risks for exposure, risk taking, and alcohol use. It was concluded that several factors contribute to their relatively high drowning rates, including a possible interaction between overestimation of abilities and heavy alcohol use.

Adolescent↗

PubMed1996

Parents and procedures: a randomized controlled trial.

INTRODUCTION: Previous work has shown that parents prefer to be present when their children undergo common invasive procedures, although physicians are ambivalent about parental presence. PURPOSE: To determine the effect of a parent-focused intervention on the pain and performance of the procedure, anxiety of parents and clinicians, and parental satisfaction with care. POPULATION: Children younger than 3 years old undergoing venipuncture, intravenous cannulation, or uretheral catheterization. SETTING: Pediatric emergency department of Boston City Hospital. DESIGN: Randomized controlled trial with three groups; parents present and given instructions on how to help their children; parents present, but no instructions given; and parents not present. INTERVENTION: The parents were instructed to touch, talk to, and maintain eye contact during the procedure. RESULTS: A total of 431 parents was randomized to the intervention (N = 153), present (N = 147), and not present (N = 131) groups. The groups were equivalent with respect to measured sociodemographic variables and parents' previous experience in the pediatric emergency department. No differences emerged with respect to pain (3-point scale measured by parent and clinician, and analysis of cry); performance of the procedure (number of attempts, completion of procedure by first clinician, time); clinician anxiety; or parental satisfaction with care. Parents who were present were more likely to rate the pain of the children as extreme/severe (52%) in comparison to clinicians (15%, kappa .07, poor agreement) and were significantly less anxious than parents who were not present. CONCLUSION: Overall, the intervention was not effective in reducing the pain of routine procedures. Parental presence did not negatively affect performance of the procedure or increase clinician anxiety. Parents who were present were less anxious than those who were not present. CLINICAL IMPLICATION: In general, parents have indicated that they want to be present when their children undergo procedures. The results of this study challenge the traditional belief that parental presence negatively affects our ability to successfully complete procedures. We should encourage parents who want to be present to stay during procedures.

Adult↗

PubMed1995

[Prevalence of risk factors in cerebral ischemia].

The prevalence of risk factors for ischaemic stroke is described in 270 patients with transient ischaemic attacks or ischaemic stroke. Smoking was the most common risk factor (46%) followed by hypertension (30%) and increased levels of serum cholesterol (26%). Diabetes mellitus, atrial fibrillation and earlier myocardial infarction were less common risk factors. Ninety-one patients (34%) had two or more risk factors. In conclusion, vascular risk factors are frequently present in patients with transient ischaemic attacks or ischaemic stroke. It is still not yet clarified if risk factor modification is of any value in prevention of stroke recurrence.

Aged↗

PubMed1995

Gene expression of urea cycle enzymes following two-thirds partial hepatectomy in the rat.

The effect of reduction of functional liver mass on the expression of enzyme systems for hepatic urea synthesis was assessed in rats following two-thirds partial hepatectomy. Results were related to normal, fed rats and to sham-operated rats, with identical timing for surgery and feeding. Among the five urea cycle enzymes the mRNA steady-state level was higher in hepatectomized than in sham-operated rats for carbamoyl phosphate synthetase and arginino-succinate lyase. The level for albumin mRNA remained close to that of the controls. Relative transcription rates were found to be increased for carbamoyl phosphate synthetase, arginino-succinate synthase and arginase. For albumin the transcription rate was drastically reduced initially, but recovered gradually during the experimental period. The data indicate that the expression of urea cycle enzymes, in particular that of carbamoyl phosphate synthetase which is the rate-limiting step, is up-regulated by partial hepatectomy. This helps to maintain urea synthesis rate at a normal or near normal level during the period of reduced liver mass, confirming metabolic studies. In contrast, the transcription for albumin was reduced. The immediate increase in urea cycle enzyme expression during the period of acute hepatocyte loss is consistent with the view that it is vitally important that urea synthesis, in contrast to e.g. albumin synthesis, remains intact when the metabolic capacity of the liver is reduced.

Albumins↗

PubMed1994

[Symptomatic treatment of amyotrophic lateral sclerosis].

During a twelve year period 58 patients with motor neurone disease were admitted to the Department of Neurology, Odense University Hospital. The medical records were reviewed and different aspects of symptomatic treatment for these patients were recorded retrospectively. After the first admission 55% of the patients received out-patient treatment, while 31% had no further contact to the Department of Neurology. Forty-nine patients developed bulbar symptoms. Of these patients 41% were referred to a laryngologist, 27% were referred to a speech therapist and 10% to a nutritionist. Seven patients had a gastrostomy, while feeding tube was used by at least six patients. At the time of follow up 49 patients had died, 63% in hospital. At least 22 patients were treated with morphine in the last period of their lives. In order to improve the symptomatic treatment in motor neurone disease we suggest that these patients are treated at the neurological departments by interdisciplinary teams with particular interest in motor neurone disease.

Adult↗