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Biomedical subjects

L Olsson

Publications and source records attributed to L Olsson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Reduction of postoperative morbidity and mortality in patients with rectal cancer following the introduction of a colorectal unit.

BACKGROUND: Surgery for rectal cancer is associated with high morbidity and mortality rates. The reason for this has been much debated. This population-based study reports the findings on postoperative morbidity and mortality after rectal cancer surgery following the introduction of a centralized colorectal unit in a county central hospital, supervised by a colorectal surgeon using the most recent techniques. METHODS: All consecutive patients with rectal cancer who underwent surgery at four county hospitals in the Västmanland county in Sweden during 1993-1996 (n = 133) were compared with patients who underwent surgery at the new colorectal unit in the county central hospital from 1996 to 1999 (n = 144). RESULTS: The number of operating surgeons was reduced from 26 to four. The postoperative mortality rate decreased from 8 to 1 per cent (P = 0.002) and the total postoperative complication rate was reduced from 57 to 24 per cent (P < 0.001). Surgical complications dropped from 37 to 11 per cent (P < 0.001). The relaparotomy rate fell from 11 to 4 per cent (P < 0.05). Postoperative stay in hospital was reduced from a median of 13 to 9 days (P < 0.001). CONCLUSION: The new organization, with centralized rectal cancer surgery using modern techniques, reduced postoperative mortality and overall morbidity rates to less than half.

Adult↗
PubMed2001

The impact of GAL6, GAL80, and MIG1 on glucose control of the GAL system in Saccharomyces cerevisiae.

The role of the proteins encoded by the GAL80 gene, the MIG1 gene and the GAL6 gene in glucose control of galactose consumption by Saccharomyces cerevisiae was studied by physiological characterisation of various GAL mutant strains. Dynamic experiments with the CEN.PK 113-7D wild-type strain and a deltagal80deltamig1 double-mutant strain in aerobic nitrogen-limited continuous cultivations at a dilution rate of 0.1 h(-1), showed simultaneous glucose and galactose consumption by the deltagal80deltamig1 strain. The wild-type strain did not consume galactose in the presence of glucose. Aerobic batch cultivations on glucose-galactose mixtures with the wild-type strain and with recombinant strains with a de-regulated GAL system (the deltagal80deltamig1 strain, a deltagal6 deleted strain, a deltagal6deltagal80deltamig1 triple mutant, and a deltagal6deltagal80deltamig1 triple mutant harbouring a GAL4 high-copy vector) were carried out. Generally, a reduction of glucose control lowered the maximum specific growth rate on glucose and increased the ethanol yield obtained on galactose with more than 100%. In contrast to the wild-type strain, the deltagal6deltagal80deltamig1 triple mutant strain consumed glucose and galactose simultaneously, and this strain also showed the highest ethanol production with an overall ethanol yield of 0.35 g g-1 sugar, which is 17% higher than the yield on glucose obtained with the wild-type strain. GAL80 and MIG1 were demonstrated to be responsible for the majority of the glucose control on the GAL system, whereas GAL6 has a minor role in glucose control. Deletion of GAL6 was shown to have a major impact on biomass and ethanol formation when cells were grown on galactose, and from the data obtained we speculate that Gal6 may be involved in mRNA degradation of the GAL gene transcripts.

Culture Media↗
PubMed2001

Ability for anaerobic growth is not sufficient for development of the petite phenotype in Saccharomyces kluyveri.

Saccharomyces cerevisiae is a petite-phenotype-positive ("petite-positive") yeast, which can successfully grow in the absence of oxygen. On the other hand, Kluyveromyces lactis as well as many other yeasts are petite negative and cannot grow anaerobically. In this paper, we show that Saccharomyces kluyveri can grow under anaerobic conditions, but while it can generate respiration-deficient mutants, it cannot generate true petite mutants. From a phylogenetic point of view, S. kluyveri is apparently more closely related to S. cerevisiae than to K. lactis. These observations suggest that the progenitor of the modern Saccharomyces and Kluyveromyces yeasts, as well as other related genera, was a petite-negative and aerobic yeast. Upon separation of the K. lactis and S. kluyveri-S. cerevisiae lineages, the latter developed the ability to grow anaerobically. However, while the S. kluyveri lineage has remained petite negative, the lineage leading to the modern Saccharomyces sensu stricto and sensu lato yeasts has developed the petite-positive characteristic.

Anaerobiosis↗
PubMed2000

The role of metabolic engineering in the improvement of Saccharomyces cerevisiae: utilization of industrial media.

Metabolic engineering has become a very important approach to strain improvement in parallel with classical strain development. Although Saccharomyces cerevisiae has been domesticated for ethanol and bread production, there are still some fundamental problems associated with its industrial use. The industrially used carbon sources often consist of a sugar mixture, and due to glucose repression these sugars are utilized sequentially, resulting in prolonged production time. In this article we discuss the application of metabolic engineering for construction of glucose-derepressed strains and specify advantages as well as difficulties associated with this approach.

Journal Article↗
PubMed2000

Physiological studies in aerobic batch cultivations of Saccharomyces cerevisiae strains harboring the MEL1 gene.

Physiological studies of Saccharomyces cerevisiae strains harboring the MEL1 gene were carried out in aerobic batch cultivations on glucose-galactose mixtures and on the disaccharide melibiose, which is hydrolyzed by the enzyme melibiase (Mel1, EC 3.2.1.22) into a glucose and a galactose moiety. The strains examined (T200, T256, M24, and TH1) were all derived from the bakers' and distillers' strain of S. cerevisiae, DGI 342. All the strains showed a significant higher ethanol yield when growing on glucose, and half the biomass yield, compared with growth on galactose. The maximum specific uptake rates were 2.5-3.3-fold higher on glucose than on galactose for all the strains examined, and hence, ethanol production was pronounced on glucose due to respiro-fermentative metabolism. The T256 strain and the T200 strain having the MEL1 gene inserted in the HXK2 locus and the LEU2 locus, respectively, hydrolyzed melibiose with low specific hydrolysis rates of 0.03 C-mol/g/h and 0.04 C-mol/g/h, respectively. This resulted in high biomass yields on melibiose in the order of 10 g/C-mol compared with 3.7 g/C-mol for M24 and 1.6 g/C-mol for TH1. The M24 strain, constructed by classical breeding, and the mig1/gal80 disrupted and melibiase-producing strain TH1, were superior in their ability to hydrolyze melibiose into glucose and galactose showing specific melibiose hydrolysis rates of 0.17 C-mol/g/h and 0.24 C-mol/g/h, respectively. Hence, high ethanol yields on melibiose were obtained with these two strains. Growth on the glucose-galactose mixtures showed a reduction of glucose control successfully obtained in the M24 strain and the TH1 strain.

Aerobiosis↗
PubMed2000

Simultaneous overexpression of enzymes of the lower part of glycolysis can enhance the fermentative capacity of Saccharomyces cerevisiae.

Recombinant S. cerevisiae strains, with elevated levels of the enzymes of lower glycolysis (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase, phosphoglycerate kinase, enolase, pyruvate kinase, pyruvate decarboxylase and alcohol dehydrogenase) were physiologically characterized. During growth on glucose the enzyme levels in the recombinant strains (YHM4 and YHM7) were 1.1-3.4-fold higher than in the host strain (CEN.PK.K45). The recombinant strains were grown in aerobic or anaerobic batch cultures on glucose or a mixture of glucose and galactose. The specific ethanol production rates in the recombinant strains were the same as for the host strain and the physiological behaviour of the recombinant strains and the host strain was similar. When the cellular demand for ATP was increased by means of glucose pulses (final concentrations of 3.9 g/l or 2.0 g/l, respectively) to aerobic chemostat cultures maintained at a dilution rate of 0.08/h, the specific carbon dioxide production rate (qCO(2)) of CEN.PK.K45 accelerated at 6x10(-3) mmol/g/min(2) during the first 15 min, whereas during the same time period the qCO(2) of YHM7 accelerated twice as fast at 12x10(-3) mmol/g/min(2), indicating a higher fermentative capacity in the recombinant strain.

Aerobiosis↗
PubMed2000

Increasing galactose consumption by Saccharomyces cerevisiae through metabolic engineering of the GAL gene regulatory network.

Increasing the flux through central carbon metabolism is difficult because of rigidity in regulatory structures, at both the genetic and the enzymatic levels. Here we describe metabolic engineering of a regulatory network to obtain a balanced increase in the activity of all the enzymes in the pathway, and ultimately, increasing metabolic flux through the pathway of interest. By manipulating the GAL gene regulatory network of Saccharomyces cerevisiae, which is a tightly regulated system, we produced prototroph mutant strains, which increased the flux through the galactose utilization pathway by eliminating three known negative regulators of the GAL system: Gal6, Gal80, and Mig1. This led to a 41% increase in flux through the galactose utilization pathway compared with the wild-type strain. This is of significant interest within the field of biotechnology since galactose is present in many industrial media. The improved galactose consumption of the gal mutants did not favor biomass formation, but rather caused excessive respiro-fermentative metabolism, with the ethanol production rate increasing linearly with glycolytic flux.

Bacterial Proteins↗
PubMed2000

Metabolic engineering of Saccharomyces cerevisiae.

Comprehensive knowledge regarding Saccharomyces cerevisiae has accumulated over time, and today S. cerevisiae serves as a widley used biotechnological production organism as well as a eukaryotic model system. The high transformation efficiency, in addition to the availability of the complete yeast genome sequence, has facilitated genetic manipulation of this microorganism, and new approaches are constantly being taken to metabolicially engineer this organism in order to suit specific needs. In this paper, strategies and concepts for metabolic engineering are discussed and several examples based upon selected studies involving S. cerevisiae are reviewed. The many different studies of metabolic engineering using this organism illustrate all the categories of this multidisciplinary field: extension of substrate range, improvements of producitivity and yield, elimination of byproduct formation, improvement of process performance, improvements of cellular properties, and extension of product range including heterologous protein production.

Biotechnology↗
PubMed1999

Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site.

Applying a homology search method previously described, we identified a sequence in the extracellular dimerization site of the erythropoietin receptor, distant from the hormone binding site. A peptide identical to that sequence was synthesized. Remarkably, it activated receptor signaling in the absence of erythropoietin. Neither the peptide nor the hormone altered the affinity of the other for the receptor; thus, the peptide does not bind to the hormone binding site. The combined activation of signal transduction by hormone and peptide was strongly synergistic. In mice, the peptide acted like the hormone, protecting against the decrease in hematocrit caused by carboplatin.

Animals↗
PubMed1999

Derepression of galactose metabolism in melibiase producing bakers' and distillers' yeast.

Beet molasses is widely used as a growth substrate for bakers' and distillers' yeast in the production of biomass and ethanol. Most commercial yeasts do not fully utilise the carbohydrates in molasses since they are incapable of hydrolysing the disaccharide melibiose to glucose and galactose. Also, expression of genes encoding enzymes for the utilisation of carbon sources that are alternatives to glucose is tightly regulated, sometimes rates of yeast growth and/or ethanol production. The GAL genes are regulated by specific induction by galactose and repression during growth on glucose. In an industrial distillers' yeast, two genes interacting synergistically in glucose repression of galactose utilization, MIG1 and GAL80, have been disrupted with MEL1, encoding melibiase. The physiology of the wild-type strain and the recombinant strains was investigated on mixtures of glucose and galactose and on molasses. The recombinant strain started to ferment galactose when 9.7 g 1(-1) glucose was still present during a batch fermentation, whereas the wild-type strain did not consume any galactose in the presence of glucose. The ethanol yield in the recombinant strain was 0.50 g ethanol g sugar (-1) in an ethanol fermentation on molasses, compared with 0.48 g ethanol g sugar (-1) for the wild-type strain. The increased ethanol yield was due to utilization of melibiose in the molasses.

Culture Media↗
PubMed1999

Investigation of the impact of MIG1 and MIG2 on the physiology of Saccharomyces cerevisiae.

The gene functions of MIG1 and MIG2 are well known for their role in glucose control in Saccharomyces cerevisiae. A prototrophic mig1 disruptant (T468) and mig1mig2 double disruptant (T475) as well as their congenic wild-type strain (CEN.PK 113-7D) were analysed for changes in their peripheral metabolism (batch cultivations on sugar mixtures) and central metabolism (batch and continuous cultivations as well as acceleratostats). Sucrose metabolism was alleviated of glucose control in the mig1 disruptant, and even more so in the mig1mig2 disruptant compared with their wild-type strain. The lag phase in a batch cultivation grown on a glucose-galactose mixture was reduced by 50% in either disruptant, i.e. additional disruption of MIG2 in a mig1 background did not further alleviate galactose metabolism from glucose control. In contrast, both disruptants exhibited a more stringent glucose control of maltose metabolism compared with the wild-type strain. Growing on glucose, the mig1mig2 double disruptant exhibited a 12% higher specific growth rate than the wild-type strain, as well as a significantly higher respiratory capacity.

Culture Media↗
PubMed1998

Access to tetrachlorophthalimide-protected ethyl 2-amino-2-deoxy-1-thio-beta-D-glucopyranosides.

Ethyl 2-deoxy-2-tetrachlorophthalimido-1-thio-beta-D-glucopyranoside (7) was prepared from glucosamine hydrochloride in four steps with a 20-25% overall yield. Formation of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-tetrachlorophthalimido-beta-D- glucopyranoside (5) was found to be crucial for this reaction sequence since the corresponding alpha-1-acetate did not react in Lewis-acid-catalyzed ethylthio glycosidations. Formation of the beta-1-acetate (5) was achieved by treatment of 3,4,6-tri-O-acetyl-2-deoxy-2-tetrachlorophthalimido-alpha-D-glucop yranosyl bromide (4) with acetic acid under silver zeolite promotion. This was necessary because conditions normally used for beta-1-acetate formation were not tolerated by the tetrachlorophthalimido (TCP) group.

Carbohydrate Sequence↗
PubMed1998

Cleanup and analysis of sugar phosphates in biological extracts by using solid-phase extraction and anion-exchange chromatography with pulsed amperometric detection.

A cleanup method based on anion-exchange solid-phase extraction (SPE) was developed to render biological extracts suitable for the analysis of hexose phosphates with a modified anion-exchange chromatography method and pulsed amperometric detection. The method was applied to cell extracts of Saccharomyces cerevisiae obtained by using cold methanol as quenching agent and chloroform as extraction solvent. It was shown that pretreatment of the cell extract with SPE markedly improved the quality of the liquid chromatography analysis with recoveries of the sugar phosphates close to 100%. Furthermore, the method allowed for sample enrichment and the original extraction procedure could be simplified by implementing SPE early in the extraction protocol.

Cell Fractionation↗
PubMed1998

Carbon catabolite repression of invertase during batch cultivations of Saccharomyces cerevisiae: the role of glucose, fructose, and mannose.

When Saccharomyces cerevisiae are grown on a mixture of glucose and another fermentable sugar such as sucrose, maltose or galactose, the metabolism is diauxic, i.e. glucose is metabolized first, whereas the other sugars are metabolized when glucose is exhausted. This phenomenon is a consequence of glucose repression, or more generally, catabolite repression. Besides glucose, the hexoses fructose and mannose are generally also believed to trigger catabolite repression. In this study, batch fermentations of S. cerevisiae in mixtures of sucrose and either glucose, fructose or mannose were performed. It was found that the utilization of sucrose is inhibited by concentrations of either glucose or fructose higher than 5 g/l, and thus that glucose and fructose are equally capable of exerting catabolite repression. However, sucrose was found to be hydrolyzed to glucose and fructose, even when the mannose concentration was as high as 17 g/l, indicating, that mannose is not a repressing sugar. It is suggested that the capability to trigger catabolite repression is connected to hexokinase PII, which is involved in the in vivo phosphorylation of glucose and fructose.

Biomass↗
PubMed1997

A peptide derived from an extracellular domain selectively inhibits receptor internalization: target sequences on insulin and insulin-like growth factor 1 receptors.

Certain peptides derived from the alpha1 domain of the major histocompatibility class I antigen complex (MHC-I) inhibit receptor internalization, increasing the steady-state number of active receptors on the cell surface and thereby enhancing the sensitivity to hormones and other agonists. These peptides self-assemble, and they also bind to MHC-I at the same site from which they are derived, suggesting that they could bind to receptor sites with significant sequence similarity. Receptors affected by MHC-I peptides do, indeed, have such sequence similarity, as illustrated here by insulin receptor (IR) and insulin-like growth factor-1 receptor. A synthetic peptide with sequence identical to a certain extracellular receptor domain binds to that receptor in a ligand-dependent manner and inhibits receptor internalization. Moreover, each such peptide is selective for its cognate receptor. An antibody to the IR peptide not only binds to IR and competes with the peptide but also inhibits insulin-dependent internalization of IR. These observations, and binding studies with deletion mutants of IR, indicate that the sequence QILKELEESSF encoded by exon 10 plays a key role in IR internalization. Our results illustrate a principle for identifying receptor-specific sites of importance for receptor internalization, and for enhancing sensitivity to hormones and other agonists.

Adipocytes↗
PubMed1997

Silencing MIG1 in Saccharomyces cerevisiae: effects of antisense MIG1 expression and MIG1 gene disruption.

Silencing of MIG1, a transcription factor imposing carbon catabolite repression on invertase, was attempted, either by disrupting the gene or by expressing antisense copies of the gene. The performance of the recombinant strains in bioreactor batch cultivations on sucrose, in the presence of glucose, was compared with that of the wild-type strain under the same conditions. In the delta migI strain, the rate of sucrose utilization was independent (10 mmol/g/h) of the glucose concentration. During the cultivations with the wild-type strain and the antisense strains, two distinct phases were observed. The rates of sucrose hydrolysis were < 1 mmol/g/h and 9 to 10 mmol/g/h in the first and second phases, respectively. Entry into the second cultivation phase was characterized by a decline in glucose concentration below 12 mmol/liter. As expected, disruption of MIG1 resulted in a relief of glucose repression. However, silencing of MIG1 expression was not achieved by expressing antisense MIG1, even though antisense MIG1 RNA was sufficiently stable to be detected. In the wild-type and delta migI strains, the specific growth rate was 0.32 to 0.33 h-1, whereas it was lower in the antisense strains, 0.25 to 0.30 h-1.

Base Sequence↗