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Biomedical subjects

M Eriksson

Publications and source records attributed to M Eriksson.

At least 163 records · Page 9Linked to original sources
PubMed1997

Carbon dioxide and light regulation of promoters controlling the expression of mitochondrial carbonic anhydrase in Chlamydomonas reinhardtii.

Nuclear genes coding for carbonic anhydrase, a major mitochondrial constituent in Chlamydomonas reinhardtii grown under limited CO2, were characterized. Two genes, ca1 and ca2, were found within 7 kb of genomic DNA, organized 'head to head' in a large inverted repeat. The DNA sequences for the two genes were very similar, even in the promoter regions and in introns, indicating that the repeat is a result of a recent duplication. To study gene regulation, elements from the upstream region of ca1 were fused to the arylsulphatase reporter gene. After transformation, the expression of arylsulphatase was regulated similarly to the endogenous ca1/ca2 genes, even when the promoter was trimmed down to 194 nt. Expression could not be detected when 5% CO2 was bubbled into the growth medium, but was induced within hours after transfer to air. The ca1 promoter was not induced in low light, but at intermediate light levels its activity was dependent on the irradiance. O2 concentration had no effect on the promoter activity, indicating that photorespiratory metabolites are not triggering the response. The availability of cells transformed with a CO2-regulated reporter gene should facilitate further studies on the metabolic adaptations that occur in some green algae in response to the external CO2 level.

Animals↗
PubMed1997

Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding.

BACKGROUND: Ribonucleotide reductase (RNR) is an essential enzyme in DNA synthesis, catalyzing all de novo synthesis of deoxyribonucleotides. The enzyme comprises two dimers, termed R1 and R2, and contains the redox active cysteine residues, Cys462 and Cys225. The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals. The pathway for the radical has previously been suggested from crystallographic results, and is supported by site-directed mutagenesis studies. Most RNRs are allosterically regulated through two different nucleotide-binding sites: one site controls general activity and the other controls substrate specificity. Our aim has been to crystallographically demonstrate substrate binding and to locate the two effector-binding sites. RESULTS: We report here the first crystal structure of RNR R1 in a reduced form. The structure shows that upon reduction of the redox active cysteines, the sulfur atom of Cys462 becomes deeply buried. The more accessible Cys225 moves to the former position of Cys462 making room for the substrate. In addition, the structures of R1 in complexes with effector, effector analog and effector plus substrate provide information about these binding sites. The substrate GDP binds in a cleft between two domains with its beta-phosphate bound to the N termini of two helices; the ribose forms hydrogen bonds to conserved residues. Binding of dTTP at the allosteric substrate specificity site stabilizes three loops close to the dimer interface and the active site, whereas the general allosteric binding site is positioned far from the active site. CONCLUSIONS: Binding of substrate at the active site of the enzyme is structurally regulated in two ways: binding of the correct substrate is regulated by the binding of allosteric effectors and binding of the actual substrate occurs primarily when the active-site cysteines are reduced. One of the loops stabilized upon binding of dTTP participates in the formation of the substrate-binding site through direct interaction with the nucleotide base. The general allosteric effector site, located far from the active site, appears to regulate subunit interactions within the holoenzyme.

Allosteric Regulation↗
PubMed1997

Status of MAX II.

A new third-generation VUV synchrotron radiation ring called MAX II has just been built and commissioned in Lund, Sweden. Owing to tight boundary conditions regarding economy, space and manpower some novel techniques have been used in the design of the ring. The present status of the ring as well as the motivation for the parameter choices and techniques chosen are presented.

Journal Article↗
PubMed1997

Brilliance--an overview.

One of the most important figures of merit for third-generation sources is the brilliance. An intuitive physical picture of the diffraction properties of synchrotron radiation is presented in this paper. The consequences of these diffraction properties on the design of third-generation light sources is also discussed.

Journal Article↗
PubMed1997

Lipoprotein(a) as a determinant of coronary heart disease in young women.

BACKGROUND: Lipoprotein(a) [Lp(a)] appears to be a risk factor for coronary heart disease (CHD) in men. The role of Lp(a) in women, however, is less clear. METHODS AND RESULTS: We examined the ability of Lp(a) to predict CHD in a population-based case-control study of women 65 years of age or younger who lived in the greater Stockholm area. Subjects were all patients hospitalized for an acute CHD event between February 1991 and February 1994. Control subjects were randomly selected from the city census and were matched to patients by age and catchment area. Lp(a) was measured 3 months after hospitalization by use of an immunoturbidometric method (Incstar) calibrated to the Northwest Lipid Research Laboratories (coefficient of variation was < 9%). Of the 292 consecutive patients, 110 (37%) were hospitalized for an acute myocardial infarction, and 182 were hospitalized (63%) for angina pectoris. The mean age for both patients and control subjects was 56 +/- 7 years. Of participants, 74 patients (25%) and 84 control subjects (29%) were premenopausal. The distributions of Lp(a) were highly skewed in both patients and control subjects, with a range from 0.001 to 1.14 g/L. Age-adjusted odds ratio for CHD in the highest versus the lowest quartile of Lp(a) was 2.3 (95% confidence interval [CI], 1.4 to 3.7). After adjustment for age, smoking, education, body mass index, systolic blood pressure, total cholesterol, triglycerides, and HDL, the odds ratio was 2.9 (95% CI, 1.6 to 5.0). The odds ratios were similar when myocardial infarction and angina patients were compared with their respective control subjects. The odds ratios were 5.1 (95% CI, 1.4 to 18.4) and 2.4 (95% CI, 1.3 to 4.5) in premenopausal and postmenopausal women, respectively. CONCLUSIONS: These results suggest that Lp(a) is a determinant of CHD in both premenopausal and postmenopausal women.

Adult↗
PubMed1997

Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects.

The clinical reliability of measuring cholecystokinin (CCK) peptides in the cerebrospinal fluid (CSF) has not been fully elucidated. Therefore, we have assayed CCK-8S and CCK-4 in CSF obtained from 14 healthy male subjects, lumbar-punctured at the L4-5 level following a strictly standardised procedure. CSF concentrations of free CCK-8S and free CCK-4 were used as dependent variables while age, height, body weight, atmospheric pressure and some other factors served as independent variables. It was shown that the CCK-8S ratio between the second (7-12 ml) and first (0-6 ml) CSF fractions, correlated significantly with the atmosphere pressure at the time of puncture. Neither CCK-8S nor CCK-4 displayed concentration gradients in CSF. The CCK-4 levels, expressed as pmol l-1 in the total amount of CSF were found to be positively correlated with the neuraxis distance in the lying position and negatively with the neuraxis distance in the sitting position. Furthermore, CCK-4, expressed as pmol l-1 per min of tapping-time (pmol l-1 min-1), showed a negative correlation with storage time, presumably mirroring a proteolytic process. CCK-8S and CCK-4 intercorrelated positively independently of whether expressed as pmol l-1 or pmol l-1 min-1. In conclusion, the results of this exploratory study indicate that the neuraxis distance (in the sitting and lying positions) and storage-time have to be accounted for when interpreting data on CSF levels of CCK-4. Attention has to be paid to the potential influence of atmospheric pressure on the concentration ratio of CCK-8S.

Adult↗
PubMed1997

Early or late bath during the first stage of labour: a randomised study of 200 women.

OBJECTIVE: To compare obstetric outcome after a bath offered to women on two different occasions during the first stage of labour. The aim of the study was to determine whether an early bath affected the progress of labour and the use of analgesia when compared with a late bath during the first stage of labour. DESIGN: A randomised prospective pilot-study. SETTING: The delivery ward at Ostra Hospital in Göteborg. PARTICIPANTS: Two hundred women, at low obstetric risk. INTERVENTIONS: The women were randomised to either the 'early bath group' or the 'late bath group'. The women in the 'early bath group' had a bath before a cervical dilatation of 5 cm, while the women in the 'late bath group' had a bath after the cervix was 5 cm dilated. MEASUREMENTS AND FINDINGS: The women in the 'early bath group' had a longer time period from established labour to delivery (9.8 hours) compared to the 'late bath group' (8.5 hours) (p < 0.004). A higher proportion of women in the 'early bath group' needed oxytocin administration (57%) compared to the 'late bath group' (30%) (p < 0.01). Epidural analgesia was used by 27% of the women in the 'early bath group' and by 9% in the 'late bath group' (p < 0.001). One baby in the 'early bath group' had clinical signs of infection and required antibiotic treatment. No cases of amnionitis or endometritis were present in the women. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The findings suggest that a bath during the first stage of labour should preferably be used after a cervical dilatation of 5 cm to avoid prolonged labour, and an increased use of oxytocin and epidural analgesia.

Adult↗
PubMed1997

Homologous and heterologous protein import into mitochondria isolated from the green alga Chlamydomonas reinhardtii.

We have established a homologous system for studying mitochondrial protein import in Chlamydomonas reinhardtii, using C. reinhardtii precursor proteins and mitochondria isolated from C. reinhardtii. The precursors of the F1 alpha ATP synthase subunit and the Rieske FeS protein were imported into mitochondria with high efficiency, while the F1 beta subunit precursor was imported with much lower efficiency. The import of heterologous precursor proteins from higher plants was also less efficient. The precursor of the C. reinhardtii PsaF chloroplast protein was converted into a protease-protected form upon incubation with mitochondria. In vitro processing studies revealed that in contrast to the situation in higher plants, the processing of the precursors was catalysed by a soluble, matrix-located peptidase.

Animals↗
PubMed1997

Angioid streaks are part of a familial syndrome of dyserythropoietic anaemia (CDA III).

Congenital dyserythropoietic anaemia type III (CDA III) is a rare disease inherited in an autosomal dominant way and characterized by mild to moderate haemolytic anaemia. Most patients are adapted to their disease and have no or few complaints. Bone marrow examination shows a characteristic picture with erythroid hyperplasia and multinucleate erythroblasts. 20% of patients in a Swedish family affected with the CDA III condition have monoclonal gammopathy or multiple myeloma. By linkage and recombination analysis in the same family, the gene linked to the CDA III condition (CDAN3) has been located to chromosome 15q22. In this paper we report the observation of visual disturbances with macular degeneration and angioid streaks in six patients with CDA III and discuss the apparent association between CDA III, angioid streaks and monoclonal gammopathy. We suggest that this triad forms a previously unreported syndrome.

Adult↗
PubMed1997

Low-density lipoprotein metabolism and its association to plasma lipoprotein(a) in the nephrotic syndrome.

Patients with nephrotic syndrome have multiple abnormalities of lipoprotein metabolism, but the cause and exact nature of these abnormalities have not been established. In the present study we have determined the kinetics of plasma low-density lipoprotein (LDL) apoB in seven nephrotic patients demonstrating an elevated LDL apoB production rate (25.7 +/- 6.4 vs. 13.1 +/- 0.3 mgkg-1 day-1; P < 0.001) but a normal LDL apoB fractional catabolic rate (FCR) (0.31 +/- 0.04 vs. 0.33 +/- 0.008 pools day-1; NS) compared with 41 healthy control subjects. However, two out of the seven patients had a markedly low LDL apoB-FCR. Serum albumin was inversely correlated with the LDL apoB production rate (R = -0.82; P < 0.05). Plasma lipoprotein (a) [Lp(a)] levels were significantly (P < 0.001) increased in the nephrotic patients compared with control subjects. Significant correlations were observed between log Lp(a) and LDL apoB production rate (R = 0.90; P < 0.01), VLDL-cholesterol (R = 0.95; P < 0.001) and VLDL-triglycerides (R = 0.80; P < 0.05) respectively. In summary, the present study suggests that nephrotic hyperlipidaemia may be caused by at least two independent mechanisms. The elevated LDL apoB production rate is highly correlated with the prevailing levels of serum albumin, whereas some nephrotic patients seem to have a decreased LDL apoB clearance, suggesting impaired LDL receptor-mediated clearance. The present results also suggest that the elevated plasma Lp(a) levels in nephrosis are related to an increased hepatic synthesis rather than a decreased catabolism of lipoproteins.

Adolescent↗
PubMed1997

Effect of lignocaine and pH on propofol-induced pain.

Propofol has the disadvantage of pain on injection. A higher partition of propofol in the aqueous phase of the preparation causes a higher incidence of pain on injection while addition of 1% lignocaine to propofol reduces pain. The low concentration of this local anaesthetic and the rapid pain relief observed indicates that mechanisms other than local anaesthesia are involved, that is change in pH. We performed a clinical study to investigate the influence of lignocaine and pH on pain during injection of 1% Diprivan. Ten parts of 1% Diprivan were mixed with one part of saline, 1% lignocaine or hydrochloric acid to achieve the same pH as that after addition of lignocaine. Diprivan 1% mixed with 1% lignocaine and with hydrochloric acid gave mean pain ratings (1-10) of 0.32 (SD 0.75) (n = 25) and 0.88 (1.30) (n = 24), respectively. These ratings were significantly lower than ratings after injection of a saline-Diprivan mixture (2.18 (2.06), n = 22). The pH of the 1% Diprivan formulation decreased after mixing with 1% lignocaine. The concentration of propofol in the aqueous phase was lower when 1% Diprivan was mixed with 1% lignocaine (0.376 g litre-1) or HCl (0.392 g litre-1) compared with 1% Diprivan and saline (0.476 g litre-1) mixed in the same proportion. Thus pH changes may modify propofol-induced pain on injection by a mechanism different from the effect of the local anaesthetic on the vascular endothelium. Our findings may explain why lignocaine mixed with propofol causes less pain than injection of lignocaine followed by propofol.

Adolescent↗
PubMed1997

Vitamin A exerts potential therapeutic effects in the endotoxaemic pig.

BACKGROUND: Pretreatment with an injection of vitamin A has beneficial effects on cardiac and pulmonary functions in normally bred endotoxaemic pigs. The present study was performed in order to elucidate whether the response of an ongoing infusion of E. coli can be modulated by a single injection of vitamin A. METHODS: Sixteen healthy (not vitamin A-depleted) pigs were anaesthetized, monitored, mechanically ventilated and subjected to an infusion of E. coli endotoxin (10 micrograms.kg-1.h-1). This infusion resulted within 30 min in a progressive haemodynamic derangement. When the mean pressure in the pulmonary artery was twice the baseline value, vitamin A (460 IU.kg-1) or a corresponding volume of vehicle was injected intravenously. After sacrificing the animals, the right lung was excised and weighed, and biopsy specimens were taken from the left lung for microscopical examination. RESULTS: Mean arterial blood pressure was significantly less affected (P < 0.01) between the 1st and 6th hour in endotoxaemic pigs treated with vitamin A than in those given vehicle. The mean lung weight in the vitamin A-treated pigs was significantly lower than that in the vehicle group (164 +/- 5.3 vs 199 +/- 19.8 g; P < 0.01). Microscopical examination showed significantly less oedema (0.93 +/- 0.17 vs 2.00 +/- 0.26; P < 0.01) and microatelectasis (0.56 +/- 0.17 vs 1.75 +/- 0.31; P < 0.01) in the vitamin A group. Endotoxaemia was also accompanied by an initial, steep decline in neutrophil counts in all animals; this decrease was significantly less pronounced (P < 0.05) in vitamin A-injected pigs than in the vehicle-injected group. The major difference was a more rapid restitution in the vitamin A group. CONCLUSION: Several manifestations of endotoxaemia were expressed less in the vitamin A group. Thus, vitamin A may turn out to be a tool in the management of endotoxaemia.

Animals↗
PubMed1997

Analgesia in newborns given oral glucose.

There is evidence that newborn babies feel pain even at the lowest gestational ages when they can survive. Because sweet solutions such as sucrose, given orally, may relieve pain in neonates, we decided to compare the effects of two concentrations of glucose (normally used for intravenous infusions) and of breast milk in a randomized controlled trial in 120 babies requiring heel-prick tests. Glucose solutions and breast milk are readily available in the neonatal department. No other treatment was given. Our results strongly suggest that 1 ml of a 30% glucose solution given orally alleviates mild pain significantly and can be used for this purpose in newborns. Breast milk and 10% glucose did not have a similar effect.

Administration, Oral↗