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Biomedical subjects

A Sundqvist

Publications and source records attributed to A Sundqvist.

At least 19 recordsLinked to original sources
PubMed2001

Functional knockout of the corepressor CtBP by the second exon of adenovirus E1a relieves repression of transcription.

The C-terminal binding protein (CtBP) acts as a transcriptional corepressor upon recruitment to transcriptional regulators. In contrast, interaction between CtBP and the adenovirus E1A protein is required for efficient activation of E1A-responsive genes, suggesting that E1A might block CtBP-mediated repression. Recruitment of CtBP to a promoter, either as a Gal4CtBP fusion or through an interaction with a Gal4 fusion protein expressing the CtBP interacting domain (CID) of E1A, resulted in transcriptional repression. The second exon of E1A, containing the CID, alleviated repression by Gal4E1ACID-recruited CtBP, but not Gal4CtBP-mediated repression, suggesting that E1A prevented repression by blocking promoter recruitment of CtBP. E1ACID was also sufficient to derepress transcription from several cotransfected promoter constructs. Furthermore, inducible expression of E1ACID in established cell lines resulted in significant changes of endogenous gene expression, possibly by sequestration of CtBP. Together, these data indicated that CtBP might act as a wide-range regulator of transcription. Although CtBP was shown to interact with histone deacetylases (HDACs), transcriptional repression by a Gal4CtBP fusion protein was not sensitive to inhibition of HDACs by trichostatin A (TSA). In contrast, TSA eliminated E1ACID derepression of E1A second exon-responsive promoters. Although the reason for this difference remains to be experimentally verified, it is possible that the requirement for HDACs might differ depending on the mechanism by which CtBP becomes promoter recruited.

Adenovirus E1A Proteins↗
PubMed1999

Valproate monotherapy in juvenile myoclonic epilepsy: dose-related effects on electroencephalographic and other neurophysiologic tests.

A neurophysiologic test battery (consisting of a 24-hour, seven-channel electroencephalogram [EEG], EEG spectral analysis, multiple sleep latency test, visual evoked potentials, critical flicker fusion, and visual contrast sensitivity) was administered twice to 16 patients with juvenile myoclonic epilepsy (JME) in a double-blind, randomized, crossover study comparing two daily doses of sodium valproate (VPA), 1000 mg and 2000 mg. Clinical observation time was 6 months for each dose. Mean total VPA concentration during low-dose treatment was 470.4 mmol/L and during high-dose treatment was 700.0 mmol/L. Ten patients had seizures during low-dose treatment, but only three of these showed spike-wave activity on EEGs. During high-dose treatment, nine patients had seizures; five of these had spike-wave activity. EEG power spectrum did not change between doses. The other tests also showed no change between doses. Our results suggested that EEG and our selection of other neurophysiologic tests were of limited value for monitoring seizure frequency and clinical effects of VPA.

Adolescent↗
PubMed1998

The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex.

Binding of the C-terminal binding protein, CtBP, to the adenovirus E1A moiety of a Gal4-E1A fusion protein abolishes conserved region (CR) 1-dependent transcription activation. In contrast, a non-promoter targeted E1A peptide, capable of binding CtBP, can induce transcription from the proliferating cell nuclear antigen (PCNA) promoter. CtBP is shown here to bind the histone deacetylase HDAC1, suggesting that a promoter targeted CtBP-HDAC1 complex can silence transcription from the PCNA promoter through a deacetylation mechanism. Expression of the CtBP binding domain of E1A is sufficient to alleviate repression, possibly due to the displacement of the CtBP-HDAC1 complex from the promoter.

Adenovirus E1A Proteins↗
PubMed1998

Valproate as monotherapy for juvenile myoclonic epilepsy: dose-effect study.

Sodium valproate enteric-coated tablets were used in this double-blind, randomized, cross-over study of 16 patients with juvenile myoclonic epilepsy comparing 1000 mg and 2000 mg VPA daily in b.i.d. administration with 6 months of observation on each dose. Myoclonic, absence, and generalized tonic-clonic seizures were registered separately. Subjective side-effects were monitored, and a computerized neuropsychologic test battery was performed on each dose. There was no significant difference in seizure frequency between the two doses. Only 25% of the patients were seizure free throughout the study despite concentrations well within the normally proposed therapeutic range for VPA. During the higher dose, 37.5% of the patients had an improved seizure control, but 25% of the patients had an increase in seizure frequency compared to the lower dose. However, there was no correlation between VPA concentrations and subjective side-effects or neuropsychologic test results. Our observations point out the possibility that the common strategy of increasing plasma levels in difficult-to-treat patients until side effects occur should perhaps be reconsidered, but this suggestion needs further confirmation.

Adolescent↗
PubMed1997

Analysis of the fusion protein gene of the porcine rubulavirus LPMV: comparative analysis of paramyxovirus F proteins.

Complementary DNA clones representing the fusion (F) protein gene of the porcine rubulavirus LPMV were isolated and sequenced. The F gene was found to be 1,845 nucleotides long containing one long open reading frame capable of encoding a protein of 541 amino acids. The cleavage motif for F0 into F1 and F2 is His-Arg-Lys-Lys-Arg. A sequence comparison and a phylogenetic analysis was performed in order to identify possible functional domains of paramyxovirus fusion proteins and also to classify the porcine rubulavirus. The F gene of LPMV is most closely related to the human mumps virus and simian virus type 5 F genes, and is therefore classified into the rubulavirus genus. A coding region for a small hydrophobic protein was however not found between the F and hemagglutinin-neuraminidase (HN) genes as previously found in both SV5 and mumps.

Amino Acid Sequence↗
PubMed1997

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.

Chromosome Mapping↗
PubMed1997

Pharmacokinetics of valproic acid in patients with juvenile myoclonic epilepsy on monotherapy.

Two different doses of sodium valproate (VPA), 500 mg b.i.d. and 1,000 mg b.i.d. as enteric-coated tablets, were used in this randomized, double-blind, cross-over monotherapy study of 16 patients with juvenile myoclonic epilepsy. Observation time was 6 months on each dose and included admittance for a 12-h serum concentration-time curve. There was a nonlinear relation between dose and concentration, with a negative deviation from the linear relation for total concentration and a positive deviation for the unbound fraction. Clearance for total concentration increased during high-dose treatment, but intrinsic clearance did not differ between doses. We measured the variation of repeated total and unbound VPA concentrations in up to 6 monthly samples on each dose. The coefficient of variation was 20.7% for total and 29.9% for unbound concentration on the lower dose, and 16.5% for total and 28.5% for unbound concentration on the higher dose. This difference between doses is not statistically significant. There was good correlation between the concentration taken before morning dose and AUC for one dose interval, especially during high dose, but the morning concentration was not the trough level. We conclude that the pharmacokinetic requirements for therapeutic drug monitoring of VPA are established.

Adolescent↗
PubMed1996

Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region.

Linkage analysis in separately ascertained families of probands with juvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated "EJM1"), on chromosome 6p, predisposing to a trait defined as either clinical JME, its associated electroencephalographic abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed in 19 families in which a proband and at least one first- or two second-degree relatives have clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was carried out under the assumptions of autosomal dominant inheritance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region formally excluded (LOD score < -2) by using multipoint analysis varies depending on the assumptions made concerning inheritance parameters and the proportion of linked families, alpha-that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected individuals as unknown or excluding a subset of four families in which pyknoleptic absence seizures were present in one or more individuals did not alter these conclusions.

Adolescent↗
PubMed1995

Red cell folate levels in pregnant epileptic women.

Red cell folate concentrations were determined in 74 epileptic women in early pregnancy in a prospective study. All patients were treated continuously with antiepileptic drugs since before conception. The most frequently used drugs were carbamazepine (n = 39) and phenytoin (n = 26). Sixty-four patients (86%) were on monotherapy. Blood samples for red cell folate and antiepileptic drug concentrations were drawn before folate supplementation. Red cell folate levels in patients, 468 nmol.l-1, did not differ from those in non-epileptic, drug-free, pregnant women, 416 nmol.l-1 or from those in non-pregnant age-matched healthy controls, 412 nmol.l-1. No correlation was found between red cell folate concentrations and doses or plasma levels of phenytoin or carbamazepine.

Adult↗
PubMed1994

Linkage analysis of idiopathic generalised epilepsy in families of probands with Juvenile Myoclonic Epilepsy and marker loci in the region of EPM 1 on chromosome 21 q: Unverricht-Lundborg disease and JME are not allelic variants.

The locus for Unverricht-Lundborg disease, EPM 1, has recently been mapped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus model for JME and evidence has been obtained for genetic heterogeneity within the JME/IGE phenotype. EPM 1 was therefore investigated as a candidate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers around the EPM 1 gene region using different models of inheritance. Multipoint linkage analysis provided definite exclusion for 20cM around PFKL, the closet linked marker to EPM 1, under three out of four models tested. These results strongly suggest that the EPM 1 gene is not linked to the phenotype expressed in these families, and therefore that Unverricht-Lundborg disease and juvenile myoclonic epilepsy are not allelic variants.

Adolescent↗
PubMed1994

[Nursing aspects in pain treatment].

Pain, the concept of pain and how pain is connected with culture are discussed in this article. The experience of pain in individual. It can not be questioned. The primary task of nursing is to help and support a patient to cope with pain in spite of the fact whether there is a cause for pain or not. Besides pharmacotherapy there are other possibilities to help a patient, e.g. by taking care of the surroundings, offering interesting subjects to think about, using imagination, relaxation, cognitive behavioral therapy, massage, therapeutic touch and thermat and cryotherapy.

Analgesia↗
PubMed1993

Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myoclonic epilepsy: no evidence for an epilepsy locus in the HLA region.

Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6S89, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype.

Adolescent↗
PubMed1992

The haemagglutinin-neuraminidase glycoprotein of the porcine paramyxovirus LPMV: comparison with other paramyxoviruses revealed the closest relationship to simian virus 5 and mumps virus.

The complete nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene of the porcine paramyxovirus LPMV, was determined from cDNA derived from viral genomic RNA. The gene was 1906 nucleotides long including a putative gene end and poly A signal. One long open reading frame was found encoding a protein of 576 amino acids with a calculated molecular weight of 63,324. The protein contains four potential N-glycosylation sites and a major hydrophobic region near the N-terminal, suggesting a membrane anchor domain. Comparison of the deduced amino acid sequence of the LPMV HN protein with that of other paramyxovirus HN proteins, revealed the highest amino acid identity to simian virus 5 of 43% and mumps virus of 41%.

Amino Acid Sequence↗
PubMed1991

Identification of the porcine paramyxovirus LPMV matrix protein gene: comparative sequence analysis with other paramyxoviruses.

The complete nucleotide sequence of the gene encoding the matrix protein (M) of the porcine paramyxovirus LPMV has been determined. The gene is 1376 nucleotides long including 5' and 3' non-coding sequences with a protein-coding sequence of 1107 nucleotides. The deduced protein, containing 369 amino acids with a calculated Mr of 41,657, is hydrophobic overall with a net positive charge of +17.5. Comparative sequence analysis revealed high amino acid homology to other paramyxovirus M proteins, with the highest degree of identity (46%) with the human mumps virus. This is strong evidence that the porcine paramyxovirus LPMV is a genuine member of the paramyxovirus genus.

Amino Acid Sequence↗
PubMed1990

The structural proteins of a porcine paramyxovirus (LPMV).

The porcine paramyxovirus is a newly identified agent of a fatal disease in piglets, endemic in Mexico since 1980, where it was seen around the town of La Piedad, Michoacan, Mexico (hence LPM virus). At least six [35S]methionine-labelled proteins could be resolved by SDS-PAGE and five of them were clearly immunoprecipitated. Selective labelling of LPMV-infected cells with [3H]glucosamine revealed two bands with an Mr of about 66K and 59K, corresponding to the two viral glycoproteins, the haemagglutinin-neuraminidase protein and the fusion protein. Labelling of virus with [32P]orthophosphate disclosed one band with an Mr of 52K, corresponding to the phosphoprotein. Analysis of nucleocapsids obtained from purified virus or from a permanently infected cell line revealed one major band with an Mr of 68K, the nucleoprotein. Two other proteins were also identified, the large protein and the matrix protein, with apparent Mr of about 200K and 40K, respectively. The protein migration pattern of LPMV was compared, by SDS-PAGE, with that of Newcastle disease virus, bovine parainfluenza 3 virus and Sendai virus. Differences in the Mr of LPMV proteins and the proteins of these paramyxoviruses were observed. We propose that LPMV should be classified as a novel member of the genus Paramyxovirus.

Animals↗
PubMed1987

Acyclic guanosine analogs as inhibitors of human cytomegalovirus.

The acyclic guanosine analogs R- and S-enantiomers of 9-(3,4-dihydroxybutyl)guanine [(R)- and (S)-DHBG], 9-(4-hydroxybutyl)guanine (HBG), and 9-(2-hydroxyethoxymethyl)guanine (ACV) were examined for their effects on human cytomegalovirus (CMV) replication and on CMV DNA synthesis in cell culture as well as for their ability as triphosphates to interact with CMV DNA polymerase. Production of early CMV antigens was not affected. All analogs inhibited CMV DNA synthesis and late viral antigen synthesis. Primary CMV isolates were less susceptible to all tested analogs than was the laboratory strain CMV Ad.169. The triphosphate of ACV was the most potent inhibitor of CMV DNA polymerase, with an observed Ki of 0.0076 microM. The corresponding Ki values of the triphosphates of (R)-DHBG, (S)-DHBG, and HBG were 3.5, 13.0 and 0.23 microM, respectively. All triphosphates of the analogs given above inhibited CMV DNA polymerase in a competitive manner with respect to dGTP. The triphosphates of the analogs also inhibited reactions when the synthetic template poly(dC)oligo(dG)12-18 was used, whereas no inhibition was observed with poly(dA)oligo(dT)12-18. None of the triphosphate analogs supported DNA synthesis in the absence of dGTP, showing that no analog was an alternative substrate to dGTP.

Acyclovir↗