Biomedical subjects

K Forsman

Publications and source records attributed to K Forsman.

At least 19 recordsLinked to original sources

PubMed2000

Relationship between calf muscle size and strength after achilles rupture repair.

The object was to study the relationships between calf muscle size and strength in 85 patients an average of 3.1 years after repair of achilles tendon rupture. The isokinetic calf muscle strength results were excellent or good for 73% of the patients, whereas calf muscle size was normal in only 30%. The average plantar flexion peak torque per unit muscle cross-sectional area was higher on the injured side than on the uninjured side. The average calf muscle cross-sectional area deficit was 15+/-9% (p<0.001) of that on the unaffected side, while the average plantar flexion peak torque deficit was speed-dependent, being 9+/-18%, 10+/-18 and 2+/-13% of that on the unaffected side at 30, 90, and 240 degrees/sec (p<0.001). The correlation between cross-sectional area and peak torque varied in the range 0.52-0.61 at 30, 90 and 240 degrees/sec (p<0.001).

Achilles Tendon↗

PubMed1998

Identification of the gene responsible for Best macular dystrophy.

Best macular dystrophy (BMD), also known as vitelliform macular dystrophy (VMD2; OMIM 153700), is an autosomal dominant form of macular degeneration characterized by an abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. In pursuit of the disease gene, we limited the minimum genetic region by recombination breakpoint analysis and mapped to this region a novel retina-specific gene (VMD2). Genetic mapping data, identification of five independent disease-specific mutations and expression studies provide evidence that mutations within the candidate gene are a cause of BMD. The 3' UTR of the candidate gene contains a region of antisense complementarity to the 3' UTR of the ferritin heavy-chain gene (FTH1), indicating the possibility of antisense interaction between VMD2 and FTH1 transcripts.

Amino Acid Sequence↗

PubMed1998

Oligomeric interaction of the PapB transcriptional regulator with the upstream activating region of pili adhesin gene promoters in Escherichia coli.

Transcriptional regulation of the pap genes, which encode fimbrial adhesins in uropathogenic Escherichia coli, depends on an upstream activating region. This region contains binding sites for a transcription factor, PapB, which is a member of a growing family of putative regulatory proteins found in several virulence-associated fimbrial gene systems. To assess the nature of the PapB binding sites, we studied different naturally occurring variants and a number of in vitro constructed mutant binding sites. DNase I footprinting analysis and visualization of the PapB-DNA complex by atomic force microscopy showed that the protein occupied a DNA region of more than 50 bp. Purified PapB protein was shown to recognize a motif including a 9 bp repeat sequence containing T/A triplets at a conserved position. PapB binding was affected by distamycin, and the results were consistent with the possibility that the binding to DNA occurred through minor groove interaction. From these analyses and estimation of the relative number of PapB proteins per binding site, we suggest that PapB binds the DNA in an oligomeric fashion and may function as an architectural factor in the transcriptional control of adhesin expression.

Adhesins, Bacterial↗

PubMed1998

Outcome and prognostic factors of achilles rupture repair using a new scoring method.

A new clinical scoring system, including subjective assessment of symptoms and evaluation of ankle range of motion and isokinetic measurement of ankle plantar flexion and dorsiflexion strengths, is presented in 101 patients (86 men, 15 women) who had repair of a closed Achilles tendon rupture. Twenty-one patients were competitive athletes and 70 were recreational athletes. Eighty-one percent of the ruptures were related to sports, and 32% occurred while playing volleyball. Twenty-six patients had previous Achilles tendon symptoms. At followup, an average of 3.1 years after repair, the overall result scores were excellent in 34 cases, good in 46, fair in 17, and poor in four. Only age was a predictor of overall results. The isokinetic strength scores were excellent or good in 72 cases, fair in 18, and poor in 11. Presence of systemic diseases, activity level, previous Achilles tendon symptoms, and later return to physical exercise were predictors of strength results. Gender, body weight, height, period between rupture and operation, surgeon, rupture site, operative method, complications, and thickness, width, and area of the Achilles tendon at followup were not related significantly to the outcome.

Achilles Tendon↗

PubMed1997

Ameloblastin gene (AMBN) maps within the critical region for autosomal dominant amelogenesis imperfecta at chromosome 4q21.

Amelogenesis imperfecta (AI) is a broad group of hereditary enamel defects that is characterized by a high degree of clinical diversity. Recently, the local hypoplastic form of autosomal dominant AI (AIH2) has been mapped to human chromosome 4q in a 17.6-cM region. This locus has been further refined to a 4-Mb interval between D4S2421 and Albumin. Recently, a cDNA clone for an enamel matrix protein, ameloblastin (AMBN), has been isolated. In this report, we have isolated a PAC human genomic clone containing the human AMBN gene. The AMBN was mapped by two color fluorescence in situ hybridization using two P1 genomic clones for sequence tagged site (STS) markers, D4S400 and D4S409, which flank the critical AIH2 region. Our results place AMBN at 4q21 between D4S409 (4q13) and D4S400 (4q21). Furthermore, the AMBN PAC genomic clone was shown to contain three STS markers, D4S2604, D4S2670, and D4S2609, which are contained within the critical region defined by six Swedish families with AIH2. AMBN is therefore a strong candidate gene for AIH2.

Amelogenesis Imperfecta↗

PubMed1997

Mapping of the locus for autosomal dominant amelogenesis imperfecta (AIH2) to a 4-Mb YAC contig on chromosome 4q11-q21.

Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of inherited enamel defects. We recently mapped a locus for autosomal dominant local hypoplastic amelogenesis imperfecta (AIH2) to the long arm of chromosome 4. The disease gene was localized to a 17.6-cM region between the markers D4S392 and D4S395. The albumin gene (ALB), located in the same interval, was a candidate gene for autosomal dominant AI (ADAI) since albumin has a potential role in enamel maturation. Here we describe refined mapping of the AIH2 locus and the construction of marker maps by radiation hybrid mapping and yeast artificial chromosome (YAC)-based sequence tagged site-content mapping. A radiation hybrid map consisting of 11 microsatellite markers in the 5-cM interval between D4S409 and D4S1558 was constructed. Recombinant haplotypes in six Swedish ADAI families suggest that the disease gene is located in the interval between D4S2421 and ALB. ALB is therefore not likely to be the disease-causing gene. Affected members in all six families share the same allele haplotypes, indicating a common ancestral mutation in all families. The AIH2 critical region is less than 4 cM and spans a physical distance of approximately 4 Mb as judged from radiation hybrid maps. A YAC contig over the AIH2 critical region including several potential candidate genes was constructed.

Albumins↗

PubMed1997

Refined genetic localization of the Best disease gene in 11q13 and physical mapping of linked markers on radiation hybrids.

Best's macular dystrophy, also known as vitelliform macular degeneration type 2 (VMD-2), is an autosomal dominant eye disorder that causes reduced visual acuity. It generally manifests itself in the teenage years. The gene mutated in VMD-2 patients may provide valuable insight into the biological mechanisms of the far more common disorder age-related macular degeneration. The VMD-2 gene has been localized to 11q13 between UGB and Fc epsilon RI. In order to clone the gene positionally, a large Swedish VMD-2 family dating back to the 17th century was studied for recombinations. Since the last study, another 40 microsatellite markers have been analyzed in the family; the closest centromeric flanking marker, D11S4076, revealed two recombinations and the closest telomeric flanking marker, UGB, revealed one recombination. The recombinations have occurred in affected individuals, which eliminates the potential problem of reduced penetrance. The order and physical distance between 22 markers located at proximal 11q13 were analyzed on the G3 Stanford radiation-reduced cell hybrids. The data suggest that the VMD-2 region flanked by the microsatellite markers D11S4076 and UGB is approximately 980 kb.

Centromere↗

PubMed1995

A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13.

Inherited retinal dystrophy is a common cause of visual impairment. Cone dystrophy affects the cone function and is manifested as progressive loss of the central vision, defective color vision, and photophobia. Linkage was demonstrated between progressive cone dystrophy (CORD5) and genetic markers on chromosome 17p12-p13 in a five-generation family. Multipoint analysis gave a maximum lod score of 7.72 at the marker D17S938. Recombinant haplotypes in the family suggest that the cone dystrophy locus is located in a 25-cM interval between the markers D17S926/D17S849 and D17S804/D17S945. Furthermore, one recombination was detected between the disease locus and a microsatellite marker in the candidate gene RCV1, encoding the retinal protein recoverin. Two additional candidate genes encoding retinal guanylate cyclase (GUC2D) and pigment epithelium-derived factor (PEDF) are located at 17p13.1. Moreover, loci for retinitis pigmentosa and Leber congenital amaurosis have been mapped to the same region. Identification of the cone dystrophy locus may be of importance not only for identifying functional genes in the cone system, but also for identifying genes for other retinal disorders.

Chromosome Mapping↗

PubMed1994

Fine mapping of Best's macular dystrophy localizes the gene in close proximity to but distinct from the D11S480/ROM1 loci.

The Best's macular dystrophy (BMD) gene has previously been mapped to the 11q13 region. In this study, recombination data localizes the BMD gene to the 6-cM genetic interval between the markers Fc epsilon RI and D11S480/ROM1 in a large Swedish 12-generation BMD family. Mutation analyses of the candidate gene ROM1 did not reveal any mutations that could explain the disease phenotype. However, one recombination event between intragenic ROM1 polymorphisms and the BMD phenotype was detected. Therefore, it is highly unlikely that mutations in the ROM1 gene cause BMD. Identification of the disease gene will elucidate the pathophysiological mechanism in BMD, which may also be of importance in other retinopathies such as age-related macular degeneration.

Alleles↗

PubMed1994

Localization of a gene for autosomal dominant amelogenesis imperfecta (ADAI) to chromosome 4q.

Amelogenesis imperfecta (AI), is an inherited odontological disease which affects the formation of enamel. We report a linkage analysis study performed on three Swedish families, where the affected members had an autosomal dominant variant of AI (ADAI) clinically characterized as local hypoplastic. Significant linkage to microsatellite markers on chromosome 4q were obtained. Recombinations localized the ADAI locus to a chromosome region which contains both a locus for the dental disorder dentinogenesis imperfecta and the albumin gene. Serum albumin has been suggested to play a role in enamel formation, and the albumin gene is therefore a candidate gene for this genetic disease.

Amelogenesis Imperfecta↗

PubMed1993

Non-invasive magnetocardiographic localization of ventricular pre-excitation in the Wolff-Parkinson-White syndrome using a realistic torso model.

This study was performed to evaluate the accuracy of magnetocardiography in non-invasive localization of the ventricular pre-excitation site in patients suffering from the Wolff-Parkinson-White (WPW) syndrome. Twelve WPW patients were studied, in whom the pre-excitation caused serious supraventricular arrhythmias refractory to drug therapy. Magnetocardiographic measurements were performed in a magnetically shielded room, and non-invasive localization was computed from preprocessed magnetic signals using a current dipole source in a realistically shaped digital torso. All patients underwent intra-operative multicatheter mapping and subsequent dissection of the accessory atrioventricular connection. The intra-operative localization results were marked on magnetic resonance images of the heart, where magnetocardiographic results were also superimposed to allow comparison. The average of the three-dimensional differences between the magnetocardiographic and the invasive results was 2.1 +/- 0.9 cm. In all cases, the computed localization result was in the same or adjacent anatomical region as the intra-operative result. The present results show that the magnetocardiographic method using a realistic torso model is capable of localizing pre-excitation sites with sufficient accuracy to provide extra information so that non-pharmacological therapeutic interventions can be applied.

Adult↗

PubMed1992

Antirepression function in Escherichia coli for the cAMP-cAMP receptor protein transcriptional activator.

The cAMP receptor protein (CRP) complex (cAMP-CRP) is a global regulator of gene expression. It influences transcription from a number of promoters in Escherichia coli, including two divergently oriented promoters in the pap pili-adhesin gene system. To further define the role of cAMP-CRP in pap regulation we monitored protein-DNA interactions in vitro and levels of pap transcription in vivo in wild-type and mutant pap-containing clones. The results showed that activation was mediated by a single cAMP-CRP-binding site centered at nucleotide positions -215.5 and -115.5 relative to the transcriptional start points. A target for the pap-specific regulatory protein PapB was localized adjacent to the cAMP-CRP-binding site. The long-range effects exerted from the protein-binding sites were consistent with the idea that cAMP-CRP caused a change in the local DNA conformation and that a nucleoprotein complex (involving cAMP-CRP and PapB) was formed in the region between the pap promoters. Moreover, transcription became independent of activation of cAMP-CRP and the PapB protein in a mutant lacking the nucleoid-associated protein H-NS. Our findings suggest that the cAMP-CRP complex mediates its positive regulatory function by alleviating transcriptional silencing and, as such, plays a role as antirepressor.

Adhesins, Escherichia coli↗

PubMed1992

The gene for Best's macular dystrophy is located at 11q13 in a Swedish family.

A large Swedish family with more than 250 cases of Best's macular dystrophy has been clinically and genetically studied. The gene was traced to a couple born in central Sweden in the 17th century. Highly significant evidence for genetic linkage to DNA markers on chromosome 11q13 was detected. A lod score of 15.12 was obtained at recombination fraction 0.01 with DNA marker INT2 (also called FGF3). The retinally expressed gene ROM1, which maps to the same chromosomal region is a candidate for this genetic disease.

Chromosomes, Human, Pair 11↗

PubMed1991

Magnetocardiographic localisation and modelling.

In our magnetocardiographic (MCG) localisation studies, two modelling approaches have been applied: (a) modelling the sources with dipole and quadrupole moments in a general multipole expansion and using a homogeneous, semi-infinite volume conductor, and (b) using a single current dipole source in a homogeneous, realistically shaped torso. Both approaches have been successfully applied in localising the premature ventricular excitation site in patients suffering from the Wolff-Parkinson-White syndrome. In addition, we have participated in developing a model of propagation of electrical activation in the ventricles. Anisotropic conductivity properties and spiral arrangement of myocardial fibres are included in the model.

Heart Function Tests↗

PubMed1990

Transcriptional silencing and thermoregulation of gene expression in Escherichia coli.

Expression of specific adhesive properties by bacteria in general seems to be regulated to fit the environmental conditions. An example is the transcriptional regulation of digalactoside-specific binding by uropathogenic strains of Escherichia coli. The fimbrial structures (pili) on the bacterial surface carry the adhesin and are present during growth at 37 degrees C but are not produced by cells at lower temperatures, such as 25 degrees C. Thermoregulation of expression is due to temperature-dependent transcription of a regulatory cistron in the pilus-adhesin gene cluster. We have now identified and characterized a new regulatory locus (drdX) and show that a histone-like bacterial protein has an important role in this novel example of thermoregulation of transcription.

Adhesins, Bacterial↗

PubMed1989

Autoregulation and multiple DNA interactions by a transcriptional regulatory protein in E. coli pili biogenesis.

An operon mediating biogenesis of digalactoside-binding pilus-adhesin of serotype F13 in uropathogenic Escherichia coli includes the regulatory gene papB. The papB gene product was found to act as transcriptional activator of an operon which includes the papB gene and several pap cistrons encoding the proteins of the pilus polymer. Studies of how pap gene expression was affected by increasing amounts of PapB protein in the cells showed that high levels did not stimulate transcription but caused repression. Results from in vitro studies demonstrated that the PapB protein was a sequence-specific DNA-binding protein. Binding studies using gel mobility shift assays and DNase I protection (footprinting) showed that PapB protein binds to three separate sites. A sequence greater than 200 bp upstream of the promoter, and directly adjacent to a binding site for the cAMP receptor protein-cAMP complex, appeared as a preferential PapB binding site. A second site was localized to sequences overlapping the -10 region of the promoter and a third binding site was found within the coding sequence of the papB gene itself. The data suggest that the PapB protein has a dual function as activator/repressor of pilus-adhesin transcription and that its autoregulatory mode of action involves differential binding to separate sites.

Adhesins, Escherichia coli↗

PubMed1989

Regulatory genes in the thermoregulation of Escherichia coli pili gene transcription.

Expression of several different pilus adhesins by Escherichia coli is subject to thermoregulation. The surface-located fimbrial structures are present during growth at 37 degrees C but are not produced by cells grown at lower temperatures, such as 25 degrees C. As a step toward understanding the molecular mechanism, we have studied the role of different cistrons of a cloned pilus adhesin gene cluster (pap) from a uropathogenic E. coli isolate. By promoter cloning, mRNA analysis, and expression of subcloned genes in trans, we have identified the papI gene as the mediator of thermoregulation at the level of pilus adhesin gene transcription. Expression of the major pilus subunit gene (papA) and several other pilus protein cistrons appeared to be dependent on stimulation by the papB and papI gene products. Constructs carrying different pap DNA regions indicated that none of the known Pap proteins acts directly as thermosensor. The chromosomal rpoH gene and RpoH sigma factor did not appear to be required for pap transcription, and the thermoregulation of pilus gene transcription must be different from that of the heat shock regulon. By overexpressing the papI gene product from an expression plasmid in trans, we could circumvent the temperature regulation and turn on production of pilus adhesin at low temperature. Our results suggest that the level of mRNA encoding the PapI activator is limiting at low growth temperatures and that thermoregulation is due to a determinant in the papI-papB intercistronic region.

Adhesins, Escherichia coli↗

PubMed1988

Functional and structural homology among regulatory cistrons of pili-adhesin determinants in Escherichia coli.

Expression of the digalactoside-binding Pap pili involves two trans-acting regulatory genes, papB and papI. Using pap-lac operon fusions and DNA hybridization probes derived from pap DNA we tested whether or not other pili-adhesin determinants from different Escherichia coli strains encode homologs to the pap regulatory genes. Digalactoside-specific clones of serotypes F72 and F11 complemented papB and papI mutants of the Pap (serotype F13) clone and DNA hybridization analysis showed that the clones are homologous in the DNA sequences encoding the two regulatory genes. Similar results were obtained with an S-pili determinant which mediates binding to sialic acid-containing receptors and the findings suggest that the regulatory regions may be more conserved than other genes in different pili-adhesin gene clusters. Determinants for type 1-pili (mannose-specific binding) and for pili associated with enterotoxigenic E. coli (K88, K99, CFAI, CFAII) did not appear to contain DNA sequences homologous to papB or papI. E. coli strain J96, which was the origin of the pap DNA, was found to carry two additional copies of papB-papI homologous sequences in the chromosome. In strains expressing more than one kind of pili the trans-active gene products thereby may allow for regulatory interaction between separate pili-adhesin gene systems.

Base Sequence↗