Biomedical subjects

T Martinsson

Publications and source records attributed to T Martinsson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Incidence of, and reasons for, tooth mortality among mentally retarded adults during a 10-year period.

The aim of the study was to investigate the reasons for, and incidence of, tooth mortality over a 10-year period in mentally retarded adults receiving regular dental care. The number of teeth present in 115 individuals (mean age in 1984 was 41.0, range 19-83 years) was registered in 1984 and 1994. The reasons for tooth mortality, medication utilization, frequency of dental care visits and cooperation during dental treatment were registered and related to tooth loss. The average incidence of tooth mortality was 3.72 teeth during the 10-year period. The mean number of dental care visits per year was 6.6. Most of the 428 teeth (58%) were lost due to periodontal disease. The preventive dental care given was not sufficient to arrest oral diseases. The data indicate, however, that achievement of cooperation in dental care situations not only makes dental treatment possible, but also leads to a decreased incidence of tooth mortality.

Adult↗

PubMed1999

Dominant hereditary inclusion-body myopathy gene (IBM3) maps to chromosome region 17p13.1.

We recently described an autosomal dominant inclusion-body myopathy characterized by congenital joint contractures, external ophthalmoplegia, and predominantly proximal muscle weakness. A whole-genome scan, performed with 161 polymorphic markers and with DNA from 40 members of one family, indicated strong linkage for markers on chromosome 17p. After analyses with additional markers in the region and with DNA from eight additional family members, a maximum LOD score (Zmax) was detected for marker D17S1303 (Zmax=7.38; recombination fraction (theta)=0). Haplotype analyses showed that the locus (Genome Database locus name: IBM3) is flanked distally by marker D17S945 and proximally by marker D17S969. The positions of cytogenetically localized flanking markers suggest that the location of the IBM3 gene is in chromosome region 17p13.1. Radiation hybrid mapping showed that IBM3 is located in a 2-Mb chromosomal region and that the myosin heavy-chain (MHC) gene cluster, consisting of at least six genes, co-localizes to the same region. This localization raises the possibility that one of the MHC genes clustered in this region may be involved in this disorder.

Chromosome Mapping↗

PubMed1999

Analysis of three suggested psoriasis susceptibility loci in a large Swedish set of families: confirmation of linkage to chromosome 6p (HLA region), and to 17q, but not to 4q.

Psoriasis is known to be a heterogeneous disease with so far three reported major psoriasis susceptibility loci on chromosome 4q, 6p and 17q. In this study we investigated three reported gene locations by nonparametric and parametric linkage analysis in a large family set consisting of 104 families (153 sib pairs) from Sweden. We could confirm linkage to chromosome 6p. A maximum heterogeneous lod score of 2.78 was reached at locus D6S276 (alpha = 0.60). Allelic association studies within the HLA region indicated linkage disequilibrium at locus TNFbeta with a significant p value of 0.0009. Furthermore, we obtained weak evidence of linkage to the locus on chromosome 17q while no evidence of linkage could be found to the chromosome 4q region.

Chromosomes, Human, Pair 17↗

PubMed1999

Variable expression and absence of mutations in p73 in primary neuroblastoma tumors argues against a role in neuroblastoma development.

In neuroblastoma, a childhood tumor of neural crest, a tumor suppressor gene located at 1p36 has been implicated to play a major role in tumor aggressiveness and clinical prognosis. We have examined 30 different staged primary neuroblastoma tumors using RT-PCR, for expression of the p73 gene located at 1p36.3, and its correlation to other clinical and biological features of these tumors. No correlation between expression of p73 and MYCN-amplification or 1p-deletion could be found, five of ten 1p-deleted tumors showed detectable levels of p73, and no mutations could be detected, neither in the retained alleles nor in any other parts of the material. In five 1p-deleted cases the origin of deletion were determined, two were of maternal and three of paternal origin. Both tumors with maternal 1p-loss showed detectable levels of p73, whereas the three with paternal loss did not. This suggests that p73 is expressed from the paternal allele only in advanced staged neuroblastoma tumors. Furthermore, it suggests absence of correlation between p73-expression and stage in these tumors. In conclusion, we could find no evidence for p73 being the neuroblastoma tumor suppressor gene in 1p36.

Chromosomes, Human, Pair 1↗

PubMed1999

Congenital variant Rett syndrome in a girl with terminal deletion of chromosome 3p.

A girl fulfilling four/five of six inclusion criteria and eight/nine of 11 supportive criteria for atypical Rett syndrome had a cytogenetic deletion of chromosome 3p, del(3)(pter-->3p25.1 approximately 25.2). The deletion was situated on the maternally derived chromosome and by molecular analysis the deletion breakpoint was shown to be between DNA markers D3S3589 and D3S1263.

Child↗

PubMed1999

Beneficial effects of ropivacaine in rat experimental colitis.

Ropivacaine, a new, long-acting local anesthetic agent, has been shown to have beneficial effects in the treatment of ulcerative colitis. Treatment with this drug results in prompt symptomatic relief. The aim of this study was to examine the effects of ropivacaine on mucosal healing and to investigate whether ropivacaine can restore the decreased colonic contractility seen in the diseased state. Colitis was induced in rats by a single intrarectal administration of trinitrobenzene sulfonic acid. Mucosal healing was assessed after 1 week of therapy. The effects on colonic contractility were examined either after 1 week of treatment or by application of the drugs to untreated, inflamed rat colon segments placed in organ baths. After the induction of colitis, daily intracolonic treatment with ropivacaine for 1 week reduced morphological damage and myeloperoxidase activity. One week of treatment also restored the contractile response to acetylcholine. By adding ropivacaine directly to untreated inflamed colonic segments in organ baths, the contractile response to acetylcholine was increased compared with controls. For comparison, the effects of budesonide and 5-aminosalicylic acid were also examined. Ropivacaine improved mucosal healing and restored colonic motor activity in experimental colitis, similar to budesonide but superior to 5-aminosalicylic acid.

Acetylcholine↗

PubMed1999

Ropivacaine inhibits serum-induced proliferation of colon adenocarcinoma cells in vitro.

Ropivacaine, a new long-acting local anesthetic, is currently being investigated for the treatment of ulcerative colitis. In view of the increased incidence of dysplasia and neoplasia associated with ulcerative colitis, it is important that the medical treatment of these patients does not stimulate cell proliferation further. This study was performed to evaluate the effect of ropivacaine on the proliferation of human colon adenocarcinoma cells (HT-29 and Caco-2) in vitro. A serum-induced proliferation assay of human colon adenocarcinoma cells was used. Ropivacaine inhibited the growth of HT-29 and Caco-2 cells in a dose-dependent manner. Fifty percent inhibition of growth was found at a ropivacaine concentration of 250 microM when the HT-29 cells were cultured in 1% fetal calf serum and of 550 microM when the HT-29 cells were cultured in 10% serum. The effective concentrations are within the range of the therapeutic concentrations obtained in the colon of patients treated rectally with ropivacaine. Lidocaine, hydrocortisone, and 5-aminosalicylic acid were found to be less potent than ropivacaine in inhibiting proliferation. Ropivacaine caused a dose-dependent membrane depolarization that appeared to correlate with the inhibited cell proliferation, whereas the effect was not related to inhibition of leukotriene B4 or prostaglandin E2. In conclusion, the antiproliferative activity of ropivacaine, combined with previously reported anti-inflammatory activities, makes this drug an interesting new alternative for the local treatment of ulcerative colitis.

Amides↗

PubMed1998

A large deletion disrupts the exon 3 transcription activation domain of the BRCA2 gene in a breast/ovarian cancer family.

We describe the identification of a large deletion in the BRCA2 gene as the disease-causing mutation in a Swedish breast/ovarian cancer family. The 5068-bp deletion encompassed the 3' region of exon 3, including the 3' splice site and most of intron 3, and it resulted on the mRNA level in an inframe exon 3 skipping. The junction site also included an insertion of 4 bp (CCAT). The mutation (nt504del5068insCCAT) resulted in a genotype absent of the two transcription activation regions localized to exon 3. The breast cancer phenotype associated with the described mutation resembled the phenotype of breast cancer found in both BRCA1 and BRCA2 mutation carriers. This is the first report of a large deletion as the disease-causing mutation in the BRCA2 gene.

Adult↗

PubMed1998

Autosomal dominant myopathy with congenital joint contractures, ophthalmoplegia, and rimmed vacuoles.

We describe a new myopathy in a large family with 19 affected cases. Inheritance was autosomal dominant. Characteristic clinical features were congenital joint contractures, which normalized during early childhood, external ophthalmoplegia, and proximal muscle weakness. Muscle atrophy was most prominent in the pectoralis and quadriceps muscles. The clinical course was nonprogressive in childhood, but most adult cases experienced deterioration of muscle function, starting from 30 to 50 years of age. The major histopathological change of skeletal muscle in childhood was focal disorganization of myofilaments. In adults with progressive muscle weakness, the muscle biopsies showed dystrophic changes and rimmed vacuoles with cytoplasmic and intranuclear inclusions of 15- to 21-nm filaments. These findings suggests that this new disease should be classified as a variant of hereditary inclusion body myopathy.

Actin Cytoskeleton↗

PubMed1998

Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT gene.

Neuroblastoma is a heterogeneous childhood tumour of the sympathetic nervous system, in which deletions of chromosomal region 1p and amplification of the MYCN oncogene correlate with aggressive tumour behaviour. However, the majority of neuroblastoma tumours show neither of these aberrations, indicating that other chromosomal regions may be involved in tumorigenesis. Here, we report findings of loss of heterozygosity (LOH) on chromosome 3. In our neuroblastoma material, nine of 59 (15.3%) tested tumours showed allelic loss of chromosome 3p markers. We found significant clinical and biological differences between tumours with the loss of one entire chromosome 3 vs tumours with partial loss in chromosome region 3p. All children with tumours with whole chromosome 3 loss are long-term survivors, whereas all children with tumours showing partial 3p LOH have died from tumour progression. A consensus region found to be deleted in all the tumours with 3p deletions was defined by markers D3S1286 and D3S1295, i.e. 3p25.3-p14.3, distal to the FHIT gene.

Acid Anhydride Hydrolases↗

PubMed1998

Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A.

Carbohydrate-deficient glycoprotein syndrome type 1A (CDGS1A) is an inherited disorder with multisystemic abnormalities resulting from failure to generate sufficient lipid-linked oligosaccharide precursor or to transfer the sugar chain to many glycoproteins. Cultured fibroblasts from these patients have reduced incorporation of mannose into glycoproteins which can be corrected by adding D-mannose to the culture medium. Providing dietary mannose to elevate mannose concentrations in vivo therefore might remedy some of the underglycosylation in the patients. Five children with CDGS1A aged 15 months to 14 y completed a protocol of enteral supplementation with D-mannose 100 mg/kg every 3 h for 9 d. The mean S-mannose level increased from 32 microM (range 22-42 microM) to a trough value of 72 microM (range 39-103 microM). No serious side effects were observed. Surprisingly, the mean serum concentration of four glycoproteins (transferrin, alpha1-antitrypsin, antithrombin, and thyroxine-binding globulin) tended to decrease, and the mean serum concentration of carbohydrate-deficient transferrin (CDT) increased. Furthermore, the initially present abnormal isoforms of these glycoproteins and of protein C became more prominent and/or additional abnormal isoforms appeared. This short-term trial does not support a benefit of mannose to the deficient glycosylation of CDGS1A patients.

Adolescent↗

PubMed1998

The Swedish National Dental Insurance's periodontal diagnosis. Used on an individual level.

The Swedish National Dental Insurance Board requires a periodontal diagnosis (FKF 2030 86.12GR) from general practitioners before treating patients, a process which is expensive. The Swedish National Dental Insurance-index (SNDI-index) is based on clinical data and radiographs and every tooth is assigned a rating between 0 and 4. From the time of introduction of the Swedish National Dental Insurance plan in 1974, data can have been collected for 1.7 million patients if the regulations were followed according to the Swedish National Dental Insurance Board in Stockholm, Sweden. It is of interest to examine whether all of these collected periodontal data reflect periodontal status. In this study includings 56 individuals, the Swedish National Dental Insurance-index, used on an individual level, correlated significantly with the individual changes in bone support (as percent of toothlength) of the tooth in 1979 (rs = -0.80, t = -9.7, p < 0.001, ci 95% = -0.88(-)-0.68) as well as in 1989 (rs = -0.79, t = -9.5, p < 0.001, ci 95% = -0.87(-)-0.67).

Alveolar Bone Loss↗

PubMed1997

Fine mapping of the gene for carbohydrate-deficient glycoprotein syndrome, type I (CDG1): linkage disequilibrium and founder effect in Scandinavian families.

Carbohydrate-deficient glycoprotein syndrome type I (CDG I) is characterized clinically by severe nervous system involvement and biochemically by defects in the carbohydrate residues in a number of serum glycoproteins. The CDG1 gene was recently localized by us to a 13-cM interval in chromosome region 16p13. In this study 44 CDG I families from nine countries were analyzed with available markers in a region ranging from marker D16S495 to D16S497, and haplotype and linkage disequilibrium analyses were performed. One specific haplotype was found to be markedly overrepresented in CDG I patients from a geographically distinct region in Scandinavia, strongly indicating that CDG I families in this region share the same ancestral CDG1 mutation. furthermore, analysis of the extent of the common haplotype in these families indicates that the CDG1 gene is located in the region defined by markers D16S513-AFMa284wd5-D16S768-D16S406-D16S502 . The critical CDG1 region, in strong linkage disequilibrium with markers AFMa284wd5, D16S768, and D16S406, thus constitutes less than 1 Mb of DNA and less than 1 cM in the very distal part of the CDG1 region defined by us previously.

Chromosome Mapping↗

PubMed1997

Effects of ropivacaine on eicosanoid release from human granulocytes and endothelial cells in vitro.

OBJECTIVE: To examine the effects of ropivacaine, currently being investigated for treatment of ulcerative colitis, on the release of arachidonic acid metabolites. MATERIAL: Human granulocytes and endothelial cells. TREATMENT: Ropivacaine, lidocaine, hydrocortisone, 5-aminosalicylic acid or acetylsalicylic acid (10-1000 microM). METHODS: Leukotriene B4, 5-hydroxyeicosatetraenoic acid, 6-keto PGF1 alpha and 15-hydroxyeicosatetraenoic acid were measured using immuno assays. Wilcoxon signed rank test was used for statistical calculations. RESULTS: Ropivacaine dose-dependently inhibited zymosan-induced release of leukotriene B4 and 5-hydroxyeicosatetraenoic acid whereas the release after ionophore stimulation was not affected. Ropivacaine was more potent than 5-aminosalicylic acid but less potent compared to hydrocortisone. Ropivacaine had only a weak inhibitory effect on the release of 15-hydroxyeicosatetraenoic acid from zymosan- or ionophore-stimulated cells. In contrast to hydrocortisone and 5-aminosalicylic acid, ropivacaine only weakly affected the release of 6-keto PGF1 alpha after stimulation with thrombin. CONCLUSIONS: The inhibited release of 5-lipoxygenase products may account for some of the anti-inflammatory effects of ropivacaine seen in the treatment of ulcerative colitis.

6-Ketoprostaglandin F1 alpha↗

PubMed1997

Homozygous deletion of the neurofibromatosis-1 gene in the tumor of a patient with neuroblastoma.

The neurofibromatosis type 1 (von Recklinghausen, NF1) gene has been proposed as a suppressor gene in tumors associated with neurofibromatosis. Recent publications have indicated that the NF1 gene can be rearranged in neuroblastoma cell lines. We analyzed DNA from a neuroblastoma patient with NF1 inherited as a familial trait on the paternal side. Using PCR and Southern techniques we showed that the patient had a constitutional deletion of several exons of the paternally derived NF1 gene and that the maternal copy of the gene had been deleted in the tumor of the patient. This is the first instance of a homozygous deletion reported in a primary neuroblastoma tumor. This suggests that NF1 inactivation in involved in the development or progression of some neuroblastomas in agreement with the hypothesized two hit model of inactivation for a tumor suppressor. These results are concordant with other groups that have detected unbalanced translocations t(1;17) in neuroblastoma tumors, with a breakpoint in chromosome 17 that may coincide with the location of the NF1 gene.

Blotting, Southern↗

PubMed1997

Representational difference analysis and loss of heterozygosity studies detect 3p deletions in neuroblastoma.

In an attempt to identify genes involved in neuroblastoma, we scanned neuroblastoma tumour DNAs for homozygous deletions by representational difference analysis (RDA). The RDA produced several difference products, nine of which represented hemizygous deletions located on chromosome 1 or 3. In order to detect deletions, a genomewide loss of heterozygosity (LOH) screening with polymorphic markers was performed. Allelic losses on a number of different chromosomes were detected, mainly in favourable neuroblastomas (stage 1, 2 and 4S). The most frequently deleted region, apart from 1p, was chromosomal region 3p. A more detailed study was made in this region, which showed that 9 out of 58 (16%) tested neuroblastoma tumours showed allelic loss in the same region on chromosome 3p, i.e. 3pter-14.2. Thus, both RDA and LOH studies showed chromosome region 3p as being frequently involved in deletions and/or rearrangements in neuroblastoma tumours. Therefore, it is possible that one or more of the 3p genes implicated in the development of other cancers also play a role in neuroblastoma development and/or progression.

Child↗

PubMed1997

Delimitation of a critical tumour suppressor region at distal 1p in neuroblastoma tumours.

We analysed DNA from 68 neuroblastoma tumours for loss of heterozygosity (LOH) on the distal chromosome 1p (1p-LOH) using PCR-based DNA polymorphisms. Fifteen tumours (22%) displayed 1p-LOH. The shortest region of overlap (SRO) for the deletions was defined proximally by marker D1S244 and distally by marker D1S80. The CDC2L1 locus, located on chromosome 1p36, has been put forward as a neuroblastoma tumour suppressor. We analysed coding regions of the CDC2L1 gene in a subset of aggressive neuroblastoma tumours with known allelic loss for different 1p-markers. Single-stranded conformation polymorphism, heteroduplex and sequencing analysis of tumour DNA did not reveal any significant changes in the coding region. Using a DNA sequence polymorphism, we showed, in a primary tumour with an interstitial allelic deletion, that this tumour had both alleles of the CDC2L1 locus retained in the tumour. Thus, we showed that the neuroblastoma tumour suppressor critical region on 1p in our material is defined by loci D1S244 and D1S80 and that the CDC2L1 locus is distal to the critical region.

Child↗

PubMed1997

Structural and immunochemical identification of Le(a), Le(b), H type 1, and related glycolipids in small intestinal mucosa of a group O Le(a-b-) nonsecretor.

Total nonacid glycosphingolipids were isolated from small intestine mucosal scrapings of a red cell blood group O Le(a-b-) nonsecretor cadaver. Glycolipids were extracted and fractionated into five fractions based on chromatographic and immunostaining properties. These glycolipid fractions were then analysed by thin-layer chromatography for Lewis activity with antibodies reactive to the type 1 precursor (Le(c)), H type 1 (Le(d)), Le(a) and Le(b) epitopes. Fractions were structurally characterized by mass spectrometry (EI-MS and EI-MS/MS-TOF) and proton NMR spectroscopy. EI-MS/MS-TOF allowed for the identification of trace substances in fractions containing several other glycolipid species. Consistent with the red cell phenotype, large amounts of lactotetraosylceramide (Le(c)-4) were detected. Inconsistent with the red cell phenotype, small quantities of Le(a)-5, H-5-1 and Le(b)-6 glycolipids were immunochemically and structurally identified in the small intestine of this individual. By EI-MS/MS-TOF several large glycolipids with 9 and 10 sugar residues were also identified. The extensive carbohydrate chain elongation seen in this individual with a Lewis negative nonsecretor phenotype supports the concept that Lewis and Secretor blood group fucosylation may be a mechanism to control type 1 glycoconjugate chain extension.

ABO Blood-Group System↗