Biomedical subjects

T Hansen

Publications and source records attributed to T Hansen.

At least 55 records · Page 3Linked to original sources

PubMed2005

Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1alpha mutation carriers.

AIMS: Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity. The present study was undertaken to compare the plasma insulin responses to glucose and tolbutamide in HNF-1alpha mutation carriers with those of healthy control subjects. METHODS: Seven mutation carriers; three normoglycaemic, two with impaired glucose tolerance, and two with newly detected diabetes, underwent an oral glucose tolerance test and a tolbutamide-modified intravenous glucose tolerance test with measurements of plasma insulin. Twenty-two healthy subjects served as controls. RESULTS: The plasma insulin response to intravenous glucose was reduced in the HNF-1alpha mutation carriers compared to the control subjects, with an area under the curve (median (interquartile range)) of 812 min pmol/l (421, 1647) and 1933 min pmol/l (1521, 2908), respectively (P = 0.03). In striking contrast, the plasma insulin response to tolbutamide was preserved, with an area under the curve of 2109 min pmol/l (1126, 3172) and 2250 min pmol/l (1614, 3276) in the mutation carriers and control subjects, respectively. CONCLUSIONS: HNF-1alpha mutation carriers are characterized by preserved tolbutamide-induced insulin secretion. Compared to healthy subjects, our MODY3 individuals did not show any increased serum insulin response to tolbutamide, suggesting that HNF-1alpha mutation carriers are not characterized by sulphonylurea hypersensitivity.

Adult↗

PubMed2005

Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release.

AIMS: Recently, a novel human G protein-coupled receptor 40 (GPR40), which is predominantly expressed in pancreatic islets, was shown to mediate an amplifying effect of long-chain fatty acids on glucose-induced insulin secretion. The present aim was to examine the coding region of GPR40 for variation and to assess whether identified variants confer an increased risk of Type 2 diabetes or altered insulin release. METHODS: Mutation analysis was performed in 43 patients with Type 2 diabetes, 18 normal glucose-tolerant subjects, and 3 maturity-onset of diabetes in the young (MODY) X patients using direct sequencing. Genotyping was performed using polymerase chain reaction (PCR)-generated primer extension products analysis by high throughput chip-based mass spectrometry (MALDI-TOF). The potential impact of GPR40 mutations on [(3)H]-myo-inositol turnover was estimated in COS-7 cells after stimulation with various concentrations of 5,8,11-eicosatriynoic acid. RESULTS: Two nucleotide substitutions, an Arg211His polymorphism and a rare Asp175Asn mutation, were identified. Both variants showed EC(50) values similar to the wild type. However, the maximal efficacy of the rare Asp175Asn was 39% lower compared with the wild type (P = 0.01). The Arg211His polymorphism had a similar allele frequency among 1384 Type 2 diabetic patients [MAF%; 23.4 (95% CI: 21.8-25.0)] and 4424 middle-aged glucose-tolerant subjects [24.1% (23.2-25.0)]. A genotype-quantitative trait study of 5597 non-diabetic, middle-aged subjects from the Inter99 cohort showed no significant differences in oral glucose tolerance test (OGTT)-derived estimates of insulin release between carriers of various GPR40 genotypes. CONCLUSIONS: Variations in the coding region of GPR40 do not appear to be associated with Type 2 diabetes or insulin release alterations.

Case-Control Studies↗

PubMed2005

Studies of relationships between the GLUT10 Ala206Thr polymorphism and impaired insulin secretion.

AIMS: This study aimed to investigate if the previously observed association between the GLUT10 Ala206Thr polymorphism and variation in fasting and oral glucose-induced serum insulin concentrations could be replicated in a large-scale population-based cohort of Danish whites. METHODS: The GLUT10 Ala206Thr polymorphism was genotyped in a case-control study of 880 Type 2 diabetic patients and 4372 glucose-tolerant control subjects. The latter group was also enrolled in an assessment of fasting and post-OGTT circulating levels of plasma glucose and serum insulin in relation to genotype. The variant was genotyped by analysis of PCR-generated primer extension by matrix-assisted laser desorption/ionization time-of-flight analysis. RESULTS: The Ala206Thr variant was equally frequent among Type 2 diabetic patients and glucose-tolerant subjects (P = 0.9) and there was no difference in the distribution of genotype groups (P = 1.0). In the 4372 glucose-tolerant subjects there was no statistically significant association between the polymorphism and levels of fasting and post-oral glucose tolerance test plasma glucose and serum insulin along with the insulinogenic index and the homeostasis model of assessment for insulin resistance and insulin secretion. Likewise, in an age-stratified subgroup comprising 1264 subjects, we observed no relationships between the GLUT10 polymorphism and the selected metabolic features. CONCLUSIONS: The GLUT10 Ala206Thr polymorphism is not associated with Type 2 diabetes in the Danish population. Furthermore, in the present large-scale cohort, the polymorphism does not associate with phenotypes such as fasting and oral glucose-induced levels of plasma glucose and serum insulin.

Adult↗

PubMed2005

Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity.

BACKGROUND: Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) is a recently identified homologue of the tissue specific coactivator PGC-1alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1alpha is involved in adipogenesis, mitochondrial biogenesis, fatty acid beta oxidation, and hepatic gluconeogenesis. METHODS: We studied variation in the coding region of human PPARGC1B in Danish whites and related these variations to the prevalence of obesity and type 2 diabetes in population based samples. RESULTS: Twenty nucleotide variants were identified. In a study of 525 glucose tolerant subjects, the Ala203Pro and Val279Ile variants were in almost complete linkage disequilibrium (R2 = 0.958). In a case-control study of obesity involving a total of 7790 subjects, the 203Pro allele was significantly less frequent among obese participants (p = 0.004; minor allele frequencies: normal weight subjects 8.1% (95% confidence interval: 7.5 to 8.8), overweight subjects 7.6% (7.0 to 8.3), obese subjects 6.5% (5.6 to 7.3)). In a case-control study involving 1433 patients with type 2 diabetes and 4935 glucose tolerant control subjects, none of the examined variants were associated with type 2 diabetes. CONCLUSIONS: Variation of PGC-1beta may contribute to the pathogenesis of obesity, with a widespread Ala203 allele being a risk factor for the development of this common disorder.

Aged↗

PubMed2005

Concordance for multiple sclerosis in Danish twins: an update of a nationwide study.

The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study, virtually all Danish MS cases among twins born before 1983 with onset of MS after 1948 and diagnosis before I January 1997 were identified. Of 13 286 MS cases, 178 were twins and, of these 164 twin pairs were discordant and seven were concordant. We found significantly higher proband-wise concordance among monozygotic twins than dizygotic twins, with estimated proband-wise concordances of 24% (95% confidence interval (CI): 5-39%) for monozygotic and 3% (95% CI: 0-8%) for dizygotic twins. Thus, a monozygotic twin whose co-twin has MS has a 24% risk of developing the disease, while the corresponding risk for a dizygotic twin is only 3%. Our results largely confirm previously published concordance estimates and indicate that genetic factors are of importance in susceptibility to MS.

Adult↗

PubMed2005

Genetics of common forms of glycaemia with pathological impact on vascular biology: are we on the right track?

The common forms of abnormal glucose regulation including type 2 diabetes and impaired glucose tolerance with pathological implications on vascular biology have a complex aetiology involving multiple cross-talks between genetic influences and important environmental modifying factors. Due to complexity of the genetics and the clinical heterogeneity of these disorders it has proven difficult to apply the same methodological approaches that have recently given insights into the molecular genetics of several single-gene disorders of glucose metabolism. This review gives some reflections on the challenges posed by the current hypotheses about the genetics of the widespread forms of abnormal glucose regulation as well as on the strengths and limitations of the methodological approaches applied to unravel the genetic components of common disorders. Also, we review recent progress in relation to a model for the pathogenesis of the various stages of abnormal glucose regulation based on the concepts of thrifty genes of metabolism and pro-inflammation and genes responsible for the appearance of impaired pancreatic beta-cell function and insulin signalling under the pressure of a westernized environment.

Animals↗

PubMed2004

Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion.

AIMS/HYPOTHESIS: Polymorphisms of the butyrylcholinesterase gene (BCHE) are reported to associate with Alzheimer's disease and a recent study found a significant association of the BCHE K variant (G1615A/Ala539Thr) with Type 2 diabetes. The objectives of our study were to examine whether the BCHE K variant is associated with Type 2 diabetes or estimates of pancreatic beta cell function in large-scale populations of glucose-tolerant Caucasians. METHODS: The variant was genotyped in association studies comprising a total of 1408 Type 2 diabetic patients and 4935 glucose-tolerant control subjects. Genotype-phenotype studies were carried out in the 4935 glucose-tolerant control subjects. RESULTS: There was no difference in allele frequency between Type 2 diabetic patients and control subjects (20.3% [95% confidence interval: 18.8-21.8] vs 20.4% [19.6-21.2], non-significant). In the genotype-phenotype studies we found no consistent association with BMI, fasting or post-OGTT plasma glucose, serum insulin or serum C-peptide levels. CONCLUSIONS/INTERPRETATION: The present study does not support the suggestion that the BCHE K polymorphism is associated with Type 2 diabetes or with estimates of pancreatic beta cell function in large-scale Danish Caucasian populations.

Amino Acid Substitution↗

PubMed2004

Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity.

AIMS/HYPOTHESIS: Beta cell loss in Type 1 and Type 2 diabetes mellitus may result from apoptosis and necrosis induced by inflammatory mediators. The suppressor of cytokine signalling (SOCS)-3 is a natural inhibitor of cytokine signalling and also influences insulin signalling. SOCS3 could therefore be a candidate gene in the development of Type 1 and Type 2 diabetes mellitus. METHODS: Mutation analysis of the SOCS3 gene was performed in 21 patients with Type 1 diabetes mellitus and in seven healthy subjects. An identified promoter variant was examined in (i) 250 families with Type 1 diabetic family members (1097 individuals); (ii) 212 glucose-tolerant first-degree relatives of Type 2 diabetic patients; and (iii) 370 population-based young, healthy subjects who were unrelated. RESULTS: Three mutations were identified in the promoter region, but none in the coding region or the 3'UTR. Two of the three mutations had allele frequencies below 1% whereas the C -920-->A substitution had a minor allele frequency of 8%. In the group of young healthy subjects the insulin sensitivity index was higher among homozygous carriers of the A-allele than among heterozygous and wild-type subjects ( p=0.027, uncorrected). The same trend was found in the group of first-degree relatives of Type 2 diabetic patients. No association or linkage was found to Type 1 diabetes mellitus. CONCLUSIONS/INTERPRETATION: Homozygosity for the A-allele of the C -920-->A promoter polymorphism of the SOCS3 gene may be associated with increased whole-body insulin sensitivity, but deserves further investigation.

Adolescent↗

PubMed2004

Haemangiopericytoma of the thyroid gland in combination with Hashimoto's disease.

We present a hitherto unique case of haemangiopericytoma (HP) of the thyroid gland in a 15-year-old female patient suffering from Hashimoto's disease for several months. Since angiogenesis has been discussed to play a major role in both diseases, we examined the expression of vascular endothelial growth factor (VEGF), VEGF receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs). Most interestingly, strong expression of PDGFR alpha and beta was found in spindle-shaped tumour cells and tumour vessels in HP, while VEGF and VEGFR type I and -II were negative in these regions. In contrast, VEGF was expressed in the lymphoid infiltrate of Hashimoto's disease. Since PDGFR-beta is commonly expressed in pericytes, we suggest that the strong expression discovered in this study further supports the view that HP is derived from pericytes. The combination of HP and Hashimoto's disease is most probably a coincidental event. However, this case confirms previous reports demonstrating that in patients with Hashimoto's disease different neoplasias can occur.

Adolescent↗

PubMed2004

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release.

AIMS/HYPOTHESIS: The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals. METHODS: We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middle-aged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes. RESULTS: There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middle-aged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels. CONCLUSIONS/INTERPRETATION: The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.

Adult↗

PubMed2004

[Cystic myoepithelioma. A rare differential diagnosis of a cystic lesion of the parotid gland].

By sonography, we found a sharply demarcated tumor with cystic areas in the parotid gland of a 41 year old male, indicating Warthin's tumor. Subtotal parotidectomy was performed. Microscopy showed an encapsulated tumor with myoepithelial cells and, in particular, central pseudocysts. Immunohistochemically, the tumor cells expressed cytokeratin 5/6 and S-100 protein as well as smooth muscle-actin. These features led to the diagnosis of a cystic myoepithelioma. Histopathologically, several different lesions of the salivary glands should be considered in the differential diagnosis of myoepithelioma, especially of this hitherto unique case in the parotid gland. The differential diagnoses are reviewed and discussed. Treatment is by surgical resection. Because of the tendency of myoepitheliomas to recur and to malignant transformation, tumor-free margins are recommended.

Adult↗

PubMed2004

[Proposal for the classification of the periprosthetic membrane from loosened hip and knee endoprostheses].

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.

Arthroplasty, Replacement, Hip↗

PubMed2004

Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration.

This study analyzed the effect of the platelet count in platelet-rich plasma (PRP) on bone regeneration in vivo. Twenty male New Zealand white rabbits were used. PRP was produced using the Platelet Concentrate Collection System (PCCS) (3i, Miami, FL, USA). After inducing ketamine-xylazine anaesthesia, a self-tapping titanium screw (Branemark MK III TiUnite, 3.75 x 7 mm) was inserted in each distal femur; the femurs were randomized so that one side was treated with PRP while the other (control) was not. Intravital fluorochrome staining was performed on days 1, 7 (1.5 ml of 2% doxycycline/kg bodyweight), 14 (6% xylenol orange, 1.5 ml/kg), and 21 (1% calcein green, 5 ml/kg). Animals were euthanized on day 28 (n = 20). Specimens were prepared for histomorphological evaluation according to Donath and Breuner [J. Oral Pathol. 11 (1982) 318]. Comparing the bone regeneration (fluorochrome staining) in the 4-week implants (n = 19), the only significant difference (sign test, P = 0.004) was seen with intermediate platelet concentrations (n = 9,503,000-1,729,000 platelets/microl PRP). There were no differences in the bone/implant contact rates between the test and the control side among the three groups. The platelet concentration required for a positive PRP effect on bone regeneration seems to span a very limited range. Advantageous biological effects seem to occur when PRP with a platelet concentration of approximately 1,000,000/microl is used. At lower concentrations, the effect is suboptimal, while higher concentrations might have a paradoxically inhibitory effect. On the other hand, the effect of this type of platelet concentrate was not beneficial to accelerate the osseointegration of enosseous dental implants.

Animals↗

PubMed2004

[Myospherulosis of the middle ear -- a rare differential diagnosis of cholesteatoma].

BACKGROUND: Myospherulosis is a chronic-inflammatory lesion that is most commonly iatrogenic of origin and occurs in tissues exposed to petrolatum-based products. The disease does not exhibit characteristic symptoms and is therefore not diagnosed in some instances. In previous otorhinolaryngological studies, myospherulosis was mainly found in paranasal sinuses, while only four otitic cases have been reported. METHODS: A 48-year-old female Egyptian patient suffered from bilateral chronic otitis media that had been treated in Egypt by tympanoplasty. The patient presented few months later at the university ENT department (Mainz) with deteriorated otorrhea and otalgia. Clinical, otoscopical, and radiological examination led to the diagnosis of cholesteatoma. During revision surgery of the right side, ointment-like material was found, which was embedded in granulation tissue. Middle ear biopsies were taken from both sides and routinely processed for standard histological examination and transmission electron microscopy. RESULTS: Histological examination of the right middle ear biopsy showed cystic tissue spaces lined by histiocytes and foreign-body giant cells in a fibrous stroma. In the tissue spaces, scattered debris and sac-like structures containing round spherules of aggregated erythrocytes were found. In addition, erosion of adjacent bone matrix was seen. Diagnosis of myospherulosis was made. By contrast, histological evaluation of the left middle ear biopsy revealed cholesterol granuloma. CONCLUSION: Myospherulosis of the middle ear has been hitherto diagnosed in a very few otitic cases, but might be overlooked as it mimicks other chronic proliferative and inflammatory lesions such as cholesteatoma in the present case. Thus myospherulosis should be considered in otitic cases with a suspicious history (exposure to petrolatum-based products). Furthermore, patients with myospherulosis have a significantly higher likelihood of developing postoperative complications. Since the lesion exhibits distinct histological findings, microscopy plays a central role for the diagnosis of this important disease.

Cholesteatoma, Middle Ear↗

PubMed2004

The user perspective: respected or rejected in mental health care?

The purpose of this study was to examine the extent to which patient views influence treatment planning by measuring the level of agreement between patients and health workers regarding patient needs as well as the impact of patient wishes on decision making when viewpoints conflict. Data on patient characteristics and needs were collected for a sample of 1080 patients within Norwegian mental health care using patient interviews and health worker ratings. Results of the assessment were then reviewed by multidisciplinary treatment teams responsible for making decisions regarding patient needs for services. On average, patients, health workers, and teams identified 4.3 (SD = 4.2), 9.3 (SD = 5.5), and 10.3 (SD = 5.7), respectively, of 40 possible needs per patient. In cases where patient and health workers disagreed on the presence of a need, the teams tended to concur with the health worker. Interestingly, health care workers and teams were far more inclined than their patients to identify needs related to professional monitoring and follow-up. Results may indicate that contemporary tenets in mental health care regarding user involvement and autonomy are not sufficiently emphasized in practice.

Adult↗

PubMed2004

Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene and the relationship to beta-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitus.

AIMS: In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to beta-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene has been associated with decreased serum insulin and C-peptide responses during an oral glucose tolerance test (OGTT) in glucose-tolerant subjects. The aims of the present study were to evaluate the influence of the polymorphism on the serum insulin and C-peptide responses to an OGTT in glucose-tolerant women with and without previous GDM and to investigate if this polymorphism is associated with GDM. METHODS: The Ala/Val98 polymorphism was measured in 376 women of Danish origin with previous GDM, and in 724 age-matched and 310 middle-aged glucose tolerant women using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The allelic frequency of the Ala/Val98 polymorphism was 0.043 [95% confidence interval (CI) 0.028, 0.057] in women with previous GDM vs. 0.037 (95% CI 0.028, 0.047) in age-matched and 0.039 (95% CI 0.024, 0.054) in middle-age women. Among 117 glucose-tolerant women with previous GDM, 10 carriers of the Ala/Val98 polymorphism had a non-significant 27% and 22% reduction in serum C-peptide and insulin levels, respectively, at 30 min during an OGTT. Seventy-eight control subjects carrying the Ala/Val98 polymorphism had a 10% (P = 0.001) and 16% (P = 0.004) reduction in serum C-peptide and insulin levels, respectively, compared with 956 Ala/Ala control subjects. CONCLUSIONS: The Ala/Val polymorphism at codon98 of HNF-1alpha is not associated with GDM in Danish women. However, the codon 98 variant is associated with a significant impairment of serum insulin and C-peptide responses during an OGTT in glucose-tolerant women without previous GDM.

Adult↗

PubMed2003

The FOXC2 -512C>T variant is associated with hypertriglyceridaemia and increased serum C-peptide in Danish Caucasian glucose-tolerant subjects.

AIMS/HYPOTHESIS: The transcription factor FOXC2 plays a key role in adipocyte differentiation and the FOXC2 gene is a candidate gene for Type 2 diabetes, obesity and dyslipidaemia. We investigated whether the FOXC2 -512C>T promoter variant is associated with Type 2 diabetes or its intermediary phenotypes in glucose tolerant subjects. METHODS: The variant was genotyped using PCR-RFLP in 705 unrelated Type 2 diabetic patients, 505 unrelated glucose-tolerant control subjects and 219 glucose-tolerant offspring of Type 2 diabetic probands. RESULTS: The frequency of the T-allele was 58% (95% CI 56-61%) and 59% (56-62%) among the Type 2 diabetic patients and the unrelated glucose-tolerant control subjects, respectively ( p=0.6). Among the glucose-tolerant subjects, the T-allele carriers had higher fasting serum triglyceride ( p=0.03), fasting serum C-peptide concentrations ( p=0.009) and insulinogenic index ( p=0.04). Furthermore, in glucose-tolerant women, the waist-to-hip ratio was significantly higher in carriers of the T-allele. CONCLUSION/INTERPRETATION: Our data suggest that the FOXC2 -512C>T variant is not associated with Type 2 diabetes. However, among glucose-tolerant subjects the variant is associated with hypertriglyceridaemia and increased fasting serum C-peptide.

Base Sequence↗

PubMed2003

Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the synovial membranes of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: The aim of this study was to define and compare the expression of fibronectin (Fn) isoforms in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Using monoclonal antibodies specific for total Fn, extra domain (ED)-A Fn, ED-B Fn, and oncofetal glycosylated Fn, we studied the expression of the Fn isoforms in synovium. Furthermore, in situ hybridization for the detection of ED-B Fn mRNA including a double labeling technique for the detection of cell type was applied. RESULTS: Strong expression of total Fn, ED-A Fn, oncofetal glycosylated Fn and, to a lesser extent, ED-B Fn could be demonstrated in the synovial lining layer in both RA and OA. Stromal and vessel expression of Fn isoforms was more prominent in RA tissue. Pannus tissue showed strong labeling with ED-B Fn. CONCLUSION: The expression of alternatively spliced isoforms of Fn is associated with tissue remodeling and, as a partial process of this phenomenon, with neovascularization rather than underlying disease, X-ray status, or parameters of acute inflammation. In the lining layer, Fn expression correlates with hyperplasia associated with cell recruitment but not with proliferative status. Most remarkably, the expression of ED-B Fn in pannus tissue seems to be associated with the invasive phenotype described in RA tissue.

Alternative Splicing↗