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T Hansen

Publications and source records attributed to T Hansen.

At least 19 recordsLinked to original sources

Studies of the associations between functional beta2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects.

AIMS/HYPOTHESIS: Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results. MATERIALS AND METHODS: We investigated both of these variants in 7,808 unrelated, middle-aged white people for their association with obesity in a case-control study, quantitative trait analysis and meta-analysis. Moreover, both variants were investigated for their potential influence on measures of hypertension and type 2 diabetes by case-control and quantitative trait analyses. RESULTS: The present study did not find consistent evidence for an association of these beta2-adrenergic receptor variants with obesity or hypertension; neither did the quantitative trait analyses show any effect of the variants on obesity-related traits. However, both the Gly allele of the Arg16Gly variant and the Glu allele of the Gln27Glu variant showed nominal association with systolic blood pressure. Furthermore, there was a nominal association of the Arg16 allele frequency and genotype distribution with type 2 diabetes; however, no influence on quantitative biochemical phenotypes related to type 2 diabetes was found. A nominal association of the Arg/Gly genotype with the metabolic syndrome was also observed (p=0.003). Logistic regression analyses provided no evidence of a synergistic or an additive effect of these variants on obesity, hypertension or diabetes. CONCLUSIONS/INTERPRETATION: After studying 7,808 middle-aged white subjects, we were unable to demonstrate any consistent associations between two common amino acid polymorphisms of the beta2-adrenergic receptor and obesity, hypertension or type 2 diabetes.

Adult↗

Increasing the sensitivity of delta13C and delta15N abundance measurements by a high sensitivity elemental analyzer connected to an isotope ratio mass spectrometer.

A common elemental analyzer system connected to a temperature-controlled gas chromatography (GC) column and coupled to an isotope ratio mass spectrometer was improved to decrease the determination limit for a simultaneous stable isotope ratio measurement of nitrogen and carbon dioxide. The additional use of a special ashtray system to collect the combustion residuals permitted more time-efficient work. These modifications to the elemental analyzer allowed precise measurements to be made down to 1.5 microg nitrogen and 10 microg carbon for stable isotope analysis. Low system background values and an acceptable signal-to-noise ratio have made an additional blank correction for these low sample measurements unnecessary. We provide a precision of this stable isotope analysis for lowest amounts of 1.2-2 microg nitrogen with a standard deviation of +/-0.496 per thousand (n = 27) and for 8.2-15 microg carbon with a standard deviation of +/-0.257 per thousand (n = 31) across different sample runs under stipulated conditions. This application can be established in an automatic mode without cryofocusing procedures.

Carbon Isotopes↗

The prevalence and quantification of atherosclerosis in an elderly population assessed by whole-body magnetic resonance angiography.

OBJECTIVE: The principal aim of the present study was to explore the feasibility of using whole-body magnetic resonance angiography to assess atherosclerosis in different vascular territories in a cohort of elderly. METHODS AND RESULTS: Three hundred six 70-year-old subjects (145 women, 161 men) recruited from a population-based cohort study (Prospective Investigation of the Vasculature in Uppsala Seniors, ie, the PIVUS study) underwent 1.5-T whole-body magnetic resonance angiography with gadodiamide. The arteries were divided into 26 segments. In total, 7956 vessel segments were evaluated with 7900 segments (99.3%) possible to evaluate. Of these, 7186 segments (91%) were normal. Luminal narrowing of > or = 50% was observed in 9 (1.5%) of the renal arteries, 12 (1.8%) of the carotid arteries, in 31 segments (1.1%) of the pelvic/upper leg territories, and in 136 segments (6.2%) of territories in the lower leg. Approximately one-third of the sample had no vascular abnormalities, one-third had stenoses of < 50%, and the remainder had stenoses > or = 50% or occlusions. Six subjects (2%) had aortic aneurysms. In subjects without evident vascular disease, 26% had significant vascular abnormalities. CONCLUSIONS: Whole-body magnetic resonance angiography performed with a clinical scanner can be used for quantifying atherosclerosis in different vascular territories in a single examination in an elderly population.

Age Distribution↗

Elevated pressure selectively blunts flow-evoked vasodilatation in rat mesenteric small arteries.

BACKGROUND AND PURPOSE: The present study investigated mechanisms underlying impaired endothelium-dependent vasodilatation elicited by elevating the intraluminal pressure in rat mesenteric small arteries. EXPERIMENTAL APPROACH: Arterial segments (internal diameter 316+/-2 microm, n=86) were mounted in a pressure myograph. The effect of elevating pressure from 50 to 120 mmHg for 1 h before resetting it to 50 mmHg was studied on endothelium-dependent vasodilatation. KEY RESULTS: In arteries constricted with U46619 in the presence of indomethacin, shear stress generated by flow, evoked vasodilatation that was abolished by an inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (1 mM), whereas acetylcholine-induced vasodilatation was unchanged. After elevation of intraluminal pressure for 1 h and then resetting it to 50 mmHg, vasodilatation induced by shear stress and the NO donor, S-nitrosopenicillamine was inhibited, while vasodilatation induced by a guanylyl cyclase activator, BAY 412272, and acetylcholine was unaltered. Superoxide levels sensitive to polyethylene glycol superoxide dismutase were increased in segments exposed to elevated pressure. A superoxide scavenger, tempol (300 microM), a general endothelin receptor antagonist, SB 217242 and the selective ET(A) receptor antagonist, BQ 123 preserved shear stress-evoked vasodilatation. CONCLUSIONS AND IMPLICATIONS: The present study shows that transient exposure to an elevated intraluminal pressure selectively inhibits flow-evoked NO-mediated vasodilatation, probably through activation of endothelin receptors and increased formation of superoxide. In contrast, elevation of pressure did not affect the acetylcholine-evoked endothelium-derived hyperpolarizing factor type vasodilatation in mesenteric small arteries.

Acetylcholine↗

Infected osteoradionecrosis of the mandible: follow-up study suggests deterioration in outcome for patients with Actinomyces-positive bone biopsies.

Infected osteoradionecrosis (IORN) is one of the major complications of oral cancer radiotherapy. Recent studies showed a high prevalence of Actinomyces in IORN. In this study, the clinical follow up of IORN patients (n=25; 20 male, 5 female) with regard to Actinomyces detection in the mandible was analyzed. Within 1.6-119 months of follow up, disease control was achieved in almost 90% of the patients with Actinomyces-negative bone biopsies, but only in 25% of the Actinomyces-positive group. The presence of Actinomyces was associated with a significantly higher risk of treatment failure (P=0.004; Fisher's exact test). This held true when the data were controlled for 'extent of bone destruction', 'type of surgery' and 'soft-tissue closure' in a logistic regression analysis (P=0.018; Wald test). Since Actinomyces was detected in a significant number of patients with non-healing mucosal defects, this microbe may promote the persistence of chronic non-healing inflammatory processes. Actinomyces positivity defines a subpopulation with a clinically deteriorated course of mandibular IORN.

Actinomyces↗

Variants in the 5' region of the neuropeptide Y receptor Y2 gene (NPY2R) are associated with obesity in 5,971 white subjects.

AIMS/HYPOTHESIS: The gene encoding neuropeptide Y receptor Y2 (NPY2R) is widely expressed in the central nervous system, with particularly high abundance in the hypothalamus, which is known to be important for appetite regulation. We tested whether variations in NPY2R are associated with obesity. METHODS: The coding region of NPY2R was analysed for mutations in 48 obese Danish white subjects and two silent substitutions were identified: SNPs 1 and 2 (rs1047214 and rs2880415). SNP1 and additional reported variants (SNPs 3-6 [rs11099992, rs12649641, rs2342676 and rs6857530]) located in the 5' region were examined in 5,971 Danish white subjects. Since SNPs 1-2 and 4-6, respectively, were in tight linkage disequilibrium large-scale analyses of genetic epidemiology were restricted to SNPs 1, 3 and 4. RESULTS: Homozygous carriers of the minor A allele of SNP4 were more common among obese subjects; the AA frequency was 15.9 (95% CI 15.2-16.6) among 4,837 non-obese subjects (BMI <30 kg/m(2)) vs 19.0 (95% CI 17.2-20.8) among 960 obese subjects (BMI > or =30 kg/m(2)), odds ratio 1.24 (95% CI 1.04-1.48), p=0.02. SNPs 1-3 were not associated with obesity. CONCLUSIONS/INTERPRETATION: Common variants rs12649641, rs2342676 and rs6857530 in the 5' region of NPY2R are associated with obesity in Danish white subjects.

5' Untranslated Regions↗

Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects.

AIMS/HYPOTHESIS: Plasma cell membrane glycoprotein 1 (PC-1) inhibits insulin signalling by direct interaction with the insulin receptor alpha subunit. This inhibition is enhanced by the minor Q allele of the K121Q polymorphism (rs1044498) in the gene (ENPP1) encoding PC-1. This polymorphism has been studied in relation to insulin resistance, type 2 diabetes and obesity in several populations with conflicting results. We assessed the impact of the ENPP1 K121Q polymorphism on type 2 diabetes, obesity and quantitative metabolic traits in 7,333 Danes. SUBJECTS AND METHODS: The K121Q polymorphism was genotyped in the population-based Inter99 study cohort (5,961 subjects) and in a group of 1,386 patients with type 2 diabetes. All subjects were Danish whites. RESULTS: No significant associations with type 2 diabetes or related quantitative metabolic traits, including measures of insulin resistance, were detected. However, a meta-analysis of the present and published studies revealed an association with type 2 diabetes (odds ratio per Q allele, 1.17 [95% CI 1.10-1.25], p=1x10(-6)). In case-control studies comparing subjects of different BMI strata, we observed a putative association of the codon 121 QQ genotype with being overweight (BMI>25 kg/m(2); odds ratio 1.63 [95% CI 1.09-2.46], p=0.015), an association not observed when comparing other levels of BMI or when analysing BMI as a quantitative trait. CONCLUSIONS/INTERPRETATION: In a meta-analysis, the ENPP1 codon 121 Q allele associates with type 2 diabetes. However, a similar association was not found in the present study of Danish white subjects. The effect of this variant on obesity in Danish subjects is contentious and further study is needed.

Adult↗

Genetic analysis of the estrogen-related receptor alpha and studies of association with obesity and type 2 diabetes.

BACKGROUND: The estrogen-related receptor alpha (ERRalpha or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRalpha (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction with the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), ERRalpha regulates key enzymes involved in the beta-oxidation of fatty acids. RESULTS: By screening 48 overweight or obese subjects for variants in the exons, exon-intron boundaries and 1000 base pairs (bp) of the promoter region of ESRRA using bi-directional nucleotide sequencing, we identified seven variants. Four rare variants had minor allele frequencies (MAF) below 1%: Pro369Pro, Gly406Asp, 3'UTR+418G>A, 3'UTR+505C>A. Two single-nucleotide polymorphisms, Pro116Pro and IVS6+65C>T (MAF 15%), were in complete linkage disequilibrium (LD) (r (2)=1). We also confirmed the presence of a reported 23 bp microsatellite repeat (ESRRA23). The Pro116Pro and ESRRA23 variants were not associated with obesity, type 2 diabetes or related phenotypes in a large population-based study of 6365 Danish whites. The two variants were examined for interactions with variants in the peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -beta; however, no evidence of epistatic effects between the variants was demonstrated. CONCLUSION: The ESRRA23 and Pro116Pro variants of the gene encoding ERRalpha are not associated with obesity, type 2 diabetes or related quantitative traits in the examined Danish whites.

Aged↗

Association of a microsatellite in FASL to type II diabetes and of the FAS-670G>A genotype to insulin resistance.

Type II diabetes is caused by a failure of the pancreatic beta-cells to compensate for insulin resistance leading to hyperglycaemia. There is evidence for an essential role of an increased beta-cell apoptosis in type II diabetes. High glucose concentrations induce IL-1beta production in human beta-cells, Fas expression and concomitant apoptosis owing to a constitutive expression of FasL. FASL and FAS map to loci linked to type II diabetes and estimates of insulin resistance, respectively. We have tested two functional promoter polymorphisms, FAS-670 G>A and FASL-844C>T as well as a microsatellite in the 3' UTR of FASL for association to type II diabetes in 549 type II diabetic patients and 525 normal-glucose-tolerant (NGT) control subjects. Furthermore, we have tested these polymorphisms for association to estimates of beta-cell function and insulin resistance in NGT subjects. We found significant association to type II diabetes for the allele distribution of the FASL microsatellite (P-value 0.02, Bonferroni corrected). The FAS-670G>A was associated with homeostasis model assessment insulin resistance index and body mass index (P-values 0.02 and 0.02). We conclude that polymorphisms of FASL and FAS associate with type II diabetes and estimates of insulin resistance in Danish white subjects.

3' Untranslated Regions↗

Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents.

INTRODUCTION: Randomly estimated fasting hyperglycaemia in an asymptomatic individual may represent the first sign of pancreatic beta-cell dysfunction. OBJECTIVE: We aimed at specifying the genetic aetiology of asymptomatic hyperglycaemia in a cohort of children and adolescents. SUBJECTS AND METHODS: We analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38 males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a randomly found blood glucose level above 5.5 mmol/l. In addition to fasting glycaemia and circulating levels of insulin and C-peptide, the subjects were tested by an oral glucose tolerance test and an intravenous glucose tolerance test and screened for mutations in the genes encoding glucokinase (GCK), HNF-1alpha (TCF1), Kir6.2 (KCNJ11) (if aged <2 years) and HNF-4alpha (HNF4A) (those with a positive family history of diabetes). RESULTS AND DISCUSSION: We identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1 mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had impaired glucose tolerance or diabetes mellitus of unknown origin. In 23 subjects, an impairment of blood glucose levels was not confirmed. We conclude that 39 of 82 paediatric patients (48%) with randomly found fasting hyperglycaemia suffered from single gene defect conditions, MODY2 being the most prevalent. An additional 11 patients (13%) progressed to overt T1DM. The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations.

Adolescent↗

A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis.

OBJECTIVE: To investigate whether the efficacy of interferon-beta (IFNbeta) treatment of relapsing-remitting MS (RR-MS) was influenced by type, dose, and frequency of administration. METHODS: From June 1996 through October 1997, the authors offered participation to all Danish RR-MS patients who met the following criteria: definite MS, at least two relapses within 2 years, age 18 to 55, and an Expanded Disability Status Scale (EDSS) score of < or = 5.5. The study was multicenter, controlled, open-label, randomized, head-to-head comparing IFNbeta-1a 22 microg once a week (n = 143) with IFNbeta-1b 250 microg every other day (n = 158), both subcutaneously, for 24 months. Patients who declined randomization were offered treatment with IFNbeta-1b 250 microg every other day (n = 120). The primary end-points were the annualized relapse rate, the time to first relapse, and neutralizing antibody formation. The secondary endpoint was time to sustained progression. RESULTS: The annual relapse rates were virtually equal in the two arms of the randomized study (IFNbeta-1a: 0.70; IFNbeta-1b: 0.71); so were the time to first relapse and the time to sustained progression. In the nonrandomized patients (IFNbeta-1b), the annual relapse rate was not significantly different, but the time to progression was shorter. CONCLUSION: In this study, 250 microg interferon-beta-1b administered every other day did not prove clinically superior to once-a-week administration of 22 microg interferon-beta-1a.

Adjuvants, Immunologic↗

The multifunctional roles of the four-and-a-half-LIM only protein FHL2.

Numerous cellular processes require the concerted action of multiple proteins that assemble in functional complexes. Protein-protein interaction domains allow specific proteins to combine with certain partners. Specificity of protein-protein association can be obtained by an interaction code predicted by conserved amino acid sequences. One of the protein-protein interaction motifs is the LIM domain, a conserved cysteine-rich module present in more than 100 different human proteins. The human four-and-a-half-LIM-only protein family consists of the members FHL1, FHL2, FHL3, FHL4 and ACT. They are expressed in a cell- and tissue-specific manner and participate in various cellular processes, including regulation of cell survival, transcription and signal transduction. Here, we review the current knowledge of the best-studied member of this family, FHL2. We describe the transcription regulation, the expression profile, the interaction partners, the subcellular localization, the biological functions and discuss the possible involvement of FHL2 in human diseases.

Amino Acid Sequence↗

[Intramuscular nodular fasciitis--a clinicopathological study with emphasis on myogenic giant cells].

Nodular fasciitis is a frequently occurring pseudosarcomatous fibrous proliferation which usually affects the subcutaneous tissue. In the present study, we investigated tissue specimens from 26 patients with intramuscular nodular fasciitis. The median age of patients was 31 years, with the tumors occurring mainly in the extremities (11 patients) and the trunk (11 patients). These had an average size of 2.6 cm. Males predominated (male:female 9:4). Histological examination revealed a proliferation of myofibroblasts (positive for smooth muscle-actin) embedded in a myxoid or fibrous stroma. In 25/26 cases, myogenic giant cells were observed (positive for desmin, negative for smooth-muscle actin and CD 68). Less frequently (11/26 patients), osteoclastic giant cells were found (positive for CD 68, negative for desmin and smooth-muscle actin). In intramuscular nodular fasciitis, myogenic giant cells are encountered more often than previously described. They are relevant for the differential diagnosis of sarcoma and fibromatoses, since they can be misinterpreted as neoplastic giant cells. However, the uniformity of the myofibroblastic proliferate and the myogenic phenotype of the giant cells without proliferative activity (no mitoses, negativity for Ki-67) lead to a correct diagnosis.

Adult↗

Solitary extramedullary plasmacytoma and granulomatous sialadenitis of the parotid gland preceding a B-cell non-Hodgkin's lymphoma.

A patient with swelling of the left parotid gland of four-months' duration, sicca syndrome (xerophthalmia and xerostomia) and a history of progressive systemic sclerosis with an incomplete form of the CREST syndrome was referred to our department. On ultrasound a parotid mass of reduced echogenicity without any enlarged cervical lymph nodes was found. Ultrasonographically guided fine-needle biopsy could not provide any definitive diagnosis. After partial parotidectomy with complete tumor removal the histologic exam showed an extramedullary plasmacytoma with concurrent non-necrotizing granulomatous sialadenitis of the parotid gland. Complete systemic work-up excluded multiple myeloma, leukemia, lymphoma and sarcoidosis. Post-operative radiotherapy of the left parotid region and left neck including the supraclavicular lymph node area was performed. Six months after surgery an aggressive B-cell non-Hodgkin's lymphoma was diagnosed.

Aged↗

[Massive adenomyosis in a patient with uterus septus completus].

Septate uterus is a malformation caused by the defective resorption of the Müllerian ducts. It may be incomplete, or -- less frequently -- complete. We present a case of a uterus septus completus with special emphasis on the endometrial changes. We describe a 46-year-old female patient (nullipara) with a known uterus septus suffering from hypermenorrhea. Sonography demonstrated a massively enlarged uterus with several nodes. Hysterectomy was performed and tissue specimens were routinely processed. Macroscopical examination revealed a 1 230 g-weight uterus septus completus. In particular, the myometrium was enlarged and exhibited a cystic cut surface with several nodes measuring up to 4.5 cm. Histologically, we found prominent adenomyosis with several leiomyomas. Patients with uterine malformations are known to suffer from endometrial dysfunction, most commonly due to endometriosis. However, massive adenomyosis in combination with leiomyomas, as presented in this case report, has not been described so far. These endometrial changes are important, since they significantly contribute to infertility.

Adenomyoma↗

Low-grade fibrosarcoma--report on 39 not otherwise specified cases and comparison with defined low-grade fibrosarcoma types.

AIMS: Low-grade fibrosarcomas are tumours that mainly affect the extremities and trunk of adults of either sex. Among these, low-grade fibromyxoid sarcoma (FMS), hyalinizing spindle cell tumour with giant collagen rosettes (HST) and sclerosing epithelioid fibrosarcoma (SEF) are well-established entities. In this study, our aim was to describe a group of low-grade fibrosarcomatous tumours, which could not be encompassed by these entities. These low-grade fibrosarcomas, not otherwise specified (FNOS) were provisionally designated as 'fibrosarcoma, low-grade fibroblastic type'. METHODS AND RESULTS: In the soft tissue tumour registry we found 39 FNOS (46%), 31 FMS (36%), 11 SEF (13%) and four HST (5%). FNOS occurred in older patients than FMS (mean age 56.3 years versus 33.7 years). They mainly showed fibrous features, but myxoid areas could also be seen. While cells tended to be loosely arranged in the myxoid areas, densely packed sheets with a storiform pattern, fascicular arrangements or regions without a defined growth pattern were observed in the fibrous areas. However, neither whirling nor swirling patterns were found. Arcade-like vessels were not visible; pseudolipoblasts did not occur. FNOS exhibited increased atypia and mitotic count compared with the other sarcomas studied [FNOS, mean value 4.6 mitoses/10 high-power field (HPF); FMS, 0.7/10 HPF). Follow-up data were available in 21 FNOS patients. In seven cases (33.3%), local recurrences were reported. Three patients (14.3%) developed metastases and all of them died of tumour. CONCLUSIONS: The term 'fibrosarcoma, low-grade fibroblastic type' should be used as a diagnosis of exclusion. Further studies should elucidate whether it represents a distinct fibrosarcoma type.

Adult↗

IRS1, KCNJ11, PPARgamma2 and HNF-1alpha: do amino acid polymorphisms in these candidate genes support a shared aetiology between type 1 and type 2 diabetes?

AIMS: Type 1 diabetes mellitus (T1DM) is a chronic disorder primarily triggered by environmental and immunological factors in genetically susceptible individuals. Despite the fact that there are indications of common aetiological features of T1DM and type 2 diabetes (T2DM), variation in genes involved in insulin secretion and insulin signalling has to a large extent been ignored as potential modifiers in the pathogenesis of T1DM. Recent studies suggest, however, that proven T2DM susceptibility gene variants may be involved in the pathogenesis of T1DM. The objective of this study was to estimate the impact of four selected amino acid polymorphisms -IRS-1 Gly972Arg, Kir6.2 Glu23Lys, HNF-1alpha Ala98Val and PPARgamma2 Pro12Ala in a Danish population of T1DM families. METHODS: All variants were genotyped in 490 simplex- and multiplex-T1DM families applying polymerase chain reaction-restriction fragment length polymorphism, and results were evaluated by means of a transmission disequilibrium test (TDT) analysis. RESULTS: TDT analysis revealed that the Arg972 IRS-1, the Lys23 Kir6.2 and the Val98 HNF-1alpha variants were transmitted from heterozygous parents to affected probands at frequencies of 49.1%, 47.0% and 54.1%, respectively (p > 0.05 for all). This was similar to the rate of transmission to unaffected siblings. The transmission rate of the Ala12 PPARgamma2 variant to affected probands was 46.5% (p > 0.05) which differed significantly from the transmission to unaffected offspring (p = 0.024). A combined analysis of the present and published pertinent data of 1691 transmissions showed a significantly decreased transmission of the PPARgamma2 Ala12 allele to affected probands (p = 0.0045). CONCLUSIONS: The Pro12Ala variant of PPARgamma2 is associated with T1DM, the minor Ala allele conferring a reduced risk. This same finding has been reported in patients with T2DM.

Adolescent↗