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Biomedical subjects

T Hansen

Publications and source records attributed to T Hansen.

At least 91 records · Page 5Linked to original sources
PubMed2001

Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function.

Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy, and 46 type 2 diabetic patients with an impaired beta-cell function by combined single-strand conformation polymorphism (SSCP) and heteroduplex analysis. Analysis of the promoter and nine exons including intron-exon boundaries of the HNF-1beta gene revealed one novel silent polymorphism and three previously reported intronic variants. The silent polymorphism (I91I) was found in one patient with late-onset type 2 diabetes. One of the intronic variant (IVS6+26T-->C) was examined further. Among 584 type 2 diabetic patients the allelic frequency was 13.1% (11.2-15.0%) compared to 11.6% (8.6-14.5%) in 229 glucose tolerant control subjects (NS). No difference in insulin secretion during an OGTT was seen between carriers of the different IVS6+26T-->C genotypes among the 229 middle-aged control subjects, nor among 302 glucose tolerant 60-year-old Danish Caucasians. Mutation analysis of the four exons comprising the DCoH gene revealed a previously described A-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects.

Adult↗
PubMed2001

[A benign form of osteopetrosis. Case report].

Osteopetrosis is a disease in which a disturbance in the resorption of bone formed by endochondral ossification takes place. The cause of the osteoclast insufficiency is unknown. In the literature, the etiology of the disease is discussed in relation to the complete absence of cathepsin K synthesis, a cysteine protease. In our case report, we demonstrated cathepsin K expression in the osteoclast cells of the benign form of osteopetrosis. We also found the macrophage marker CD 68 in these osteoclast cells, whereas other mononuclear phagocytic cells were not present in the vicinity of osteoclasts. The inhibition of osteoclast cells by phagocytes is unlikely.

Antigens, CD↗
PubMed2001

Polymorphisms in the neurogenin 3 gene (NEUROG) and their relation to altered insulin secretion and diabetes in the Danish Caucasian population.

UNLABELLED: AIM/HYPOTHESIS. Neurogenin 3 (NEUROG3) is a member of the subfamily of basic-helix-loop-helix (bHLH) transcription factors involved in differentiation of the endocrine pancreas and therefore a possible candidate gene for maturity-onset diabetes of the young (MODY) and Type II (non-insulin-dependent) diabetes mellitus. METHODS: Using Polymerase-chain-reaction single-stranded-conformation polymorphism, we examined the coding region including the 5'-untranslated and 3'- untranslated regions of the NEUROG3 in a group of 133 diabetic patients comprising 19 MODY patients, 19 patients with dominant Type I diabetes, and 31 early-onset and 64 late-onset Type II diabetic patients. RESULTS: We found two missense mutations, Glyl67Arg and Serl99Phe, as well as two non-coding variants in the 5' UTR, a c --> t nucleotide variant at position -10 upstream of the start codon in one MODY patient and a 2 base pair (CA) deletion polymorphism at position -44/-45. Allele frequencies measured in 377 diabetic patients and in 217 glucose-tolerant control subjects were: Gly167Arg, 0.04 (95 % CI: 0.02-0.06) and 0.04 (0.02-0.06); Ser199Phe, 0.31 (0.26-0.36) and 0.30 (0.24-0.36); -44-45delCA, 0.33 (0.31-0.35) and 0.35 (0.32-0.38), respectively. Both Ser199Phe and the -44-45delCA were in linkage disequilibrium (chi2 > 60) but the Ser199Phe and the -44-45delCA polymorphism were not associated with consistent changes in fasting- or glucose-induced insulin secretion in 249 glucose-tolerant offspring (first-degree relatives) of Type II diabetic parents or in 217 unrelated middle-aged glucose tolerant subjects. CONCLUSION/INTERPRETATION: Genetic variability in NEUROG3 is not associated with dominant Type I diabetes, MODY, Type II diabetes or changes in insulin secretion in the Danish Caucasians examined subjects.

3' Untranslated Regions↗
PubMed2001

Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus.

AIM/HYPOTHESIS: Phosphatase and tensin homologue deleted from chromosome ten (PTEN) has recently been characterized as a novel member in the expanding network of proteins regulating the intracellular effects of insulin. By dephosphorylation of phosphatidyl-inositol-(3, 4, 5)-trisphosphate (PIP3) the PTEN protein regulates the insulin-dependent phosphoinositide 3-kinase (PI3K) signalling cassette and accordingly might function as a regulator of insulin sensitivity in skeletal muscle and adipose tissue. In this study we tested PTEN as a candidate gene for insulin resistance and late-onset Type II (non-insulin-dependent) diabetes mellitus in a Danish Caucasian population. METHODS: The nine exons of the PTEN, including intronic flanking regions were analysed by PCR-SSCP and heteroduplex analysis in 62 patients with insulin-resistant Type II diabetes. RESULTS: No mutations predicted to influence the expression or biological function of the PTEN protein but four intronic polymorphisms were identified: IVS1-96 A-->G (allelic frequency 0.22, 95 % CI: 0.12-0.32), IVS3 + 99 C-->T (0.01, CI: 0-0.03), IVS7-3 TT-->T (0.10, CI: 0.03-0.18) and IVS8 + 32 G-->T (0.35, CI: 0.23-0.47). The IVS8 + 32 G-->T polymorphism was used as a bi-allelic marker for the PTEN locus and examined in 379 patients with Type II diabetes and in 224 control subjects with normal glucose tolerance. The IVS8 + 32 G-->T polymorphism in the PTEN was not associated with Type II diabetes and it did not have any effect on body-mass index, blood pressure, HOMA insulin resistance index, or concentrations of plasma glucose, serum insulin or serum C peptide obtained during an oral glucose tolerance test (OGTT). CONCLUSION/INTERPRETATION: Variability in the PTEN is not a common cause of Type II diabetes in the Danish Caucasian population.

Adipose Tissue↗
PubMed2001

Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus.

AIM/HYPOTHESIS: This study aimed to investigate if variability in the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) gene is associated with Type II (non-insulin-dependent) diabetes mellitus. METHODS: The PGC-1 gene was examined in 53 Type II diabetic patients applying single strand conformational polymorphism analysis followed by nucleotide sequencing. Identified variants were genotyped in an association study comprising 483 Type II diabetic patients and 216 glucose-tolerant control subjects. A replication study was done in an additional 201 Type II diabetic patients and 293 glucose-tolerant subjects. Furthermore, a potential interaction between the Pro12Ala polymorphism of PPAR-gamma2 and the PGC-1 Gly482Ser variant on risk of Type II diabetes was investigated. RESULTS: A total of seven variants (Ser74Leu, IVS2 + 52C-->A, Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, and Thr612Met) were identified and investigated in an association study. Six of the variants showed no association with Type II diabetes in the initial study. However, the Gly482Ser polymorphism, was more frequent among Type II diabetic patients (37.0 %) than among glucose-tolerant subjects (30.8 %) (p = 0.032). In a replication study the difference in allele frequencies of the Gly482Ser variant remained significant (p = 0.0135). The combined study yielded an allele frequency of 37.3 % (34.7-39.9) for Type II diabetic patients and 30.5 % (27.7-33.4) for glucose-tolerant subjects (p = 0.0007). No interaction between this variant and the Pro12Ala polymorphism of PPAR-gamma2 was observed. CONCLUSION/INTERPRETATION: A widespread Gly482Ser polymorphism of PGC-1 is associated with a 1.34 genotype relative risk of Type II diabetes.

Aged↗
PubMed2001

Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians.

AIMS/HYPOTHESIS: We examined whether the Pro12-Ala polymorphism of the human peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene was related to altered insulin sensitivity among glucose-tolerant subjects or a lower accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent) diabetes mellitus among Scandinavian Caucasians. METHODS: The Pro12Ala polymorphism was examined using PCR-RFLP Whole-body insulin sensitivity measured under hyperinsulinaemic-euglycaemic conditions was estimated in a population-based sample of 616 glucose tolerant Swedish Caucasian men at age 70. In addition, insulin sensitivity index was measured using IVGTT and Bergman minimal modelling in a population-based sample of 364 young healthy Danish Caucasians. Finally, we evaluated whether the polymorphism predicted Type II diabetes and IGT in 841 seventy-year-old Swedish men. A case-control study was carried out in 654 unrelated Danish Type II diabetic patients and 742 Danish glucose tolerant subjects matched for age and sex. RESULTS: Whole-body insulin sensitivity was significantly improved in carriers compared with non-carriers of the Ala-allele of the codon 12 polymorphism in Swedish Caucasian men (6.0+/-2.5 vs 5.6+/-2.5 mg kg(-1) x min(-1) x mU/l](-1) x 100, p = 0.044). The same tendency, but not significant, was observed in the insulin sensitivity index among the group of young healthy Danish Caucasians. The incidence of Type II diabetes and IGT among the Swedish subjects at the age of 70 was similar in the three genotype-groups of the Pro12Ala variant and the Ala-allele was not related to a lower prevalence of Type II diabetes in Danish Caucasians. CONCLUSION/INTERPRETATION: The Ala-allele of the PPAR-gamma2 polymorphism is associated with improved whole body insulin sensitivity among Swedish Caucasians.

Aged↗
PubMed2001

Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus.

AIMS/HYPOTHESIS: We aimed to examine the promoter of SUR1 for genetic variation and to determine if variants were associated with Type II (non-insulin-dependent) diabetes mellitus or measures of beta-cell function. METHODS: We examined 465 bp upstream of the ATG site in 46 Type II diabetic patients and 15 glucose tolerant control subjects by SSCP-heteroduplex analysis. RESULTS: We identified an a --> t substitution 437 bp upstream of the ATG site. The allelic frequency was similar in 455 unrelated Type II diabetic patients and in 203 glucose tolerant control subjects matched for age (0.036, [95 % CI 0.019-0.053] vs 0.034 [95 % CI 0.009-0.059]; p = 0.92). Among the glucose tolerant subjects there were no differences between non-carriers (n = 189) and carriers (n = 14) of the variant in fasting values or 30 min values of plasma glucose and serum insulin during an oral glucose tolerance test. In a study of 233 glucose tolerant offspring of and spouses to Danish Caucasian Type II diabetic patients, non-carriers (n = 193) and carriers (n = 37) of the -437 a/t polymorphism did not differ in glucose or tolbutamide stimulated insulin response during an intravenous glucose tolerance test with intravenous tolbutamide injection [AUCs-insulin (0-8) min, 2290 +/- 1660 vs 2308 +/- 1935 pmol/l x min and AUCs-insulin(20-30 min), 3113 +/- 2033 vs. 3393 +/- 2830 pmol/l x min, respectively]. CONCLUSION/INTERPRETATION: We have identified a novel a/t polymorphism of the SUR1 gene promoter which is not associated with Type II diabetes mellitus or measures of beta-cell function. Previous reported non-functional variants of SUR1 associated with Type II diabetes mellitus still need to be accounted for.

ATP-Binding Cassette Transporters↗
PubMed2001

Detection of mRNA by non-radioactive direct primed in situ reverse transcription.

There are various techniques to detect mRNA in tissue specimens. Among these in situ hybridization is widely applied, and for the detection of small quantities of RNA in situ reverse transcriptase polymerase chain reaction (in situ RT-PCR) has been applied. Furthermore in situ transcription, where signal is produced by direct incorporation of labeled nucleotides during production of a cDNA by reverse transcription, has been shown by a few investigators. We present a non-radioactive in situ reverse transcriptase (in situ RT) protocol which is at least as sensitive as in situ hybridization but avoids probe production and long procedures of preincubation, incubation, and washing. Digoxigenin-labeled UTP is incorporated into a cDNA produced by in situ reverse transcription of mRNA. This method is combined with the fast and sensitive immunogold-silver detection system allowing demonstration of the mRNA within 7 h compared to days in the case of in situ hybridization. Contrary to in situ RT-PCR this new method of in situ RT has no background problems due to non-specific amplification or diffusion of the reaction product.

Animals↗
PubMed2001

Visual filling-in for computing perceptual surface properties.

The visual system is constantly confronted with the problem of integrating local signals into more global arrangements. This arises from the nature of early cell responses, whether they signal localized measures of luminance, motion, retinal position differences, or discontinuities. Consequently, from sparse, local measurements, the visual system must somehow generate the most likely hypothesis that is consistent with them. In this paper, we study the problem of determining achromatic surface properties, namely brightness. Mechanisms of brightness filling-in have been described by qualitative as well as quantitative models, such as by the one proposed by Cohen and Grossberg. We demonstrate that filling-in from contrast estimates leads to a regularized solution for the computational problem of generating brightness representations from sparse estimates. This provides deeper insights into the nature of filling-in processes and the underlying objective function one wishes to compute. This particularly guided the proposal of a new modified version of filling-in, namely confidence-based filling-in which generates more robust brightness representations. Our investigation relates the modeling of perceptual data for biological vision to the mathematical frameworks of regularization theory and linear spatially variant diffusion. It therefore unifies different research directions that have so far coexisted in different scientific communities.

Animals↗
PubMed2001

Expression of cysteine proteinases cathepsins B and K and of cysteine proteinase inhibitor cystatin C in giant cell tumor of tendon sheath.

The expression of cysteine proteinases cathepsins B and K and of the endogenous inhibitor of cysteine proteinases, cystatin C, was investigated in tissue specimens of patients with giant cell tumor of tendon sheath (GCTTS). Expression of both enzymes was examined by immunohistochemistry in tissue specimens of 14 patients with GCTTS. Applying double-labeling techniques, the coexpression of cathepsin B and its major endogenous inhibitor cystatin C was additionally studied. Cells expressing the respective proteins were further characterized with the macrophage markers HAM56 and anti-CD68 (clone PG-M1). Cathepsin B could be detected in numerous HAM56-positive mononuclear cells (MC), but only in very few giant cells (GC). In contrast, cathepsin K was predominantly identified in GC that were also strongly immunoreactive for cystatin C and CD68. Coexpression of cathepsin B and cystatin C occurred only in a few MC. The strong expression of both cathepsin B and K suggests that in GCTTS, bone erosion might be mediated not only by pressure of the proliferative tissue, but also by matrix-degrading cysteine proteinases. Because previous studies showed that osteoclasts express high levels of CD68, cathepsin K, and cystatin C but not of cathepsin B, our study contributes to the view that GC of GCTTS and osteoclasts are closely associated.

Adult↗
PubMed2001

Expression of matrix-degrading cysteine proteinase cathepsin K in cholesteatoma.

Cholesteatoma is a nonneoplastic lesion of the middle ear space or mastoid that is histologically characterized by a progressive bone erosion of the ossicles and surrounding bone. Several matrix-degrading enzymes have been implicated as mediators of this bone erosion. Because the novel cysteine proteinase cathepsin K has been shown to play a central role in bone resorption, we examined the expression of this enzyme in tissue specimens of cholesteatoma. Tissue specimens of 9 patients with cholesteatoma were obtained during middle-ear surgery. Expression of cathepsin K mRNA was determined by RT-PCR using specific primers. Immunohistochemical analysis of cathepsin K protein expression in tissue sections was performed by using the streptavidin-alkaline phosphatase technique. Expression of both cathepsin K mRNA and protein was detected in areas affected by cholesteatoma, whereas specimens of nonaffected ear cartilage and surrounding tissue were not positive. In addition, cathepsin K was detected in numerous multinucleated giant cells, particularly osteoclasts at the site of bone degradation. In contrast, keratinized squamous epithelium was negative for cathepsin K. These data demonstrate that the matrix-degrading cysteine proteinase cathepsin K may be involved in bone erosion in cholesteatoma. Strong expression of this collagenolytic enzyme in osteoclasts suggests that these cells are mainly involved in cathepsin K-mediated bone destruction.

Adult↗
PubMed2001

The expression of cathepsins in osteoclast-like giant cells of an anaplastic thyroid carcinoma with tracheal perforation.

Anaplastic carcinoma of the thyroid gland (ACT) is a rapidly growing neoplasm with a very poor prognosis. In this study, we examined an ACT with osteoclast-like giant cells expressing matrix--degrading cysteine proteinases and their endogeneous inhibitor cystatin C. Bronchoscopic evaluation of a 50-year-old man suffering from hoarseness, dysphagia, and dyspnea revealed an irregular tumor mass infiltrating into the trachea and the cricothyroid ligament region. On histological examination, a necrotizing undifferentiated anaplastic carcinoma with osteoclast-like giant cells was detected. An immunohistochemical study of the tumor tissue was performed using a panel of 15 antibodies, including double labeling techniques. Most of the osteoclast-like multinucleated giant cells (MGC) expressed CD68 and cathepsin K. Colocalization of cathepsin B and its endogenous inhibitor cystatin C occurred in the majority of MGC. Mononuclear cells (MC) were positive for cathepsin B, cystatin C, and CD 68, but only faintly for cathepsin K. Expression of cathepsins B and K in the MGC of the ACT might contribute to the invasive behavior of this tumor, thus promoting metastatic ability and destruction of the cartilagenous trachea.

Biomarkers, Tumor↗
PubMed2001

High-dose proton-pump inhibitors as a diagnostic test of gastro-oesophageal reflux disease in endoscopic-negative patients.

BACKGROUND: To evaluate a high dose of a proton-pump inhibitor as a diagnostic test in endoscopy-negative patients presenting with symptoms indicating gastro-oesophageal reflux disease. METHODS: 64 patients were studied in a prospective, randomized, double-blind study, using a cross-over design. After a run-in period with the diary registration of basic GORD symptoms and recording of the consumption of antacid tablets, the patients were given either 60 mg of lansoprazole once daily or placebo in randomized order. Symptoms were recorded, as well as antacid tablets taken in order to relieve pain. GORD was determined by 24-h oesophageal pH monitoring. The test was considered positive when consumption of antacid tablets was reduced > or = 75% compared to pretreatment. RESULTS: In the GORD group, 29 (85%) tested positive during active treatment compared to 3 (9%) when on placebo. Corresponding figures for the non-GORD patients were 50% and 27%, giving a test sensitivity and specificity of 85% and 73%, respectively. During active treatment, VAS scores for acid regurgitation, heartburn and over all were significantly lowered in GORD patients, compared to heartburn only in the non-GORD group. CONCLUSIONS: 60 mg lansoprazole once daily for 5 days is an easy to use method for diagnosing GORD in endoscopy-negative patients. Using 24-h oesophageal pH monitoring as the reference method, the sensitivity was relatively high, while the specificity was lower. Further studies are needed to determine how a PPI could be used as a diagnostic test in GORD.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Diabetic microvascular complications are not associated with two polymorphisms in the GLUT-1 and PC-1 genes regulating glucose metabolism in Caucasian type 1 diabetic patients.

BACKGROUND: An XbaI polymorphism in the gene encoding the glucose transporter, GLUT-1, is associated with development of diabetic nephropathy in Chinese type 2 diabetic patients. In addition, an amino acid variant (K121Q) in the gene encoding the glycoprotein plasma cell differentiating antigen (PC-1), a specific inhibitor of insulin receptor signalling, has been reported to predict a faster progression of nephropathy in Italian and British type 1 diabetic patients. METHODS: The XbaI and K121Q polymorphisms were determined by PCR-RFLP in Danish type 1 diabetic patients with nephropathy (122 men/77 women, age 40.9+/-9.6 years, diabetes duration 27+/-8 years) and type 1 diabetic patients with persistent normoalbuminuria (118 men/74 women, age 42.7+/-10.2 years, diabetes duration 26+/-9 years). Proliferative retinopathy was present in 156 patients (40%), while 67 patients (17%) had no diabetic retinopathy. RESULTS: There were no differences in the frequency of GLUT-1 XbaI genotypes between type 1 diabetic patients with diabetic nephropathy and type 1 diabetic patients with normoalbuminuria: 72 (41%)/87 (50%)/16 (9%) vs 94 (49%)/74 (39%)/24 (13%) had GLUT-1 XbaI +/+, +/- or -/- genotype respectively (NS). The frequency of PC-1 KK, KQ and QQ genotypes were 141 (71%)/52 (26%)/6 (3%) vs 138 (73%)/45 (24%)/7 (4%) in patients respectively with and without nephropathy (NS). Neither were associations between the investigated polymorphisms and simplex or proliferative retinopathy revealed. CONCLUSIONS: Neither the PC-1 K121Q nor the GLUT-1 XbaI polymorphism contribute to the genetic susceptibility of diabetic microvascular complications in Danish type 1 diabetic patients.

Adolescent↗
PubMed2001

Novel type of glucose-6-phosphate isomerase in the hyperthermophilic archaeon Pyrococcus furiosus.

Glucose-6-phosphate isomerase (phosphoglucose isomerase [PGI]) (EC 5.3.1.9) from the hyperthermophilic archaeon Pyrococcus furiosus was purified 500-fold to homogeneity. The enzyme had an apparent molecular mass of 43 kDa and was composed of a single type of subunit of 23 kDa indicating a homodimeric (alpha(2)) structure. Kinetic constants of the enzyme were determined at the optimal pH 7 and at 80 degrees C. Rate dependence on both substrates followed Michaelis-Menten kinetics. The apparent K(m) values for glucose-6-phosphate and fructose-6-phosphate were 8.7 and 1.0 mM, respectively, and the corresponding apparent V(max) values were 800 and 130 U/mg. The enzyme had a temperature optimum of 96 degrees C and showed a significant thermostability up to 100 degrees C, which is in accordance with its physiological function under hyperthermophilic conditions. Based on the N-terminal amino acid sequence of the subunit, a single open reading frame (ORF; Pf_209264) was identified in the genome of P. furiosus. The ORF was characterized by functional overexpression in Escherichia coli as a gene, pgi, encoding glucose-6-phosphate isomerase. The recombinant PGI was purified and showed molecular and kinetic properties almost identical to those of the native PGI purified from P. furiosus. The deduced amino acid sequence of P. furiosus PGI did not reveal significant similarity to the conserved PGI superfamily of eubacteria and eucarya. This is the first description of an archaeal PGI, which represents a novel type of PGI.

Amino Acid Sequence↗
PubMed2001

Subcellular localization of bilirubin in rat brain after in vivo i.v. administration of [3H]bilirubin.

Bilirubin appears to be toxic in vitro to several cellular functions localized to different subcellular compartments. It would therefore be useful to know what concentrations of bilirubin might be found in cell organelles in vivo. Rats were anesthetized and allocated to one of three groups: control, hypercarbia, and hyperosmolality. Each rat received a 5-min bolus dose of bilirubin 50 mg/kg i.v. (containing approximately 200 microCi [(3)H]bilirubin). Rats were killed 10 or 30 min after the start of the bilirubin infusion. Each brain was homogenized, and subcellular fractions were isolated by high-speed gradient centrifugation in sucrose media. The gradients were separated into aliquots of 2 mL, and the protein content was determined in each aliquot. Radioactivity was determined by scintillation counting, and the content of bilirubin per milligram of protein was calculated. Statistical comparisons were performed with Kruskal-Wallis nonparametric ANOVA. There were highly significant differences in bilirubin content per milligram of protein among subcellular compartments in all groups and at both time points. In all groups there were relatively high concentrations of bilirubin in the myelin fraction, an interesting observation in light of the theory that membranes are the primary target of bilirubin toxicity. The very high concentration of bilirubin relative to protein in cytoplasm, ribosomes, and mitochondria in the hyperosmolar group are also notable in light of data from hyperbilirubinemic animals in which changes in electrophysiology or energy metabolism only appeared after hyperosmolar opening of the blood-brain barrier. The present data may be useful in planning in vitro studies of bilirubin toxicity in cell organelles.

Animals↗
PubMed2001

A prevalent polymorphism in the promoter of the UCP3 gene and its relationship to body mass index and long term body weight change in the Danish population.

Variability of the uncoupling protein 3 (UCP3) promoter has been associated with increased body mass index (BMI) and altered lipid profiles. Here we tested the hypothesis that variation of the UCP3 promoter is associated with either juvenile or maturity-onset obesity or body weight change over a 26-yr follow-up among Danish subjects. Mutation screening of approximately 1 kb 5' upstream of the UCP3 gene revealed one previously described -55 C-->T variant. The frequency of the polymorphism was evaluated by restriction fragment length polymorphism analysis in four groups of subjects: 1) a group of 744 obese Danish men who at the draft board examinations had a body mass index (BMI) of at least 31 kg/m(2), 2) a randomly selected control group consisting of 857 draftees, 3) 258 middle-aged subjects, and 4) 409 60-yr-old subjects. The frequency of the T allele was 26.0% (95% confidence interval, 23.8-28.2%) among the obese draftees and 26.9% (24.8-29.0%) in the control group (P = 0.6). The variant was not associated with BMI at a young age or with weight gain after a 26-yr follow-up. The frequency of the T allele was 29.5% (25.6-33.4%) in the middle-aged group and 25.8% (22.8-28.8%) among the 60-yr-old subjects. The polymorphism was not associated with increased BMI or percent body fat in these 2 groups. It is concluded that this variant does not play a major role in the development of common obesity among Danish subjects.

Adult↗