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Biomedical subjects

B F Hansen

Publications and source records attributed to B F Hansen.

At least 19 recordsLinked to original sources
PubMed2006

Partial rescue of in vivo insulin signalling in skeletal muscle by impaired insulin clearance in heterozygous carriers of a mutation in the insulin receptor gene.

AIMS/HYPOTHESIS: Recently we reported the coexistence of postprandial hypoglycaemia and moderate insulin resistance in heterozygous carriers of the Arg1174Gln mutation in the insulin receptor gene (INSR). Controlled studies of in vivo insulin signalling in humans with mutant INSR are unavailable, and therefore the cellular mechanisms underlying insulin resistance in Arg1174Gln carriers remain to be clarified. SUBJECTS, MATERIALS AND METHODS: We studied glucose metabolism and insulin signalling in skeletal muscle from six Arg1174Gln carriers and matched control subjects during a euglycaemic-hyperinsulinaemic clamp. RESULTS: Impaired clearance of exogenous insulin caused four-fold higher clamp insulin levels in Arg1174Gln carriers compared with control subjects (p<0.05). In Arg1174Gln carriers insulin increased glucose disposal and non-oxidative glucose metabolism (p<0.05), but to a lower extent than in controls (p<0.05). Insulin increased Akt phosphorylation at Ser473 and Thr308, inhibited glycogen synthase kinase-3alpha activity, reduced phosphorylation of glycogen synthase at sites 3a+3b, and increased glycogen synthase activity in Arg1174Gln carriers (all p<0.05). In the insulin-stimulated state, Akt phosphorylation at Thr308 and glycogen synthase activity were reduced in Arg1174Gln carriers compared with controls (p<0.05), whereas glycogen synthase kinase-3alpha activity and phosphorylation of glycogen synthase at sites 3a+3b were similar in the two groups. CONCLUSIONS/INTERPRETATION: In vivo insulin signalling in skeletal muscle of patients harbouring the Arg1174Gln mutation is surprisingly intact, with modest impairments in insulin-stimulated activity of Akt and glycogen synthase explaining the moderate degree of insulin resistance. Our data suggest that impaired insulin clearance in part rescues in vivo insulin signalling in muscle in these carriers of a mutant INSR, probably by increasing insulin action on the non-mutated insulin receptors.

Adult↗
PubMed2006

Genotypic relatedness of yeasts in thrush and denture stomatitis.

BACKGROUND/AIM: Candida is an opportunistic pathogen. Understanding its genetic characters might increase our understanding of the pathogenesis of candidosis. We examined the genetic relationships of yeasts from the most common forms of oral candidosis: thrush and denture stomatitis. METHODS: Yeasts were sampled from palate, buccal mucosa, gingival sulci/periodontal pockets and/or denture fitting surface of 19 thrush patients and 22 denture stomatitis patients. Random amplified polymorphic DNA and the Dendron computer-assisted program were used to determine the genotypic relatedness of the yeasts. RESULTS: A dendrogram generated from 105 thrush isolates had similarity coefficients (S(AB)) ranging from 0.58 to 1 with four clusters derived at S(AB) 68%. Another dendrogram was generated from 91 isolates from denture stomatitis, with S(AB) ranging from 0.59 to 1. Three clusters were established at S(AB) 71%. In a composite dendrogram incorporating the thrush and denture stomatitis data and orally healthy data compiled from a previous study, five genotypic clusters were generated at S(AB) 68%. Cluster II, the most dominant, comprised isolates from thrush, denture stomatitis and healthy conditions, while clusters III and IV contained yeasts mainly from thrush. CONCLUSIONS: Palatal yeast carriage was significantly increased in thrush and denture stomatitis, also after radiation, chemotherapy and denture wearing. The buccal mucosa was favorable for yeast colonization regardless of oral condition. Yeasts in thrush were more diverse than in conditions of oral health. The common clone (II) of infecting yeasts and commensals suggested that commensals could induce thrush and denture stomatitis, whereas the unique clones in thrush (III, IV) might have been established through strain replacement or maintenance with minor genetic variation.

Adolescent↗
PubMed2005

Short hard palate in prenatal trisomy 21.

OBJECTIVE: The aim of the present study was for the first time to examine on postmortal material the total midpalatal length of the hard palate and the length of its two components (the maxillary and palatine parts) in trisomy 21 fetuses, and to compare the results to normal standards. DESIGN: Material from 31 human fetuses with genetically verified trisomy 21 was studied. The fetuses were derived from legally induced or spontaneous abortions. Palates were, after sectioning, radiographed in lateral projection (Grenz Ray radiographic apparatus). Cephalometric measurements were performed with a digital caliper. Statistically, the length measurements for the two groups were compared, adjusting for crown rump length (CRL) through linear regression. At two specific ages (150 and 170 mm CRL), the length of the palatal components in trisomy 21 was compared to normal standards. RESULTS: For CRL 150 mm and CRL 170 mm it appears that all three palatal lengths, total length, maxillary length, and palatinal length are significantly shorter in fetuses with trisomy 21. CONCLUSION: The main conclusion of our study is that the total palatal length in prenatal trisomy 21 is shorter than normal and that this is due both to a shortness of the maxillary and the palatine components of the hard palate.

Cephalometry↗
PubMed2003

The pre-natal development and osseous growth of the human cerebellar field.

OBJECTIVES: To describe the pre-natal development of the bones that enclose the cerebellum and part of the brain stem (the neuro-osteological cerebellar field) in the mid-sagittal plane. DESIGN: Radiographic, cephalometric and histologic examination of normal pre-natal human fetuses; 50 normal fetuses, with crown-rump length of 18-227 mm and approximate gestational age from 6 to 26 weeks. RESULTS: The cerebellar field expressed extensive growth during development both sagittally and vertically. Because of changes in shape, the field was displaced in an anterio-caudal direction. CONCLUSION: In the present study we recorded normal measurements of size, shape and position of the cerebellar field. These standards can be used as references in skeletal analysis of cases with cranial abnormalities and cerebellar malformations.

Cephalometry↗
PubMed2003

The prenatal development of the human cerebellar field in Down syndrome.

OBJECTIVES: To describe the development of the osseous field enclosing the cerebellum and part of the brain stem (the neuro-osteological cerebellar field) in Down syndrome, and compare the development with normal developmental standard of the field. DESIGN: Radiographic, cephalometric and histologic examination of 58 legally or spontaneously aborted Down syndrome prenatal human fetuses; crown-rump length of 80-255 mm and approximate gestational age from 13 to 26 weeks. RESULTS: The growth of the Down syndrome cerebellar field is smaller in the sagittal and vertical directions than in normal fetuses. CONCLUSION: In the present study the pathological development of the cerebellar field was described in a genotypic sample. In combining normal and pathological development of neural and osseous tissues a better understanding of the genotype/phenotype interactions is attainable and fields of common gene expression maybe defined.

Cephalometry↗
PubMed2002

Spatiotemporal expression of NGFR during pre-natal human tooth development.

OBJECTIVES: The relation between nerve growth factor receptor (NGFR) in the human pre-natal tooth buds and the dental follicle was investigated. In particular, we sought to determine if there is a specific pattern of p75NGFR expression in developing human tooth buds and their surrounding tissue. SETTING AND SAMPLE POPULATION: The Department of Orthodontics at Copenhagen University, Denmark. Histological sections from 11 fetuses, aged 11-21 gestational weeks. METHOD: The sections were studied by conventional immunohistochemistry. RESULTS: Specific spatiotemporal patterns of p75NGFR reactions were observed in the tooth buds and dental follicle: Before matrix production by the ameloblasts, the entire inner enamel epithelium and the entire dental follicle display p75NGFR immunoreactivity; after matrix production is initiated, the immunoreactivity of the matrix producing cells is lost, as is that of the dental follicle adjacent to these matrix-producing cells. CONCLUSION: A unique spatiotemporal distribution of NGFR in the pre-eruptive human tooth bud was demonstrated.

Dental Sac↗
PubMed2001

[Histological examination of the gallbladder after cholecystectomy].

BACKGROUND AND OBJECTIVES: Normally, the gallbladder is sent routinely for histological examination after cholecystectomy. From a cost-benefit point of view this may not be optimal. METHODS: Computerised records were used to identify patients with gallbladder carcinoma over a 20-year period, from 1979 to 1999, and these patient records were evaluated manually. RESULTS: The estimated cost for one histological examination was $37. During the period, 4,614 cholecystectomies were performed and 33 patients had gallbladder carcinoma. In 29 of the 33 patients, there was evident preoperative and/or peroperative suspicion of cancer, but no such suspicion in four patients. These four patients had other peroperative macroscopic abnormal findings, besides gallbladder stones. CONCLUSION: This retrospective series indicates that in the case of normal preoperative and/or peroperative macroscopic conditions (except for gallbladder stones) there is no need for histological examination of the gallbladder.

Aged↗
PubMed2001

p75NGFR immunoreactivity in normal prenatal human dorsal root ganglia.

The purpose of the present study was to examine immunohistochemically the expression of the low-affinity p75 nerve growth factor receptor in the dorsal root ganglia from 12 human fetuses (gestational ages, 10-24 weeks) located in three different spinal segments (cervical, thoracic, and lumbosacral), using a monoclonal mouse-antihuman low-affinity p75 nerve growth factor receptor antibody. The low-affinity p75 nerve growth factor receptor immunoreactivity was present within the dorsal root ganglia and the surrounding nerve fibers in all spinal segments at the different gestational ages examined. From 10 weeks of gestation, three different types of neuronal staining were observed: dorsal root ganglia neurons without low-affinity p75 nerve growth factor receptor immunoreactivity (classified as type I neurons), neurons displaying weak low-affinity p75 nerve growth factor receptor immunoreactivity (classified as type II neurons), and neurons manifesting intense low-affinity p75 nerve growth factor receptor immunoreactivity (classified as type III neurons). The distribution of the three types of neurons in the dorsal root ganglia was identical in the three spinal segments and did not change between 10 and 24 weeks of gestation. This study provides the first demonstration of the low-affinity p75 nerve growth factor receptor immunoreactivity in the dorsal root ganglia from human fetuses at different gestational ages.

Female↗
PubMed2001

Cellular mechanism of nutritionally induced insulin resistance in Psammomys obesus: overexpression of protein kinase Cepsilon in skeletal muscle precedes the onset of hyperinsulinemia and hyperglycemia.

The sand rat (Psammomys obesus) is an animal model of nutritionally induced diabetes. We report here that several protein kinase C (PKC) isoforms (alpha, epsilon, and zeta, representing all three subclasses of PKC) are overexpressed in the skeletal muscle of diabetic animals of this species. This is most prominent for the epsilon isotype of PKC. Interestingly, increased expression of PKCepsilon could already be detected in normoinsulinemic, normoglycemic (prediabetic) animals of the diabetes-prone (DP) line when compared with a diabetes-resistant (DR) line. In addition, plasma membrane (PM)-associated fractions of PKCalpha and PKCepsilon were significantly increased in skeletal muscle of diabetic animals, suggesting chronic activation of these PKC isotypes in the diabetic state. The increased PM association of these PKC isotypes revealed a significant correlation with the diacylglycerol content in the muscle samples. Altered expression/activity of PKCepsilon, in particular, may thus contribute to the development of diabetes in these animals; along with other PKC isotypes, it may be involved in the progression of the disease. This may possibly occur through inhibition of insulin receptor (IR) tyrosine kinase activity mediated by serine/threonine phosphorylation of the IR or insulin receptor substrate 1 (IRS-1). However, overexpression of PKCepsilon also mediated down-regulation of IR numbers in a cell culture model (HEK293), resulting in attenuation of insulin downstream signaling (reduced protein kinase B [PKB]/Akt activity). In accordance with this, we detected decreased 125I-labeled insulin binding, probably reflecting a downregulation of IR numbers, in skeletal muscle of Psammomys animals from the DP line. The number of IRs was inversely correlated to both the expression and PM-associated levels of PKCepsilon. These data suggest that overexpression of PKCepsilon may be causally related to the development of insulin resistance in these animals, possibly by increasing the degradation of IRs.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle.

1. 5'-AMP-activated protein kinase (AMPK) has been suggested to play a key role in the regulation of metabolism in skeletal muscle. AMPK is activated in treadmill-exercised and electrically stimulated rodent muscles. Whether AMPK is activated during exercise in humans is unknown. 2. We investigated the degree of activation and deactivation of alpha-isoforms of AMPK during and after exercise. Healthy human subjects performed bicycle exercise on two separate occasions at either a low ( approximately 50% maximum rate of O2 uptake (VO2,max) for 90 min) or a high ( approximately 75% VO2,max for 60 min) intensity. Biopsies from the vastus lateralis muscle were obtained before and immediately after exercise, and after 3 h of recovery. 3. We observed a 3- to 4-fold activation of the alpha2-AMPK isoform immediately after high intensity exercise, whereas no activation was observed after low intensity exercise. The activation of alpha2-AMPK was totally reversed 3 h after exercise. In contrast, alpha1-AMPK was not activated during either of the two exercise trials. 4. The in vitro AMP dependency of alpha2-AMPK was significantly greater than that of alpha1-AMPK ( approximately 3- vs. approximately 2-fold). 5. We conclude that in humans activation of alpha2-AMPK during exercise is dependent upon exercise intensity. The stable activation of alpha2-AMPK, presumably due to the activation of an upstream AMPK kinase, is compatible with a role for this kinase complex in the regulation of skeletal muscle metabolism during exercise, whereas the lack of stable alpha1-AMPK activation makes this kinase complex a less likely candidate.

AMP-Activated Protein Kinases↗
PubMed2000

[Eosinophilic enteritis].

We present a case of eosinophilic enteritis in a 45 year-old male with clinical and radiological signs of stenotic inflammatory ileal disease. A diagnosis of Crohn's disease was considered. He developed small bowel obstruction and sixty cm of obstructed ileum was resected. Histopathological examination revealed the diagnosis of eosinophilic enteritis primarily localized to the tunica muscularis. One year postoperatively he relapsed and small bowel X-ray demonstrated 1 m narrow and irregular ileum. He was treated with mesalamine, azathioprine, and cromoglicate, went into remission and fares well one and a half years later.

Diagnosis, Differential↗
PubMed2000

The use of the CELLection kit in the isolation of carcinoma cells from mononuclear cell suspensions.

A study was performed to evaluate in vitro the sensitivity, specificity and variability of a new immunomagnetic microbead isolation technique which provides subsequent immunological staining of captured carcinoma cells. In a mixture of peripheral blood mononuclear cells (PBMCs) and human carcinoma cells the epithelial cancer cells were isolated with the Dynal((R)) RAM IgG1 CELLection Kit using Dynabeads M-280 coated with a rat monoclonal antibody (Mab) against mouse IgG1. The rat Mab was biotinylated and attached to Dynabeads via streptavidin and a DNA linker. The anti-epithelial monoclonal mouse antibody Ber-EP4 was used as the primary capture antibody. In order to permit phenotyping of the isolated carcinoma cells the magnetic beads were removed from the carcinoma cells by DN'ase digestion of the DNA linker between the magnetic bead and the secondary antibody. In an ex vivo model system an average recovery of approximately 60% of a human colon carcinoma cell line HCC-2998 seeded in 5.10(6) PBMCs was obtained, and the recovered cells could subsequently be immunologically stained for the surface antigen CD87 (urokinase plasminogen activator receptor). No positive stained cells were found in control experiments with PBMCs without carcinoma cells. Despite a relatively low recovery, the described method will be valuable for the detection of carcinoma cells in cytospin preparations with subsequent phenotyping of the cells for expression of surface antigens. Depending on the chosen antibodies, the method may be useful for the isolation and characterisation of other cell types in various cell suspensions.

Animals↗
PubMed2000

Abnormal timing in the prenatal ossification of vertebral column and hand in Crouzon syndrome.

We report on a radiographically examined fetus (gestational age 13 weeks) with Crouzon syndrome caused by a mutation in the gene encoding the fibroblast growth factor 2 (FGFR2). We found an approximately 2-week delay in vertebral body and hand ossification with normal vertebral arch ossification, suggesting that regionally delayed skeletal maturation might be a manifestation of FGFR2 mutation syndromes. The findings support other studies indicating that different signaling pathways control skeletal maturation in vertebral bodies and vertebral arches.

Abnormalities, Multiple↗
PubMed2000

The prenatal pituitary gland--hidden and forgotten.

The sella turcica and pituitary gland in a human fetus (18 weeks gestation) with unilateral oro-ocular cleft combined with unilateral cleft lip and palate are described histologically. In this fetus the sella turcica was not a normal sella but a caudally open funnel. The adenopituitary gland tissue was positioned ectopically within the funnel canal and in the pharyngeal submucosa.

Abnormalities, Multiple↗
PubMed2000

Interobserver variation in diagnosing coeliac disease. A joint study by Danish and Swedish pathologists.

There is an almost 40-fold difference in incidence rates of symptomatic coeliac disease between Denmark and Sweden. In an attempt to explain this difference, the present study focused on the interobserver agreement when pathologists were assessing small intestinal biopsy specimens from children suspected of suffering from coeliac disease. The study was performed on 90 biopsy specimens from 73 children. Most of the biopsies came from children who turned out not to suffer from coeliac disease after a clinical evaluation including small intestinal biopsy. Using the kappa methodology, the interobserver agreement between two Danish pathologists and one Swedish pathologist, all of whom were experienced, was "moderate" to "substantial" or 0.57-0.75. Kappa indices when the pathologists evaluated selected histological elements were in the interval from 0.24 to 0.67. A comparison of a previous routine diagnostic assessment of the 90 biopsies (14 pathologists) with the results of the experienced pathologists in the present study gave kappa indices of from 0.53 to 0.57. The study could prove no major differences in the histopathological assessment of small intestinal biopsy specimens made by Danish and Swedish pathologists. The difference in clinical presentation of coeliac disease in Denmark and Sweden does not relate to differences in the histopathological assessment of small intestinal biopsies.

Adolescent↗
PubMed2000

No limiting role for glycogenin in determining maximal attainable glycogen levels in rat skeletal muscle.

We examined whether the protein level and/or activity of glycogenin, the protein core upon which glycogen is synthesized, is limiting for maximal attainable glycogen levels in rat skeletal muscle. Glycogenin activity was 27.5 +/- 1.4, 34.7 +/- 1.7, and 39.7 +/- 1.3 mU/mg protein in white gastrocnemius, red gastrocnemius, and soleus muscles, respectively. A similar fiber type dependency of glycogenin protein levels was seen. Neither glycogenin protein level nor the activity of glycogenin correlated with previously determined maximal attainable glycogen levels, which were 69.3 +/- 5.8, 137.4 +/- 10.1, and 80.0 +/- 5.4 micromol/g wet wt in white gastrocnemius, red gastrocnemius, and soleus muscles, respectively. In additional experiments, rats were exercise trained by swimming, which resulted in a significant increase in the maximal attainable glycogen levels in soleus muscles ( approximately 25%). This increase in maximal glycogen levels was not accompanied by an increase in glycogenin protein level or activity. Furthermore, even in the presence of very high glycogen levels ( approximately 170 micromol/g wet wt), approximately 30% of the total glycogen pool continued to be present as unsaturated glycogen molecules (proglycogen). Therefore, it is concluded that glycogenin plays no limiting role for maximal attainable glycogen levels in rat skeletal muscle.

Animals↗
PubMed2000

Muscle glycogen content affects insulin-stimulated glucose transport and protein kinase B activity.

We investigated the possible regulatory role of glycogen in insulin-stimulated glucose transport and insulin signaling in skeletal muscle. Rats were preconditioned to obtain low (LG), normal, or high (HG) muscle glycogen content, and perfused isolated hindlimbs were exposed to 0, 100, or 10,000 microU/ml insulin. In the fast-twitch white gastrocnemius, insulin-stimulated glucose transport was significantly higher in LG compared with HG. This difference was less pronounced in the mixed-fiber red gastrocnemius and was absent in the slow-twitch soleus. In the white gastrocnemius, insulin activation of insulin receptor tyrosine kinase and phosphoinositide 3-kinase was unaffected by glycogen levels, whereas protein kinase B activity was significantly higher in LG compared with HG. In additional incubation experiments on fast-twitch epitrochlearis muscles, insulin-stimulated cell surface GLUT-4 content was significantly higher in LG compared with HG. The data indicate that, in fast-twitch muscle, the effect of insulin on glucose transport and cell surface GLUT-4 content is modulated by glycogen content, which does not involve initial but possibly more downstream signaling events.

Animals↗