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Biomedical subjects

L Hansen

Publications and source records attributed to L Hansen.

At least 73 records · Page 4Linked to original sources
PubMed1999

Development of muscle strength in relation to training level and testosterone in young male soccer players.

Isometric and functional strength of ninety-eight 11-yr-old male soccer players at an elite (E) and nonelite (NE) level were determined (3-4 times) through a 2-yr period, and the changes were related to growth and maturation. The initial isometric strength for extension with dominant leg [1,502 +/- 35 (E) vs. 1,309 +/- 39 (NE) N], extension with nondominant leg (1,438 +/- 37 vs. 1,267 +/- 45 N), extension with both legs (2,113 +/- 76 vs. 1,915 +/- 72 N), back muscles (487 +/- 11 vs. 414 +/- 10 N), abdominal muscles (320 +/- 9 vs. 294 +/- 8 N), and handgrip (304 +/- 10 vs. 259 +/- 8 N) increased by 15-40% during the period. Broad jump increased (P < 0. 05) by 15 (E) and 10% (NE). The E players had higher (P < 0.05) initial isometric strength and broad jump performance compared with NE players, and differences were maintained throughout the period (multiple ANOVA for repeated measures) also when adjustment was made for age, dimensions, testosterone, and insulin-like growth factor I (generalized estimating equations analyses). The development of strength for both E and NE players together was significantly (P < 0. 001) related to changes in serum testosterone concentrations. The present data indicate that testosterone is important for development of strength in young boys and that, independent of serum testosterone concentration, E players have developed greater muscle strength compared with NE players.

Adolescent↗
PubMed1999

Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine.

The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is stored in the intestinal L cell in an active form, GLP-1-(7-36)amide, but more than half of the endogenous peptide circulates in an inactive, N-terminally truncated form, GLP-1-(9-36)amide. This study examined the GLP-1 newly secreted from the porcine ileum, in vitro (isolated perfused preparation) and in vivo (anesthetized pig), to determine where this conversion occurs. Although the GLP-1 extractable from the porcine ileum is predominantly the intact peptide (94.6+/-1.7%), a large proportion of the GLP-1 that is secreted has already been degraded to the truncated form both in vitro (53.8+/-0.9% intact) and in vivo (32.9+/-10.8% intact). In the presence of a specific dipeptidyl peptidase IV (DPP IV) inhibitor (valine-pyrrolidide), the proportion of intact GLP-1 released from the perfused ileum was increased under both basal (99% intact; P < 0.05) and stimulated (86-101% intact; P < 0.05) conditions. Immunohistochemical and histochemical studies revealed specific DPP IV staining in the brush border epithelium as well as in the capillary endothelium. Double staining showed juxtapositioning of DPP IV-positive capillaries and GLP-1-containing L cells. From these results, we suggest that GLP-1 is degraded as it enters the DPP IV containing blood vessels draining the intestinal mucosa.

Animals↗
PubMed1999

A novel Phe75fsdelT mutation in the hepatocyte nuclear factor-4alpha gene in a Danish pedigree with maturity-onset diabetes of the young.

Mutations in 5 different genes [the hepatocyte nuclear factor (HNF)-4alpha), glucokinase, HNF-1alpha, insulin promoter factor-1, and HNF-1beta genes] have been shown to cause maturity onset diabetes of the young (MODY). About 50% of all known MODY in Danish Caucasian MODY probands can be explained by mutations in the HNF-1alpha gene (MODY3). To estimate the prevalence of MODY caused by mutations in the HNF-4alpha gene (MODY1), we screened 10 non-MODY3 probands for mutations in the minimal promoter and the 12 exons of the HNF-4alpha gene. One of the probands had a novel frameshift mutation (Phe75fsdelT) in exon 2 of the HNF-4alpha gene, resulting in a premature termination of translation after 117 amino acids of the messenger RNA encoded by that allele. The mutation cosegregated with diabetes in the pedigree and was not detected in 84 unrelated Danish Caucasian healthy glucose-tolerant control subjects or in 84 type 2 diabetic patients. At the time of examination, 4 of 6 mutation carriers were treated with insulin and 2 with oral hypoglycemic medication. Two mutation carriers had late-diabetic complications. Even though the HNF-4alpha protein is known to be important in the regulation of genes involved in lipid metabolism, carriers of the mutation did not differ from age and sex-matched control subjects, in regard to levels of fasting serum total cholesterol, serum high-density lipoprotein-cholesterol, and serum triglyceride. In conclusion, by screening 10 non-MODY3 probands for mutations in the HNF-4alpha gene, we identified 1 diabetes-associated frameshift mutation (Phe75fsdelT), suggesting that defects in HNF-4alpha are a rare cause of MODY in Denmark.

Adult↗
PubMed1999

Analysis of the relationship between fasting serum leptin levels and estimates of beta-cell function and insulin sensitivity in a population sample of 380 healthy young Caucasians.

OBJECTIVE: Circulating leptin levels correlate positively with the degree of obesity and prolonged hyperinsulinaemia increases serum leptin levels. Moreover, insulin secreting beta-cells express functional leptin receptors indicating a functional relationship between leptin and insulin. The aim of this study was to examine the relationship between fasting serum leptin levels and measures of insulin sensitivity and beta-cell function in a population-based sample of 380 young healthy Caucasians. DESIGN AND METHODS: Multiple regression analysis was employed to analyse the relationship between fasting serum leptin levels and levels of fasting serum insulin, insulin sensitivity index and acute insulin response (AIR) in a population-based study of 380 young healthy Caucasians who underwent a combined intravenous glucose and tolbutamide tolerance test. RESULTS AND CONCLUSION: Serum leptin levels were positively correlated to measures of adiposity and were 3.2 times higher in women than in men (P<0.00001). In multiple regression analyses adjusting for age, percentage body fat, waist circumference and maximal aerobic capacity, a significant positive correlation was observed between the fasting serum leptin concentrations and both fasting serum insulin levels (P<0.0001) and AIR (P = 0.014) for women. No significant interrelation of these variables was found in men. However, for both genders a significant negative correlation was observed between fasting serum leptin levels and measures of insulin sensitivity index (P = 0.007).

Adolescent↗
PubMed1999

Mutational analysis of the coding regions of the genes encoding protein kinase B-alpha and -beta, phosphoinositide-dependent protein kinase-1, phosphatase targeting to glycogen, protein phosphatase inhibitor-1, and glycogenin: lessons from a search for genetic variability of the insulin-stimulated glycogen synthesis pathway of skeletal muscle in NIDDM patients.

The finding of a reduced insulin-stimulated glucose uptake and glycogen synthesis in the skeletal muscle of glucose-tolerant first-degree relatives of patients with NIDDM, as well as in cultured fibroblasts and skeletal muscle cells isolated from NIDDM patients, has been interpreted as evidence for a genetic involvement in the disease. The mode of inheritance of the common forms of NIDDM is as yet unclear, but the prevailing hypothesis supports a polygenic model. In the present study, we tested the hypothesis that the putative inheritable defects of insulin-stimulated muscle glycogen synthesis might be caused by genetic variability in the genes encoding proteins shown by biochemical evidence to be involved in insulin-stimulated glycogen synthesis in skeletal muscle. In 70 insulin-resistant Danish NIDDM patients, mutational analysis by reverse transcription-polymerase chain reaction-single strand conformation polymorphism-heteroduplex analysis was performed on genomic DNA or skeletal muscle-derived cDNAs encoding glycogenin, protein phosphatase inhibitor-1, phophatase targeting to glycogen, protein kinase B-alpha and -beta, and the phosphoinositide-dependent protein kinase-1. Although a number of silent variants were identified in some of the examined genes, we found no evidence for the hypothesis that the defective insulin-stimulated glycogen synthesis in skeletal muscle in NIDDM is caused by structural changes in the genes encoding the known components of the insulin-sensitive glycogen synthesis pathway of skeletal muscle.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1998

Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo.

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.

Animals↗
PubMed1998

Adult-onset motor neuron disease in three cats.

Motor neuron diseases of domestic animals have rarely been described. Three cats with adult-onset, chronic, progressive generalized muscle weakness characterized initially by trembling on exertion and later by extreme difficulty in walking, cervical ventroflexion, dysphagia, and marked muscle atrophy were elevated. Spinal reflexes were evident early but were nondetectable as the disease progressed. Electromyography revealed fibrillation potentials, with nerve conduction velocities within the reference range. Histologic examination of muscle specimens revealed denervation. Marked neuron loss and gliosis were detected in the ventral horns of the spinal cord, with atrophy of ventral nerve rootlets. Less dramatic neuron loss was seen in brain stem motor nuclei. Electron microscopic examination of the ventral horns disclosed hypertrophied astrocytes, with densely arrayed intermediate filaments, swollen axons with large filamentous accumulations, and many macrophages with lipofuscin-like inclusions. Clinical and pathologic findings were consistent with a progressive neurodegenerative disease affecting spinal and some bulbar motor nuclei.

Age of Onset↗
PubMed1998

Topical retinoic acid reduces skin papilloma formation but resistant papillomas are at high risk for malignant conversion.

Retinoic acid (RA) was topically applied to the skin of Sencar mice during the promotion phase of specific tumor induction protocols that produce papillomas at low (12-O-tetradecanoylphorbol-13-acetate promoted, TPA) or high (mezerein-promoted) risk for premalignant progression and malignant conversion. RA consistently reduced the yield of papillomas and carcinomas in both protocols, but the frequency of malignant conversion in papillomas that emerged during RA treatment was not reduced. When TPA was reapplied after cessation of RA treatment, the number of papillomas increased 2-fold, suggesting that RA had not eliminated initiated cells. In vitro, RA prevented the emergence of transformed keratinocytes in an assay that mimics malignant conversion, suggesting that RA can suppress conversion if applied during the stage of premalignant progression. Examination of tumor markers at weeks 14 and 22 of the tumor-induction experiments in vivo indicated that papillomas evolving during RA treatment exhibited a phenotype of high progression risk, even in the TPA-promoted groups. In the majority of these tumors, the alpha6beta4 integrin and retinoid X receptor alpha transcripts were detected suprabasally, indicating an advanced state of premalignant progression. RA-treated tumors also expressed higher levels of transcripts for transforming growth factor (TGF)-beta1 and localized TGF-beta1 peptide in the basal portions of the tumor fronds. Because up-regulated expression of TGF-beta1 suppresses papilloma formation, these studies suggest a mechanism whereby RA can prevent papilloma eruption via a TGF-beta intermediate, but papillomas resistant to RA may have altered TGF-beta signaling and progress to carcinomas at an increased frequency.

Administration, Topical↗
PubMed1998

Behavioral and neurochemical effects of the preferential dopamine D3 receptor agonist cis-8-OH-PBZI.

In the present study we investigated the in vivo pharmacological profile of the benz[e]indole cis-8-hydroxy-3-(n-propyl)],2,3a,4,5,9b-hexahydro-1H-benz[e]indole (cis-8-OH-PBZI), which has been described as a preferential dopamine D3 receptor agonist in vitro. The compound inhibited spontaneous locomotor activity in mice, an effect which was antagonized by the dopamine D3 receptor antagonist 5,6-dimethoxy-2-(di-u-propylamino) indan (U99194A). Moreover, cis-8-OH-PBZI inhibited conditioned avoidance responding in rats, a preclinical test indicative of antipsychotic efficacy, at doses which did not induce catalepsy. Doses of cis-8-OH-PBZI (6 and 12 mg/kg) that inhibited spontaneous locomotor activity in rats did not affect interstitial levels of dopamine and dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens or dorsolateral striatum. In contrast to the effect of the dopamine receptor agonist (+/-)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphythalene (7-OH-DPAT), cis-8-OH-PBZI did not induce locomotor activity in reserpinized mice. In conclusion, cis-8-OH-PBZI exhibits a pharmacological profile that suggests it has antipsychotic activity but lacks the motoric side effects often associated with antipsychotic medication. The data suggest a mechanism requiring the activation of postsynaptic dopamine D3 receptors and support the hypothesis that these receptors mediate inhibitory behavioral effects.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

nNOS expressing neurons in the entorhinal cortex and hippocampus are affected in patients with Alzheimer's disease.

Nitric oxide is a multifunctional molecule that acts as messenger/modulator in synaptogenesis and potential neurotoxin and is synthesized by three isozymes of Nitric oxide synthase (NOS). The role of NOS in Alzheimer's disease (AD) is unclear. For example, neurons in the entorhinal cortex (EC) that are highly vulnerable to neurodegeneration in AD express low levels of NOS and while it has been suggested that the inducible form of NOS is upregulated in AD, it is still not clear if the constitutive expressed isozyme (nNOS) is involved in the process of neurodegeneration. In order to better understand the role of nNOS in the pathogenesis of AD, sections from the EC and hippocampus (HC) of AD and control cases were immunohistochemically analyzed by single- and double-immunolabeling using antibodies against nNOS and PHF-tau. Semiquantitative assessment of numbers of nNOS expressing neurons in different areas of the HC and EC showed a remarkable loss of nNOS expressing neurons in the entorhinal cortex layer II and--less severe--CA1 and CA3 of the hippocampus in patients with AD. In addition, double-immunolabeling studies revealed that nNOS is strongly associated with neurofibrillary tangles and plaques. These findings indicate that nNOS expressing neurons are highly susceptible to neurodegeneration and that nNOS might contribute to the pathogenesis of AD.

Aged↗
PubMed1998

Significance of mat and shoe softness during prolonged work in upright position: based on measurements of low back muscle EMG, foot volume changes, discomfort and ground force reactions.

The aim of the investigation was to study the significance of mat and shoe softness during prolonged work in an upright position based on some physiological, biomechanical and comfort measurements related to the lower extremities and the low back. Eight healthy female volunteers performed 2 h of simulated standing and 2 h of standing/walking work tasks in the laboratory using four combinations of soft shoes, clogs, soft mat and concrete. Thus, each subject performed a total of eight 2 h work tests. The following parameters were measured pre-experimentally and one or more times during 2 h: total foot volume, vascular volume and interstitial volume of the left foot, EMG from the lumbar paraspinals, movement of centre of gravity (only during standing), biomechanical heel impact (only during standing/walking), perceived discomfort in lumbar back, legs and feet, whole body oxygen uptake, arterial blood pressure and heart rate. Using soft shoes rather than clogs during standing/walking work implies approximately a halving of the foot oedema formation and the heel impact. The effects due to the introduction of the soft mat are negligible. The local circulatory responses in the feet and the EMG-signs of paravertebral muscle fatigue are larger during standing compared to standing/walking work. The two investigated work types in this study differ regarding exposures as well as responses. Thus, it is recommended to shift between these postures and seated work during the working hours to improve job exposures.

Adult↗
PubMed1998

Acute adrenal insufficiency following unilateral radical nephrectomy: a case report.

Adrenal insufficiency following unilateral radical nephrectomy has not been previously described in medical literature. We present a 78-year-old male patient who experienced a difficult postoperative course with vague findings, and was ultimately diagnosed with acute adrenal insufficiency. Treatment with glucocorticoids and mineralocorticoids resulted in prompt control of the disease.

Adrenal Insufficiency↗
PubMed1998

Metaphors of mind and society. The origins of German psychiatry in the revolutionary era.

Johann Christian Reil's long polemic, Rhapsodieen über die Anwendung der psychischen Curmethode der Geisteszerrütungen (1803), is a call for the reform of the treatment of the insane. It also marks a transition from the Kantian approach to physiology of his earlier work to the Naturphilosophie that increasingly characterized his publications after this time. In this essay I first survey the historiographical debates of recent years concerning society and the emergence of psychiatry. I then examine the social-cultural context of the late Aufklärung in Prussia, out of which Reil's work emerged, before sketching the intellectual background of the Rhapsodieen, which lies in the development of German physiology since the 1750s. The heart of my work is a close analysis of Reil's theory of mental illness. Here I tease out his political and cultural imagery and note the ways in which his originally Enlightenment assumptions shifted toward the Romantic amid the anxieties of the revolutionary era.

Germany↗
PubMed1998

Hereditary dysphasic disinhibition dementia: a frontotemporal dementia linked to 17q21-22.

OBJECTIVE: The clinical and pathologic features of hereditary dysphasic disinhibition dementia (HDDD) are described to determine whether it is a variant of known dementias. BACKGROUND: Several dementing disorders have clinical and pathologic similarities with AD, Pick's disease, and the "nonspecific" dementias. A detailed description of clinical and pathologic presentation will aid classification, but ultimately the discovery of causative gene(s) will define these disorders. METHODS: The authors performed a clinical assessment: gross and microscopic pathologic evaluation of brain tissue, genetic linkage studies, and sequence analyses. RESULTS: HDDD is an autosomal-dominant frontotemporal dementia with many similarities to Pick's disease. Salient clinical features are global dementia with disproportionate dysphasia and "frontotemporal" symptoms. A linkage between HDDD and 17q21-22 was shown, with a maximum lod score of 3.68 at zero recombination. CONCLUSIONS: Several dementias have been linked to the same region and have been termed frontotemporal dementia with parkinsonism linked to chromosome 17. These disorders may represent phenotypic variants arising from mutations within a common gene.

Adult↗
PubMed1998

Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene.

The high-affinity sulfonylurea receptor (SUR1) is, as a subunit of the ATP-sensitive potassium channel, an important regulator of insulin secretion in the pancreatic beta-cell. The aim of this study was to examine if genetic variability of the SUR1 gene was associated with NIDDM or altered pancreatic beta-cell function. Mutational analysis of all the 39 SUR1 exons, including intron-exon boundaries, in 63 NIDDM patients revealed two missense variants, five silent variants in the coding region, and four intron variants. The two missense variants (Asp673Asn and Ser1369Ala) and two sequence variants (ACC-->ACT, Thr759Thr and a c-->t intron variant in position -3 of the exon 16 splice acceptor site) were examined for association with NIDDM and for a possible influence on insulin and C-peptide secretion after intravenous glucose and tolbutamide loads in a random sample of unrelated, healthy, young Danish Caucasians. The Asp673Asn variant in exon 14 was only identified in one NIDDM patient, and the allelic frequency of the Ser1369Ala was similar among 247 control subjects (0.38 [95% CI 0.34-0.42]) and 406 NIDDM patients (0.40 [0.37-0.43]). The allelic frequency of the silent exon 18 Thr775Thr variant was 0.051 (0.035-0.067) in NIDDM patients (n=392) and 0.027 (0.013-0.041) in control subjects (n=246; chi2=4.99, P=0.03). The allelic frequency of the intron variant was similar among NIDDM patients (0.45 [0.42-0.48]) and control subjects (0.44 [0.40-0.48]). Of 386 NIDDM patients, 17 had the combined genotype exon 18 C/T and intron -3c/-3t (0.044 [0.024-0.064]), whereas 3 of 243 control subjects had the same combined genotype (0.012 [0-0.026]; chi2=4.87, P=0.03; odds ratio: 3.69 [1.07-12.71]). Of 380 unrelated, healthy, young Danish Caucasians, 10 (0.026 [0.010-0.042]) had the combined at-risk genotype. These subjects had, on average, a 50% reduction in serum C-peptide and a 40% reduction in serum insulin responses upon tolbutamide injection (P=0.002 and P=0.05, respectively) but normal serum C-peptide and insulin responses upon glucose injection. In conclusion, a silent polymorphism in exon 18 of the SUR1 gene is associated with NIDDM in a Danish Caucasian population. In combination with an intron variant, the association is higher, and young, healthy carriers of the intragenic combination have reduced serum C-peptide and insulin responses to a tolbutamide load.

ATP-Binding Cassette Transporters↗
PubMed1998

Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders.

The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP) (also known as a-synuclein) is a presynaptic terminal molecule that accumulates in the plaques of Alzheimer's disease. Recent studies have shown that a mutation in NACP is associated with familial Parkinson's disease, and that Lewy bodies are immunoreactive with antibodies against this molecule. To clarify the patterns of accumulation and differences in abnormal compartmentalization, we studied NACP immunoreactivity using double immunolabeling and laser scanning confocal microscopy in the cortex of patients with various neurodegenerative disorders. In Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease, NACP was found to immunolabel cortical Lewy bodies, abnormal neurites, and dystrophic neurites in the plaques. Double-labeling studies showed that all three of these neuropathological structures also contained ubiquitin, synaptophysin, and neurofilament (but not tau) immunoreactivity. In contrast, neurofibrillary tangles, neuropil threads, Pick bodies, ballooned neurons, and glial tangles (most of which were tau positive) were NACP negative. These results support the view that NACP specifically accumulates in diseases related to Lewy bodies such as Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease and suggests a role for this synaptic protein in the pathogenesis of neurodegeneration.

Aged↗