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Biomedical subjects

J N Nielsen

Publications and source records attributed to J N Nielsen.

At least 19 recordsLinked to original sources
PubMed2006

Molecular factors of 5-fluorouracil metabolism in colorectal cancer: analysis of primary tumor and lymph node metastasis.

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) are predictive markers for tumor response to 5-fluorouracil-based therapies. To determine whether gene expression values measured in primary cancer tissue would be useful for prediction of response of lymph node metastases, the expressions of these genes were quantitatively analyzed in 35 pairs of primary colorectal cancer (CRC) and corresponding lymph node metastases using real-time PCR. DPD and TP mRNA levels were significantly lower in the primary colorectal tumor and lymph node metastases compared with the normal adjacent stroma tissue (p<0.01), whereas TS mRNA levels were significantly higher in the primary tumor and lymph node metastases than in the normal adjacent tissue (p<0.001). Median gene expression levels of TP and TS did not differ significantly between primary colorectal tumor and corresponding lymph node metastasis but median DPD gene expression levels in the lymph node metastases were significantly higher compared to matched primary colorectal tumors (p=0.015). There was a significant correlation for DPD, TP and TS gene expression levels between primary colorectal tumor specimens and the matched lymph node metastasis. These results suggest that biopsies of the tumor of origin may be valid for determining predictive markers for chemotherapy response in patients with metastatic CRC.

Aged↗
PubMed2005

The insulin-like growth factor system and markers of inflammation in adult patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). Recent studies have demonstrated significant changes in the IGF system in IBD patients. The aim of the present study was to investigate correlations between the IGF system and markers of inflammation in IBD. METHODS: A cross-sectional study comprising 99 IBD patients (Crohn's disease (CD, n = 50) and ulcerative colitis (UC, n = 49)). Correlations between markers of inflammation and IGF-I, IGF-II and IGFBP-3 were examined in CD and UC patients in remission and relapse. The patients were clinically scored using Crohn's Disease Activity Index (CDAI) for CD patients and Activity Index (AI) for UC patients. RESULTS: In the UC group we found correlations between IGF-I and CRP (r(s) = Spearman's rho) (r(s) = -0.40, p < 0.01) and albumin (r(s) = 0.46, p < 0.001), IGFBP-3 and albumin (r(s) = 0.36, p < 0.01) and AI score (r(s) = -0.31, p < 0.05). IGF-II correlated with CRP (r(s) = -0.42, p < 0.01), IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), AI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). In the CD group we found correlations between IGF-I and CRP (r(s) = -0.40, p < 0.05), and albumin (r(s) = -0.46, p < 0.01), IGFBP-3 and albumin (r = 0.36, p < 0.01). IGF-II correlated with IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), CDAI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). CONCLUSIONS: IGF-I, IGF-II and IGFBP-3 are correlated to albumin and IGF-I and IGF-II are correlated to CRP in IBD patients. Further, IGF-II is correlated to IL-6 in IBD patients. This may suggest a correlation between inflammation and the IGF system with involvement in muscle and bone catabolism in IBD.

Adult↗
PubMed2005

Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids.

BACKGROUND: Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract. Polyunsaturated omega-3 fatty acids given orally may reduce the secretion of proinflammatory cytokines and hereby downregulate the inflammatory process. AIM: To assess the effects of enteral fatty acids, in the form of Impact Powder (Novartis, Switzerland), as adjuvant therapy to corticosteroid treatment on the proinflammatory and anti-inflammatory cytokine profiles in patients with active Crohn's disease. METHODS: The proinflammatory and anti-inflammatory cytokines were measured in plasma from 31 patients with active Crohn's disease. Patients were randomized for oral intake of omega-3 fatty acid (3-Impact Powder) or omega-6 fatty acids (6-Impact Powder). Clinical and biochemical markers of inflammation were studied at baseline and after 5 and 9 weeks. RESULTS: Within the 3-Impact Powder group, no significant changes in concentrations of interleukin-6, interferon-gamma, monocyte chemoattractant protein-1, interleukin-2, interleukin-5 and interleukin-10, whereas a significant differences in concentration of interleukin-1beta and interleukin-4 were observed during therapy. Within the 6-Impact Powder group a significant changes in concentrations of interleukin-1beta, interleukin-6, interferon-gamma, monocyte chemoattractant protein-1, interleukin-2, interleukin-4, interleukin-5 and interleukin-10 were observed. CONCLUSIONS: The 3-Impact Powder showed immunomodulatory properties and might inhibit an increase of proinflammatory cytokines in contrast to the 6-Impact Powder.

Administration, Oral↗
PubMed2003

A possible role for AMP-activated protein kinase in exercise-induced glucose utilization: insights from humans and transgenic animals.

Exercise-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism, but the actual signals to glucose transport in response to muscle contraction have not been identified. The 5'-AMP-activated protein kinase (AMPK) has emerged as a putative mediator of contraction-induced glucose transport, although no conclusive evidence has been provided so far. Recent experiments in AMPK transgenic mice suggest that glucose transport induced by 5-amino-4-imidazolecarboxamide riboside (AICAR) or hypoxia is mediated by AMPK. In contrast, contraction-induced glucose transport in rodent skeletal muscle induced by electrical stimulation in vitro or in situ is not influenced or is only partially reduced by abolishing both or one of the catalytic AMPK subunits. This is compatible with exercise studies done in humans, where no tight correlation is found between AMPK activity and glucose uptake during exercise. Taken together, these results question an essential role of AMPK in exercise-induced glucose uptake and imply that one or more additional pathways are involved in mediating glucose transport in skeletal muscle during exercise.

AMP-Activated Protein Kinases↗
PubMed2003

Transgenic models--a scientific tool to understand exercise-induced metabolism: the regulatory role of AMPK (5'-AMP-activated protein kinase) in glucose transport and glycogen synthase activity in skeletal muscle.

The AMPK (5'AMP-activated protein kinase) is becoming recognized as a critical regulator of energy metabolism. However, many of these effects in muscle metabolism have been ascribed to AMPK based on the use of the unspecific activator AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside). Using mouse models in which AMPK activity has been specifically blocked (kinase dead) or knocked out we and others have been able to conduct studies gaining more conclusive data on the role of AMPK in muscle metabolism. In this mini-review focus is on AMPK and its regulatory role for glucose transport and GS (glycogen synthase) activity in skeletal muscle, indicating that AMPK is a GS kinase in vivo which might influence GS activity during exercise and that AMPK is involved in AICAR/hypoxia-induced glucose transport but not or only partially in contraction-stimulated glucose transport.

AMP-Activated Protein Kinases↗
PubMed2003

Signalling to glucose transport in skeletal muscle during exercise.

Exercise-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism. Although the signalling events that increase glucose transport in response to muscle contraction are not fully elucidated, the aim of the present review is to briefly present the current understanding of the molecular signalling mechanisms involved. Glucose uptake may be regulated by Ca++-sensitive contraction-related mechanisms possibly involving protein kinase C, and by mechanisms that reflect the metabolic status of the muscle and may involve the AMP-activated protein kinase. Furthermore the p38 mitogen activated protein kinase may be involved. Still, the picture is incomplete and a substantial part of the exercise/contraction-induced signalling mechanism to glucose transport remains unknown.

AMP-Activated Protein Kinases↗
PubMed2003

Regulation of glycogen synthase in skeletal muscle during exercise.

Glycogen synthase (GS) catalyses the incorporation of uridine diphosphate-glucose into glycogen in skeletal muscle. In concert with the glucose transport step, GS activity is thought to be rate-limiting in the disposal of glucose as muscle glycogen. Glycogen synthase is regulated by both allosteric factors (primarily glucose 6-phosphate) and covalent modification by reversible phosphorylation and dephosphorylation leading to inactivation and activation of GS, respectively. Exercise activates both stimulatory and inhibitory regulators of GS and it is thought that the resultant activity of GS during exercise depends on the relative strength of opposing signals. However, the mechanisms by which exercise regulates GS activity are not fully understood. Glycogen breakdown, the GM-protein phosphatase 1 complex and possibly cellular relocalization of GS may be considered important factors involved in the stimulation of GS activity during exercise, while adenosine monophosphate-activated protein kinase and plasma adrenaline (via protein kinase A) can be considered as essential for the exercise-induced inhibitory signals to GS.

AMP-Activated Protein Kinases↗
PubMed2001

Glycogen synthase localization and activity in rat skeletal muscle is strongly dependent on glycogen content.

1. The influence of muscle glycogen content on glycogen synthase (GS) localization and GS activity was investigated in skeletal muscle from male Wistar rats. 2. Two groups of rats were obtained, preconditioned with a combination of exercise and diet to obtain either high (HG) or low (LG) muscle glycogen content. The cellular distribution of GS was studied using subcellular fractionation and confocal microscopy of immunostained single muscle fibres. Stimulation of GS activity in HG and LG muscle was obtained with insulin or contractions in the perfused rat hindlimb model. 3. We demonstrate that GS translocates from a glycogen-enriched membrane fraction to a cytoskeleton fraction when glycogen levels are decreased. Confocal microscopy supports the biochemical observations that the subcellular localization of GS is influenced by muscle glycogen content. GS was not found in the nucleus. 4. Investigation of the effect of glycogen content on GS activity in basal and insulin- and contraction-stimulated muscle shows that glycogen has a strong inhibitory effect on GS activity. Our data demonstrate that glycogen is a more potent regulator of glycogen synthase activity than insulin. Furthermore we show that the contraction-induced increase in GS activity is merely a result of a decrease in muscle glycogen content. 5. In conclusion, the present study shows that GS localization is influenced by muscle glycogen content and that not only basal but also insulin- and contraction-stimulated GS activity is strongly regulated by glycogen content in skeletal muscle.

Animals↗
PubMed2001

Regulation of muscle glucose transport during exercise.

In the present short review some factors affecting glucose utilization during exercise in skeletal muscle will be briefly described. Special focus will be put on the glucose transport step across the sarcolemma. Glucose transporters (GLUT4) are expressed at a surprisingly similar level in the different muscle fiber types in human skeletal muscle in contrast to findings in the rat. When working at the same absolute work load muscle glucose transport is decreased in trained compared with untrained muscle in part due to a decrease in GLUT4 translocation to the sarcolemma in trained muscle. However, when trained and untrained muscle are stressed severely by a workload taxing 100% of their peak oxygen uptake in a glycogen-depleted state, then glucose uptake is larger in trained than in untrained muscle and correlates with muscle GLUT4 content. Finally, the possible role of the AMP-activated protein kinase (AMPK) in regulating glucose uptake during exercise is discussed. It is indicated that at present no experiments definitively link activation of AMPK to activation of muscle glucose transport during exercise.

Biological Transport↗
PubMed2001

GLUT-4 translocation in skeletal muscle studied with a cell-free assay: involvement of phospholipase D.

GLUT-4-containing membranes immunoprecipitated from insulin-stimulated rat skeletal muscle produce the phospholipase D (PLD) product phosphatidic acid. In vitro stimulation of PLD in crude membrane with ammonium sulfate (5 mM) resulted in transfer of GLUT-4 (3.0-fold vs. control) as well as transferrin receptor proteins from large to small membrane structures. The in vitro GLUT-4 transfer could be blocked by neomycin (a PLD inhibitor), and neomycin also reduced insulin-stimulated glucose transport in intact incubated soleus muscles. Furthermore, protein kinase B(beta) (PKB(beta)) was found to associate with the GLUT-4 protein and was transferred to small vesicles in response to ammonium sulfate in vitro. Finally, addition of cytosolic proteins, prepared from basal skeletal muscle, and GTP nucleotides to an enriched GLUT-4 membrane fraction resulted in in vitro transfer of GLUT-4 to small membranes (6.8-fold vs. unstimulated control). The cytosol and nucleotide-induced GLUT-4 transfer could be blocked by neomycin and N-ethylmaleimide. In conclusion, we have developed a cell-free assay that demonstrates in vitro GLUT-4 transfer. This transfer may suggest release of GLUT-4-containing vesicles from donor GLUT-4 membranes involving PLD activity and binding of PKB(beta) to GLUT-4.

Adenosine Triphosphate↗
PubMed2001

The association between daytime attendance and out-of-hours frequent attendance among adult patients in general practice.

BACKGROUND: Frequent attenders (FAs) account for a large proportion of daytime consultations in general practice. However, no studies have so far been conducted to establish whether daytime FAs are also out-of-hours FAs. AIM: To analyse the association between daytime attendance and out-of-hours frequent attendance. DESIGN OF STUDY: A registry-based study of individual face-to-face contacts with general practice during daytime and out of hours, based on National Health Insurance files. SETTING: General practices in Aarhus County, Denmark (630,000 inhabitants). METHOD: A total of 416,172 adults, i.e. all adults registered with a general practice during a 12-month period from November 1997 to October 1998 were included. Odds ratios (OR) for frequent attendance out of hours were stratified for age, sex, and frequency of contacts during daytime were calculated. RESULTS: A strong association was observed between daytime level of attendance and out-of-hours level of attendance (OR = 2.9-6.3 among patients with low daytime attendance, OR = 33.7-99.8 among daytime FAs). Daytime FAs accounted for one-third of the daytime contacts, one-third of the out-of-hours contacts, and 42% of out-of-hours FAs. More than half of the daytime FAs did not attend out of hours. Two per cent of the out-of-hours FAs had no contacts during the daytime. CONCLUSION: Frequent attendance in daytime was very strongly associated with frequent attendance out of hours, and daytime FAs accounted for a large proportion of all contacts with general practice.

Adult↗
PubMed2000

Physiological response to acute endotoxemia in swine: effect of genotype on energy metabolites and leptin.

Certain high lean gain swine genotypes have greater sensitivity to pathogen and nonpathogen stressors evident by reduced productivity and increased mortality during disease stress or in suboptimal production environments. Saline (control) and an immunologic challenge (LPS; 25 microg lipopolysaccharide/kg BW) were administered to three genetic populations (each pig used as its own control): high lean (H), moderate lean terminal cross (MT), and moderate lean maternal cross (MM). LPS induced anorexia, and significantly increased body temperature and circulating TNF-alpha, cortisol, and NEFA in all genotypes (P < 0.0004). LPS reduced circulating glucose, insulin, and IGF-1 in all genotypes (P < 0.05). The LPS-induced hypoglycemia was significantly greater in MM versus MT and H pigs (P < 0.03). The hypoinsulinemia was significantly greater in MM versus H pigs (P < 0.02). MM pigs recovered from hypoinsulinemia slower than MT pigs (P < 0.03). Control insulin was higher in H versus MT pigs (P < 0.08), but relative to basal, the insulin response to LPS was similar. Plasma haptoglobin response to LPS was lower for MM versus MT and H pigs (P < 0.02), and tended to be lower in MT versus H pigs (P < 0.09). LPS treatment caused similar decreases in plasma IGF-1 concentrations among genotypes. Ten hours after LPS treatment, leptin mRNA abundance in adipose tissue was significantly reduced (relative to control) in MM and H pigs (P < 0.02) but not in MT pigs (P > 0.05). Physiological differences in leptin, a potent regulator of food intake and energy metabolism, may be important factors in the genetic variation in sensitivity to environmental stress.

Adipose Tissue↗
PubMed2000

Fiber type-specific expression of GLUT4 in human skeletal muscle: influence of exercise training.

The fiber type-specific expression of skeletal muscle GLUT4 and the effect of 2 weeks of low-intensity training were investigated in 8 young untrained male subjects. Single muscle fibers were dissected from a vastus lateralis biopsy sample. Based on myosin heavy chain (MHC) expression, fibers were pooled into 3 groups (MHC I, MHC IIA, and MHC IIX), and the GLUT4 content of 15-40 pooled fibers was determined using SDS-PAGE and immunological detection. The GLUT4 content in pooled muscle fibers expressing MHC I was approximately 20% higher (P < 0.05) than that in muscle fibers expressing MHC IIA or MHC IIX. No difference in GLUT4 could be detected between fibers expressing MHC IIA or MHC IIX. Two weeks of exercise training increased (P < 0.05) the peak power output of the knee extensors by 13%, the maximal activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase by 21 and 18%, respectively, and the GLUT4 protein content by 26% in a muscle homogenate. Furthermore, a 23% increase (P < 0.05) in GLUT4 was seen in fibers expressing the MHC I isoform after exercise training for 2 weeks. No change was seen in fibers expressing MHC IIA or MHC IIX. In conclusion, our data directly demonstrate that GLUT4 is expressed in a fiber type-specific manner in human skeletal muscle, although fiber type differences are relatively small. In addition, low-intensity exercise training recruiting primarily fibers expressing MHC I increased GLUT4 content in these fibers but not in fibers expressing MHC IIA or MHC IIX, indicating that GLUT4 protein content is related more to activity level of the fiber than to its fiber type, which is defined by expression of contractile protein.

Adult↗
PubMed1998

A trauma-like elevation of plasma cytokines in humans in response to treadmill running.

1. Elevated levels of cytokines, especially interleukin (IL)-6 and IL-1ra, can be measured in the plasma of athletes after exhaustive long term exercise. 2. The present study investigates the kinetics of several cytokines and chemokines in ten male athletes before, during and after 2.5 h of treadmill running at 75 % of maximal oxygen consumption (VO2,max). Blood was sampled before, every half-hour during running and every hour in the following 6 h recovery period. 3. The plasma concentration of IL-6 increased after 30 min of running, and peaked at the end of running with a 25-fold increase compared with the pre-exercise value. IL-1ra increased only after running, and peaked after 2 h of rest with an 18-fold increase compared with the pre-exercise value. No changes were found in the concentrations of IL-1beta, tumour necrosis factor (TNF)alpha, IL-15 and macrophage inflammatory protein (MIP)-1beta, and the concentrations of IL-8 and MIP-1alpha were below detection limits. 4. The results suggest that very early events in exercise trigger the release of IL-6, and that the cytokine response to exercise has similarities to that observed after trauma.

Adult↗
PubMed1998

[Does a computerized price comparison module reduce prescribing costs in general practice?].

The aim was to assess the trends in prescribed defined daily doses (DDD) and drug expenses before and after the introduction of a computerized cost containment module. On January 1993 the module was introduced in 20 practices in Aarhus County that used the computer record system APEX. Two control groups were made. From the Public Health Insurance in Aarhus County (600,000 inhabitants) data were collected during 1992 and 1993. Compared with te controls there were no changes in prescribed DDD, reimbursement for prescribed drugs, and reimbursement per prescribed DDD in the intervention group after the introduction of the module. Cost containment procedures should be more intensive than just giving the doctors a computer-assisted decision aid.

Decision Making, Computer-Assisted↗
PubMed1997

Crystal structure of a peptide nucleic acid (PNA) duplex at 1.7 A resolution.

The crystal structure of a PNA duplex reveals both a right- and a left-handed helix in the unit cell. The helices are wide (28A), large pitched (18bp) with the base pairs perpendicular to the helix axis, thereby demonstrating that PNA besides adapting to oligonucleotide partners also has a unique structure by itself.

Base Composition↗
PubMed1997

Does a computerized price comparison module reduce prescribing costs in general practice?

OBJECTIVE: We aimed to assess the trends in prescribed defined daily doses (DDD) and drug expenses before and after the introduction of a computerized cost containment module into the computer record system of a defined group of GPs. The GPs' expectations for and experiences with the module were examined. METHOD: We performed a controlled follow-up study on antecedent data before and after intervention. A questionnaire was administered to the intervention group at the introduction and 1 year later. Data on prescribing were collected in the database of the Health Insurance Aarhus County, as a normal routine for accounting. The GPs were not aware of the ongoing cost supervision study. Additional cost information software was introduced on 1 January 1993 to 20 practices with 28 GPs. The software assisted the GPs in a semiautomatic way to identify and prescribe the cheapest drugs. The subjects comprised 158 practices including 231 GPs in Aarhus County, Denmark. Questionnaires were sent to the 20 intervention practices. The main outcome measures were prescribed DDD, reimbursement for prescribed drugs, and reimbursement per prescribed DDD quarterly during 1992 and 1993. RESULTS: Compared with the controls there were no changes in prescribed DDD, reimbursement for prescribed drugs, and reimbursement per prescribed DDD in the intervention group after the introduction of the module. CONCLUSION: Simply giving a random group of GPs computer assistance to choose less expensive drugs did not reduce expenditure per DDD. Cost containment procedures should be more intensive than just giving the doctors a computer-assisted decision aid.

Case-Control Studies↗