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E Knudsen

Publications and source records attributed to E Knudsen.

At least 19 recordsLinked to original sources
PubMed2005

Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment.

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for myocardial ischaemia, cardiac arrhythmia, sudden death, and heart failure, all common findings in patients with type 2 diabetes. AIM: To determine the prevalence of, and risk factors for, LVH in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment. DESIGN: Cross-sectional study. METHODS: From 1994 to 1998, M-mode echocardiography was performed by one experienced examiner in 262 consecutive, normoalbuminuric Caucasian type 2 diabetic patients, all with blood pressure <160/95 mmHg and not taking antihypertensive medication. Mean +/- SD age was 54 +/- 10 years, 109 were women, and median known duration of diabetes was 4 (range 1-28) years. Body mass index (BMI) was 28 +/- 5 kg/m(2), and blood pressure 134 +/- 13/79 +/- 8 mmHg, all means +/- SD. Median urinary albumin excretion rate was 9 (range 2-30) mg/24 h. RESULTS: The prevalence of LVH indexed to height(2.7) was 43% (95%CI 38-50%), and was similar in men and women. BMI, HbA(1c) and log urinary albumin excretion were significantly associated with left ventricular hypertrophy in a logistic regression model, whereas sex, age, known duration of diabetes and blood pressure were not. Similar results were obtained for left ventricular mass index. DISCUSSION: LVH was frequent in our normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment. Several potentially modifiable risk factors, such as raised BMI, poor glycaemic control and elevated urinary albumin excretion rate, were associated with LVH.

Adult↗
PubMed2005

Mucosal vaccination delays or prevents prion infection via an oral route.

In recent years major outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. These disorders are associated with a conformational change of a normal protein, PrP(C) (prion protein cellular), to a toxic and infectious form, PrP(Sc) (prion protein scrapie). None of the prionoses currently have an effective treatment. A limited number of active immunization approaches have been shown to slightly prolong the incubation period of prion infection. Active immunization in wild-type animals is hampered by auto-tolerance to PrP and potential toxicity. Here we report that mucosal vaccination with an attenuated Salmonella vaccine strain expressing the mouse PrP, is effective at overcoming tolerance to PrP and leads to a significant delay or prevention of prion disease in mice later exposed orally to the 139A scrapie strain. This mucosal vaccine induced gut anti-PrP immunoglobulin (Ig)A and systemic anti-PrP IgG. No toxicity was evident with this vaccination approach. This promising finding suggests that mucosal vaccination may be a useful method for overcoming tolerance to PrP and preventing prion infection among animal and potentially human populations at risk.

Administration, Oral↗
PubMed2004

Macrophages in spleen and liver direct the migration pattern of rat neutrophils during inflammation.

OBJECTIVE: The exact fate of polymorphonuclear neutrophilic granulocytes (PMN; neutrophils) after their mobilization from the bone marrow is not known. It is believed that they, after a relatively short lifespan (1-3 d), become apoptotic and phagocytosed by macrophages. We have recently shown that transfused neutrophils sequestrate not only in lungs, liver and spleen, but also to a large extent in the bone marrow, possibly because of uptake by macrophages. Hence, we studied if inactivation of macrophages would alter the pattern of neutrophil migration. METHODS: We used transfused congenic or syngeneic neutrophils in rats with or without sterile peritonitis, induced by a casein preparation (Bacto-Tryptone). To perturb macrophage function, we either killed them with liposome-encapsulated clodronate or overloaded them with inert phagocytosable particles. Transfused neutrophils were tracked with flow cytometric or radiometric methods. RESULTS: Not more than a small portion of the neutrophils migrated to the inflamed peritoneal cavity under any circumstance. Their ecotaxis to liver and spleen was reduced in rats with liver and spleen macrophages either congested with polystyrene particles or depleted by clodronate. The bone marrow uptake and blood retention of transfused neutrophils were increased in macrophage-depleted rats 18 h after transfusion. In rats depleted of liver macrophages only, the sequestration in the liver was reduced, without detectably changed uptake in bone marrow and spleen. CONCLUSION: Macrophages are instrumental to the neutrophil migration stream in the organism, and their function in this regard is robust and not easily decreased by inert phagocytosable particles or a killing agent.

Animals↗
PubMed2000

Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in type I diabetic patients.

AIMS/HYPOTHESIS: Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three polymorphisms in the genes coding for AGTR1 (A1166-->C), angiotensin converting enzyme (ACE/ID) and angiotensinogen (M235T) on risk of developing diabetic nephropathy. Furthermore, we investigated the relation between a random measurement and long-term measurements of haemoglobin A1c (HbA1c). METHODS: We studied Caucasian patients with Type I (insulin-dependent) diabetes mellitus and nephropathy (120 men 74 women, age 41.1 +/- 9.6 years, diabetes duration 28 +/- 8 years) and long-standing Type I diabetic patients with persistent normoalbuminuria (112 men 69 women, age 42.5 +/- 10.0 years, diabetes duration 27 +/- 9 years). Genotyping was PCR-based and metabolic control estimated from all measurements of HbA1c done in each patient [average (range) n = 31 (6-74)]. The median observation time (range) was 13.5 (2-14) years. RESULTS: Type I diabetic patients with a history of poor glycaemic control (HbA1c above the median, 8.7%) had an increased risk of diabetic nephropathy compared with patients with a better metabolic control, OR (95% CI): 9.2 (5.8-14.7). The magnitude of this risk was similar in carriers and non-carriers of the mutations. The risk of nephropathy in patients with HbA1c above compared with below the median in carriers of the mutant C1166-allele, D-allele, or T235-allele were 7.6 (95% CI: 3.9-14.8), 10.4 (6.0-17.8) and 9.8 (5.4-17.9), respectively. A significant correlation (r = 0.74, p < 0.001) existed between a random and long-term measurements of HbA1c with a small mean difference (limits of agreement) [0.2 (-1.8 to 2.1)%] between the two estimates. CONCLUSION/INTERPRETATION: Poor metabolic control is a major risk factor for diabetic nephropathy in Caucasian Type I diabetic patients. This risk was similar in carriers and non-carriers of the mutant alleles of the AGTR1 (A1166-->C), ACE/ID and angiotensinogen-M235T polymorphisms. The HbA1c value measured at random reflects rather closely average long-term HbA1c values.

Adolescent↗
PubMed1998

Cell proliferation, apoptosis and accumulation of lipid droplets in U937-1 cells incubated with eicosapentaenoic acid.

The monocytic cell line U937-1 was cultured in the presence of eicosapentaenoic acid (20:5, n-3) (EPA) or oleic acid (18:1, n-9) (OA). EPA caused a dose-dependent inhibition of cell proliferation, whereas OA had no effect. At the highest EPA concentrations, 120 and 240 microM, inhibition of cell proliferation was accompanied by initiation of apoptosis. A concentration of 60 microM EPA caused a 35% reduction in cell proliferation without inducing apoptosis, and was therefore used for further studies. Addition of antioxidants or inhibitors of eicosanoid synthesis had no influence on the reduced cell proliferation after EPA treatment. The inhibition required continuous presence of EPA in the incubation medium as the cells resumed a normal proliferation rate when they were placed in EPA-free medium. The inhibition of proliferation was not accompanied by differentiation into macrophage-like cells, as expression of serglycin and the ability to perform respiratory burst was unaffected by EPA. Expression of CD23 mRNA increased when the cells were incubated with EPA, but to a smaller extent than after retinoic acid (RA) or PMA treatment. Furthermore, expression of the monocytic differentiation markers CD36 and CD68 was lower in cells treated with EPA or OA when compared with untreated cells. The cell cycle distribution of U937-1 cells was similar in cells incubated with EPA or PMA, whereas RA-treated cells accumulated in the G1 phase. Side scatter increased in cells incubated with EPA and OA, which was ascribed to an accumulation of lipid droplets after examination of the cells by electron microscopy. The number of droplets per cell was higher in cells exposed to EPA than OA. The cellular triacylglycerol (TAG) increased 5.5- and 15.5-fold after incubation with OA and EPA respectively. No difference in the cellular content of cholesterol compared with untreated cells was observed. The TAG fraction in EPA-treated cells contained high amounts of EPA and docosapentaenoic acid and minor amounts of docosahexaenoic acid, whereas OA-treated cells had high levels of OA in the TAG. In cells incubated with a sulphur-substituted EPA, only minor effects on cell proliferation and no accumulation of cellular TAG were observed. These findings may indicate the existence of other mechanisms for regulation of cell behaviour by very-long-chain polyunsaturated n-3 fatty acids than the well established lipid peroxide and eicosanoid pathways.

Antioxidants↗
PubMed1997

[Doctor's delay].

Explore the source record for details and available documents.

Gastroscopy↗
PubMed1997

Functional analysis of wild-type and malignant glioma derived CDKN2Abeta alleles: evidence for an RB-independent growth suppressive pathway.

The tumor suppressor gene CDKN2A (p16/MTS1/INK4A), which encodes the cyclin-dependent kinase inhibitor p16(INK4a), is a target of 9p21 deletions during the malignant progression of human gliomas. This gene also encodes a second protein product (human p16beta, murine p19ARF), which originates from an unrelated exon of CDKN2A (exon 1beta) spliced onto exon 2 in an alternate reading frame. Cell cycle arrest by p16beta is caused by an as yet unidentified pathway. In order to test the candidacy of p16beta as a glioma suppressor, we replaced p16(INK4a), p15(INK4b) and p16beta wild-type as well as a series of seven glioma-derived p16beta alleles (R87H, A112V, R120H, A121V, G125R, A128A and A128V), into glioma cell lines that had either CDKN2A-/RB+ (U-87MG and U-251MG) or CDKN2A+/RB- (LN-319) endogenous backgrounds and demonstrated that p16beta can act as a functional glioma cell growth suppressor. Moreover, p16beta, but not p16(INK4a) or p15(INK4b) inhibited the growth of RB-negative LN-319 cells, indicating that p16beta likely exerts its effects through an RB-independent pathway. In vitro and in vivo assays of pRB phosphorylation were consistent with this interpretation. Since none of the glioma-derived p16beta mutations inactivated their growth suppressive activities, it appears that mutations in CDKN2A exon 2 (which is shared in the coding sequences of p16(INK4a) and p16beta) likely exclusively target p16(INK4a).

Alleles↗
PubMed1997

Cloning, functional activities and in vivo tissue distribution of rat NKR-P1+ TCR alpha beta + cells.

We have successfully cloned nine NKR-P1+ TCR alpha beta + cells from PVG rat spleens, utilizing murine macrophage inflammatory protein-1 alpha (MIP-1 alpha) and IL-2. These clones are either double negative (DN, CD4-CD8-), which included clones 3.31, 3.71, 4.19, 4.59 and 4.65, or single positive (SP, CD4+CD8-), which included clones 1.64, 3.8, 3.76 and 3.78. No CD8+ clone was recovered. All nine clones are restricted in terms of their expression of the V beta antigens, since they express V beta 8.2 but not V beta 8.5, V beta 10 or V beta 16. These clones are agranular and they fall to generate NK or LAK activity upon incubation with IL-2, IL-12 or their combination. On the basis of their production of intracellular cytokines they can be divided into three categories: (I) SP clones (1.64, 3.8, 3.76 and 3.78) do not produce IL-2 or IL-4, but produce IFN-gamma and IL-12, and they vary in their production of IL-1, RANTES or tumor necrosis factor (TNF)-alpha; (II) DN clones 4.59 and 4.65 produce IL-1 alpha and IFN-gamma only, and fall to produce other cytokines; and (III) DN clones 3.31, 3.71 and 4.19 produce IL-1 alpha, IL-1 beta, IL-2, IL-12, IFN-gamma, RANTES and TNF-alpha. From all the clones examined only DN clones 3.31 and to a lesser degree 4.19 produce IL-4. In vivo tissue localization of clones 3.8, 3.31 and 4.59 shows that these cells distribute into the liver and bone marrow 24 h post i.v. administration. Their accumulation in the liver and bone marrow along with their ability to secrete various cytokines suggest that these cells may influence the generation, differentiation or apoptosis of immune or hematopoietic cells.

Animals↗
PubMed1996

Zinc, copper and magnesium absorption from a fibre-rich diet.

Zinc, copper and magnesium absorption and retention from a high-fibre and high-phytate diet of conventional foods were investigated in 8 healthy subjects. Fractional absorption of the three minerals was estimated from fecal monitoring of zinc, copper and magnesium stable isotopes added to one day's diet. In addition, apparent absorption, retention and endogenous losses were estimated for the respective minerals based on fecal and urinary excretion over the last 16 days of 21 days constant intake. The diet contained 1 mmol phytic acid, 29 g dietary fiber, 140 mumol zinc, 13 mumol copper, and 9 mmol magnesium per 10 MJ. The absorption of zinc, copper and magnesium was 29 +/- 12% (x +/- SD) (48 +/- 20 mumol), 44 +/- 7% (8 +/- 1 mumol) and 46 +/- 6% (5 +/- 1 mmol), respectively. The retained amounts of minerals were -7 +/- 19 mumol, -5 +/- 4 mumol, and -3 +/- 1 mmol, respectively and the estimated endogenous intestinal losses were 40 +/- 20 mumol, 12 +/- 4 mumol and 3 +/- 1 mmol, respectively. In conclusion, the fractional absorption of zinc, copper and magnesium from the fibre-rich diet was not sufficient to cover intestinal and urinary losses of these elements, resulting in negative balances.

Adult↗
PubMed1996

Sequestration patterns of transfused rat neutrophilic granulocytes under normal and inflammatory conditions.

The fate of polymorphonuclear neutrophilic granulocytes (PMN) after their mobilization from the bone marrow of healthy individuals is not clearly understood. It has been suggested that there is a continuous utilization of these cells in widespread, subclinical inflammatory foci, where they are ultimately degraded. The goal of the present experiments was to determine whether an alternative ecotaxis ("homing") exists, namely sequestration and degradation of PMN by mononuclear phagocytes exposed to the bloodstream in the liver, spleen and bone marrow. Blood PMN were collected from donor rats, labelled with 51 Cr, and injected i.v. into 2 syngeneic rats, one of them having an induced sterile peritonitis. After various time intervals up to 18 h, the rats were killed and exsanguinated. As expected, we found cell-bound radioactivity in liver, spleen, and bone marrow. The bone marrow uptake of PMN appeared to be much lower in the inflammation rats than in the normal controls. These findings were confirmed in PMN transfer experiments using PVG rats congenic for the RT7 alloantigenic system. Here, transfused blood leukocytes were traced with fluorescent, monoclonal HIS41 antibodies and flow cytometry. A possible corticosteroid effect on the bone marrow sequestration could not be substantiated. Uptake and degradation of PMN takes place in organs containing phagocytes exposed to the bloodstream. Sequestration of PMN in the bone marrow is apparently down-regulated in inflammatory states, perhaps increasing the PMN availability to inflamed tissue.

Animals↗
PubMed1995

Zinc and manganese bioavailability from human milk and infant formula used for very low birthweight infants, evaluated in a rat pup model.

The bioavailability of zinc and manganese from diets used for very low birthweight infants was investigated in a rat pup model using radioisotopes. The effect of protein source and content and of pasteurization was evaluated, and two different approaches for evaluation of zinc and manganese bioavailability from the studied human milk and infant formula for very low birthweight infants was high. Liver uptake of 65Zn from labeled premature infant diets in sucklings rat pups was 26-29%, and absorption calculated as the difference between administered dose and nonabsorbed activity 6 h after oral intubation was 93-95%. Retention of manganese calculated as the sum of 54Mn retained by organs and carcass was 85-95% from human milk and premature infant formula, and absorption calculated from nonabsorbed activity was 83-88% after 6 h. Fortification of early human milk significantly increased the bioavailability of zinc. No effect of pasteurization of human milk was found on zinc or manganese bioavailability. Liver zinc uptake was found to be a more sensitive parameter than absorption for evaluation of diets with a high zinc bioavailability. Measurement of retained activity of manganese in carcass and organs was judged to be the preferred parameter for evaluation of diets with high manganese availability.

Absorption↗
PubMed1995

Zinc absorption estimated by fecal monitoring of zinc stable isotopes validated by comparison with whole-body retention of zinc radioisotopes in humans.

Knowledge about zinc availability from human diets is limited due to methodological difficulties. Recently developed stable isotope techniques for estimating dietary zinc absorption were compared with radioisotope techniques in five men and three women. Stable and radioactive zinc isotopes were simultaneously administered. Fecal excretion of the isotopes as well as whole-body retention of the radioactive zinc isotope was monitored. Concentration of stable zinc isotope label in fecal samples was determined by inductively coupled plasma mass spectrometry by fully quantitative measurements and from inductively coupled plasma mass spectrometry isotope ratios combined with analysis of total zinc content using atomic absorption spectrometry. Zinc absorption estimated from whole-body retention was 27 +/- 6% (mean +/- SD), estimated zinc absorption obtained by fecal monitoring of radioisotope was 26 +/- 9%, and the two stable zinc measurements resulted in values of 29 +/- 12 and 33 +/- 12%, respectively. There was no significant difference in zinc absorption estimated from whole-body retention and with the fecal monitoring methods. Recovered stable zinc isotope label was significantly lower than recovered radioisotope. For individual fecal samples, systematic differences of 16% and 12%, respectively (P < 0.05), between the radioisotope recovery and the recovery of stable isotopes with the two methods for measurement was observed. The stable zinc isotope technique for measurement of zinc absorption resulted in mean results similar to those of the radioisotope technique, but with a larger variation in the measurements.

Adult↗
PubMed1991

[Treatment of infectious diseases with antibacterial drugs in general practice].

A survey of systemic treatment with antimicrobial drugs in general medical practice at Holstebro, Jutland, in March 1987 is presented. The two pharmacies of the town recorded all prescriptions to individual patients. The diagnoses were recorded by questionnaire, which was returned by all involved physicians. A total of 969 persons, equivalent to 2.4 per cent of the population and 5.7 per cent of all Health Service contributions, were treated: 39% for upper and 18% for lower respiratory infection, 18% for urogenital infection and 7% for skin infection. 6% were recorded under "miscellaneous". In 12% of the cases no diagnosis was stated. 48% were treated with V-penicillin, 20% with ampicillin, 17% with erythromycin and 3% with tetracycline. The investigation shows a tendency towards less than optimal strategies as regards infections of the respiratory passages and the urinary system. Too often a "wide-spectrum therapy" was chosen. This choice meant a prolonged term of treatment and larger day-and-night doses leading to unnecessary expense. Short-term treatment of uncomplicated infection of the urinary system and otitis media were not recorded.

Adolescent↗
PubMed1987

Retinoids and systemic chemotherapy in cases of advanced mycosis fungoides. A report from the Scandinavian Mycosis Fungoides Group.

In cases of advance mycosis fungoides, the systemic chemotherapy combination of bleomycin, cyclophosphamide and prednisolone was given to 8 cases, and the same 3-drug combination with the addition of oral retinoids given to 12 cases. All cases were in a progressive phase of the disease. Remission was obtained in 5/8 cases treated with the combination and in 7/12 cases treated with the combination plus retinoids. The remissions were complete in half of the cases, but relapse occurred within 3 to 6 months in all but 2 cases. The two treatment patient groups were not fully comparable but the conclusion is that the addition of retinoids to systemic chemotherapy combination regimens is of some advantage. There still exists, however, need of more adequate treatment modalities in advanced mycosis fungoides.

Bleomycin↗