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Biomedical subjects

L Iversen

Publications and source records attributed to L Iversen.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Development in mortality, incidence and lethality of ischemic heart disease in Denmark 1982-1992].

In Denmark, as in many other Western countries, a decline in mortality from ischaemic heart disease (IHD) has been observed. The present study assesses whether the decline in IHD mortality is due to a decrease in incidence and/or case-fatality, and whether parallel changes occurred in the various manifestations of IHD requiring hospitalization. The National Patient Register of hospital discharges and the Causes-of-Death Register were linked and all cases of first admission for IHD including acute myocardial infarction (AMI) and fatal first manifestation of IHD since 1977 in the entire Danish population were identified. Cases of AMI and IHD were considered as incident cases if no admission for these diagnoses had occurred during the preceding five years for the same person. Sex-specific, age-standardized annual mortality, incidence and case-fatality rates of AMI (ICD8 code 410), narrowly defined IHD (NIHD, ICD8 codes 410-4) and broadly defined IHD (BIHD, ICD8 codes 410-4, 427 & 795-6) were calculated for the period 1982 through 1992. During the entire period the age-standardized mortality of AMI, NIHD and BIHD decreased in both men and women. The incidence of AMI and NIHD decreased, while the incidence of BIHD remained constant. Case-fatality of AMI decreased in both men and women, while case-fatality of NIHD and BIHD decreased in men and in women aged 0-64 years only. The declining mortality from IHD in Denmark may be partly due to declining incidence as well as declining case-fatality, but changes in disease manifestation or a diagnostic drift may also contribute, since more broadly defined diagnostic groups showed less or no decline in incidence.

Adult↗
PubMed1997

Evaluation of the urinary cortisol: creatinine ratio in the diagnosis of hyperadrenocorticism in dogs.

The diagnostic accuracy of the urinary cortisol:creatinine ratio (CCR), with the cortisol being measured by ELISA, was evaluated by subjecting data from 18 dogs with and 20 dogs without hyperadrenocorticism to receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (W 0.93, SE(w) 0.044) was much higher than 0.5, indicating that the CCR did distinguish between dogs with and without hyperadrenocorticism. A cutoff value of about 60 x 10(-6) was associated with the highest sensitivity (1.0) and specificity (0.85). At the disease prevalence rate of the present study (0.47), the positive and negative predictive values were 0.87 and 1.0, respectively. These numbers indicate that canine hyperadrenocorticism may be safely excluded when the CCR is below 60 x 10(-6) but that a test of higher specificity (eg, the ACTH stimulation test) should be used to confirm the diagnosis of canine hyperadrenocorticism when the CCR is above 60 x 10(-6).

Adrenocortical Hyperfunction↗
PubMed1997

Duplex Doppler measurements of renal blood flow in a dog with Addison's disease.

Abnormal intrarenal flow in a seven-year old female Tibetan terrier with Addison's disease was demonstrated by duplex Doppler examination. Abnormal flow may reflect renal vasoconstriction due to increased activity of the renin-angiotensin system. Although not pathognomonic, an increased resistive index (> 0.70) in an otherwise ultrasonographically normal kidney can be due to Addison's disease and the technique may prove valuable as a quick non-invasive tool in the management of this disease.

Addison Disease↗
PubMed1997

Significance of leukotriene-A4 hydrolase in the pathogenesis of psoriasis.

The 5-lipoxygenase (5-LO) product of arachidonic acid, leukotriene (LT-)B4, is considered to play a significant role in the pathogenesis of psoriasis. In vitro LTB4 is a potent chemoattractant for leukocytes, and it increases DNA synthesis in human cultured keratinocytes. Intradermal injection of LTB4 into human skin in vivo results in a wheal and flare reaction, and topical application produces intraepidermal microabscesses and induces hyperproliferation. Furthermore, LTB4 has been determined in biologically active amounts in psoriatic skin lesions. Despite the importance of LTB4 in psoriasis, the capacity of the human epidermis to synthesize LTB4 has remained controversial. Recently, a very limited 5-LO activity was reported in human epidermis. Thus, it was shown that human epidermis can contribute significantly to LT formation by transcellular LT synthesis. By this mechanism, LTA4 released from activated leukocytes is further transformed into LTB4 in the keratinocytes by the LTA4 hydrolase. Transcellular metabolism may be of importance in psoriasis where neutrophils migrate into the epidermis, because in human neutrophils the LTA4 hydrolase has been shown as the rate-limiting step in LTB4 formation. The LTA4 hydrolase was localized in the epidermis by activity determination, by inhibition of enzyme activity with known LTA4 hydrolase inhibitors, by Western blotting and by immunohistochemical staining. Moreover the enzyme was purified and further characterized from human cultured keratinocytes and human epidermis. Because of these recent results it is concluded that LTB4 is of significance in the pathogenesis of psoriasis, and it is suggested that future work should focus on developing potent LTA4 hydrolase inhibitors for treatment of psoriasis.

Amino Acids↗
PubMed1996

LTA4 hydrolase in human skin: decreased activity, but normal concentration in lesional psoriatic skin. Evidence for different LTA4 hydrolase activity in human lymphocytes and human skin.

Leukotriene A4 (LTA4) hydrolase which transforms LTA4 into the proinflammatory compound LTB4 has been identified in human epidermis. The purpose of this study was to investigate the potential role of this enzyme in psoriasis, in which LTB4 is present in biologically active concentrations. The concentration and activity of LTA4 hydrolase was determined in normal skin and in matched samples of involved and uninvolved psoriatic skin. The enzyme content was determined using an affinity-purified antibody. This antibody was also used for immunohistochemical staining of skin biopsies. Immunohistochemically LTA4 hydrolase was localized predominantly in the basal and spinous layers in normal skin and in involved and uninvolved psoriatic skin. The LTA4 hydrolase content varied between 2.8 and 3.1 micrograms enzyme/mg protein and was found to be similar in normal and psoriatic skin, involved as well as uninvolved. In contrast, the activity of the enzyme was decreased significantly in involved psoriatic skin (9.9 +/- 2.1 micrograms LTB4/mg enzyme per min) compared with matched uninvolved psoriatic skin (16.4 +/- 3.5 micrograms LTB4/mg enzyme per min), but was decreased only insignificantly compared with normal skin (12.4 +/- 1.8 micrograms LTB4/mg enzyme per min). It was found that the conversion of LTA4 to LTB4 results in inactivation of LTA4 hydrolase activity. This finding is compatible with the idea that the decreased LTA4 hydrolase activity in involved psoriatic skin reflects transcellular LTB4 formation in vivo. In peripheral lymphocytes the enzyme content was 1.3 +/- 0.3 microgram enzyme/mg protein in normal lymphocytes and 1.4 +/- 0.3 microgram enzyme/mg protein in psoriatic lymphocytes, which was significantly lower than in the skin. In contrast, the specific LTA4 hydrolase activities in normal and psoriatic lymphocytes (23.4 +/- 1.3 and 21.3 +/- 1.7 micrograms LTB4/mg enzyme per min) were significantly higher than in normal skin. These findings may indicate the existence of LTA4 hydrolase isoforms in human lymphocytes and human skin.

Animals↗
PubMed1996

Evaluation of an immunoradiometric assay for thyrotropin in serum and plasma samples of dogs with primary hypothyroidism.

A commercially available immunoradiometric assay was used to measure the thyrotropin (TSH; thyroid-stimulating hormone) concentration in the serum and plasma of 23 dogs. The basal concentration in five dogs with histologically confirmed primary hypothyroidism (median 0.18 microg/l, range 0.16-0.72 microg/l) was slightly, but not significantly, higher than that in 13 clinically healthy dogs (median 0.09 microg/l, range 0.06-0.34 microg/l). The TSH values in 11 euthyroid dogs with various dermatological diseases (median 0.09 microg/l, range 0.05-0.53 microg/l) were significantly lower than in the hypothyroid dogs, but there was considerable overlap. The assay alone was therefore not capable of giving a firm diagnosis.

Animals↗
PubMed1996

Trends in mortality, incidence and case fatality of ischaemic heart disease in Denmark, 1982-1992.

BACKGROUND: In Denmark, as in many other Western countries, a decline in mortality from ischaemic heart disease (IHD) has been observed. The present study assesses whether the decline in IHD mortality is due to a decrease in incidence and/or case-fatality, and whether parallel changes occurred in the various manifestations of IHD requiring hospitalization. METHODS: The National Patient Register of hospital discharges and the Causes-of-Death Register were linked and all cases of first admission for IHD including AMI and fatal first manifestations of IHD since 1977 in the entire Danish population were identified. Cases of AMI and IHD were considered as incident cases if no admission for these diagnoses had occurred during the preceding 5 years. Sex-specific, age-standardized annual mortality, incidence and case-fatality rates of AMI (ICD8 code 410), narrowly defined IHD (NIHD, ICD8 codes 410-4) and broadly defined IHD (BIHD, ICD8 codes 410-4, 427 and 795-6) were calculated for the period 1982-1992. RESULTS: During the entire period the age-standardized mortality of AMI, NIHD and BIHD decreased in both men and women. The incidence of AMI and NIHD decreased, while the incidence of BIHD remained constant. Case fatality of AMI decreased in both men and women, while case fatality of NIHD and BIHD decreased in men and in women aged 0-64 years only. CONCLUSION: The declining mortality from IHD in Denmark may be partly due to declining incidence as well as declining case fatality, but changes in disease manifestation or diagnostic drift may also contribute because more broadly defined diagnostic groups showed less or no decline in incidence.

Adolescent↗
PubMed1996

Cyclosporin A down-regulates the LTA4 hydrolase level in human keratinocyte cultures.

Leukotriene A4 hydrolase is a key enzyme in the biosynthesis of leukotriene B4, a potent pro-inflammatory compound. The purpose of this study was to determine the capacity of antiinflammatory and anti-proliferative compounds to regulate the levels and activity of leukotriene A4 hydrolase in cultured human keratinocytes. The content of leukotriene A4 hydrolase was determined by Western blot analysis, and the activity of leukotriene A4 hydrolase was expressed as the leukotriene B4 formation after incubation of keratinocyte cultures with leukotriene A4. Leukotriene B4 was measured by revered-phase high performance liquid chromatography. Preincubation for 10 min of the cultured keratinocytes with the leukotriene A4 hydrolase inhibitor RP 64699 (0.1-10 microM) caused a significant dose-dependent inhibition of leukotriene B4 formation (IC50 = 0.7 microM). Cyclosporin A (0.1 micrograms/ml and 1.0 micrograms/ml) had no direct effect on leukotriene A4 hydrolase activity, but after incubation for 72 h there was a decrease in the mean leukotriene B4 formation per culture dish (35% and 48%, respectively). The decreased leukotriene B4 formation was caused mainly by a decrease in the mean leukotriene A4 hydrolase content per mg protein (30.1% at 0.1 micrograms/ml cyclosporin A and 40.0% at 1.0 micrograms/ml cyclosporin A), although keratinocyte proliferation was also slightly decreased. Incubations with 1.25-dihydroxyvitamin D3 (10(-7)-10(-10) M), all-trans retinoic acid (10(-6)-10(-10) M), eicosartienoic acid (10(-6)-10(-8) M), dexamethasone (10(-5)-10(-7) M), interferon-gamma (10 and 100 units/ml) or methotrexate (0.1-10 micrograms/ml) had no effect on either the leukotriene B4 formation or the amount of leukotriene A4 hydrolase in keratinocyte cultures. These results show that cyclosporin A, in contrast to other anti-inflammatory and anti-proliferative compounds, inhibits the level of leukotriene A4 hydrolase in keratinocyte cultures. Since similar cyclosporin A concentrations are obtained during treatment of psoriasis with cyclosporin A, the effect on leukotriene A4 hydrolase may play a role in the anti-inflammatory action of cyclosporin A.

8,11,14-Eicosatrienoic Acid↗
PubMed1995

[Late effects of occupational organic brain damage in painters 6-8 years after diagnosis. Occurrence of mental and psychosomatic health problems and utilization of health services].

With the object of illustrating effects on health and social functions of occupational organic brain damage, a questionnaire study was carried out in 1986 concerning 192 brain-damaged painters and a reference group of 341 other painters. The study was repeated in 1990 to elucidate effects six to eight years after diagnosis. In 1986 a high prevalence of mental and psychosomatic symptoms was found among the brain-damaged painters. The prevalence correlated with severity of the disease, occupational situation and social network. In 1990 the same level of symptoms was found. In the reference group the prevalence of symptoms increased from 1986 to 1990. Besides the major difference in the prevalence of symptoms between the two groups, the level of symptoms correlated to the occupational situation in both groups. Twenty-seven percent of the brain-damaged painters were still at work in 1990. The high symptom level among the brain-damaged painters is considered to be chronic.

Adult↗
PubMed1995

Purification and characterization of leukotriene A4 hydrolase from human epidermis.

The leukotriene A4 hydrolase is a central enzyme in leukotriene B4 formation. Unlike 5-lipoxygenase, leukotriene A4 hydrolase activity is present in normal human epidermis, where it is likely to be involved in transcellular leukotriene formation. In this study the leukotriene A4 hydrolase was purified from human epidermis and human cultured keratinocytes and compared with leukotriene A4 hydrolase from human neutrophils. To purify leukotriene A4 hydrolase from human epidermis a new non-specific affinity chromatography column, with the leukotriene A4 hydrolase inhibitor bestatin coupled to AH-Sepharose, was introduced. The epidermal leukotriene A4 hydrolase was purified to apparent homogeneity and the molecular weight was determined to be approximately 70,000 Da by SDS-PAGE. The pI was 5.1-5.4 for the epidermal as well as the keratinocyte and neutrophil leukotriene A4 hydrolase, as determined by chromatofocusing. Only minor differences in the amino acid composition were seen between the three enzyme sources. The optimal pH for the hydrolase activity was 7.5-8.5 for the epidermal and neutrophil leukotriene A4 hydrolases. Finally, it was also shown that the epidermal leukotriene A4 hydrolase undergoes suicide inactivation when transforming leukotriene A4 into leukotriene B4. It was concluded that there is a close resemblance between the epidermal leukotriene A4 hydrolase and the hydrolase found in other cell types. Therefore, the human epidermis may be a good model for the in vivo study of transcellular leukotriene formation.

Cells, Cultured↗
PubMed1995

Interleukin 13 suppresses cytokine production and stimulates the production of 15-HETE in PBMC. A comparison between IL-4 and IL-13.

We examined the ability of rIL-13 to regulate rIL-l alpha induced IL-1 beta, IL-1 receptor antagonist (IL-1ra) and IL-8 production in cultured peripheral blood mononuclear cells (PBMC), endothelial cells and fibroblasts. Furthermore we examined whether rIL-13 could influence the production of the arachidonic acid products LTB4, 12-HETE and 15-HETE by PBMC. rIL-1 alpha-stimulated PBMC cultures secreted high levels of IL-1 beta and IL-8; this could be inhibited to the level of unstimulated control cells by co-incubation with rIL-13 (10 ng/ml). IL-13 induced a 3-fold increase of the IL-1ra secretion which was inhibited by rIFN-gamma. In the presence of both rIL-1 alpha and rIL-13, endothelial cells increased IL-8 secretion, whereas dermal fibroblasts remained unchanged. Of the arachidonic acid metabolites examined, the greatest change was observed in the formation of 15-HETE. In unstimulated PBMC cultures the amount of 15-HETE was less than 4 ng/10(6) cells, whereas after addition of rIL-13 we measured a formation of 139 +/- 6.2 ng/10(6) cells. The effect of rIL-13 on the 15-HETE formation in PBMC was abolished by addition of 100 U/ml rIFN-gamma. rIL-13 only induced minor changes in the LTB4 and 12-HETE formation. Compared to IL-4, IL-13 induced a similar alteration of the cytokine cascade and arachidonic acid metabolism, supporting the hypothesis that the two cytokines use a common receptor complex or signal pathway.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1995

Characterization of the aminopeptidase activity of epidermal leukotriene A4 hydrolase against the opioid dynorphin fragment 1-7.

Leukotriene A4 hydrolase is a bifunctional cytosolic enzyme, which both hydrolyses leukotriene A4 (LTA4) into leukotriene B4 (LTB4) and exerts aminopeptidase activity against opioid peptides. In the present study we have investigated whether the peptides angiotensin I and II, bradykinin, kallidine, histamine, dynorphin fragment 1-7 and substance P can act as substrates for epidermal and neutrophil LTA4 hydrolase. Among the tested substrates, dynorphin fragment 1-7 was found to be the best substrate for the enzyme. The aminopeptidase activity of epidermal and neutrophil LTA4 hydrolase against dynorphin fragment 1-7 was further characterized. The enzyme was purified from human epidermis and human neutrophils by anion exchange chromatography (Q-Sepharose) and affinity chromatography on a column with the LTA4 hydrolase inhibitor bestatin coupled to AH-Sepharose. The incubation of the dynorphin fragment 1-7 with LTA4 hydrolase resulted in the formation of tyrosine. The presence of the N-terminal amino acid tyrosine is essential for the interaction of opioids with their receptors, and this finding indicates that the LTA4 hydrolase can inactivate dynorphin fragment 1-7. After the two purification steps no other aminopeptidases acting at the N-terminal tyrosine of dynorphin fragment 1-7 was present in the preparation. This was demonstrated by the abolishment of the degradation at the N-terminal end of dynorphin fragment 1-7 when preincubating the enzyme preparation with LTA4 before the incubation with the dynorphin fragment 1-7. The abolishment of the aminopeptidase activity shows that activation of the hydrolase part of the enzyme, with conversion of LTA4 into the potent proinflammatory compound LTB4, results in an inhibition of the aminopeptidase activity of the enzyme. As a result, the catabolism of dynorphin fragment 1-7 and probably of other opioid peptides is inhibited, resulting in sustained biological effects of these opioids. This phenomenon may be important for the maintenance of inflammation in skin conditions, such as psoriasis and atopic dermatitis, in which LTB4 is formed.

Amino Acid Sequence↗
PubMed1995

An improved radioimmunoassay for the determination of canine growth hormone based on commercially available reagents.

Determination of canine growth hormone (cGH) is of importance when evaluating the growth hormone status in dogs, for instance when diagnosing pituitary dwarfism and acromegaly. At present, analysis for the cGH content in canine blood has mainly been restricted to specialized laboratories which have had the capacity to develop suitable methods. We therefore formulated the objective of the present study to be the development of a generally accessible method utilizing commercially available reagents. We describe a radioimmunoassay (RIA) for the determination of cGH which was based on reagents developed for the determination of porcine growth hormone (pGH), thereby drawing benefit from the similarity between growth hormones from the two species. The RIA method was characterized by satisfying precision and accuracy parameters: intra- and inter-assay coefficients of variation (CV%) were 4-27% and 4-20%, respectively, depending on the cGH concentration of the samples. Recovery of added cGH and parallelism between standard curve and sample dilutions were acceptable, thus indicating identity between the calibrator system and the material under investigation (i.e. plasma samples). When measuring individual plasma samples or samples taken during clonidin response tests from normal dogs, dogs suffering from pituitary dwarfism and from dogs suffering from acromegaly, the results were comparable with previous findings.

Acromegaly↗
PubMed1995

Incorporation of 15-hydroxyeicosatrienoic acid in specific phospholipids of cultured human keratinocytes and psoriatic plaques.

15-hydroxyeicosatrienoic acid, 15-HETrE, the 15-lipoxygenase product of dihomogammalinolenic acid (DGLA), can inhibit the biosynthesis of the proinflammatory eicosanoids leukotriene B4 (LTB4) and 12-hydroxyeicosatetraenoic acid (12-HETE). The purpose of the present study was to investigate the incorporation of [14C]15-HETrE in specific membrane phospholipids of cultured human keratinocytes in vitro. [14C]15-HETrE was rapidly incorporated into keratinocytes. When a plateau was reached after 3 hours, 15% of the added radioactivity was incorporated into lipids; 96.5% into phospholipids (PL) and 3.5% into neutral lipids (NL). Within the phospholipid classes, [14C]15-HETrE showed selectivity for incorporation into phosphatidylinositol (PI). The mean proportion of [14C]15-HETrE in the PI, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was 83.2%, 8.5% and 8.3%, respectively. We then investigated the incorporation of 15-HETrE in epidermal phospholipids of psoriatic skin intralesionally injected with 15-HETrE. Four patients took part in the study. In each patient four identical plaques were injected with 0.65 ml of 2.0 microM, 6.2 microM, 18.6 microM of 15-HETrE (0.4 micrograms, 1, 2 micrograms and 3.6 micrograms respectively) or 0.65 ml of 0.88% NaCl twice a week. After 3 wk keratome biopsies were obtained from the treated plaques. Phospholipids extracted from the skin biopsies were separated into major classes by two-dimensional thin layer chromatography. 15-HETrE was then released from specific phospholipids after treatment with phospholipase A2 and identified by reverse phase and straight phase high performance liquid chromatography. There was a dose-dependent incorporation of 15-HETrE into the specific phospholipids PI and PC. When expressed as ng 15-HETrE/micrograms phospholipid phosphate, 15-HETrE accumulated preferentially in PI.(ABSTRACT TRUNCATED AT 250 WORDS)

8,11,14-Eicosatrienoic Acid↗
PubMed1994

Human epidermis transforms exogenous leukotriene A4 into peptide leukotrienes: possible role in transcellular metabolism.

Leukotriene B4 formation can take place by cell interaction between keratinocytes and neutrophils. Thus, keratinocytes without proven 5-lipoxygenase activity can transform neutrophil-derived leukotriene A4 into leukotriene B4. The purpose of the present study was to investigate whether human epidermis is able to transform leukotriene A4 sequentially into the peptide leukotrienes (LTC4, LTD4 and LTE4). Epidermis isolated using the suction blister technique or keratomed skin specimens were incubated with either neutrophils or exogenously added leukotriene A4. Peptide leukotrienes were determined by integrated optical density after RP-HPLC separation, and the identity of leukotrine C4 was confirmed by (1) the retention time similarity with authentic leukotriene C4; (2) the UV spectrum determined with an on-line diode array detector; and (3) conversion by gamma-glutamyl transpeptidase of the peak coeluting with authentic leukotriene C4 into a new peak coeluting with authentic leukotriene D4. The results of this study showed that while human epidermis cannot form detectable amounts of peptide leukotrienes by itself, it can transform exogenous leukotriene A4 into peptide leukotrienes. Furthermore, coincubation of human epidermis and neutrophils resulted in a marked increase (90%) in peptide leukotriene formation when compared with neutrophils alone, indicating that human epidermis can transform neutrophil-derived leukotriene A4 into peptide leukotrienes. These results indicate that human skin contains leukotriene C4 synthase activity capable of producing significant amounts of leukotriene C4 from leukotriene A4, and that the keratinocytes may play a more active role in peptide leukotriene formation in the skin than previously thought.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗
PubMed1994

Purification and some properties of glyceraldehyde 3-phosphate dehydrogenase from Synechococcus sp.

Glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.13) was purified 386 fold to apparent homogeneity from the thermophilic cyanobacterium Synechococcus sp. grown at optimum light intensities in batch cultures. The molecular mass of the tetrameric form of the enzyme was 160 kDa as determined by gel filtration and sucrose gradient centrifugation in a phosphate buffer containing DTT. The pH optimum for the oxidation of NADPH was broad (6-8) and the enzyme had a pI of 4.5. The turnover number was 36,000 min-1 at 40 degrees C. The activation energy was 12.4 Kcal for t > 29 degrees C and 20.6 Kcal for t < 29 degrees C. The specific absorption coefficient, A 1% 1cm 280 mm of the pure enzyme in phosphate buffer at pH 6.8 was 15.2. By SDS gel electrophoresis molecular masses of 78 kDa and 39 kDa were found, indicating that the purified enzyme is a tetramer, probably a homotetramer. When Tris was used as buffer in the homogenization and phosphate and DTT were omitted, a high molecular form with a molecular mass above 500 kDa was found. This form was less active than the purified tetrameric form. Acetone and other organic solvents stimulated the native enzyme several fold.

Cyanobacteria↗