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M Kjeld

Publications and source records attributed to M Kjeld.

At least 19 recordsLinked to original sources
PubMed2002

Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine.

BACKGROUND: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps, and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period. AIM: To assess if MMR vaccination is associated with subclinical intestinal inflammation, which is central to the autistic "enterocolitis" theory. METHODS: We studied 109/58 infants, before and two and four weeks after immunisation with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin). RESULTS: Neither vaccination was associated with any significant increase in faecal calprotectin concentrations. CONCLUSIONS: The failure of the MMR vaccination to cause an intestinal inflammatory response provides evidence against the proposed gut-brain interaction that is central to the autistic "enterocolitis" hypothesis.

Analysis of Variance↗
PubMed2000

Serum thyroglobulin as a risk factor for thyroid carcinoma.

Samples from a biological serum bank taken up to 23 years prior to diagnosis of thyroid carcinoma were analysed for human thyroglobulin, thyroid-stimulating hormone and thyroxin. After exclusions, the final study material consisted of 59 cases of papillary and follicular carcinomas. These cases were compared with 164 controls, matched for sex, age and time of sample taking. The most interesting finding was that concentrations of thyroglobulin in serum were abnormally elevated in cases compared with controls, equal to or above 30 microg/L, with odds ratio 7.0 (CI 3.1-15.7). This elevation of serum thyroglobulin occurred in 44% of the carcinoma cases. Sensitivity was around 50 for measurements taken up to 15 years prior to diagnosis, but 21 when the interval was over 15 years. Specificity was 89. No differences were found between cases and controls in values for thyroid-stimulating hormone and thyroxin.

Adenocarcinoma, Follicular↗
PubMed1999

Evidence of Brucella infection in marine mammals in the North Atlantic Ocean.

Between 1983 and 1996 a total of 1386 samples of serum were taken from four species of seal and three species of whale in the waters west of Iceland, the area of pack-ice north-west of Jan Mayen, the northern coast of Norway and the Kola Peninsula, the waters west of Svalbard, and the Barents Sea; they were tested for the presence of anti-Brucella antibodies with an indirect ELISA (protein G conjugate). The positive sera were re-tested with classical brucellosis serological tests, such as the serum agglutination test, the EDTA-modified serum agglutination test, the Rose Bengal test, and the complement fixation test, as well as an anti-complement ELISA. Anti-Brucella antibodies were detected in all the species investigated, except for the bearded seal (Erignathus barbatus), with the following prevalences: hooded seals (Cystophora cristata) 35 per cent; harp seals (Phoca groenlandica) 2 per cent; ringed seals (Phoca hispida) 10 per cent; minke whales (Balaenoptera acutorostrata) 8 per cent; fin whales (Balaenoptera physalus) 11 per cent; and sei whales (Balaenoptera borealis) 14 per cent. An isolate belonging to the genus Brucella was obtained from the liver and spleen of one of the seropositive minke whales. The findings suggest that antibodies against the surface lipopolysaccharide of Brucella species are widely distributed among marine mammals in the North Atlantic Ocean.

Agglutination Tests↗
PubMed1998

Inhibitory effects of meta-iodo-benzylguanidine (MIBG) on endothelial histamine receptor binding.

Meta-iodo-benzylguanidine (MIBG), a selective inhibitor of mono-ADP-ribosylation, has been shown to inhibit histamine induced inositol-trisphosphate and prostacyclin production. The purpose of this study was to evaluate the effect of MIBG on the binding of histamine to the H1-receptor and to study its effects on phospholipid metabolism in human endothelial cells. The effects of MIBG and MIBA (meta-iodo-benzylamine), which does not affect cellular ADP-ribosylation, on agonist induced cGMP production in cultured HUVEC's were measured by RIA and a binding study carried out to evaluate their effects on the binding of [3H]mepyramine to membrane fractions. MIBG (0.3 mM) reduced histamine induced cGMP production by 90.8% but did not inhibit the cGMP production induced by other agonists. MIBA had no effect. MIBG also reduced the binding of [3H]mepyramine (1.0 nM) to membrane fractions with IC50 at 0.094 mM and maximal inhibition (83%) at 0.22mM MIBG. The calculated Ki was 0.076mM. MIBG and MIBA altered phospholipid metabolism in a similar way as the cationic amphiphilic drug propranolol. MIBA caused up to 42% reduction in [3H]mepyramine binding, probably due to its inhibition of nonspecific binding. These results indicate that MIBG reduces histamine induced cGMP production by inhibiting its binding to H1-receptors and alters phospholipid metabolism in cultured endothelial cells in a similar way as known cationic amphiphilic drugs.

3-Iodobenzylguanidine↗
PubMed1998

Potentiating effects of pertussis toxin on leukotriene C4 induced formation of inositol phosphate and prostacyclin in human umbilical vein endothelial cells.

Leukotriene C4 is an arachidonic acid metabolite and an important mediator of inflammation and anaphylaxis that is known to induce production of prostacyclin in endothelial cells. The goal of this study was to examine the signal transduction mechanisms activated by leukotriene C4 stimulation. Formation of inositol phosphates was measured to determine the activation of phospholipase C and pertussis toxin was used to explore the role of G-proteins. Additionally, we evaluated the role of protein kinase C in these events, especially whether there was an interaction between pertussis toxin mediated effects and the activity of protein kinase C. Leukotriene C4 induced a dose- and time-dependent formation of inositol phosphates and prostacyclin. The response to leukotriene C4 was greater than the response to leukotriene D4 even after treatment with L-serine borate complex, suggesting the presence of a specific leukotriene C4 receptor. Exposure to pertussis toxin potentiated, time-dependently, the leukotriene C4 induced formation of inositol phosphates and prostacyclin through a mechanism which was altered by manipulation of protein kinase C activity. The exact mechanism is not clear but our results are consistent with a postulated dual mechanism of phospholipase C control, in which leukotriene C4 induced stimulation is attenuated by a pertussis toxin sensitive G-protein.

Borates↗
PubMed1997

A role for tyrosine phosphorylation in generation of inositol phosphates and prostacyclin production in endothelial cells.

We have examined the effects of the protein tyrosine phosphatase inhibitor pervanadate on activation of signal transduction in human umbilical vein endothelial cells. Endothelial cells responded to pervanadate treatment by increasing tyrosine phosphorylation of cellular proteins, including phospholipase C (PLC) gamma 1, generating inositol phosphates (IPs), releasing arachidonic acid, and producing prostacyclin (prostaglandin [PG] I2). The dose and time responses for these events were similar. Tyrosine phosphorylation and formation of IPs in response to pervanadate were reduced by both staurosporine and genistein. Short-term incubation with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, which inhibits thrombin-induced IP generation, did not affect the IP response to pervanadate. To investigate the possible involvement of tyrosine phosphorylation in thrombin or histamine-induced IP generation and PGI2 production, we examined the effects of costimulation with pervanadate and either thrombin or histamine. These responses proved to be different. While the tyrosine phosphorylation of PLC gamma 1 was enhanced after cotreatment with thrombin and pervanadate compared with pervanadate alone, costimulation with pervanadate and histamine resulted in no more tyrosine phosphorylation of PLC gamma 1 than after pervanadate alone. Similarly, while cotreatment with pervanadate and thrombin caused synergistic increase in IP generation, costimulation with pervanadate and histamine resulted in an additive response. However, PGI2 responses to costimulation of pervanadate with either thrombin or histamine were both synergistic. Furthermore, stimulation with histamine, thrombin, or pervanadate all caused tyrosine phosphorylation of a mitogen-activated protein kinase (ERK1/p44). The results suggest that a tyrosine phosphorylation-dependent mechanism has a role in the phosphoinositide signal transduction pathway of human endothelial cells. Moreover, thrombin- but not histamine-induced generation of IPs appears to be partly caused by tyrosine phosphorylation of PLC gamma 1.

Arachidonic Acid↗
PubMed1996

Design and in vivo testing of 17 beta-estradiol-HP beta CD sublingual tablets.

17 beta-Estradiol is almost insoluble in water. The effect of various cyclodextrins and two different polymers, polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC), on the aqueous solubility of 17 beta-estradiol was investigated. 17 beta-Estradiol was dissolved in aqueous 50% w/v 2-hydroxypropyl-beta- cyclodextrin (HP beta CD) solution containing 0.25% (w/v) CMC and the dry 17 beta-estradiol-HP beta CD complex formed by lyophilisation of the solution. Sublingual tablets from the dry complex were produced by direct compression. The dissolution of 17 beta-estradiol from tablets containing the drug in a lyophilised HP beta CD complex was determined. For reference the dissolution of 17 beta-estradiol was determined from tablets containing physical mixture of 17 beta-estradiol and HP beta CD or tablets containing 17 beta-estradiol without HP beta CD. Sublingual tablets containing 17 beta-estradiol-HP beta CD in the lyophilised complex demonstrated the fastest dissolution profile and those tablets were selected for further studies in humans. Six postmenopausal women received a sublingual tablet containing 17 beta-estradiol-HP beta CD complex equivalent to 100 micrograms 17 beta-estradiol. Blood samples were collected over a 12 h period and the 17 beta-estradiol plasma concentration was determined. 17 beta-Estradiol was rapidly absorbed from the sublingual tablets, resulting in a peak 17 beta-estradiol plasma concentration of 568 +/- 97 pmol/l 15 min after administration of the tablets, followed by a biphasic elimination.

Administration, Sublingual↗
PubMed1994

Endothelin secretion is regulated by cyclic AMP and phosphatase 2A in endothelial cells.

Endothelin is a 21 amino acid peptide secreted by endothelial cells and is the most potent vasoconstrictor known. The present study examines regulatory mechanisms of endothelin secretion, focusing on the role of protein phosphorylation. Endothelin secretion was measured by radioimmunoassay in primary cultures of human umbilical vein endothelial cells. While treatment that raised cAMP levels reduced the basal endothelin secretion rate, agents that elevated cGMP had no effect. Downregulation or inhibition of protein kinase C resulted in decreased endothelin secretion, suggesting that protein kinase C regulates endothelin secretion in the opposite direction to cAMP dependent protein kinases. Okadaic acid, at concentrations that selectively inhibit protein phosphatases 2A, reduced the endothelin secretion and the effects of okadaic acid and db-cAMP were additive. Endothelin production was stimulated by fetal calf serum and by the protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7), but was inhibited by the calmodulin antagonist trifluoperazine. The present findings that regulators of cAMP-dependent protein kinases, protein kinase C, calmodulin, and protein phosphatase 2A all affect endothelin secretion suggest that endothelin secretion is controlled by phosphorylation/dephosphorylation of as yet unidentified regulatory proteins within the cell.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Snoring, hypertension, and the sleep apnea syndrome. An epidemiologic survey of middle-aged women.

The lower limit of the prevalence of sleep apnea syndrome (SAS) was estimated among women 40 to 59 years old by a two-stage procedure. In the first stage 2,016 questionnaires were mailed. The response rate was 75.6 percent. Daytime sleepiness was reported by 8.2 percent, habitual snoring by 11.2 percent, and intermittent snoring by 21.7 percent. There were altogether 128 women described with systemic hypertension and these women were more than twice as often habitual snorers. Logistic multiple regression analyses showed almost a threefold increase in the predicted prevalence of hypertension among intermittent and habitual snorers compared with nonsnorers in the age group 40 to 49 years old and a 60 percent increase in the 50- to 59-year-old age group. In the second stage, a group of 97 women highly suspected of SAS were selected because of their habitual snoring and daytime sleepiness. Eventually, 35 of these came for night studies and 14 were found to have SAS. Among the 35 women, 12 were hypertensive and nine of these had SAS. We estimated the lower limit of the prevalence of SAS to be 2.5 percent for women 40 to 59 years old. It is concluded that SAS is a relatively common occurrence among women, especially postmenopausal ones, and it is strongly related to hypertension.

Adult↗
PubMed1992

Role of ADP-ribosylation in endothelial signal transduction and prostacyclin production.

ADP-ribosylation of proteins by the enzymatic transfer of ADP-ribose from NAD has been implicated in a number of biological processes. We report that inhibitors of ADP-ribosylation, most notably the novel inhibitor of arginine specific cellular mono(ADP-ribosyl) transferase, meta-iodobenzylguanidine (MIBG) as well as nicotinamide, L-arginine methyl ester (LAME) and guanyltyramine, inhibit histamine-induced endothelial production of inositol phosphates, release of arachidonic acid and production of prostacyclin (PGI2). Those same responses were unaffected by MIBG when triggered by thrombin or leukotriene C4. These findings suggest that ADP-ribosylation serves a role in histamine-induced production of prostacyclin and imply differences in transduction pathways employed by the different agonists.

3-Iodobenzylguanidine↗
PubMed1989

Endothelial inositol phosphate generation and prostacyclin production in response to G-protein activation by AlF4-.

In order to elucidate the role of guanine-nucleotide-binding proteins (G-proteins) in endothelial prostacyclin (PGI2) production, human umbilical vein endothelial cells, prelabelled with either [3H]inositol or [3H]arachidonic acid, were stimulated with the non-specific G-protein activator aluminium fluoride (AlF4-). AlF4- caused a dose- and time-dependent generation of inositol phosphates, release of arachidonic acid and production of PGI2. The curves for the three events were similar. When the cells were stimulated in low extracellular calcium (60 nM), they released [3H]arachidonic acid and produced PGI2, but depleting the intracellular Ca2+ stores by pretreatment with the Ca2+ ionophore A23187 totally inhibited both events, although the cells still responded when extracellular Ca2+ was added. The Ca2+ ionophore did not inhibit the generation of inositol phosphates in cells maintained at low extracellular Ca2+. Pertussis toxin pretreatment (14 h) altered neither inositol phosphate nor PGI2 production in response to AlF4-. To investigate the functional role of the diacylglycerol/protein kinase C arm of the phosphoinositide system, the cells were pretreated with the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) or the protein kinase C inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7). TPA inhibited the AlF4(-)-induced inositol phosphate generation but stimulated both the release of arachidonic acid and the production of PGI2. H7 had opposite effects both on inositol phosphate generation and on PGI2 production. These results suggest that AlF4(-)-induced PGI2 production is mediated by a pertussis-toxin-insensitive G-protein which activates the phosphoinositide second messenger system. This production of PGI2 can be modulated by protein kinase C activation, both at the level of inositol phosphate generation and at the level of arachidonic acid release.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Beta-adrenoceptor agonists and hypoxia in sheep fetuses.

Sheep fetuses, near term, were studied to test the influence of a tocolytic beta agonist, terbutaline, on fetal responses to hypoxia. After fetal exteriorization the drug was administered intravenously to the mother in three different doses: The max group comprised 11 ewes receiving 67-134 micrograms min-1. Seven ewes were given 30 micrograms min-1 and eight ewes were infused with 10 micrograms min-1. Seventeen fetuses served as controls. Hypoxia was induced by intermittent complete occlusions of the maternal abdominal aorta. Maternal terbutaline levels were high (range 50-748 nmol l-1) in the max group and the 30-micrograms group, whereas those in the 10-micrograms group were in the clinical range (range 11-58 nmol l-1). Fetuses in the max and 30-micrograms groups reacted to moderate hypoxia with excessive responses of heart rate, blood pressure myocardial contractility and ST waveform changes and a 50% mortality rate during severe hypoxia as compared with 12% in the control animals. Ten micrograms min-1 did not decrease the survival but caused an increase in myocardial workload and a negative energy balance during severe hypoxia.

Animals↗
PubMed1989

Effects of L-tryptophan on daytime arousal.

A double-blind placebo-controlled study was carried out on 20 subjects to examine the early morning sedative effects of 2 g of L-tryptophan. Using brain mapping technique, 16-channel EEG recordings were topographically displayed. A distinct increase in theta amplitude, predominantly in the central region, together with an alpha reduction was observed after L-tryptophan administration, signs characterizing the EEG of drowsiness. Subjective self-rated sleepiness increased after the ingestion of L-tryptophan. Psychomotor performance, assessed by means of various psychometric tests, was not affected by this low dose of L-tryptophan.

Adult↗
PubMed1984

Familial elevation of serum thyroxine binding globulin in an Icelandic family.

A kindred of four generations with inherited elevation of serum thyroxine binding globulin (TBG) is reported. To our knowledge this is the twelfth kindred reported with this disorder. Of the 35 family members studied, 10 females and 5 males had elevated serum TBG. The patients were clinically euthyroid. The pedigree data was consistent with an X-chromosome linked mode of inheritance.

Adolescent↗
PubMed1979

Renal handling of homologous radioiodinated thyrotrophin in the rat.

Previously, TSH metabolism and tissue distribution in the rat were studied using heterologous hormone and/or unphysiological doses. We injected iv [131I]rTSH (S.A. 100 micronCi/microgram) in physiological doses (10 ng) to KI blocked male rats. Two to 180 min after which TCA precipitable 131I was measured in the kidney, liver, muscle, fat and testis. The highest TCA precipitable radioactivity concentration, peak value 12% at 30 min; organ/blood ratio, 16, was found in the kidney. With the kidney validated as the major site of localization of TSH, the renal localization and handling of [125I]rTSH was studied by autoradiography. Radioactivity was confined to the cortex. Two to 30 min samples showed 125I in Bowman's space and luminal parts of the proximal tubular cells while samples from 60 to 180 min revealed activity in contraluminal areas, suggesting glomerular filtration and tubular re-absorption. Gel-filtration of supernatants of kidney homogenates revealed progressive diminution of the TSH peak and the appearance of a smaller MW peak. We conclude that (1) the kidney is the major site of localization and metabolism of homologous TSH, (2) the renal handling of TSH involves both glomerular filtration and tubular re-absorption.

Animals↗
PubMed1977

Outcome of sub-total thyroidectomy for thyrotoxicosis in Iceland and Northeast Scotland.

A comparative study of the outcome of surgical treatment for thyrotoxicosis was carried out in two countries with dissimilar dietary iodine levels. In the area with a high iodine level (Iceland) the prevalence of post-operative hypothyroidism was five times lower, but recurrent hyperthyroidism was five times higher, than in the area with lower iodine levels (northeast Scotland). The total morbidity reached comparable levels in the two samples. The prevalence of positive thyroid antibody tests and serum thyrotrophin levels was lower and the functional capacity of the thyroid remnant higher in the area with the higher dietary iodine intake. The study provides further evidence that there are important regional differences in the prevalence of factors known to influence the response to surgical treatment of thyrotoxicosis which should be taken into account when planning treatment services.

Adult↗
PubMed1975

Prolactin studies in "functionless" pituitary tumours.

Hyperprolactinaemia was found in all 17 women and in one out of six men who presented with hypogonadism and a radiologically enlarged sella turcica but no other clinical endocrine dysfunction. Some of the women also had galactorrhoea. The greater the level of hyperprolactinaemia in these 18 patients the larger their sellae turcica except in two patients with unusual features. The sella turcica was usually asymmetrically enlarged and there was rearly an upward extension of tumour, though the sella floor often showed some erosion on tomography. An oral dose of bromocriptine suppressed the hyperprolactinaemia in mose patients at the same rate as in normal post-partum women. Nine of the 18 patients with hyperprolactinaemia had low basal luteinizing hormone (LH) levels. The LH responsiveness to 100 mug of LH-releasing hormone (LHRH) was tested in 12, and eight showed subnormal values. Of eight biopsy specimens obtained four showed acidophil granules on light microscopy, and in five granules of various sizes were seen on electron microscopy.

Adult↗