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Biomedical subjects

K Larsen

Publications and source records attributed to K Larsen.

At least 19 recordsLinked to original sources
PubMed1999

Interferon-gamma elicits a G-protein-dependent Ca2+ signal in human neutrophils after depletion of intracellular Ca2+ stores.

Interferon-gamma (IFN-gamma) has multiple effects on Ca2+ signalling in polymorphonuclear neutrophils (PMNs), including evoked cytosolic Ca2+ transients, increased capacitative calcium influx and increased sequestration of Ca2+ in intracellular stores. The present study was conducted to elucidate the mechanism behind the Ca2+ transients. As observed before, the IFN-gamma-evoked Ca2+ signals were apparent when extracellular Ca2+ was removed. A new finding was that the proportion of responding cells and the extent of calcium release increased with increasing time in EGTA buffer. As assessed by N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated Ca2+ release, the intracellular stores were depleted during this incubation period, and the extent of depletion correlated well with the appearance of IFN-gamma-induced Ca2+ signals. This store dependence of the IFN-gamma-induced Ca2+ signals was confirmed by the appearance of IFN-gamma-evoked Ca2+ signals in the presence of extracellular Ca2+ after store depletion by thapsigargin. The appearance of IFN-gamma-mediated Ca2+-signals in the presence of EGTA indicates that IFN-gamma stimulates Ca2+ release from intracellular stores. This was confirmed by the inability of the calcium transportation blocker La3+ to abolish the IFN-gamma response and the total abrogation of the response by the phospholipase C inhibitor U73122. Although these latter results imply a role for inositol 1,4,5-trisphosphate(IP3) in IFN-gamma signalling, comparison of IFN-gamma-evoked responses with fMLP responses revealed clear differences that suggest different signal-transduction pathways. However, responses to fMLP and IFN-gamma were both depressed by pertussis toxin, and the IFN-gamma responses were, in addition, inhibited by the tyrosine kinase inhibitor genistein. Further evidence of the involvement of tyrosine kinase was a slight stimulatory effect of the protein tyrosine phosphatase inhibitor sodium orthovanadate. The PI-3K activity was of minor importance. In conclusion, we present evidence of a novel signal-transduction mechanism for IFN-gamma in PMNs, dependent on tyrosine kinase activity, a pertussis toxin-sensitive G protein and phospholipase C activity.

Adult↗
PubMed1999

Bradykinin elevates cytosolic Ca2+ concentration in smooth muscle cells isolated from rat duodenum.

The effect of bradykinin on the cytosolic Ca2+ concentration were measured in single, Fura-2 loaded, smooth muscle cells isolated from rat duodenum. All cells responded with a Ca2+ signal when exposed to bradykinin. The bradykinin response consisted of an initial Ca2+ spike followed by a plateau. Pre-treatment of single muscle cells with either the phospholipase C blocker U-73122 or thapsigargin, which is a potent inhibitor of the endoplasmic reticulum Ca2+-ATPase, inhibited the response to bradykinin. Pre-treatment of the cells with EGTA or La3+ to inhibit the Ca2+ influx, abolished the response induced by bradykinin. We conclude that bradykinin applied to single smooth muscle cells from rat duodenum, increases cytosolic Ca2+ by emptying intracellular Ca2+ stores, and by contribution from extracellular Ca2+. In contrast to bradykinin-induced response in isolated rat duodenum (a relaxation followed by a contraction), we did not observe a biphasic effect of bradykinin on cytosolic Ca2+ in single muscle cells. Bradykinin may thus cause relaxation of duodenal smooth muscle indirectly through an effect on neighbouring cells as dilatation is brought about by this agent in blood vessels.

Animals↗
PubMed1998

Intestinal parasites in swine in the Nordic countries: prevalence and geographical distribution.

In Denmark (DK), Finland (FIN), Iceland (I), Norway (N), and Sweden (S), 516 swine herds were randomly selected in 1986-1988. Individual faecal analyses (mean: 27.9 per herd) from eight age categories of swine showed that Ascaris suum, Oesophagostomum spp., Isospora suis, and Eimeria spp. were common, while Trichuris suis and Strongyloides ransomi-like eggs occurred sporadically. Large fatteners and gilts were most frequently infected with A. suum with maximum prevalences of 25-35% in DK, N and S, 13% in I and 5% in FIN. With the exception of the remarkably low A. suum prevalence rates in FIN, no clear national differences were observed. Oesophagostomum spp. were most prevalent in adult pigs in the southern regions (21-43% in DK and southern S), less common in the northern regions (4-17% adult pigs infected), and not recorded in I. I. suis was common in piglets in DK, I, and S (20-32%), while < 1% and 5% were infected in N and FIN, respectively. Eimeria spp. had the highest prevalences in adult pigs (max. 9%) without clear geographical differences. I. suis and Eimeria spp. were recorded for the first time in I, and I. suis for the first time in N.

Age Factors↗
PubMed1998

Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction.

BACKGROUND: Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. METHODS: 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15-30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). FINDINGS: Postoperative cognitive dysfunction was present in 266 (25.8% [95% CI 23.1-28.5]) of patients 1 week after surgery and in 94 (9.9% [8.1-12.0]) 3 months after surgery, compared with 3.4% and 2.8%, respectively, of UK controls (p<0.0001 and p=0.0037, respectively). Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for late postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. INTERPRETATION: Our findings have implications for studies of the causes of cognitive decline and, in clinical practice, for the information given to patients before surgery.

Abdomen↗
PubMed1998

The effect of catalase amplification on immortal lens epithelial cell lines.

Utilizing a human beta-actin promoter, a catalase cDNA expression vector was constructed. This construct was used to transfect two immortal cell lines, mouse alpha TN4-1 and rabbit N/N 1003A. The catalase activity was increased about 3.4 fold in the alpha TN4-1 cells and 38 fold in the N/N 1003A cells. Some changes in other enzyme activities were also observed as a result of the transfections. Surprisingly, the ability to degrade H2O2 in the extracellular environment of the cells did not markedly change as a result of the catalase amplification. However, the ability to resist H2O2 stress was dramatically altered. Non-protein thiol (NP-SH) levels, choline uptake and glyceraldehyde phosphate dehydrogenase (GPD) activity were all markedly decreased in the non-transfected cells when they were subjected to 300 microM H2O2. However, in both transfected cell lines, these parameters remained in the normal range during H2O2 stress. The results obtained upon observing aspects of DNA metabolism were more complicated. While on H2O2 stress, non-transfected cell lines showed a marked decrease in thymidine incorporation, only the transfected alpha TN4-1 line remained in the normal range. Thymidine incorporation in transfected rabbit N/N 1003A cells was decreased compared to normal cells. In contrast, studies on single strand DNA breaks indicated that transfected rabbit cells had little damage compared to the significant DNA damage observed in the normal cells. The normal N/N 1003A cells were also much more susceptible to H2O2 induced damage than normal alpha TN4-1 cells, suggesting that the high GSH peroxidase activity observed in the rabbit cells may be detrimental since the low glutathione reductase activity in such cells results in an accelerated depletion of glutathione. The overall results suggest that augmenting lens catalase may prevent cataract development caused by H2O2 stress.

Animals↗
PubMed1998

Glucose metabolism in chronic diabetic foot ulcers measured in vivo using microdialysis.

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0.5-1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the 133Xewashout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8.0 +/- 1.0 mmol l-1 vs. 8.5 +/- 1.1 mmol l-1) (P < 0.02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3.2 +/- 0.2 mmol l-1 vs. 2.1 +/- 0.3 mmol l-1) (P < 0.01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.

Aged↗
PubMed1998

IFN-gamma induces calcium transients and increases the capacitative calcium entry in human neutrophils.

We have previously reported that long-term priming of human polymorphonuclear neutrophilic granulocytes (PMN) with interferon-gamma (IFN-gamma) increased the fMLP-stimulated calcium influx. We now show that also after short-term incubation with IFN-gamma, PMN calcium metabolism is modulated. Single adherent cells in three different calcium-containing buffers (high, normal, and low [Ca2+]) were stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor thapsigargin (Tg) after about 5 min preincubation with IFN-gamma. The results of this protocol indicated that IFN-gamma increases both calcium influx and calcium sequestration. Store dependent Ca2+ influx, directly measured on readdition of calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced in IFN-gamma-treated cells. This effect of IFN-gamma was enhanced by the tyrosine kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium concentrations, IFN-gamma induced calcium transients in 20%-60% of the cells. The proportion of PMN responding with Ca2+ transients increased with decreasing extracellular calcium concentration. Average lagtime from addition of IFN-gamma to a response that could be measured was 7.3 sec, and average increase in [Ca2+] above the basal level was 790 nM. These IFN-gamma-induced transients could not be depressed by herbimycin A. Thus, IFN-gamma can increase capacitative calcium influx, induce calcium transients, and possibly affect calcium sequestration in human PMN.

Calcium↗
PubMed1997

Glucocorticoid treatment for nasal polyps. The use of topical budesonide powder, intramuscular betamethasone, and surgical treatment.

BACKGROUND: The treatment of nasal polyps is controversial, and medical treatment alone has been little investigated to our knowledge. OBJECTIVE: To examine the efficacy of therapy using only topical budesonide powder and topical budesonide powder supplemented with surgical removal or intramuscular betamethasone. DESIGN: Randomized, double-blind comparison of 2 dosages and additional treatment, if therapy failed. After 1 year, treatment with medication was stopped, and the demand for renewed treatment was monitored for another year. PATIENTS: Patients with bilateral nasal polyps who demanded treatment were consecutively enrolled in a hospital outpatient clinic or specialty private practice. During a 15-month period from 1990 to 1992, a total of 126 patients entered the 2-year study. INTERVENTIONS: In phase 1, randomized and double-blind treatment with a topical medication, budesonide powder, 800 micrograms or 400 micrograms daily, or a placebo was given for 1 month. In phase 2, randomized and double-blind treatment with budesonide powder, 800 micrograms or 400 micrograms daily, was given. At the end of phase 1, failed therapy was supplemented by randomly assigned treatment of either surgical removal or a single injection of sustained released betamethasone. In phase 3, treatment with the medication was discontinued, and patients were monitored for another year. The time when treatment was required again was noted. The present article deals with phases 2 and 3. MAIN OUTCOME MEASURES: Patients' scores of treatment efficacy as well as symptoms and signs. Semiquantitative measurement of sense of smell and calculation of peak expiratory flow rate index based on nasal and oral peak expiratory flow. RESULTS: In all outcome measures, a comparison of the data before treatment with the corresponding figures during phase 2 showed statistically significant efficacy. The clinical course was described at the end of phase 2. About 85% of the patients, including those who received additional therapy because the initial therapy failed, rated total or substantial control over the symptoms. The 2 dosages investigated showed equal results. These findings were consistent with the signs recorded and the peak expiratory flow rate index. The results of phase 3 showed that 50% of patients had demanded treatment after 4 months, while 34% managed without medication after 1 year. CONCLUSIONS: The clinical course in this study showed that most patients with nasal polyps do well with medical treatment. Therefore, surgery was required in few patients. However, the potential of medical treatment should be further explored in future studies.

Administration, Inhalation↗
PubMed1997

A long-term follow-up study of nasal polyp patients after simple polypectomies.

A long-term follow-up study was performed on randomly selected patients after simple snare polypectomies. There were 243 patients, of whom 211 underwent endoscopic examination. There were 154 males and 57 females and median age was 57.7 years. Median period of follow-up was 8 years (range, 38-145 months). The median number of polypectomies was 1.6 (range, 1-15). Polyp eosinophilia was recorded in 97% of the cases. From life-table analysis the 5-year rate for two or less polypectomies was 80% (95% confidence intervals, 75-86%). Symptoms and findings were recorded at a median time of 56 months from the last polypectomy. At this time 70% of the patients denied blocked nose or excessive secretions. Seventeen per cent of the group claimed loss of sense of smell, while 28% stated that it was poor. At follow-up, large polyps were found in 3% of the patients, moderately sized ones in 30% and small in 42%. No polyps were visible in 25%. Patients with asthma (26%) had more polypectomies than those without (median, 2.4 versus 1.4). Patients with a history of non-steroidal antiinflammatory drug intolerance (7%) had the highest number of polypectomies. Previous troublesome sinusitis and allergy seemed not to exert major influence on the number of polypectomies needed. In the primary care of nasal polyp patients, the majority only need minor or limited surgery or only medical treatment.

Adult↗
PubMed1997

Chlamydia pneumoniae in children with otitis media.

In this study the polymerase chain reaction was used to test for the presence of Chlamydia pneumoniae DNA in 118 middle-ear aspirates from 20 children with acute otitis media (AOM) and 53 children with otitis media with effusion (OME). C. pneumoniae was detected in 8 samples obtained from 5 children with OME and, together with Streptococcus pneumoniae, in a sample from 1 child with AOM. The mean age of these five children (6.6 +/- 1.4 years) was significantly higher than that of the 48 children with OME in whom C. pneumoniae could not be detected (4.3 +/- 1.9 years). The presence of C. pneumoniae in 9.4% of the examined children with OME suggests that C. pneumoniae might be a significant supplementary factor in the etiology of this common children's disease.

Acute Disease↗
PubMed1997

Interleukin-8 and chemotactic activity of middle ear effusions.

The importance of interleukin (IL)-8 in the chemotactic activity of middle ear effusions (MEEs) was evaluated. There was a significantly higher IL-8 concentration in MEEs of children with acute otitis media (AOM) (n = 17; 136 ng/mL) than in children with otitis media with effusion (OME) (n = 28; 65 ng/mL). The IL-8 concentration in MEEs with bacteria (149 ng/mL) was significantly higher than in MEEs without bacteria (66 ng/mL). MEEs from children with AOM and OME had equally higher chemotactic activity than the diluent alone (23.3% and 24.8% vs. 9.2%). The chemotactic activity was not altered by the presence of bacteria nor did it correlate with IL-8 concentration. Fractionation of MEEs by gel chromatography demonstrated that the main chemotactic activity could clearly be separated from the IL-8 activity, thus excluding IL-8 as a main chemotactic component in MEEs.

Bacterial Infections↗
PubMed1997

Influenza virus M1 protein binds to RNA through its nuclear localization signal.

The RNA-binding activity of influenza A virus M1 protein was studied by cross-linking the protein to viral RNA followed by sequence analysis of the oligoribonucleotide bound to the protein as well as sequence analysis of the M1 peptide bound to the RNA. M1 was found to bind to RNA without any RNA sequence specificity, as verified in a series of filter-binding experiments using a large variety of nucleic acids including DNA. The peptide sequence that bound to the RNA was the RKLKR nuclear localization signal of M1. Site-specific mutagenesis of recombinant M1 showed that most of the basic residues in that region had to be mutated in order to inhibit RNA-binding. We also constructed an M1 mutant that no longer bound to RNA but which was still able to inhibit the in vitro transcription activity of isolated viral ribonucleoprotein, albeit to a lower extent. Mutation of the zinc-binding sequence had no effect on RNA-binding or transcription-inhibition activity.

Amino Acid Sequence↗
PubMed1997

Plasminogen activators in human nasal polyps and mucosa.

Fibrinolysis is one of the processes that are involved in inflammation. In this study we have investigated if it is also involved in bilateral nasal polyposis, a disease with an inflammatory component. Fibrinolytic activity in the nasal mucosa and nasal polyps has been studied in 10 patients with bilateral nasal polyposis. Tissue-type plasminogen activator (t-PA) and urokinase-like plasminogen activator (u-PA) activities and antigen levels have been determined in polyp tissue and control nasal mucosa. t-PA activity is higher in nasal mucosa (median: 4.26 i.u./mg) as compared with nasal polyps (median: 0.65 i.u./mg; p = 0.03); u-PA activity is slightly lower in nasal mucosa (median: 0.040 i.u./mg) as compared to polyps (median: 0.065 i.u./mg; not significant). The percentage of u-PA to t-PA is 7.9% in nasal mucosa and 22.8% in nasal polyps (p < 0.01). The shift towards a higher u-PA/t-PA ratio in nasal polyps suggests an inflammatory process. Plasma levels of C-reactive protein are all within normal limits, which may suggest that PA activity is restricted to a local inflammatory reaction in the airway mucosa. The higher u-PA/t-PA ratio in nasal polyps and the higher levels of u-PA, when compared with the findings in other organs affected by inflammation, indicate that u-PA plays a part in the inflammatory events resulting in nasal polyps.

Adult↗
PubMed1997

Regulations as Prevention Strategies for Shiftwork Problems.

The study examines how the Danish system of regulations stemming from collective agreements and legislation and its associated participatory structures operate at the local level in relation to shiftwork and health and safety issues in a regional hospital system consisting of seven hospitals. The study analyzed ward reports of each employee's employment and working hours, local agreements about working time for deviations from legislation, and accounts from meetings in Co-operation Committees and Health and Safety Committees with respect to shiftwork issues from 1980 to 1994. The results showed that part-time employment, especially for those working on fixed evening and night shifts, was a dominant feature in the shiftwork arrangements. A majority of wards were found to have mixtures of employees working rotating or fixed shifts. Each hospital had local agreements that extended the number of work days between periods with days off and reduced the daily resting period to its minimum. None of the meetings of the Health and Safety Committees dealt with shiftwork, and when shiftwork and working time were on the agendas of the Co-operation Committees, health and safety aspects did not feature in the conclusions. The absence of consideration of health and safety aspects is discussed in relation to the uncertainty of the general regulatory principles for work organization and scheduling. The paper concludes that in order to utilize the potential af the participatory structures in developing prevention strategies for shiftwork problems, it is important to clarify responsibilities and cooperation between the two participatory committees.

Journal Article↗
PubMed1996

A novel type of DNA-binding protein interacts with a conserved sequence in an early nodulin ENOD12 promoter.

The pea genes PsENOD12A and PsENOD12B are expressed in the root hairs shortly after infection with the nitrogen-fixing bacterium Rhizobium leguminosarum bv. viciae or after application of purified Nod factors. A 199 bp promoter fragment of the PsENOD12B gene contains sufficient information for Nod factor-induced tissue-specific expression. We have isolated a Vicia sativa cDNA encoding a 1641 amino acid protein, ENBP1, that interacts with the 199 bp ENOD12 promoter. Two different DNA-binding domains were identified in ENBP1. A domain containing six AT-hooks interacts specifically with an AT-rich sequence located between positions -95 and -77 in the PsENOD12B promoter. A second domain in ENBP1 is a cysteine-rich region that binds to the ENOD12 promoter in a sequence non-specific but metal-dependent way. ENBP1 is expressed in the same cell types as ENOD12. However, additional expression is observed in the nodule parenchyma and meristem. The presence of three small overlapping ORFs in the 5'-untranslated region of the ENBP1 cDNA indicates that ENBP1 expression might be regulated at the translational level. The interaction of ENBP1 with a conserved AT-rich element within the ENOD12 promoter and the presence of the ENBP1 transcript in cells expressing ENOD12 strongly suggest that ENBP1 is a transcription factor involved in the regulation of ENOD12. Finally, the C-terminal region of ENBP1 shows strong homology to a protein from rat that is specifically expressed in testis tissue.

Amino Acid Sequence↗
PubMed1995

The effect of a stroke unit: reductions in mortality, discharge rate to nursing home, length of hospital stay, and cost. A community-based study.

BACKGROUND AND PURPOSE: Treatment of stroke patients in specialized stroke units has become more frequent, yet the effect of this treatment has not been determined. METHODS: In a community-based, prospective, and consecutive study of 1241 unselected acute stroke patients, we compared outcome of stroke treatment between two neighboring communities within Greater Copenhagen: the Bispebjerg community, where all acute stroke patients are treated and rehabilitated on a stroke unit, and Frederiksberg community, where all acute stroke patients are treated and rehabilitated on general neurological and medical wards. Except for the different organization of stroke treatment, the two communities and the two patient groups were comparable. Specifically, age, sex, marital status, prestroke residence, and stroke severity were not statistically different between patients treated on the stroke unit and those treated on the general neurological and medical wards. Multivariate regression analyses were used to estimate the independent influence of stroke unit treatment on outcome. RESULTS: Stroke unit treatment significantly reduced in-hospital mortality (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.34 to 0.74; P < .001), case-fatality rate (OR, 0.45; CI, 0.28 to 0.71; P < .001), 6-month mortality (OR, 0.57; CI, 0.39 to 0.82; P = .002), 1-year mortality (OR, 0.59; CI, 0.42 to 0.84; P = .003), and discharge rate to a nursing home (OR, 0.61; CI, 0.38 to 0.98; P = .04). Discharge rate to the patient's own home was significantly increased (OR, 1.90; CI, 1.30 to 2.70; P < .001). The length of hospital stay (including rehabilitation) was reduced significantly by 30% in patients treated on the stroke unit despite their lower mortality (P < .001). The savings due to stroke unit treatment were estimated at 1313 bed-days and three places at a nursing home per 100 stroke patients. CONCLUSIONS: Treatment of unselected acute stroke patients on a stroke care unit saved lives, reduced the length of hospital stay, reduced the frequency of discharge to a nursing home, and potentially reduced cost.

Aged↗
PubMed1995

Genetic anticipation in Parkinson's disease.

We studied age at onset and family history of 137 patients (probands) with the diagnosis of idiopathic Parkinson's disease (PD). Probands (N = 21) who had an affected parent, aunt, or uncle were younger (p = 0.0001) at the onset of PD (47.7 +/- 8.8 years) than were probands (N = 11) who had an affected sib only (60.3 +/- 12.9 years) and probands (N = 105) who had no affected sib, parent, aunt, or uncle (59.2 +/- 11.4 years). Age at onset of affected family members differed significantly between generations (p = 0.0001). Age at onset was earlier, by an average of 17 years, in the proband generation than in the parental generation. The intrafamily variation in the calendar year of onset was too great to suggest a common point of exposure. Our data are most compatible with genetic anticipation, which could suggest involvement of an unstable trinucleotide repeat.

Age Factors↗