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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 37 records · Page 2Linked to original sources

Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation.

BACKGROUND: In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. OBJECTIVE: To determine the degranulation status of circulating eosinophils in common allergic diseases. METHODS: Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. RESULTS: Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). CONCLUSION: In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.

Adolescent↗

Secretoneurin is released into human airways by topical histamine but not capsaicin.

BACKGROUND: The neuropeptide secretoneurin, with potential relevance to leukocyte trafficking, is present in nerves of the nasal mucosa in allergic rhinitis and may be released in response to allergen and histamine exposure. There is no information on the occurrence and mechanisms of release of secretoneurin in healthy human airways. METHODS: The presence of secretoneurin in nasal biopsies and its release in response to nasal capsaicin and histamine challenges were examined. Symptoms and lavage fluid levels of fucose were recorded as markers of effects in part produced by neural activity. Bronchial histamine challenges followed by sputum induction and analysis of secretoneurin were also carried out. RESULTS: Nerves displaying secretoneurin immunoreactivity abounded in the nasal mucosa. Nasal capsaicin challenge produced local pain (P <0.05) and increased the levels of fucose (P <0.05), but failed to affect the levels of secretoneurin. Nasal histamine challenge produced symptoms (P <0.05) and increased the mucosal output of secretoneurin (P <0.05) and fucose (P <0.05). Bronchial histamine challenge increased the sputum levels of secretoneurin (P <0.05). CONCLUSIONS: We conclude that secretoneurin is present in healthy human airways and that histamine evokes its release in both nasal and bronchial mucosae. The present observations support the possibility that secretoneurin is involved in histamine-dependent responses of the human airway mucosa.

Administration, Topical↗

Timed barium esophagogram in the assessment of patients with achalasia: reproducibility and observer variation.

SUMMARY. The timed barium esophagogram (TBE) is a further development of the barium swallow, introducing functional and dynamic dimensions to the assessment. The purpose of our study was to assess the day to day variability of TBE parameters when scored in healthy subjects, in untreated and in previously treated patients with confirmed diagnoses of achalasia and to assess the intra- and interobserver agreement. After fasting, the subjects drank 250 mL of low-density barium sulfate suspension. Radiographs of the esophagus were exposed at 1, 2 and 5 min after the start of the barium ingestion. The heights and widths of the barium column and changes in these parameters over time (esophageal emptying) were assessed. Each subject was re-tested after a median time interval of 8 days. Healthy individuals emptied their esophagi effectively and promptly with no significant amount of contrast remaining in the lumen after 2 min. In the achalasia patients all TBE variables differed profoundly compared to the controls. There was an excellent intra- and interobserver agreement for all measured variables. The reproducibility of the static TBE variables from day-to-day was good, but not so for the functional assessment of esophageal emptying, having a correlation coefficient of only 0.50. The usefulness of TBE as a clinical and research tool in achalasia patients requires further evaluation.

Adult↗

Anorexia and cachexia in prostaglandin EP1 and EP3 subtype receptor knockout mice bearing a tumor with high intrinsic PGE2 production and prostaglandin related cachexia.

Previous studies in our laboratory have suggested that prostaglandin (PG) E2 is involved in anorexia/cachexia development in MCG 101 tumor-bearing mice. However, the role of COX pathways in the pathogenesis of cancer anorexia/cachexia is not fully resolved. In the present study, we investigated the role of PGE receptors subtype EP1 and EP3 on the development of anorexia in MCG 101-bearing mice. Our results show that the absence of host EP1 or EP3 receptors did not alter the magnitude of anorexia in tumor-bearers. However, anorexia in tumor-bearing EP1 and EP3 knockouts was not improved by indomethacin treatment as observed in wild type tumor-bearers. By contrast, indomethacin improved body composition similar in EP1 and EP3 knockouts as well as in wild type tumor-bearing animals and tumor growth was retarded in EP1 and promoted in EP3 knock outs. Our results demonstrate that host EP1 and EP3 receptors are involved in the control of local tumor growth, which translates into anorexia, this being the main cause of metabolic adaptive alterations to explain weight loss in this model. Brain EP1 and EP3 subtype receptors do not seem to directly control anorexia, which leaves EP2 and EP4 as potential candidates.

Animal Feed↗

Building materials as a source of PCB pollution in Bergen, Norway.

Although PCB is a globally recognised pollutant, an understanding of its transport from man-made building materials to the environment is poorly constrained. This paper presents data from a study that was conducted in order to determine the extent of PCB usage in plaster on building façades in the Bergen area, Norway. The study was to determine whether PCB concentrations vary according to building usage type and age. One aim was also to determine the nature and extent of displacement of PCB from the façade into the surrounding soil. Buildings built between 1952 and 1979 were chosen for the study. Three different media were sampled during the study; surface soil, plaster and paint. Samples were then analysed for PCB7 content. The results show that there is a difference in PCB usage in buildings of different age and usage type. Residential buildings and schools demonstrated higher PCB concentrations in both soil and plaster than buildings designated for office use, storage, or for industrial purposes. Buildings erected in the 1950s and 1960s also show a higher PCB concentration than buildings from a later date. It appears that the usage of PCB for these purposes decreased in the 1970s. Thirty percent of the soil samples showed a higher PCB concentration than the Norwegian action level. The soil samples tend to have a higher concentration than the corresponding plaster from the adjacent wall, which probably has its cause in the high soil organic matter contents that retains PCB. Plaster has not been considered a pollution source in previous studies; therefore this study demonstrates a new source that needs to be considered in emission calculations.

Journal Article↗

A carbohydrate binding module as a diversity-carrying scaffold.

The growing field of biotechnology is in constant need of binding proteins with novel properties. Not just binding specificities and affinities but also structural stability and productivity are important characteristics for the purpose of large-scale applications. In order to find such molecules, libraries are created by diversifying naturally occurring binding proteins, which in those cases serve as scaffolds. In this study, we investigated the use of a thermostable carbohydrate binding module, CBM4-2, from a xylanase found in Rhodothermus marinus, as a diversity-carrying scaffold. A combinatorial library was created by introducing restricted variation at 12 positions in the carbohydrate binding site of the CBM4-2. Despite the small size of the library (1.6 x 10(6) clones), variants specific towards different carbohydrate polymers (birchwood xylan, Avicel and ivory nut mannan) as well as a glycoprotein (human IgG4) were successfully selected for, using the phage display method. Investigated clones showed a high productivity (on average 69 mg of purified protein/l shake flask culture) when produced in Escherichia coli and they were all stable molecules displaying a high melting transition temperature (75.7 +/- 5.3 degrees C). All our results demonstrate that the CBM4-2 molecule is a suitable scaffold for creating variants useful in different biotechnological applications.

Amino Acid Sequence↗

Surface attachment of nanoparticles using oligonucleotides.

Colloidal polymer particles are widely used in a variety of applications ranging from chromatography to surface modified bioreactors in protein arrays. In the present study, surface attachment of polystyrene particles to a polystyrene substrate has been performed using oligonucleotide hybridization. Thiolated complementary oligomers of cytosine and guanine have been covalently coupled to a pyridyl disulphide (PDS) modified polyethyleneglycol tether, forming part of a triblock copolymer which is adsorbed to the polystyrene surfaces via hydrophobic polypropylene oxide center blocks. The ability to withstand shear forces was studied using a laminar flow cell and the uptake of oligomers on the particles was quantified using two complementary techniques: UV-spectroscopy and sedimentation field flow fractionation. The possibility to tether particles in a flow cell suitable for practical use in e.g. a FIA-system is demonstrated.

Binding Sites↗

Can the survival difference between breast cancer patients in Denmark and Sweden 1989 and 1994 be explained by patho-anatomical variables?--a population-based study.

Analyses of data from cancer registries have shown a 10% unit difference in 5-year relative survival between Danish and Swedish patients with breast cancer. This study investigates the effect of age and patho-anatomic variables on this survival difference. Hospital records were collected for women over 40 years of age diagnosed in 1989 or 1994 in east Denmark and south Sweden; patho-anatomical variables and survival were compared between 2289 Danish and 1715 Swedish women. Tumours were smaller, node-negative axillae more frequent and well-differentiated tumours almost 10% more frequent in Sweden. A superior 5-year relative survival in Sweden was found in the 50- to 79-year age group. The adjusted hazard rate ratio between countries was 1.7 in 1989 and 1.3 in 1994. Conditional survival after surviving the first 5 years was similar for the two countries. Adjusting for patho-anatomical variables reduced but did not eliminate the higher risk of death among the Danish patients. Higher population death rates could explain some but not all of the residual elevated risk for Danish women.

Age of Onset↗

Disease perception and social behaviour in persistent rhinitis: a comparison between patients with allergic and nonallergic rhinitis.

BACKGROUND: Although the understanding of the pathophysiology and pharmacology of rhinitis has increased within recent years, few studies have examined the impact of rhinitis on patients' behaviour. AIM: To compare perennial allergic rhinitis (PAR) and perennial nonallergic rhinitis (PNR) in terms of patients' perception of their disease and its psychosocial concomitants. METHODS: Thirty-one PAR patients and 32 PNR patients responded to a standard symptom list and were interviewed in-depth regarding their complaints and the impact of rhinitis on their daily lives. RESULTS: PAR and PNR patients reported similar somatic and psychosocial complaints. In both disease groups the adverse effects of rhinitis were reported to be substantially limiting, particularly in social contacts, the impact appearing to be more severe in the women. CONCLUSION: Rhinitis has a severe impact on the daily lives of patients, women reporting more severe psychosocial effects. Disease perception and social adjustment appear to not depend appreciably on whether or not an objective diagnosis of rhinitis can be established.

Female↗

Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen-season model of allergic rhinitis.

BACKGROUND: Rofleponide palmitate is an esterified glucocorticosteroid pro-drug with a promising pre-clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro-drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide. OBJECTIVE: To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen-season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide). METHODS: During the pollen-free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg once daily for 10 days in a double-blind, placebo-controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen-challenge series, when symptoms were established and when the treatment had lasted for 8-10 days, were used in the analysis. RESULTS: Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01-0.001). There was no overall difference in efficacy between rofleponide palmitate 400 microg and budesonide 128 microg. CONCLUSIONS: Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 microg of rofleponide palmitate is similar to that of 128 microg of budesonide in the pollen-season model used in this study.

Administration, Intranasal↗

Association between nasal and bronchial symptoms in subjects with persistent allergic rhinitis.

BACKGROUND: The association between nasal and bronchial symptoms, and the course of bronchial responsiveness and airway inflammation in house dust mite sensitive persistent rhinitis over a prolonged time period has not been thoroughly explored. OBJECTIVE: To determine if nasal symptoms were associated with bronchial symptoms in persistent rhinitic subjects, and to assess their bronchial responsiveness and airway inflammation in comparison to nonrhinitic, nonatopic controls. The additional impact of pollen sensitivity on the lower airways in rhinitic subjects was also addressed. METHODS: Rhinitics and controls answered telephone symptom questionnaires once every 2 weeks for 1 year. Every 3 months, exhaled nitric oxide (eNO) and bronchial responsiveness to histamine were measured. RESULTS: Thirty-seven rhinitics and 19 controls completed the study. High nasal symptom scores in rhinitic subjects were associated with bronchial symptoms (OR = 1.7, 95% CI 1.2-2.5). Bronchial hyper-responsiveness was present in 32.4% of rhinitic subjects on at least one clinical visit during the year. Pollen allergy caused seasonal variation in eNO (P = 0.03). CONCLUSION: In persistent rhinitic subjects, high nasal symptom scores were associated with bronchial symptoms, and many subjects experienced bronchial hyper-responsiveness during the year. Persistent rhinitic subjects were more at risk than healthy adults of bronchial symptoms and airway inflammation, which are likely risk factors for asthma.

Adolescent↗

Symptoms of persistent allergic rhinitis during a full calendar year in house dust mite-sensitive subjects.

BACKGROUND: Little is known about the natural course of persistent rhinitis symptoms over a prolonged period. OBJECTIVE: To describe the frequency and severity of nasal symptoms and quality of life (QoL) in house dust mite-sensitive persistent rhinitic subjects and to determine if medication use was related to symptoms. METHODS: Rhinitics and controls were telephoned fortnightly for 1 year to monitor symptoms. QoL was measured every 3 months. RESULTS: Thirty-seven rhinitics and 19 controls completed the study. Total nasal symptom scores (TNSS) were 'high' for 65% (95% CI +/- 6%) of the year in rhinitic subjects. When TNSS increased by 1, the likelihood of nasal medication use increased by 25% (95% CI: 7-46%). General and specific QoL were worse in rhinitic subjects than controls (P < 0.04 and <0.0001). Rhinitics with pollen allergy (n = 21) had seasonal variation in the frequency of high nasal symptom scores (P = 0.02). CONCLUSION: Nasal symptom scores were consistently high in rhinitics, and their QoL was worse than controls, even in general QoL. An increase in nasal symptom score increased the likelihood of nasal medication use. These findings help to characterize the course of persistent rhinitis over a previously unstudied period of 1 year.

Animals↗

Risk factors for anastomotic leakage after anterior resection of the rectum.

OBJECTIVE: Surgical technique and peri-operative management of rectal carcinoma have developed substantially in the last decades. Despite this, morbidity and mortality after anterior resection of the rectum are still important problems. The aim of this study was to identify risk factors for anastomotic leakage in anterior resection and to assess the role of a temporary stoma and the need for urgent re-operations in relation to anastomotic leakage. PATIENTS AND METHODS: In a nine-year period, from 1987 to 1995, a total of 6833 patients underwent elective anterior resection of the rectum in Sweden. A random sample of 432 of these patients was analysed (sample size 6.3%). The associations between death and 10 patient- and surgery-related variables were studied by univariate and multivariate analysis. Data were obtained by review of the hospital files from all patients. RESULTS: The incidence of symptomatic clinically evident anastomotic leakage was 12% (53/432). The 30-day mortality was 2.1% (140/6833). The rate of mortality associated with leakage was 7.5%. A temporary stoma was initially fashioned in 17% (72/432) of the patients, and 15% (11/72) with a temporary stoma had a clinical leakage, compared with 12% (42/360) without a temporary stoma, not significant. Multivariate analysis showed that low anastomosis (< or = 6 cm), pre-operative radiation, presence of intra-operative adverse events and male gender were independent risk factors for leakage. The risk for permanent stoma after leakage was 25%. Females with stoma leaked in 3% compared to men with stoma who leaked in 29%. The median hospital stay for patients without leakage was 10 days (range 5-61 days) and for patients with leakage 22 days (3-110 days). CONCLUSION: In this population based study, 12% of the patients had symptomatic anastomotic leakage after anterior resection of the rectum. Postoperative 30-day mortality was 2.1%. Low anastomosis, pre-operative radiation, presence of intra-operative adverse events and male gender were independent risk factors for symptomatic anastomotic leakage in the multivariate analysis. There was no difference in the use of temporary stoma in patients with or without anastomotic leakage.

Adult↗

Prevalence of asthma and exhaled nitric oxide are increased in bleachery workers exposed to ozone.

The aims of the present study were to determine whether exposure to high peaks of ozone resulted in an increased prevalence of asthma or respiratory symptoms among bleachery workers and whether nitric oxide (NO) was elevated in the exhaled air of these workers. Bleachery workers (n=228) from three Swedish pulp mills who had been exposed to ozone, together with 63 unexposed control subjects, were investigated by means of spirometry, Phadiatop, exhaled and nasal NO and answers to a questionnaire concerning respiratory symptoms and exposure. Exposure to an ozone peak that gave rise to respiratory symptoms was defined as a "gassing". Bleachery workers reporting four or more gassings involving ozone had an increased prevalence of adult-onset asthma, wheeze, and current asthma symptoms. They also had a higher median concentration of exhaled NO in comparison with those who reported no such gassings (19.2 versus 15.7 parts per billion). No such associations were found in respect of nasal NO. The results from this study show that bleachery workers who have been repeatedly exposed to ozone gassings have an increased prevalence of adult-onset asthma. The results also indicate exhaled nitric oxide may be a marker of airway inflammation in bleachery workers who have been exposed to high peaks of ozone.

Adult↗

Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure.

Despite the fact that extensive degranulation is a likely prerequisite for a pathogenic role of eosinophils, little is known about the degranulation status of these cells in eosinophilic conditions. The present study of the ultrastructure of tissue eosinophils explores eosinophil degranulation in allergic rhinitis before and during seasonal allergen exposure. A total of 23 patients scored symptoms q.d., prior to and during the pollen season. The numbers of mucosal eosinophils and their degranulation status were determined in nasal biopsies. Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and alpha2-macroglobulin were assessed as indices of eosinophil activity and plasma exudation, respectively. Seasonal allergen exposure was associated with increased nasal symptoms, increased lavage fluid levels of ECP and alpha2-macroglobulin, and increased numbers of tissue eosinophils. In the tissue, transmission electron microscopy revealed a moderate piecemeal degranulation already prior to the season (mean+/-sd 37+/-2.7% altered granules). Seasonal allergen exposure increased this degranulation (87+/-1.8%), and produced local areas with extensive deposition of granule proteins. The degree of eosinophil degranulation correlated with levels of ECP in lavage fluids obtained at histamine challenge. In conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis features moderately degranulated eosinophils already at nonsymptomatic baseline conditions. In association with the development of symptomatic seasonal allergic rhinitis, the tissue deposition of eosinophil granule proteins is dramatically elevated through increased eosinophil numbers, together with markedly augmented degranulation of individual cells.

Adult↗

A novel selection system for potato transformation using a mutated AHAS gene.

Acetohydroxyacid synthase (AHAS) is the target enzyme for a number of herbicides. A S653N mutation in the AHAS gene results in an increased tolerance to imidazolinone herbicides. We have investigated the use of the mutated gene as selection gene for potato transformation. This resulted in a transformation system with a very high transformation frequency and low rate of escapes. The mutated AHAS gene was introduced into transformed potato together with a beta-glucuronidase (GUS) gene. Selection on 0.5 microM Imazamox yielded GUS expression in 93-100% of regenerated shoots. Furthermore the mutated AHAS gene was used as selection gene for production of high-amylopectin potato lines. The high transformation frequency was verified and potato lines with the desirable starch quality were obtained.

Acetolactate Synthase↗

Ascaris nematodes from pig and human make three antibacterial peptides: isolation of cecropin P1 and two ASABF peptides.

Organisms co-habiting with bacteria have developed efficient bactericidal agents to control their microbe-rich environment. The Ascaris nematode lives in its final development stages in the gut of its host and is believed to feed on bacteria. Ascaris suum survive in pig intestine while A. lumbricoides is the principal species in humans. Here we show that A. suum and A. lumbricoides both produce linear (cecropin P1) and cysteine-rich (ASABF) peptides with activity against either gram-negative or gram-positive bacteria, respectively. Thus nematodes rely in part on a peptide-based antibacterial system for digestion of bacteria, which may also confer protection against infection. Cecropin P1 was previously isolated from pig intestine but we can now conclude that was due to contaminating nematodes.

Amino Acid Sequence↗