[Better results in sports after use of anti-asthmatic drugs?].
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Biomedical subjects
Publications and source records attributed to L Larsson.
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In search for a possible explanation for the different susceptibility to mucosal infections in IgA-deficient (IgAd) individuals, the frequency of total immunoglobulin-secreting cells (ISC) and vaccine-specific antibody-secreting cells (ASC) in intestinal mucosa and peripheral blood was determined by the enzyme-linked immunospot (ELISPOT) assay before and after peroral vaccination with a B subunit-whole cell cholera vaccine. Two groups of IgAd individuals, frequently infected and non-infected respectively, and normal controls were studied. Before cholera vaccination there were significantly higher frequencies of total IgM and IgG ISC in the gut, but not in the blood, in the IgAd individuals than in the controls. However, there were no significant differences between healthy and infection-prone IgAd individuals in this respect. In response to oral cholera vaccination, intestinal cholera toxin (CT)-specific IgG and IgM ASC were significantly more abundant among the IgAd individuals with a history of frequent infections than among the healthy IgAd individuals and controls. A similar difference in IgG and IgM ASC, although not significant, was also noted in blood. In IgAd individuals with frequent infections the vaccine induced variable anti-CT IgM ASC responses in the gut, ranging from no increase to a few strikingly high responses. In the controls, the CT-specific responses were dominated by IgA ASC. The data show that oral cholera vaccination evoked strong CT-specific IgG ASC responses, and in some cases also strong IgM ASC responses in the intestinal mucosa of IgAd patients with a history of frequent infections. The healthy IgAd individuals unexpectedly responded with lower numbers of CT-specific IgG ASC and did not show any increase of CT-specific IgM ASC in the intestinal mucosa. Thus, inability to mount a mucosal immune response to an oral antigen cannot in itself explain recurrent infections among many IgAd individuals.
Different strategies for the application of gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) in medical microbiology research are discussed. GC can be used to determine specific microbial monomeric constituents and metabolites, so-called chemical markers, in cultures of microorganisms; in particular, analysis of cellular fatty acids has proven useful for species characterization and identification. GC-MS can be applied to study chemical markers directly in complex environmental samples, as exemplified by the analysis of airborne organic material as regards muramic acid (marker of peptidoglycan), 3-hydroxy acids (endotoxins), and ergosterol (fungal biomass). This methodological approach represents an alternative to various biological assays for characterization of airborne microbial structures, and forms a firm basis for correlating inhalation of such structures and development of symptoms. Direct GC-MS analysis of clinical samples provides possibilities for diagnosis (here exemplified by chiral separation of urine D- and L-arabinitol in disseminated candidiasis) and insight into microbial metabolism in the infected host (exemplified by observed indications of mycobacterial build-up of mycolic acids in vivo), with implications for drug development. Continued developments in MS technology will allow rapid advances to be made in GC-MS research in microbiology.
A standard method for measurement of airborne environmental endotoxin was developed and field tested in a fiberglass insulation-manufacturing facility. This method involved sampling with a capillary-pore membrane filter, extraction in buffer using a sonication bath, and analysis by the kinetic-Limulus assay with resistant-parallel-line estimation (KLARE). Cross-validation of the extraction and assay method was performed by comparison with methanolysis of samples followed by 3-hydroxy fatty acid (3-OHFA) analysis by gas chromatography-mass spectrometry. Direct methanolysis of filter samples and methanolysis of buffer extracts of the filters yielded similar 3-OHFA content (P = 0.72); the average difference was 2.1%. Analysis of buffer extracts for endotoxin content by the KLARE method and by gas chromatography-mass spectrometry for 3-OHFA content produced similar results (P = 0.23); the average difference was 0.88%. The source of endotoxin was gram-negative bacteria growing in recycled washwater used to clean the insulation-manufacturing equipment. The endotoxin and bacteria become airborne during spray cleaning operations. The types of 3-OHFAs in bacteria cultured from the washwater, present in the washwater and in the air, were similar. Virtually all of the bacteria cultured from air and water were gram negative composed mostly of two species, Deleya aesta and Acinetobacter johnsonii. Airborne countable bacteria correlated well with endotoxin (r2 = 0.64). Replicate sampling showed that results with the standard sampling, extraction, and Limulus assay by the KLARE method were highly reproducible (95% confidence interval for endotoxin measurement +/- 0.28 log10). These results demonstrate the accuracy, precision, and sensitivity of the standard procedure proposed for airborne environmental endotoxin.
Twenty-seven strains belonging to 12 Mycobacterium species were studied for 3-hydroxy fatty acid composition. Mycobacterial cells were subjected to both mild and strong acid methanolysis, after which the liberated hydroxy fatty acids were purified and analyzed by gas chromatography-mass spectrometry as methyl ester trimethylsilyl ether derivatives. Altogether, 21 3-hydroxy fatty acids containing 14 to 28 carbon atoms were detected; 10 were straight chain, 6 were 2-methyl branched chain, and 5 were 2,4,6-trimethyl branched chain. The mycobacterial strains were classified in groups according to 3-hydroxy fatty acid patterns.
A gas chromatographic procedure was developed to determine the relative amounts of D- and L-arabinitol in urine. Samples were filtered, diluted, purified through extractions, evaporated, and treated with trifluoroacetic anhydride; the arabinitol derivatives thus obtained were separated on a chiral stationary phase and registered by using an electron-capture detector. Urine samples from a patient with disseminated candidiasis had higher D-arabinitol/L-arabinitol ratios (referred to as D/L-arabinitol ratios)--up to 19.0--than samples from 96 study individuals with no signs of deep Candida infections (range, 1.1 to 4.5). D/L-Arabinitol ratios in urine samples from hospitalized patients without Candida infections were slightly higher than those in samples from healthy individuals; ratios in urine from children were slightly higher than those in adult urine samples. The D/L-arabinitol ratios in several urine samples culture positive for Candida albicans, but from patients without symptoms of disseminated candidiasis, did not differ from those in the urine of healthy individuals. The described gas chromatographic method is straightforward and can be implemented clinically to determine urine D/L-arabinitol ratios as a means of diagnosing disseminated candidiasis.
BACKGROUND: Considerable variation exists in the use of antiasthmatic drugs in different counties in Sweden. The reasons for this variation are unknown. A study was performed to determine if there is an association between sales of antiasthmatic drugs and the prevalence of obstructive airway diseases in two adjoining Swedish counties. METHOD: The prevalence of asthma-associated symptoms in the county of Jämtland where there is high drug use, and the county of Gävleborg where it is lower, was assessed in 1990 by a postal questionnaire answered by 11,300 subjects. Three age groups were included: all 16 year olds, 13% of those aged 30-39 years, and 13% of 60-69 year olds. A total of 2100 subjects reporting airway symptoms in a questionnaire and 450 asymptomatic controls were further investigated at an interview with lung function tests and, in 500 cases, with a methacholine challenge. Asthma was diagnosed in subjects reporting a typical history or repeated episodes of dyspnoea and wheezing, or dry cough combined with reversibility in FEV1, variability in peak expiratory flow, or a PC20 value of < or = 4 mg/ml. RESULTS: The prevalence of current asthma was close to 8% in all age groups in Jämtland and significantly lower (close to 6%) in all age groups in the warmer, more industrialised and more densely populated county of Gävleborg. A gender difference with a higher prevalence in women was found in Gävleborg but not in Jämtland. There was no significant difference in the use of inhaled beta 2 stimulants among subjects with asthma in the two counties. Inhaled steroids were used more often in Jämtland. However, they were used regularly by fewer than 10% of asthmatic subjects in the two younger age groups. CONCLUSION: The differences in the use of antiasthmatic drugs in these two counties reflect a difference in the prevalence of obstructive airway disease.
Even in the absence of sleep apnoea, heavy snoring may be a cause of excessive daytime sleepiness (EDS) and fatigue. The aim of this investigation was to study whether uvulopalatopharyngoplasty (UPPP) is effective in relieving snoring and excessive daytime sleepiness in nonapnoeic snoring patients. UPPP was assessed in 155 nonapnoeic, snoring patients (136 men and 19 women, mean age 45 yrs). Postoperative evaluation was made after 3 months in 105 patients, and after 12 months in 50 patients. Fifty four patients were evaluated after both 3 and 12 months. In 49 patients, a further evaluation was made after 2 yrs. The results were compared with those of 76 conservatively-treated, nonapnoeic, snoring patients, who were reinvestigated 12 months after their initial examination. The proportion of patients with frequent loud snoring had decreased postoperatively from 96 to 18%. A highly significant improvement was reported in EDS and daytime fatigue. The proportion of patients who reported problems staying awake when driving had decreased from 29 to 7%, and the number who felt rested when awakening in the morning had increased from 23 to 78 after the operation. The patients in the UPPP group had somewhat more severe symptoms before treatment than those treated conservatively. One year after treatment the situation had been reversed, with significantly more snoring and excessive daytime sleepiness in the conservatively-treated group. In conclusion, these results indicate that UPPP is effective in relieving snoring and EDS in nonapnoeic snorers.
OBJECTIVES: To study the prevalence of asthma (asthma symptoms and bronchial hyperresponsiveness) in Swedish cross country skiers compared with non-skiers and monitor changes in symptoms and bronchial hyperresponsiveness during the year. DESIGN: Cross sectional study during the winter ski season and in the summer. SETTING: Six ski clubs for élite skiers (total 47) in two different areas of Sweden. SUBJECTS: 42 élite cross country skiers and 29 non-skiing referents. MAIN OUTCOME MEASURES: Bronchial responsiveness, asthma symptoms, and lung function. RESULTS: Bronchial responsiveness was significantly greater and asthma symptoms more prevalent in the skiers than in the referents. There was no difference in bronchial responsiveness within either group between winter and summer. 15 of the 42 skiers used antiasthmatic drugs regularly and 23 had a combination of asthma symptoms and hyperresponsive airways or physician diagnosed asthma, or both. Altogether 33 skiers had symptoms of asthma or bronchial hyperresponsiveness. One of the referents had symptoms of asthma and bronchial hyperresponsiveness, and none used antiasthmatic drugs regularly. CONCLUSIONS: Asthma, asthma-like symptoms, and bronchial hyperresponsiveness are much more common in cross country skiers than in the general population and non-skiers. Strenuous exercise at low temperatures entailing breathing large volumes of cold air is the most probable explanation of persistent asthma in skiers.
Some methodological aspects and characteristics on analysis of bone and liver alkaline phosphatase (EC 3.1.3.1, ALP) isoforms by high-performance liquid chromatography (HPLC) methods are presented. Factors affecting separation (analytical column type, column temperature, mobile phase buffer, mobile phase salt, gradient elution, flow rate) and reaction conditions (substrate type, substrate concentration, fluorescent substrates, substrate buffer type, substrate buffer concentration, substrate pH, substrate activators, substrate detergent, substrate flow rate, reaction temperature, postcolumn reaction detection) are discussed. Six peaks with ALP activity were separated and quantified by our new HPLC method in normal adult nonplacental serum: one intestinal/bone, two bone, and three liver ALP isoforms. Differences between the six ALP isoforms with respect to diethanolamine buffer concentration and substrate pH were observed. Although our HPLC method offers an improved possibility to clarify the reason for an increased total ALP in the routine clinical chemistry laboratory further research is needed to clarify the cellular origins of the different bone and liver ALP isoforms.
Patients with chronic myelogenous leukemia (CML) can be cured with allogeneic bone marrow transplantation. Over the past decade, it has become clear that immunological mechanisms, in the form of graft-versus-leukemia, constitute an integral part of this therapy. Because of limitations imposed by a lack of suitable donors, age, and toxicity, only a minority of patients can be offered allogeneic bone marrow transplantation (BMT). Recently, attempts have been made to employ autologous bone marrow transplantation (ABMT) for the therapy of CML using a variety of pre- and post-transplantation manipulations. This report describes the rationale for an ongoing clinical trial using the immunomodulator roquinimex (Linomide), following autologous bone marrow transplantation, in an attempt to stimulate the immunological responses thought to be critical for successful therapy in CML.
Stone and urine composition were analysed in 75 men and 40 women with recurrent calcium oxalate stone disease (group R) and in 48 men and 19 women who had formed only one calcium-oxalate-containing stone (group S). Patients who had developed stones with a large fraction of calcium phosphate were significantly more frequent in group R than in group S. There was furthermore a higher excretion of calcium and higher calcium oxalate supersaturation levels in patients with stones containing more than 25% calcium phosphate. It was concluded from these observations that the calcium phosphate content of renal stones might be a useful factor in predicting the future course of the disease.
Thy-1 has been used as a cell surface marker for identification of mature T cells, T lymphoid precursors and the hematopoietic stem cell. The developmental program of these cells during hemato/lymphopoiesis is complex because of heterogeneity of the populations and subsequent migration. To study the differentiation of Thy-1 positive cells at precise periods of in vivo development we have used a strategy based on cell specific toxicity. In the transgenic mouse studies presented here, Thy-1 positive cells are ablated by targeting the expression of the conditional toxin Herpes simplex virus 1 thymidine kinase (tk) with Thy-1 transcriptional control elements. We demonstrate the controlled expression of HSV1 tk in Thy-1 expressing cells of adult transgenic mice and the conditional ablation of > 90% of maturing thymocytes. We describe the distinct subpopulations of cells remaining within individual ablated thymuses and show by phenotypic analyses that Thy-1 tk induced ablation enriches for CD4 low and double negative thymocytes. Furthermore, we demonstrate a differential effect of thymus directed ablation on the maturing peripheral T cell compartment at various times in mouse development. This strategy is successful for production of a conditional T lymphocyte deficiency and could be useful in the study of T lineage development and direct in vivo isolation of enriched T precursor cell populations.
A Swedish family with Paramyotonia congenita (Eulenburg) (PMC) is presented. Clinical neurological examination, neurophysiological examination (n = 5) and muscle biopsy (n = 4) were performed. Different clinical features were found in various combinations in the individual family members. The clinical symptoms were: (1) cold-induced myotonia, (2) attacks of weakness, (3) persistent weakness and (4) no symptoms but other signs of muscle affection. In the patients with myotonia, the neurophysiological examination showed spontaneous myotonic discharges which were frequent at room temperature but disappeared after cooling. Furthermore, the amplitude of M. abductor digiti minimi compound action potential, during supramaximal ulnar nerve stimulation, decreased significantly after cooling. In the patients with persistent weakness there were no spontaneous myotonic discharges, but myopathic abnormalities were found in proximal muscle. In the patients with myotonia as well as in the patients with manifest muscle weakness, muscle biopsy showed a variation of muscle fibre diameters, centrally located nuclei, occasional atrophic fibers and an atrophy of type IIB muscle fibres. These findings are unspecific but have been described in PMC patients in earlier studies. An ancestor to the family, who had myotonia, lived in the same town and at the same time as Albert Eulenburg, which may suggest that this family is a part of the originally described family (1).
A novel fast-twitch motor unit type, called the IIX-myosin heavy chain (MHC) motor unit, identified by the glycogen depletion technique together with a series of monoclonal antibodies (mAbs) specific for MHCs, has been isolated recently in the rat tibialis anterior muscle. In young animals, this unit has physiological, biochemical and morphometrical properties which separate it from the IIA- and IIB-MHC motor units. In old age, on the other hand, the IIX-MHC units display physiological, biochemical and morphometrical properties resembling the IIB-MHC motor units. Based on these results it was proposed that a transition from IIB to IIX motor units occurs during ageing. In an attempt to clarify this point, the MHC composition was identified by 6% SDS-PAGE and immunoblotting analysis, using specific mAbs antibodies, in the same fast-twitch tibialis anterior muscles in young (3-6 months, n = 9) and old (20-24 months, n = 16) rats from which the single motor units had been identified previously. The IIX-MHC comigrates together with the IIA-MHC band in 6% SDS-PAGE and only two MHC bands are observed in the rat tibialis anterior muscle, i.e. the IIA-IIX- and IIB-MHC bands. A significant increase (P < 0.001) in the average relative amount of the IIA-IIX-MHC was observed in the old (45 +/- 17%) as compared to the young (23 +/- 4%) animals, accompanied by a corresponding decrease in IIB-MHC content. It was demonstrated in immunoblotting analysis that only trace amounts of IIA-MHC were detectable in the IIA-IIX-MHC band in both young and old TA muscles, indicating a substantial increase in the IIX-MHC content in old age. Thus, the present results together with previous observations at the motor unit level strongly support an age-related motor unit transition from type IIB- to IIX-MHC.
1. Maximum velocity of shortening (Vmax) and compositions of myosin heavy chain (MHC) and myosin light chain (MLC) isoforms were determined in single fibres from the soleus or the lateral region of the quadriceps (vastus lateralis) muscles in man. Muscle samples were obtained by percutaneous biopsy, and membranes were permeabilized by glycerol treatment (chemical skinning) or by freeze-drying. 2. Types I, IIA and IIB MHCs were resolved from single fibre segments by 6% sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and five different fibre types were identified: fibres containing type I MHC, types I and IIA MHCs, type IIA MHC, types IIA and IIB MHCs, and type IIB MHC. Only a few fibres co-expressed types I and IIA MHCs but 28% of all quadriceps fibres expressed both IIA and IIB MHCs in variable proportions. Fibres co-expressing types I and IIB MHCs were not found. 3. Alkali (MLC1 and MLC3) and dithio nitrobenzoic acid (DTNB) (MLC2) myosin light chains were observed in all type II fibres in variable proportions. MLC (MLC1s and MLC2s) isoforms from type I fibres had lower migration rates than the corresponding isoforms from type II fibres (MLC1f and MLC2f). More than half of type I fibres in both soleus (65%) and quadriceps (68%) muscles also expressed 'fast' MLC3 and 36% of the type II fibres from quadriceps muscle expressed the slow isoform of MLC2. 4. Differences were observed in some mechanical characteristics of freeze-dried versus chemically skinned fibres. Maximum tension (P0) and specific tension were lower in freeze-dried types I and IIA fibres than in chemically skinned, while no differences were observed in the IIA/B fibres. The numbers of types I/IIA and IIB fibres were too low to allow statistical comparisons. In chemically skinned fibres, mean specific tension (0.20 +/- 0.01 N/mm2) did not vary with fibre type. In freeze-dried fibres, on the other hand, specific tensions varied according to MHC type: higher (P < 0.01) specific tensions were observed in types IIB (0.19 +/- 0.01 N/mm2) and type IIA/B fibres (0.18 +/- 0.04 N/mm2) than in type I fibres (0.12 +/- 0.02 N/mm2). The specific tension of type IIA fibres (0.12 +/- 0.05 N/mm2) did not differ significantly from the other fibre types. Cross-sectional areas and mean Vmax did not differ between freeze-dried and chemically skinned fibres, either when all fibres were pooled or within respective fibre types. Vmax data from all fibres of a given type, irrespective of membrane permeabilization technique, have therefore been pooled.(ABSTRACT TRUNCATED AT 400 WORDS)
Bacterial levels in dust collected from hospital air-conditioning filters were examined by chemical analysis (without prior culture). The dust was analyzed by gas chromatography-mass spectrometry after hydrolysis and derivatization. l-Glycero-d-mannoheptose and hydroxy fatty acids (3-OH 12:0 and 3-OH 14:0) (primarily found in lipopolysaccharide) and muramic acid (a chemical marker for bacterial peptidoglycan) were present at higher levels in dust collected from filters primarily contacting outdoor (as opposed to indoor) air. The ratio of l-glycero-d-mannoheptose to muramic acid in dust (compared with those of a group of gram-positive and gram-negative bacteria) suggested that both dust types contained appreciable numbers of gram-negative bacteria. There is potential for the chemical assessment of the microbial content of airborne dust.
The biochemical properties and fatty acid compositions of 16 strains of Mycobacterium haemophilum from Australian patients were studied. The strains proved to be indistinguishable from each other but could readily be differentiated from other slowly growing mycobacteria with similar cultural features. Mycolic acid analyses revealed the presence of alpha-, methoxy-, and ketomycolates. The fatty acid composition supports the validity of the fact that M. haemophilum is a distinct species. The fatty acid composition was consistent among the 16 strains, but it was unusual in that there was some resemblance to the fatty acid composition of M. leprae. The wide range of pHs (5.4 to 7.4) that supported growth of M. haemophilum on artificial medium is in keeping with suggestions that M. haemophilum exists in an environmental habitat.