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Biomedical subjects

L Larsson

Publications and source records attributed to L Larsson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Placebo-controlled study of inhaled budesonide on indices of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsies in cross-country skiers.

BACKGROUND: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. OBJECTIVE: To investigate the effect of inhaled budesonide, 400 mug twice daily, on indices of airway inflammation in 'ski asthma', defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. METHODS: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16-20) years for a mean (range) treatment period of 22 (10-32) weeks over the competitive season. RESULTS: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV(1). Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. CONCLUSIONS: We were unable to show any clear beneficial effect of budesonide in 'ski asthma'. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.

Administration, Inhalation↗
PubMed2000

Increased cell death and delayed development in the cerebellum of mice lacking the rev-erbA(alpha) orphan receptor.

The rev-erbA(alpha) gene, belonging to the steroid receptor superfamily of transcription factors, is highly conserved during evolution but little is known so far about its functions in development or in adult physiology. Here, we describe genetically altered mice lacking the rev-erbA(alpha) gene. These animals do not show any obvious phenotype in either fat tissue or skeletal muscle, despite the known regulation of rev-erbA(alpha) expression during adipocyte and myotube differentiation in vitro. However, during the second week of life, the cerebellum of rev-erbA(alpha) mutants presents several unexpected abnormalities, such as alterations in the development of Purkinje cells, delay in the proliferation and migration of granule cells from the external granule cell layer and increased apoptosis of neurons in the internal granule cell layer. Interestingly, the expression pattern of rev-erbA(alpha) suggests that the abnormalities observed in the external granule cell layer could be secondary to Purkinje cell alterations. Taken together, our data underline the importance of rev-erbA(alpha)expression for the appropriate balance of transcriptional activators and repressors during postnatal cerebellar development.

Animals↗
PubMed2000

Bone mineral density in diagnosis of osteoporosis: reference population, definition of peak bone mass, and measured site determine prevalence.

A population-based study was performed in order to compare different definitions of peak bone mass, and to apply the corresponding T-scores for different skeletal sites to a cohort of 70-yr-old women for studying the prevalence of osteoporosis. Bone mineral density (BMD) of the hip, lumbar spine, and forearm was measured by dual X-ray absorptiometry (Hologic 4500) in 296 women ages 16-31 yr and 210 women age 70 yr. Peak bone mass occurred in women in their early 20s at the proximal femur and at 28 and 31 yr at the spine and forearm, respectively. BMD cutoff levels were compared to machine-specific cutoff values for the different sites. When applied to our cohort of 70-yr-old women, the prevalence of osteoporosis at the total hip was 9-25%, depending on which peak bone mass the T-score of -2.5 was based. The prevalence in the spine was 28-33% and in the forearm 45-67%. Osteoporosis in at least one of the three measured sites was documented in 49-72% of the population sample. Our results show that the use of T-score to define osteoporosis results in a highly different prevalence rate in a given population depending on the reference population and the skeletal sites chosen for measurement.

Absorptiometry, Photon↗
PubMed2000

Aging-related changes in skeletal muscle. Mechanisms and interventions.

The aging-related motor handicap and the growing population of elderly citizens have enormous socioeconomic effects on the modern healthcare system. The mechanisms underlying impaired motor performance in old age are complex and involve the central and peripheral nervous systems and the muscle tissue itself. It is widely accepted that the aging-related loss of muscle mass, strength and quality has a significant detrimental impact on motor performance in old age and on the ability to recover from falls, resulting in an increased risk of fractures and dependency. Therefore, the prevention of falls and gait instability is a very important safety issue, and different intervention strategies have been used to improve motor performance among the aging population. There is general consensus that physical exercise is a powerful intervention to obtain long term benefits on muscle function, reduce the frequency of falls, and to maintain independence and a high quality of life in older persons. The results from studies using different types of hormone supplementation therapies have shown interesting and encouraging effects on skeletal muscle mass and function. However, the potential risks with both growth hormone and androgen treatment are not known and long term clinical trials are needed to address safety concerns and the effects on skeletal muscle. Recent advancements in cellular/molecular, physiological and molecular biological techniques will significantly facilitate our understanding of aging-related impairments of muscle function and contribute to the evaluation of different intervention strategies.

Actomyosin↗
PubMed1999

Rapid method for relative gene expression determination in human tissues using automated capillary gel electrophoresis and multicolor detection.

The aim of this study was to evaluate a direct and automated post-polymerase chain reaction (PCR) detection system to simultaneously determine the relative gene expression levels of nine cancer-related human genes. Total RNA was prepared from flash-frozen biopsies derived from human colorectal tumors or normal mucosa and reverse-transcribed to cDNA which was PCR-amplified using primer pairs corresponding to the studied genes. In each reaction, the forward primer was labeled with a fluorescent dye. The PCR products were pooled and an internal size standard with a uniquely colored fluorescent dye was added. The samples were then subjected to automated capillary gel electrophoresis. Fragment analysis software was used to calculate the relative gene expression using beta-actin as the reference gene. We found that automated capillary gel electrophoresis with multicolor detection is a rapid, accurate and highly reproducible method for separation and quantification of PCR-amplified cDNA.

Autoanalysis↗
PubMed1999

In vitro motility speed of slow myosin extracted from single soleus fibres from young and old rats.

1. Isolated soleus muscle fibres from aged rats contract more slowly than those from young rats. To determine whether this effect is due to a difference between the myosin molecules, we measured the rate at which actin filaments are driven over a myosin coated surface in the presence of ATP by using a novel in vitro motility assay where myosin is extracted from single muscle fibre segments. 2. Motility was dependent on the myosin density on the coverslip. In regions of high myosin density, actin motility was orientated parallel and anti-parallel to the direction of flow during myosin adhesion to the coverslip. In contrast, in regions of lower myosin density, actin motility was more random. The speed was about 20 % higher in the high density regions (P < 0.001). Further, the speed of filaments in the high density region, moving away or towards the fibre was less variable (P < 0.05) than that of more randomly moving filaments in the low density region. 3. The speed with myosin from slow soleus fibres of young adult rats (3-6 months old; v = 1.43 +/- 0.23 microm s-1; mean +/- s.d.) was faster (P < 0.001) than with myosin from aged rats (20-24 months old; v = 1.27 +/- 0.23 microm s-1). 4. No difference in myosin isoforms between young adult and aged fibres could be detected using electrophoretic and immunocytochemical techniques. Fibres of both ages expressed the beta/slow myosin heavy chain (MyHC) isoform and slow isoforms of essential and regulatory myosin light chains (MyLCs). 5. It is concluded that an age-related alteration in myosin contributes to the slowing of the maximum shortening velocity (V0) observed in soleus muscle fibres expressing the beta/slow MyHC isoform.

Actins↗
PubMed1999

[Quality assurance of blood gas analysis--a medical risk zone].

Blood gas analysis is fundamental to all intensive care. Although speed is essential for adequate treatment, prognosis and even survival of the patient, precision and consistency of results are equally important prerequisites for correct clinical decision making. Point-of-care testing (POCT) has become one of the predominant fields of blood gas analysis. Although modern technology and instruments are user friendly, special training and continuous updating of staff education are of paramount importance to the reliability of results. The article consists in an outline of quality requirements and discussion of appropriate procedures for assessing and maintaining quality in blood gas analysis.

Acid-Base Equilibrium↗
PubMed1999

Regulation of human muscle contraction at the cellular and molecular levels.

The rat is the most extensively characterized species with regard to regulation of muscle contraction and myofibrillar protein isoform expression, but there is reason to question whether results from small mammals, such as the rat, can be extrapolated directly to larger mammals, such as man. Studies of human muscle contraction have primarily used different in vivo muscle function measurements, i.e. measurements of force at different speeds of movement during electrical stimulation or voluntary activation. These measurements give important information on overall muscle function, but they are of limited value for our understanding of regulation of muscle contraction. In basic science, cellular- and molecular-physiological methods have been used for many years, but these techniques have so far only rarely been used in studies of human muscle contraction. Detailed studies of human muscle contraction can be performed in the short muscle fibre segments obtained by the percutaneous muscle biopsy technique both at the cellular and molecular level. The skinned fibre preparation in combination with a novel in vitro motility assay offers a unique possibility to investigate regulation of human muscle contraction at the cellular and molecular levels in the same muscle cell segment in both health and disease, i.e. in muscle cells characterized according to the type and amount of expressed myofibrillar protein isoforms.

Actin Cytoskeleton↗
PubMed1999

Acute quadriplegic myopathy following autologous peripheral blood stem cell transplantation for breast cancer.

Autologous peripheral blood stem cell transplantation (APSCT) is increasingly used in the treatment of breast cancer. We report a patient who experienced septic shock, and after treatment with antibiotics, high-dose corticosteroids and mechanical ventilation due to respiratory insufficiency, developed quadriplegia. Electroneurophysiological examination, as well as a muscle biopsy, showed a typical picture of acute quadriplegic myopathy with loss of thick filament proteins. This is, to the best of our knowledge, the first reported case of this complication following APSCT.

Acute Disease↗
PubMed1999

Use of quadrupole GC-MS and ion trap GC-MS-MS for determining 3-hydroxy fatty acids in settled house dust: relation to endotoxin activity.

Gas chromatography-mass spectrometry (GC-MS) using a quadrupole instrument and GC-tandem MS (GC-MS-MS) using an ion trap instrument were applied to determine 3-hydroxy fatty acids (3-OH FAs) with 10-18 carbon chain lengths, specific components of the endotoxin (lipopolysaccharide, LPS) of Gram-negative bacteria, in 30 house dust samples. The two methods provided similar detection sensitivity for methyl ester/trimethylsilyl derivatives of the 3-OH FAs and allowed these acids to be distinguished from co-eluting 2-OH FA derivatives. The correlation coefficients between endotoxin activity (Limulus test) and the combined amounts of 3-OH C10, 3-OH C12, and 3-OH C14 were 0.60 and 0.61 when using GC-MS and GC-MS-MS, respectively. The superior selectivity of GC-MS-MS was illustrated in analyses of sub-milligram amounts of dust, where the chromatograms achieved by GC-MS were difficult to interpret due to a high background and several closely eluting compounds. GC-MS-MS is therefore preferable to GC-MS for determining 3-OH FAs in minute (sub-milligram) amounts of dust.

Air Pollution, Indoor↗
PubMed1999

Post-operative effects on insulin resistance and specific tension of single human skeletal muscle fibres.

Surgery and accidental trauma are associated with a transient period of insulin resistance, substrate catabolism and muscle weakness. In the present study, we evaluated the changes in the force-generating capacity of chemically skinned single muscle fibres following abdominal surgery. Biopsies of the m. vastus lateralis were obtained in three patients 1 day before and 3 or 6 days after surgery. Part of the biopsy was frozen for histochemical analysis of the fibre cross-sectional area (FCSA) and myofibrillar protein content, and another part was used for single-fibre contractile measurements. All patients developed insulin resistance following surgery. The maximum velocity of unloaded shortening of single muscle fibres did not change following surgery. The FCSA did not decrease after surgery, as determined either from histochemical sections or from single fibres measured at a fixed sarcomere length of 2.76+/-0.09 microm (mean+/-S.D.). Further, the force-generating capacity of the single fibres, measured as maximal Ca(2+)-activated force (P(0)) or as P(0) normalized to FCSA (specific tension), remained unchanged, as did the myofibrillar protein content of the muscle. In conclusion, the muscle weakness associated with post-operative insulin resistance is not related to a decreased specific tension or a loss of myofibrillar proteins. Other potential cellular mechanisms underlying post-operative weakness are discussed.

Abdomen↗
PubMed1999

The effect of age on in vitro motility speed of slow myosin extracted from single rat soleus fibres.

The effect of age on the motor protein myosin was examined in a novel in vitro motility assay. Myosin was extracted from soleus fibres of young (3-6 month) and old (20-24 month) rats. All fibres expressed the type I myosin heavy chain (MyHC) and the slow isoforms of the myosin light chains (MyLCs). In vitro motility speed was significantly (P < 0.001) faster in the young adult (1.43 +/- 0.23 microm s-1) than in the aged group (1.27 +/- 0.23 microm s-1). The result indicates that the age-related decrease in contractile speed observed in slow fibres may be the effect of a change in the properties of myosin with age.

Aging↗
PubMed1999

The influence of thyroid hormone on myosin isoform composition and shortening velocity of single skeletal muscle fibres with special reference to ageing and gender.

This review summarizes the effects of altered thyroid hormone levels on the expression of myosin isoforms and contractility in single muscle fibres from fast- and slow-twitch muscles from young and old male and female rats. The differences between male and female hyperthyroid soleus muscles are suggested to be related to an interaction of thyroid hormones and sex hormones in the regulation of myosin gene expression. Additionally, the mismatch between the protein and mRNA levels of MyHCs between male and female hyperthyroid extensor digitorum longus (EDL) muscles raises the possibility of a gender-related difference in post-transcriptional, translational or post-translational regulation of MyHC isoforms by T3.

Aging↗
PubMed1999

Gender- and thyroid hormone-related transitions of essential myosin light chain isoform expression in rat soleus muscle during ageing.

In this brief review, the modulatory influence of essential myosin light chain (MLC) isoforms on muscle cell contractility is discussed. Specific interest is focused on the expression of the MLC1Sa and MLC1Sb isoforms in the slow-twitch soleus muscle in male and female rats, during ageing and after thyroid hormone treatment. According to two-dimensional gel electrophoresis analysis, the MLC1Sa/MLC1SB ratio increased during ageing in both males and females in parallel with the age-related decrease in shortening velocity reported in muscle fibres expressing the slow (type 1) myosin heavy chain (MHC) isoform. However, the MLC1Sa and MLC1Sb isoform expression responded to thyroid hormone treatment in a complex manner which did not parallel the age-related changes in shortening velocity reported in hyperthyroid animals. Thus, if MLC1Sa and MLC1Sb isoforms modulate shortening velocity in type 1 fibres, then other modulators of shortening velocity are not regulated by thyroid hormone in co-ordination with these essential MLCs.

Aging↗
PubMed1999

An overview of carbohydrate-protein interactions with specific reference to myosin and ageing.

Non-enzymatic glycosylation (glycation), a post-translational modification of proteins, results from the reaction of proteins with reducing sugars. Glycation is implicated in various pathologies like diabetes, Alzheimer's disease and it has been suggested to play an important role in the ageing process. Research on protein glycation has primarily studied extracellular proteins such as albumin, haemoglobin and collagen. However, there is increasing evidence that intracellular proteins may also be affected by glycation, and glycation of myosin is reported to decrease myosin ATPase activity. Glycated adducts are detected by various techniques such as chromatography, electrophoresis, fluorescence and immunochemistry. Inhibition or removal of these adducts has been achieved by chemical compounds such as aminoguanidine (amG), beta-mercaptoethanol (bME) and N-phenacylthiazolium bromide (PTB). In the present pilot study, using a novel in vitro motility assay, we have observed an attenuation in the motility speed of actin (approximately 13%) on myosin extracted from single muscle fibre segments after 15-min glucose incubation. Addition of bME to the incubation medium maintained actin motility speed.

Actins↗
PubMed1999

D-arabinitol--a marker for invasive candidiasis.

The five-carbon sugar alcohol D-arabinitol (DA) is a metabolite of most pathogenic Candida species, in vitro as well as in vivo, and can be determined by gas chromatography or enzymatic analysis. Endogenous DA and L-arabinitol (LA) are present in human body fluids, and serum DA and LA increase in renal dysfunction. In prospective clinical studies, elevated DA/LA or DA/creatine ratios in serum or urine have been found in immunocompromised, usually neutropenic, patients with invasive candidiasis. In addition, positive DA results have been obtained several days to weeks before positive blood cultures, and the normalization of DA levels has been correlated with therapeutic response in both humans and animals. However, to date, only a few prospective studies have been conducted in which adequate analytical methods were used. Thus, further investigation of various patient groups is needed to establish the applicability of the 'arabinitol method' in the diagnostic battery for invasive Candida infections.

Biomarkers↗
PubMed1999

PCR and other non-culture methods for diagnosis of invasive Candida infections in allogeneic bone marrow and solid organ transplant recipients.

In this prospective study 197 serum and 152 urine samples were collected from 40 bone marrow and solid organ transplant recipients with clinically suspected invasive fungal infection before, during and after empirical treatment with lipid formulation of amphotericin B or fluconazole. Serum was analysed by Candida polymerase chain reaction (PCR) and urine by measurement of D/L-arabinitol ratio. One serum from each patient was also tested for concentration of (1-->3)-beta-glucan and two commercial Candida antigens. Invasive fungal infection was diagnosed in four candidosis and one aspergillosis patients (13%). Positive PCR, elevated D/L-arabinitol ratio, (1-->3)-beta-glucan concentration and antigens were detected in nine, 15, 17, and seven patients, respectively. The agreement between PCR and D/L-arabinitol assays was poor. However, 56% agreement was observed between positive PCR and beta-glucan and/or antigen assays, and 60% agreement between positive D/L-arabinitol and beta-glucan and/or antigen assays. Combination of several non-culture assays is needed to diagnose invasive fungal infection in high-risk transplant recipients. No single test was sufficient for diagnosis.

Adolescent↗