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Biomedical subjects

L Larsson

Publications and source records attributed to L Larsson.

At least 91 records · Page 5Linked to original sources

House dust induces IL-6 and IL-8 response in A549 epithelial cells.

The in vitro potency of house dust to induce cytokine response in A549 lung epithelial cells was studied. Dusts collected from carpet, bed, shelf and floor of a villa and an apartment by vacuuming were found to trigger the production of interleukin-8 (IL-8) and interleukin-6 (IL-6) in a dose-dependent manner, and the interleukin production was several-fold higher than of swine dust (used as a positive control). The IL-8 and IL-6 production of pure Escherichia coli lipopolysaccharide was significantly lower than of the dusts and a peptidoglycan-polysaccharide complex did not show any stimulatory effect at all. The lipopolysaccharide and peptidoglycan contents of the samples were determined by gas chromatography-tandem mass spectrometry analysis of, respectively, 3-hydroxy fatty acids and muramic acid; in addition, ergosterol was monitored for fungal biomass. The inflammatory properties of house dust upon inhalation may be reflected in its high potency to induce cytokine response in lung epithelial cells.

Air Pollution, Indoor↗

Bed rest increases the amount of mismatched fibers in human skeletal muscle.

The effects of a 37-day period of bed rest on myosin heavy chain (MHC) expression on both mRNA and protein level in human skeletal muscle fibers were studied. Muscle biopsies from vastus lateralis muscle were obtained from seven healthy young male subjects before and after the bed-rest period. Combined in situ hybridization, immunocytochemistry, and ATPase histochemistry analysis of serial sections of the muscle biopsies demonstrated that fibers showing a mismatch between MHC isoforms at the mRNA and protein level increased significantly after the bed-rest period, suggesting an increase in the amount of muscle fibers in a transitional state. Accordingly, fibers showing a match in expression of MHC-1 and of MHC-2A at the mRNA and protein level decreased, whereas fibers showing a match between MHC-2X mRNA and protein increased after bed rest. Overall, there was an increase in fibers in a transitional state from phenotypic type 1 --> 2A and 2A --> 2X. Furthermore, a number of fibers with unusual MHC mRNA and isoprotein combinations were observed after bed rest (e.g., type 1 fibers with only mRNA for 2X and type 1 fibers negative for mRNA for MHC-beta/slow, 2A, and 2X). In contrast, no changes were revealed after an examination at the protein level alone. These data suggest that the reduced load-bearing activity imposed on the skeletal muscles through bed rest will alter MHC gene expression, resulting in combinations of mRNA and MHC isoforms normally not (or only rarely) observed in muscles subjected to load-bearing activity. On the other hand, the present data also show that 37 days of bed rest are not a sufficient stimulus to induce a similar change at the protein level, as was observed at the gene level.

Adenosine Triphosphatases↗

Bronchoscopy and bronchoalveolar lavage findings in cross-country skiers with and without "ski asthma".

Bronchial hyperresponsiveness to methacholine with asthma-like symptoms ("ski asthma") is frequent in elite cross-country skiers. To further the understanding of "ski asthma", 10 nonasthmatic, nonatopic controls and 30 adolescent elite skiers were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Nine skiers were atopic without allergy symptoms. Compared with controls, the macroscopic inflammatory index in the proximal airways in skiers was three-fold greater (median (interquartile range) 3.0 (2.0-5.0) versus 1.0 (0.8-2.3), p=0.008). In the BAL fluid, skiers had significantly greater total cell (p<0.05) and percentage lymphocyte (p<0.01) and mast cell counts (p<0.05). Neutrophil and eosinophil counts were not significantly different and eosinophil cationic protein was not detected. Tumour necrosis factor-alpha and myeloperoxidase were detected in 12 (40%) and six (20%) skiers, respectively. In skiers with ski asthma, the inflammatory index was greater than in nonasthmatic skiers. Lymphocyte subtypes and activation markers, and concentration of albumin, fibronectin and hyaluronan were not different from those in controls. Cross-country skiers have a minor to moderate degree of macroscopic inflammation in the proximal airways at bronchoscopy and a bronchoalveolar lavage fluid profile which differs in several respects from healthy controls. Skiers with ski asthma tend to show even higher degrees of bronchial inflammation.

Adolescent↗

Monthly measurements of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in healthy prepubertal children: characterization and relationship with growth: the 1-year growth study.

The usefulness of measurements of IGF-I or IGF-binding protein-3 (IGFBP-3) in the clinical management of growth disorders is dependent on the extent of physiologic variation in their concentrations. Our purpose was therefore to investigate the longitudinal intraindividual variation in serum concentration of IGF-I and IGFBP-3 in healthy prepubertal children. Monthly serum samples and auxologic measurements were taken over a period of 1 y from 65 prepubertal children (38 boys, 27 girls; mean age 9.1 y, range 7.8-10.8). Concentrations of IGF-I and IGFBP-3 were measured by RIA. The mean (+/-SD) serum concentration of IGF-I in the children was 165 +/- 42.0 microg/L, with a mean coefficient of variation (CV) of 13.9% around the annual mean serum concentration for each child. The corresponding mean concentration of IGFBP-3 was 3273 +/- 604.5 microg/L, and the mean CV for each child was 9.7%. These monthly longitudinal variations in IGF-I and IGFBP-3 were parallel to changes in longitudinal growth. Short-term changes (1 mo) in IGF-I were positively correlated with changes in weight (r(s) = 0.42, p < 0.0005) and body mass index (r(s) = 0.45, p < 0.0005), and negatively correlated with minor intercurrent illnesses (-0.32; p < 0.05). Seasonal fluctuations also occurred, with short term changes in IGF-I (1 mo) and IGFBP-3 (3 mo), increasing with increasing outdoor temperatures (r(s) = 0.30, p < 0.05 and r(s) = 0.39, p < 0.005, respectively). We conclude, that there are significant changes in both IGF-I and IGFBP-3 that occur in association with growth, and that IGF-I is more sensitive than IGFBP-3 to short-term changes in weight, body mass index, and intercurrent illnesses. Physiologic short-term changes must therefore be taken into consideration when using serum levels of IGF-I or IGFBP-3 in the evaluation of the short or slowly growing child.

Child↗

Isoforms of bone alkaline phosphatase: characterization and origin in human trabecular and cortical bone.

Alkaline phosphatase (ALP) is a glycoprotein and functions as an ectoenzyme attached to the cell membrane by a hydrophobic glycosyl-phosphatidylinositol (GPI) anchor. Three bone ALP (BALP) isoforms in human serum were separated and quantitated by high-performance liquid chromatography. B/I, a minor fraction, is composed on average of bone (70%) and intestinal (30%) ALP, and two major isoforms, B1 and B2. Treatment with GPI-specific phospholipase C (GPI-PLC) did not influence the activities or retention times for B1 and B2, indicating that the biochemical differences between B1 and B2 are likely to be due to different glycosylation patterns. The B/I fraction in serum, on average 4% of total ALP, was found to be composed of B1 and B2 isoforms, each with an intact hydrophobic GPI cell membrane anchor. We investigated the origin of these three BALP isoforms and osteocalcin in human femora from five healthy individuals (four males), mean age 51 years, obtained from a tissue bank. Bone was sampled from three sites: cortical bone, trabecular bone from the diaphysis, and trabecular bone from the greater trochanter. Trabecular bone, from both sites, had higher BALP activities compared with cortical bone. Conversely, the osteocalcin content of cortical bone was more than 3-fold greater than that of trabecular bone. Cortical bone had approximately 2-fold higher activity of B1 compared with B2, whereas trabecular bone had approximately 2-fold higher activity of B2 compared with B1. We observed a previously undescribed BALP isoform (B1x) in all bone samples. B1x was also observed in sera from some patients (60%) with severe renal insufficiency and on chronic dialysis therapy (n = 20). The isoforms of BALP may provide information relating to bone metabolism within specific bone compartments.

Adult↗

Integrating the Internet into health administration education: a report from AUPHA's Faculty Internet integration task force.

HRSA funded a survey to determine what Internet resources would be most useful to AUPHA membership. This manuscript describes the Internet-intensive survey methodology, reports the survey results, and lists the task force recommendations. The task force used sequential questionnaires posted on the Web to gather both potentially useful Internet resource ideas and membership perceptions of the importance of each idea. Resources recommended by survey participants and the Task Force members emphasized potential improvements to the AUPHA and AUPHA-member Web pages.

Data Collection↗

[Asthma is no obstacle for physical activity or high-level athletics].

Asthma affects 6-8 per cent of the adult population, and is often triggered by physical activity, its occurrence in conjunction with athletics is a problem commonly encountered by most doctors treating the disease. Findings in recent studies suggest that asthma may be even more prevalent among those engaged in endurance sports. The risk of sports-induced asthmatic symptoms is dependent on the type of sport and climatic conditions, being higher in endurance sports and in cold and dry air. Asthma in sports should be treated in the same way as asthma in general. Inhaled beta-agonist and steroid treatment is usually sufficient, possibly in combination with a cromolyn preparation, though doping regulations need to be taken into account.

Adult↗

[Advances in the diagnosis of mycoses. New tests detect Candida infections].

New techniques for the detection of deep fungal infections are reviewed with a focus on Candida albicans, the species most frequently isolated. The introduction provides an outline of the similarities and differences between bacteria and fungi on one hand and animal cells on the other, which are important to bear in mind in the detection and treatment of deep fungal infections. In addition to cultures of biopsy material, blood, and mucous membranes (colonisation), serum tests for such fungal constituents as antigens or beta-glucan, the PCR technique for the detection of fungal DNA, and a test for the D-/L-arabinitol ratio in urine, are all valuable approaches. As yet, no single laboratory test is available that reliably detects disseminated candidosis. Rapid, sensitive, and specific methods for mycological diagnosis need to be developed to minimize the necessity of resorting to empirical therapy when deep mycosis is suspected.

Antibodies, Fungal↗

Gender- and age-related differences in the regulatory influence of thyroid hormone on the contractility and myosin composition of single rat soleus muscle fibres.

The effects of 4 weeks of thyroid hormone (3,5,3'-triiodothyronine, T3) treatment on the myosin isoform composition and maximum velocity of unloaded shortening (V0) of single soleus muscle fibres of young (3-6 months) and old (20-24 months) female (149 fibres) and male (200 fibres) rats were studied. Gender-related differences in the up-regulation of fast myosin heavy chain (MyHC) and myosin light chain (MyLC) isoforms were observed. In the female hyperthyroid rats, pure type I fibres and fibres co-expressing type I and type IIA MyHC (type I/IIA fibres) predominated. Some fibres expressed an alpha cardiac-like MyHC isoform either purely (alpha cardiac-like fibre type) or in co-expression with IIA MyHC (alpha cardiac-like/IIA fibre type). In the male hyperthyroid rats, on the other hand, all fibres were either type I/IIA or type I/IIAX. The relative quantities of fast MyLC isoforms in type I/IIA and type I/IIAX fibres was higher in female than in male hyperthyroid rats. V0 was similar in male and female control rats, and decreased with age in both genders (P<0.001). After T3 treatment, the average V0 increased (P<0.001) in females with a concomitant up-regulation of fast MyHC and fast MyLC isoforms irrespective of age. The average V0 of the pooled fibres was higher (P<0.001) in female than in male hyperthyroid rats at both ages. In conclusion, gender- and age-related differences were observed in the regulatory influence of 4 weeks' T3 treatment on myosin isoform composition and V0 in soleus fibres. These differences are presumably related to an interaction of thyroid and sex hormones in the regulation of myosin gene expression.

Aging↗

Effects of age and gender on shortening velocity and myosin isoforms in single rat muscle fibres.

The maximum velocity of unloaded shortening (V0) and the myosin heavy chain (MyHC) and light chain (MyLC) isoform composition were determined in single fibres from soleus and extensor digitorum longus (EDL) muscles of male and female rate 3-6 and 22-24 months old. In the soleus muscle, the beta/slow (type I MyHC) isoform predominated in both young and old animals, irrespective of gender. In the EDL, fibres expressing type IIX MyHC or a combination of IIX and IIB (IIXB) MyHC isoforms were predominant in old rats, while type IIB MyHC fibres predominated in young individuals of both genders. The V0 of soleus fibres expressing the type I MyHC isoform decreased (P < 0.001) by 40% with age in spite of an unchanged MyLC composition. In the EDL, the V0 of fibres expressing IIX, IIXB and IIB MyHC isoforms did not changes with age or differ between males and females. In conclusion, similar age-related changes in V0 and MyHC composition were observed in single muscle cells from both male and female rats. The present results demonstrate that the relationship between V0 and MyHC isoform composition at the single fibre level is similar in male and female rats, and that similar qualitative changes take place during ageing in both genders.

Aging↗

Total and viable airborne bacterial load in two different agricultural environments using gas chromatography-tandem mass spectrometry and culture: a prototype study.

Airborne exposure to bacterial components found in agricultural environments can lead to pulmonary inflammation. Total (viable and nonviable) bacterial load was monitored in a stable and a dairy by a new approach, gas chromatography-tandem mass spectrometry measurement of muramic acid, a component of gram positive and gram negative bacterial peptidoglycan. Also used to assess the gram negative bacterial load were 3-hydroxy fatty acids, markers of bacterial lipopolysaccharide. Culture, an established procedure for assessing the viable bacterial portion of airborne dust, served as a basis for comparison. The muramic acid and 3-hydroxy fatty acid concentrations (total C12:0, C14:0, and C16:0) showed a correlation with an R2 of 0.81. Dust and muramic acid levels also correlated. However, although relative muramic acid levels were lower in the stable than the dairy, colony forming units (CFU) were considerably higher in the stable. The total bacterial load (estimated from muramic acid values) for both the stable and dairy was also higher than would have been predicted from culture. These results suggest that nonculture based approaches and culture provide complementary but independent measurements of airborne biopollution.

Agriculture↗

Separation among species of Mycobacterium terrae complex by lipid analyses: comparison with biochemical tests and 16S rRNA sequencing.

Fatty acids, alcohols, and mycolic acid cleavage products were determined for 13 ATCC strains and 24 clinical isolates, which were initially identified by biochemical and growth characteristics as the Mycobacterium terrae complex. The clinical isolates were also analyzed by partial sequencing of the 16S rRNA gene, which divided them into five genetic entities, M. triviale (three strains), M. terrae (four strains), M. nonchromogenicum sensu stricto (seven strains), Mycobacterium sp. strain MCRO 6 (seven strains), and Mycobacterium sp. strain 31958 (one strain). After acidic methanolysis, secondary alcohols were a characteristic feature in all members of the M. terrae complex but M. triviale. In addition to the prominent secondary alcohols, 2-octadecanol and 2-eicosanol, two previously unidentified alcohols, 2-(8,15-dimethyl)docosenol and 2-(8,17-dimethyl)tetracosenol, were detected in M. nonchromogenicum, Mycobacterium sp. strain MCRO 6, and Mycobacterium sp. strain 31958. Only 2-(8,17-dimethyl)tetracosenol was detected in trace amounts in M. terrae. Genetic differences were associated with differences in phenotypic characteristics, including growth at 42 degrees C and pyrazinamidase production. Based on fatty acid and alcohol composition and biochemical and genetic characteristics, M. non-chromogenicum and Mycobacterium sp. strains MCRO 6 and 31958 were found to be a closely related group, named the M. nonchromogenicum complex. Detected genetic variations associated with phenotypic characteristics may indicate further species separation of this complex. In conclusion, the results of gas-liquid chromatography fatty acid analysis, combined with those of a Tween 80 test, enable identification of the species of the M. terrae complex and their separation from other nonpigmented slowly growing mycobacteria.

Amidohydrolases↗

Rapid quantitative PCR determination of relative gene expression in tumor specimens using high-pressure liquid chromatography.

A reverse transcriptase polymerase chain reaction (rt-PCR) for quantification of gene expression has been optimized for analysis of folylpolyglutamate synthase (FPGS) and thymidylate synthase (TS), using beta-actin as an internal standard (house-keeping gene). Total RNA was isolated from tumor tissue, reversely transcribed to cDNA and PCR amplified with primers specific for TS, FPGS and beta-actin in separate vials. PCR products were separated and quantified by high-pressure liquid chromatography (HPLC) without addition of radioactive or fluorescent markers, which minimizes labor and occupational hazards. The day-to-day variation in the HPLC analysis was 2.7% and the within sample variations for rt-PCR/HPLC analysis of TS and FPGS were 18.5% for both assays. This method provides a tool for convenient gene expression analysis in clinical biopsies.

Chromatography, High Pressure Liquid↗

Lymphoid aggregates in endobronchial biopsies from young elite cross-country skiers.

Observation of bronchus-associated lymphoid tissue (BALT) in whole lung specimens from healthy nonsmoking adults has questioned the hypothesis that BALT is not constitutively present in healthy adult human lungs. In our study, we investigated endobronchial biopsies of the second- and third-generation carinae from 44 cross-country ski athletes and 12 healthy control subjects, all nonsmoking young adults. The skiers had a prevalence of respiratory allergy (18%), asthma-like symptoms (59%), beta2 agonist medication (25%), and methacholine bronchial hyperresponsiveness (79%). Biopsy sections were stained by immunohistochemical and hematoxylin-eosin-saffran methods. Lymphoid aggregates of more than 50 cells were identified in 28 (64%) skiers and three (25%) control subjects (p = 0.02). They were small in comparison to those found in rabbits and rats, contained T and B lymphocytes and macrophages, and were seen more frequently in skiers using beta2 agonists (p = 0.04) and with bronchial hyperresponsiveness to methacholine (p = 0.053). The frequency of these aggregates was not significantly different at the two carinal levels (p = 0.6). The aggregates were not associated with a history of respiratory allergy or asthma-like symptoms. These aggregates share some resemblance with what is usually defined as BALT. However, their exact nature and function await further clarification.

Adult↗

Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.

PURPOSE: The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated. PATIENTS AND METHODS: One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument. RESULTS: At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (>10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P < .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements. CONCLUSION: Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.

Adult↗

Serum levels of insulin-like growth factor binding proteins (IGFBP)-4 and -5 correlate with bone mineral density in growth hormone (GH)-deficient adults and increase with GH replacement therapy.

Adults with growth hormone deficiency (GHD) exhibit low bone mineral density (BMD) which improves by growth hormone (GH) replacement therapy. The insulin-like growth factor (IGF) system has an established role in mediating the effects of GH on bone and IGF binding proteins (IGFBP)-4 and IGFBP-5 have been shown to modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP-4 and IGFBP-5 and their relationship to serum levels of bone biochemical markers and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum levels of IGFBP-5 and IGFBP-4 were measured on samples from 20 patients (11 males) 22-57 years of age. All had IGF-I serum values below -2 standard deviation score. The first 6 months were placebo controlled and all received 3 years of active treatment with the mean dose 0.23 +/- 0.01 IU/kg/week divided into daily subcutaneous injections. Serum IGFBP-5 levels in GHD adults were low at baseline and positively related to total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The mean serum IGFBP-5 level increased by about 2-fold within 3 months after the initiation of GH therapy and was correlated with serum IGF-I (r = 0.719, 0.801, and 0.722 before and after 18 and 36 months, respectively,p < 0.001). A positive correlation between serum IGFBP-5 levels and lumbar spine BMD was found during GH treatment but not before. The percentage increase of serum IGFBP-5 after GH therapy showed a positive correlation with the percentage increase of total alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP-5, serum IGFBP-4 levels were positively related to body mass index (r = 0.607, p < 0.01). Baseline serum IGFBP-4 levels also correlated with total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.502, 0.590, 0.612, and 0.471, respectively,p < 0.05). The mean serum IGFBP-4 level was increased by 25% within 3 months after initiation of GH therapy and did not correlate with serum IGF-I levels. Although the above findings are consistent with the idea that GH-induced changes in serum IGFBP-5 and IGFBP-4 levels may in part mediate the anabolic effects of GH on bone tissue in adults with GHD, further studies are needed to establish the cause and effect relationship.

Adult↗

Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain.

We compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P <0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.

Aged↗