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Biomedical subjects

L Eklund

Publications and source records attributed to L Eklund.

15 recordsLinked to original sources
PubMed2001

Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice.

Type XV collagen occurs widely in the basement membrane zones of tissues, but its function is unknown. To understand the biological role of this protein, a null mutation in the Col15a1 gene was introduced into the germ line of mice. Despite the complete lack of type XV collagen, the mutant mice developed and reproduced normally, and they were indistinguishable from their wild-type littermates. However, Col15a1-deficient mice showed progressive histological changes characteristic for muscular diseases after 3 months of age, and they were more vulnerable than controls to exercise-induced muscle injury. Despite the antiangiogenic role of type XV collagen-derived endostatin, the development of the vasculature appeared normal in the null mice. Nevertheless, ultrastructural analyses revealed collapsed capillaries and endothelial cell degeneration in the heart and skeletal muscle. Furthermore, perfused hearts showed a diminished inotropic response, and exercise resulted in cardiac injury, changes that mimic early or mild heart disease. Thus, type XV collagen appears to function as a structural component needed to stabilize skeletal muscle cells and microvessels.

Animals↗
PubMed2001

Lack of cytosolic and transmembrane domains of type XIII collagen results in progressive myopathy.

Type XIII collagen is a type II transmembrane protein found at many sites of cell adhesion in tissues. Homologous recombination was used to generate a transgenic mouse line (Col13a1(N/N)) that expresses N-terminally altered type XIII collagen molecules lacking the short cytosolic and transmembrane domains but retaining the large collagenous ectodomain. The mutant molecules were correctly transported to focal adhesions in cultured fibroblasts derived from the Col13a1(N/N) mice, but the cells showed decreased adhesion when plated on type IV collagen. These mice were viable and fertile, and in immunofluorescence stainings the mutant protein was located in adhesive tissue structures in the same manner as normal alpha1(XIII) chains. In immunoelectron microscopy of wild-type mice type XIII collagen was detected at the plasma membrane of skeletal muscle cells whereas in the mutant mice the protein was located in the adjacent extracellular matrix. Affected skeletal muscles showed abnormal myofibers with a fuzzy plasma membrane-basement membrane interphase along the muscle fiber and at the myotendinous junctions, disorganized myofilaments, and streaming of z-disks. The findings were progressive and the phenotype was aggravated by exercise. Thus type XIII collagen seems to participate in the linkage between muscle fiber and basement membrane, a function impaired by lack of the cytosolic and transmembrane domains.

Amino Acid Sequence↗
PubMed2000

Structure of the mouse type XV collagen gene, Col15a1, comparison with the human COL15A1 gene and functional analysis of the promoters of both genes.

Isolation and characterization of the mouse gene for the alpha1 chain of type XV collagen (Col15a1) revealed it to be approximately 110 kb in length and contain 40 exons. Analysis of the proximal 5'-flanking region showed properties characteristic of a housekeeping gene promoter, such as an absence of TATA and CAAT boxes, the presence of several transcriptional start sites and a high G+C content. The general organization of the mouse Col15a1 gene was found to be highly similar to that of its human homologue, but the genomic area encoding the end of the N-terminal non-collagenous domain showed marked divergence from the human form. Furthermore, two exons coding for the N-terminal collagenous domain of the human alpha1(XV) chain are lacking in the mouse Col15a1 gene. Due to the lack of two exons and a codon divergence in one exon, the mouse alpha1(XV) chain contains seven collagenous domains, whereas the human equivalent contains nine. Comparison of 5'-flanking sequences indicated four domains that were conserved between the mouse and human genes. Functional analysis of the mouse promoter identified cis-acting elements for both positive and negative regulation of Col15a1 gene expression in mouse NIH/3T3 cells.

3T3 Cells↗
PubMed2000

The salt output of a nebulizer--a comparison between two nebulizer types.

The output of a nebulizer is generally defined as its weight loss during 1 min of nebulization. This mass output includes the weight loss due to evaporation of the solution required to moisten the dry air that is fed through the nebulizer. In order to compare results obtained from studies using different nebulizers we introduce the salt output as the amount of the solution that actually leaves the liquid phase as droplets and not by evaporation. The performance characteristics of a standard jet nebulizer (MA2) and a Sidestream jet neublizer were compared. Mass output was determined at different methacholine concentrations. Salt output was assessed by analysing the remaining salt in the nebulizers after 1 min of nebulization. Overall system performance in terms of forced expiratory volume in 1 sec (FEV1) reduction after 1 min of exposure to individually selected concentrations of methacholine were studied in 15 healthy, non-smoking subjects. Both nebulizer types showed a moderate linear increase of mass output with methacholine concentration. The efficiency coefficient, the quotient between salt output and mass output, was found to be 0.93 and 0.75 for the MA2 and Sidestream nebulizer respectively. These findings were explained by differences in airflow through, and temperature inside, the nebulizers. The salt output of the nebulizers proved to be better correlated to the FEV1-reduction following methacholine inhalation than did the mass output. The relative amount of the salt output that adhered to the acrylic walls of the Sidestream nebulizer drying tower was found to be 9%. We conclude that it is more appropriate to use salt output than mass output as a nebulizer performance descriptor. The study also shows the importance of determining nebulizer system performance under conditions as similar to true provocations as possible.

Equipment Design↗
PubMed1997

Cloning of mouse type XV collagen sequences and mapping of the corresponding gene to 4B1-3. Comparison of mouse and human alpha 1 (XV) collagen sequences indicates divergence in the number of small collagenous domains.

We report on full-length mouse type XV collagen cDNAs that encode a 1367-residue alpha 1(XV) chain. The amino acid sequences of the mouse and previously characterized human alpha 1(XV) chains exhibit an overall identity of 72%. The highest homology between these chains and to the structurally related type XVIII collagen is observed in their C-terminal noncollagenous domains. Although the mouse and human alpha 1(XV) chains are highly homologous and similar in their overall domain structure, the mouse chain contains only seven collagenous domains, whereas the human chain contains nine. Northern analysis of several mouse tissues indicated strong hybridization in the case of heart and skeletal muscle RNAs and moderate signals with kidney, lung, and testis RNAs. Analysis of type XV collagen mRNA levels at different stages of mouse embryonic development indicated a marked increase in the level between 11 and 15 days of development, which coincides with pronounced development of the muscles, heart, and vascular system in the mouse embryo. The mouse gene for type XV collagen was mapped by fluorescence in situ hybridization to chromosome 4, band B1-3. This result indicates that the mouse type XV collagen gene and its human counterpart are located in the chromosomal segments with conserved syntenies.

Amino Acid Sequence↗
PubMed1996

Laterally applied Ethrel causes local increases in radial growth and indole-3-acetic acid concentration in Abies balsamea shoots.

The terminal (1-year-old) shoot of quiescent, two-year-old balsam fir (Abies balsamea (L.) Mill.) seedlings was ringed with lanolin containing 0, 1 or 10 mg g(-1) Ethrel, an ethylene-generating compound, and cultured for 6 weeks under environmental conditions favorable for growth. Bud break and the elongation of the current-year terminal shoot were monitored, and the subjacent previous-year terminal shoot that had been treated with Ethrel was harvested to measure stem radial growth by microscopy, shoot ethylene evolution by gas chromatography, and cambial region indole-3-acetic acid (IAA) concentration by combined gas chromatography-mass spectrometry. Compared with the lanolin controls, Ethrel at 1 and 10 mg g(-1) did not affect bud break or longitudinal growth, but stimulated tracheid production and bark increment up to about 2-fold at the application site, though not above or below it. In addition, the 1 and 10 mg g(-1) Ethrel treatments increased the cambial region IAA concentration about 3-fold and the evolution of ethylene at least 40-fold at the application site, compared with unwounded portions of both treated and control shoots. The 10 mg g(-1) Ethrel treatment also stimulated ethylene evolution about 10-fold, both above and below the application site. However, this stimulation was not associated with an elevation in cambial region IAA concentration. Similarly, the lanolin control treatment increased ethylene evolution at the application site about 10-fold, without affecting the cambial region IAA concentration. Our results suggest that the localized stimulation of radial growth in woody shoots ringed with Ethrel is mediated by an increase in IAA concentration, which in turn is induced by a threshold, abnormally high concentration of Ethrel-derived ethylene.

Journal Article↗
PubMed1995

Interaction between indole-3-acetic acid and ethylene in the control of tracheid production in detached shoots of Abies balsamea.

We investigated the interaction between indole-3-acetic acid (IAA) and ethylene in the regulation of the seasonal periodicity of tracheid production in 1-year-old balsam fir (Abies balsamea (L.) Mill.) cuttings collected at different times during the dormant period. The cuttings were left with their buds intact or were debudded and treated either apically with IAA or 2-chloroethylphosphonic acid (Ethrel) in lanolin, laterally with IAA or Ethrel in lanolin, or basally with Ethrel, Co(2+) or Ag(+) in deionized water. The treated cuttings were then cultured for up to 5 weeks under controlled environment conditions favorable for cambial growth. No change in ethylene evolution was detected during the rest-quiescence transition, when IAA-induced tracheid production increased. The induction of cambial reactivation by IAA was associated with a rise in ethylene evolution, but there was no consistent relationship among IAA concentration, tracheid number and ethylene emission. Neither Ethrel, Co(2+) nor Ag(+) affected tracheid production when applied basally, except for 10 and 100 micro M Ethrel and 100 micro M Co(2+), which were inhibitory. In contrast, ethylene evolution was promoted by Ethrel and inhibited by Co(2+), whereas Ag(+) had no effect. Similarly, applying Ethrel apically or laterally increased ethylene evolution, but did not promote tracheid production except in the treatment in which 1 mg Ethrel g(-1) lanolin was applied laterally to cuttings treated apically with 0.1 mg IAA g(-1) lanolin, and in the treatment in which 10 mg Ethrel g(-1) lanolin was applied laterally to budded cuttings. We conclude that (1) ethylene evolution is not specifically associated with IAA-induced tracheid production, (2) ethylene does not mimic the promoting effect of IAA on tracheid production, and (3) ethylene can promote tracheid production, but only when its application results in a localized unphysiologically high concentration in the cambial region, which, in turn, induces an accumulation of IAA.

Journal Article↗
PubMed1994

Effects of hyperglycemia on in vivo adipose tissue metabolism studied with microdialysis in IDDM subjects.

The effect of hyperglycemia on in vivo adipose tissue metabolism was studied with microdialysis in seven lean patients with insulin-dependent diabetes mellitus (IDDM) receiving a constant infusion of insulin (36 pmol.m-2.min-1). Glucose was infused in a randomized fashion to maintain either a lower glucose level (6.6 +/- 0.3 mM, mean +/- SE) or hyperglycemia (11.8 +/- 0.8 mM) for 3 h. For insulin concentrations of 84 +/- 12 and 96 +/- 12 pM, hyperglycemia (11.8 +/- 0.8 mM) did not alter the plasma glycerol or lactate levels significantly but resulted in a significant (P < 0.0001) increase in plasma free fatty acid levels (0.49 +/- 0.13 vs. 0.32 +/- 0.08 mM). Plasma catecholamine levels were unchanged during hyperglycemia. Interstitial glycerol concentrations, measured in abdominal subcutaneous adipose tissue as an index of lipolysis, were not significantly influenced by hyperglycemia when compared with concentrations at the lower glucose level (92 +/- 30 vs. 106 +/- 18 microM). Moreover, hyperglycemia did not change abdominal adipose interstitial lactate levels significantly (1,248 +/- 174 vs. 1,351 +/- 159 microM during euglycemia). It may be concluded that hyperglycemia has no independent antilipolytic effect in IDDM subjects. Furthermore, in these patients, hyperglycemia gives no further lactate production in the subcutaneous adipose tissue in the presence of low physiological insulin levels.

Adipose Tissue↗
PubMed1987

Vibration in car repair work.

The main objective of the study was to find efficient hand tools which caused only minor vibration loading. Vibration measurements were carried out under standardised working conditions. The time during which car body repairers in seven companies were exposed to vibration was determined. Chisel hammers, impact wrenches, sanders and saws were the types of tools which generated the highest vibration accelerations. The average daily exposure at the different garages ranged from 22 to 70 min. The risk of vibration injury is currently rated as high. The difference between the highest and lowest levels of vibration was considerable in most tool categories. Therefore the choice of tool has a major impact on the magnitude of vibration exposure. The importance of choosing the right tools and working methods is discussed and a counselling service on vibration is proposed.

Journal Article↗
PubMed1983

Discomfort and pain from loaded passive joint structures.

Sensations of strain and pain from healthy elbow and knee joints kept in an extreme position were reported on Borg's category-ratio scale (4) by 12 male volunteers in an experimental situation. The purpose of the study was to find out whether passive joint structures give sensations of discomfort and pain when moderately loaded for a certain time in an extreme position. Sensations of discomfort and pain were reported every 15th second. The mean values of ratings followed a straight line of increasing values during the first four minutes. Great variations were found between individuals. The elbow joint was six times more sensitive to the loading dose expressed as the product of the moment of force and time than was the knee joint. After the load was removed the provoked sensation slowly decreased. Sometimes the initial after-load rating was higher than the last rating with the load. The results imply that static work postures should also be analyzed with respect to joint position.

Adult↗