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Biomedical subjects

E Larsson

Publications and source records attributed to E Larsson.

At least 37 records · Page 2Linked to original sources

Diversity and abundance of resupinate thelephoroid fungi as ectomycorrhizal symbionts in Swedish boreal forests.

Resupinate thelephoroid fungi (hereafter called tomentelloid fungi) have a world-wide distribution and comprise approximately 70 basidiomycete species with inconspicuous, resupinate sporocarps. It is only recently that their ability to form ectomycorrhizas (EM) has been realized, so their distribution, abundance and significance as mycobionts in forest ecosystems is still largely unexplored. In order to provide baseline data for future ecological studies of tomentelloid fungi, we explored their presence and abundance in nine Swedish boreal forests in which the EM communities had been analysed. Phylogenetic analyses were used to compare the internal transcribed spacer of nuclear ribosomal DNA (ITS rDNA) sequence data obtained from mycobionts on single ectomycorrhizal tips with that obtained from sporocarps of identified tomentelloid fungi. Five species of Tomentella and one species of Pseudotomentella were identified as ectomycorrhizal fungi. The symbiotic nature of Tomentella bryophila, T. stuposa, T. badia and T. atramentaria is demonstrated for the first time. T. stuposa and Pseudotomentella tristis were the most commonly encountered tomentelloid fungi, with the other species, including T. sublilacina, only being recorded from single stands. Overall, tomentelloid fungi were found in five of the studies, colonizing between 1 and 8% of the mycorrhizal root tips. Two of the five sites supported several tomentelloid species. Tomentelloid fungi appear to be relatively common ectomycorrhizal symbionts with a wide distribution in Swedish coniferous forests. The results are in accordance with accumulating data that fungal species which lack conspicuous sporocarps may be of considerable importance in EM communities.

DNA, Ribosomal↗

Expression of lactoferrin in the kidney: implications for innate immunity and iron metabolism.

BACKGROUND: Sequestering of free iron by lactoferrin (LF) is important in the defense against bacteria. In a screening for LF expression in various organs, high levels of LF mRNA were detected in human kidney. This indicated that LF is produced by the kidney and that it may participate in innate immunity of this organ. METHODS AND RESULTS: Antibody staining and in situ hybridization of paraffin-embedded kidney sections showed that LF is expressed in cells lining the distal collecting ducts of the medulla. High levels of both protein and mRNA were detected in these cells. However, a clear difference in the distribution of mRNA and protein within the tissue was observed. LF mRNA was detected along a relatively large portion of the tubuli, whereas LF antigen was found mainly in the very distal regions of the same tubuli. This indicates that LF is released by large regions of the tubuli and possibly reabsorbed in the most distal parts. Using enzyme-linked immunosorbent assay, only very low LF levels were detected in urine. CONCLUSION: The present study shows that LF is produced by the kidney and that both LF mRNA and protein are distributed in a highly ordered fashion. This latter finding, together with the very low levels of LF detected in urine, indicates that LF may contribute to the immune defense in the kidney by reduction of available free iron in the urine. Other possibilities are that LF may play a role in the iron metabolism by recovering free iron from urine and making it available for metabolic use, and that LF may participate in the antioxidant defense systems protecting the kidney against nonmicrobial oxidative injury, that is, ischemia, reperfusion and inflammation.

Blotting, Northern↗

In-vivo strain measurements to evaluate the strengthening potential of exercises on the tibial bone.

Mechanical loading during physical activity produces strains within bones. It is thought that these forces provide the stimulus for the adaptation of bone. Tibial strains and rates of strain were measured in vivo in six subjects during running, stationary bicycling, leg presses and stepping and were compared with those of walking, an activity which has been found to have only a minimal effect on bone mass. Running had a statistically significant higher principal tension, compression and shear strain and strain rates than walking. Stationary bicycling had significantly lower tension and shear strains than walking. If bone strains and/or strain rates higher than walking are needed for tibial bone strengthening, then running is an effective strengthening exercise for tibial bone.

Adult↗

Difference in dental lateral arch length between 9-year-olds born in the 1960s and the 1980s.

This study was carried out in two cohorts of 9-year-olds, born in the 1960s and the 1980s in Sweden and Norway, to test the hypothesis that there has been a change in the lateral arch space conditions of the dentition during the last decades. In Norway, 61 children born in 1963 and 58 children born in 1983 were examined. In Sweden, 66 children born in 1961 and 67 children born in 1984 were examined. Children with a prolonged sucking habit, major dentofacial anomalies, history of orthodontic treatment, and ancestors of foreign origin were excluded to avoid influence of these factors on the development of the dentition. Linear measurements were performed between the mesial surface of the first permanent molars and the distal surface of the permanent lateral incisors in the maxillary and mandibular dental arches with use of a sliding caliper. The results showed that the children born in the 1980s had significantly larger lateral arch spaces in the maxillary dental arch (P <.05) and in the mandibular dental arch (P <.01) than did the children born in the 1960s. The amount of tissue loss in the second deciduous molars (the teeth having caries lesions or having been extracted) was greater in the 1960s groups than in the 1980s groups (P <.001). Thus, the hypothesis, that there has been a change in the lateral arch space conditions during the last decades, was confirmed. The most obvious reason is the decline in caries prevalence that has occurred in the same period; thus, there has been less loss of proximal tooth material of posterior teeth.

Analysis of Variance↗

Expression of envelope proteins of endogeneous C-type retrovirus on the surface of mouse and human oocytes at fertilization.

Retrovirus genomes express, among other products, the envelop (env) proteins SU (gp70) and TM (p15E). They coexist at the viral surface membrane and are able to promote immunosuppression and membrane fusion. In mouse oocytes, endogeneous retroviruses (ERV) genomes are expressed at fertilization, and antigen epitopes of the Moloney murine leukemia virus (MuLV) env protein gp70 are recognized in the cytoplasm of the oocytes before but not after fertilization. By using a panel of monoclonal antibodies (mAbs) raised against env components, we checked with laser scanning confocal microscopy (LSCM) whether gp70 and p15E were expressed also on the oocyte surface membrane (oolemma). Since we found that both mouse and human unfertilized oocytes expressed these ERV proteins on the oolemma and that the expression enfeebled significantly after fertilization, we assume that ERV genomes could play a role at the sperm-egg binding and fusion.

Animals↗

Carvedilol treatment of kidney graft recipients with chronic rejection.

Carvedilol is an antihypertensive drug with properties that may be potentially beneficial for kidney graft recipients. The purpose of the study was to investigate if progression of an established chronic rejection may be attenuated or reversed by carvedilol. An open, single-centre, phase II, pilot study, with a 2-yr follow-up, was performed in 25 kidney graft recipients with chronic rejection or accelerated transplant atherosclerosis. Seventeen patients had stable graft function assessed by serum creatinine levels. Eight patients withdrew from the study due to lack of efficacy (increase in serum creatinine 174-477 micromol/L (46-191%) from the initial levels). However. these patients had higher serum creatinine levels and proteinuria already at the start of the study. Both systolic and diastolic blood pressure, as well as heart rate, were stable in all study patients. Low density lipoprotein (LDL)/high density lipoprotein (HDL) cholesterol ratio decreased from 4.7 +/- 1.9 at 1 month to 3.5 +/- 1.2 at 18 months (p < 0.05), and MDA plasma levels decreased from 0.714 +/- 0.119 to 0.493 +/- 0.073 micromol/L after 3 months of carvedilol treatment (p < 0.05). No attenuation of progression of chronic graft rejection by carvedilol treatment was observed in the study. It is suggested that the process of chronic rejection could not be reversed by carvedilol because the patients included in the study already had severe morphological and functional changes of the graft. In conclusion, our study demonstrated that carvedilol provides a good control of blood pressure in renal transplanted patients. Carvedilol treatment had a beneficial effect on lipid pattern and reduced lipid oxidation, but there was no obvious effect on progression of chronic rejection.

Adult↗

GDNF family ligands and receptors are differentially regulated after brain insults in the rat.

Expression of mRNAs for glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and their receptors was studied in adult rat brain using in situ hybridization after 40 kindling-evoked, rapidly recurring seizures or 10 min of global forebrain ischaemia. Following seizures, GDNF and NTN mRNAs were elevated in dentate granule cells, and c-Ret mRNA in hilar neurons and non-pyramidal cells in CA1 and CA3 regions. GFRalpha-1 mRNA levels showed more widespread increases in the dentate granule cell layer and hilus, CA1 and CA3 pyramidal layers, basolateral amygdala and parietal cortex. The expression of GFRalpha-2 mRNA increased in the piriform cortex and decreased in the CA1 region and basolateral amygdala. Forebrain ischaemia induced elevated expression of GDNF mRNA in dentate granule cells, GFRalpha-1 mRNA in the dentate granule cell layer, hilus and CA3 pyramidal layer, and GFRalpha-2 mRNA in the parietal cortex. The gene expression patterns observed here suggest that GDNF and NTN may act as target-derived factors, but also in an autocrine or paracrine manner. GFRalpha-1 can be coexpressed with GFRalpha-2 and c-Ret mRNAs in the same hippocampal or thalamic neurons, but other neurons contain GFRalpha-1 alone or together with c-Ret mRNA. The gene expression changes for the ligands, and the receptor components are region-, cell- and insult-specific, and occur independently of each other, mainly within 24 h after seizures or ischaemia. This dynamic regulation of GDNF and NTN circuits primarily at the receptor level may be important for the effectiveness of neuroprotective responses but could also trigger plastic changes, e.g. those underlying the development of epileptic syndromes.

Animals↗

Injectable dextranomer-based implant: histopathology, volume changes and DNA-analysis.

OBJECTIVE: To study the tissue reaction in and around the implant, the changes in implant volume and the DNA profile of the invading cells when a new substance, dextranomers in sodium hyaluronan solution (DiHA), was injected into experimental animals. MATERIALS AND METHODS: Nine pigs were followed up from 2 weeks to 3.5 months and 34 rats were followed up from 3 weeks to 16 months after injection of DiHA into the bladder in pigs and into the subcutaneous tissue in rats. Histopathological analysis was performed in 16 pig and 63 rat implants. In 31 of the rat implants the DNA profile was analysed. Changes in implant volume over time were estimated in 51 rat implants during the period up to 12 months after implantation. RESULTS: Histologically, in the early phases the area within and around the implant was fairly rich in cells, predominantly fibroblasts, inflammatory cells and giant cells of the foreign body type. Later in the process an increase in extracellular matrix around the microspheres and ingrowth of blood vessels was seen. No tissue necrosis or significant eosinophilia was observed around the implants. DNA measurements by flow cytometry revealed no aneuploid cells. There was a decrease in implant volume by 23% over a period of 12 months. CONCLUSIONS: DiHA does not induce any major tissue changes in and around the implants. No DNA changes were observed during the study period of 16 months. DiHA seem to be a safe and suitable injectable substance with good tissue-augmenting properties.

Animals↗

Immunizing with mouse trophoblast to obtain mouse-human cross-reacting antibodies against normal and neoplastic human trophoblast.

Monoclonal antibodies raised against living, early invasive mouse trophoblast cells were screened on paraffin sections from first- and third-trimester placentas and from hydatidiform moles and choriocarcinoma. Several mouse-human cross-reacting antibodies were recognized, which implies that mouse trophoblast cells can be used as immunogen for producing antibodies against human trophoblast. Among the new antibodies obtained, some were selected for further study. That panel includes a trophoblast specific antibody with capacity to differ between invasive and noninvasive molar tissues, and two antibodies, which detect antigen epitopes in the normal, but not in the neoplastic trophoblast.

Animals↗

Evidence for neuroprotective effects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats.

The levels of brain-derived neurotrophic factor (BDNF) vary between different forebrain areas and show region-specific changes after cerebral ischemia. The present study explores the possibility that the levels of endogenous BDNF determine the susceptibility to ischemic neuronal death. To block BDNF activity the authors used the TrkB-Fc fusion protein, which was infused intraventricularly in rats during 1 week before and 1 week after 5 or 30 minutes of global forebrain ischemia. Ischemic damage was quantified in the striatum and hippocampal formation after 1 week of reperfusion using immunocytochemistry and stereological procedures. After the 30-minute insult, there was a significantly lower number of surviving CA4 pyramidal neurons, neuropeptide Y-immunoreactive dentate hilar neurons, and choline acetyltransferase- and TrkA-positive, cholinergic striatal interneurons in the TrkB-Fc-infused rats as compared to controls. In contrast, the TrkB-Fc treatment did not influence survival of CA1 or CA3 pyramidal neurons or striatal projection neurons. Also, after the mild ischemic insult (5 minutes), neuronal death in the CA1 region was similar in the TrkB-Fc-treated and control groups. These results indicate that endogenous BDNF can protect certain neuronal populations against ischemic damage. It is conceivable, though, that efficient neuroprotection after brain insults is dependent not only on this factor but on the concerted action of a large number of neurotrophic molecules.

Animals↗

Sudden unexpected cardiac deaths among young Swedish orienteers--morphological changes in hearts and other organs.

During the years 1979-1992 an accumulation of sudden unexpected cardiac deaths (SUD) occurred among young Swedish orienteers. A reevaluation of material saved from 16 autopsies was undertaken. Myocarditis was most frequent. It was found in different stages in the majority of cases, indicating subacute or chronic disease with ongoing reparative processes. There were severe morphological changes in all cases. All but one showed a picture of fibrosis and unspecific hypertrophy and/or degenerative changes in myocytes. The hearts were classified into three groups (A-C), based on the morphological picture of the retrieved heart tissue and the macroscopic description. Group A comprised five cases in which areas with active myocarditis combined with areas of healing or healed myocarditis widely distributed in the left ventricle were the only morphological changes found. Group B comprised four cases demonstrating foci of myocarditis in different stages in the left ventricle and changes resembling those found in arrhythmogenic right ventricular dysplasia (ARVD), including degenerative changes with fibrosis and fatty infiltration located in either ventricle. Group C comprised the remaining seven cases. In none of the cases were coronary artery or valvular anomalies present, nor significant coronary sclerosis or changes outside the heart that could cause SUD.

Adolescent↗

Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants. Influence of Fas-mediated apoptosis.

Based on successful induction of donor-specific unresponsiveness by alloantigenic stimulation in several animal models of acute rejection, we hypothesized that similar immune manipulations would also inhibit the evolution of chronic rejection and transplant vasculopathy. To induce immune tolerance, DA rats received a PVG heart allograft and were immunosuppressed with cyclosporine for 30 d. At day 100 the animals were challenged with a PVG aortic allograft after either 1 or 18 h of cold ischemia. 8 wk after the aortic transplantation, the grafts were investigated for morphological changes, infiltrating cells, apoptosis, and Fas-Fas ligand expression. Control allografts showed advanced transplant arteriosclerosis, whereas tolerance-induced aortic allografts displayed reduced neointimal formation, less medial atrophy, fewer apoptotic cells, and fewer Fas- and FasL-expressing cells. Prolonged ischemic storage time did not profoundly alter the morphological changes of the allografts. Fas expression was found in T cells, macrophages, vascular smooth muscle cells, and endothelial cells, whereas FasL was expressed mainly by T cells and macrophages. FasL mRNA expression was evident throughout the entire allograft wall. In conclusion, induction of allospecific tolerance can effectively prevent transplant arteriosclerosis. Cold ischemia damage does not abrogate the beneficial effect of tolerance, but creates a separate identity of mainly endothelial lesions. Furthermore, Fas-mediated apoptosis appears to be involved in the pathological lesions seen in chronic rejection.

Animals↗

Age-dependent modulation of heparan sulfate structure and function.

Heparan sulfate interacts with growth factors, matrix components, effectors and modulators of enzymatic catalysis as well as with microbial proteins via sulfated oligosaccharide domains. Although a number of such domains have been characterized, little is known about the regulation of their formation in vivo. Here we show that the structure of human aorta heparan sulfate is gradually modulated during aging in a manner that gives rise to markedly enhanced binding to isoforms of platelet-derived growth factor A and B chains containing polybasic cell retention sequences. By contrast, the binding to fibroblast growth factor 2 is affected to a much lesser extent. The enhanced binding of aorta heparan sulfate to platelet-derived growth factor is suggested to be due to an age-dependent increase of GlcN 6-O-sulfation, resulting in increased abundance of the trisulfated L-iduronic acid (2-OSO3)-GlcNSO3(6-OSO3) disaccharide unit. Such units have been shown to hallmark the platelet-derived growth factor A chain-binding site in heparan sulfate.

Adult↗

Characterisation of ANX Sepharose 4 Fast Flow media.

ANX Sepharose 4 Fast Flow (low sub) and ANX Sepharose 4 Fast Flow (high sub) are two new media developed at Amersham Pharmacia Biotech. They are weak anion exchangers with different amounts of tertiary amine groups attached via a spacer arm to Sepharose 4 Fast Flow. They have been characterised by the separation of some model proteins under different conditions and by determination of breakthrough capacities for proteins of different molecular masses. Functional performance after storage in different solutions at ambient temperature has been monitored. Carbon release after storage at different pH and temperatures has been measured using the total organic carbon technique. The selectivity results show that these new media are interesting complements to already existing Fast Flow anion exchangers. They are very stable and can be especially useful in applications involving the purification of high-molecular-mass proteins.

Animals↗