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Biomedical subjects

E Larsson

Publications and source records attributed to E Larsson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Increased immunoreactivity of transforming growth factor-beta in human kidney transplants.

Transforming growth factor-beta (TGF-beta) has been known to be involved in the pathogenesis of various kidney diseases. TGF-beta is also a potent immunosuppressor that has been shown to be induced after allogeneic transplantation. We have studied the distribution of immunoreactive TGF-beta proteins in different compartments of 21 allogeneic transplanted kidneys that had been rejected through acute (eight interstitial or six vascular) and chronic (seven vascular) processes. This distribution was compared with that in seven non-rejected transplanted and five non-transplanted kidneys with intact morphology. There were no obvious differences between the three groups of rejected grafts and the transplanted non-rejected group for the expression of TGF-beta s. A major difference was seen between transplanted kidneys, which exhibited clearly positive TGF-beta and LTBP1 (latent TGF-beta binding protein) immunoreactivities, and the non-transplanted kidneys. The non-transplanted kidneys showed only very weak or no immunoreactivity for these proteins. The morphologically intact non-rejected grafts showed a significantly increased immunoreactivity compared with the non-transplanted kidneys. When the transplanted kidneys were classified into two groups (i.e. with or without diabetes mellitus) and compared with regard to the expression of all TGF-beta s, no difference was found. Thus, transplantation was the most important predictor for expression of TGF-beta s and LTBP1, and the largest expression increase in the allografts occurred in the interstitium, followed by the glomeruli and blood vessels. Tubuli and lymphocyte aggregates stained only faintly. The results imply that TGF-beta is induced rapidly after kidney transplantation. This induction can suppress immunoreactivation, but concomitantly promotes changes such as arteriosclerosis and fibrosis associated with rejection.

Humans↗
PubMed1996

Dummy-sucking behaviour in 3-year old Norwegian and Swedish children.

Forty 3-year-old dummy-sucking children (22 Swedes and 18 Norwegians) together with one of their parents, were shown a specially prepared videotape for 15 minutes The child had free access to its dummy while watching the video. The dummy-sucking time and sucking reactions to the different film sequences were registered. The presence or absence of a posterior crossbite was recorded as well as the upper and lower intercanine arch widths. Dummy-suckers in these populations have earlier been reported to have different prevalences of posterior crossbite. The prevalence of posterior crossbite was especially high for Swedish girls. The results showed that Norwegian boys used their dummies significantly less, and the Swedish girls had significantly narrower upper dental arches than the other children. Dummy-sucking reactions to frightening, cheerful or boring parts of the video were not significantly different among the children. All the children showed compassion for the film characters, and all the children used the dummy when going to sleep. The study lends support to the hypothesis that dummy-sucking influences arch widths and increases the likelihood for development of a posterior crossbite.

Child Behavior↗
PubMed1996

An increase in sudden unexpected cardiac deaths among young Swedish orienteers during 1979-1992.

BACKGROUND: Sixteen cases of sudden unexpected cardiac death, 15 males and one female, are known to have occurred among young Swedish orienteers from 1979 to 1992, of which seven cases occurred between 1989 and 1992. This is considered to be indicative of an increased death rate. RESULTS: Histopathological evaluation showed myocarditis in a higher than expected proportion of cases. In one such case, which we studied before the sudden unexpected death occurred, the victim had suffered a Chlamydia pneumoniae infection verified by serology, and a nucleotide sequence was found in the heart and lung by means of the polymerase chain reaction (PCR) that hybridized with a probe specific for that organism. Male Swedish orienteers do not, however, seem to have an increased rate of exposure to this agent. No further sudden unexpected deaths among young orienteers have occurred over the past 3.5 years. At the beginning of that period, attempts were made to modify training habits and attitudes.

Adolescent↗
PubMed1996

Elevated levels of the endogenous retrovirus ERV3 in human sebaceous glands.

ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. Long terminal repeat-envelope (env) gene spliced mRNAs of 9 and 3.5 kb are widely expressed in human tissues and cells, but gag-pol mRNAs have not been found. Furthermore, the env gp70 gene contains an open reading frame throughout its length. The highest expression of ERV3 mRNA detected so far is in placenta and the lowest in choriocarcinoma cell lines. We have previously shown that the human monoblastic cell line U-937 and some normal and neoplastic tissues also express high levels of ERV3 env message by Northern blot analysis; however, this method does not distinguish between mRNA expression in different cell types in tissues. In this report, we have studied the ERV3 mRNA expression in specific cell types of human skin by in situ hybridization. We found high levels expression of ERV3 env mRNA in human sebaceous glands in normal skin and dermoid cysts of the ovary. In all glands, the expression is maximal in the periphery of the lobule and ceases towards the center in the region of characteristic holocrine secretion. Since it is known that the regulation of sebaceous glands is primarily via steroid hormones, particularly androgens, it is possible that expression of ERV3 is hormone dependent.

Adolescent↗
PubMed1996

Experimental partial ureteric obstruction in newborn rats. VIII. Contralateral kidney weight after release of the obstruction.

In unilateral kidney disease, it has been suggested that the ipsilateral state could be estimated by measuring contralateral kidney size; thus, a contralateral increase should reflect an ipsilateral impairment and vice versa. This could easily be performed using ultrasound. In our experiments with partial obstruction of one ureter (created in 1- to 3-day-old rats), a consistent and stable contralateral kidney hypertrophy occurred. However, after unobstruction, the hypertrophy persisted for at least a 6-week observation period, despite the disappearance of hydronephrosis and presence of a normal weight of the ipsilateral kidney. This would undeniably hamper the diagnostic utility of kidney size determination. To find out whether or not the hypertrophy ever disappears, we have performed studies after 6, 9 and 15 weeks. (1) The weight of the unobstructed kidney was found normal except after 15 weeks. The microstructure was normal except for some minor changes. (2) The contralateral kidney was significantly heavier than controls at all checkpoints (+10, +13 and +6%). No significant regression occurred over the observation period. (3) Furthermore, the weights of both kidneys were interrelated, but the slopes were positive; thus, the contralateral hypertrophy was not greater the lesser the ipsilateral kidney weight. The reasons for the persistence of contralateral hypertrophy are discussed. The present findings do not support the idea of documenting improvement by measuring contralateral kidney size. However, repeat studies in the same individual may prove to be more sensitive and are therefore recommended until further notice.

Age Factors↗
PubMed1996

Ischemia-induced transplant arteriosclerosis in the rat. Induction of peptide growth factor expression.

Peptide growth factors have been reported to contribute to the atherogenic process, and they are known to mediate signals for vascular remodeling. Using syngeneic and allogeneic rat aorta transplant models, we analyzed the impact of cold ischemia time up to 24 hours and reperfusion injury on development of transplant arteriosclerosis during the first 2 months after transplantation. The expression of the transforming growth factor-beta (TGF-beta) family as well as the platelet-derived growth factor (PDGF) and its receptors was studied by use of immunohistochemistry, followed by semiquantitative evaluation and multivariate analysis. In the syngeneically transplanted aortas, the expression of TGF-beta 1, PDGF, and the two PDGF receptors in the neointima increased significantly with the extent of cold ischemia time. Furthermore, there was a significant induction of the latent TGF-beta binding protein in the neointima as well as TGF-beta 2 in the media, both correlating with the observation time after transplantation. In the allogeneic grafts, all examined proteins were already induced strongly 2 weeks after transplantation, even at the shortest ischemic period studied (1 hour). However, no positive correlation between growth factor expression and cold ischemia or observation time could be found. Double immunohistochemistry revealed that macrophages express PDGF and its receptors as well as TGF-beta 1. Smooth muscle cells express both types of PDGF receptors, and a few T cells express TGF-beta 1 as well as PDGF receptors. In summary, TGF-beta and PDGF are induced by allogeneic as well as ischemic stimuli in transplanted aortas, suggesting a role in the pathogenesis of transplant arteriosclerosis and representing a potential target for therapeutic intervention.

Animals↗
PubMed1996

Integrin alpha 6B beta 1 is involved in kidney tubulogenesis in vitro.

Laminin-1 has previously been shown to be of major importance for the development of kidney tubules. Antibodies against fragments E8 and E3 of laminin-1 perturb kidney development in vitro. We here studied expression of integrins alpha 6 beta 1 and alpha 6 beta 4, two known laminin receptors, during kidney development. Integrin beta 1 subunit could be detected by immunofluorescence on all cell types of embryonic mouse kidney, but we could not detect integrin beta 4 subunit in embryonic kidney by immunofluorescence or by in situ hybridization. The presence of integrin alpha 6 subunit in all epithelia of embryonic kidney was demonstrated by immunofluorescence and by in situ hybridization. RT-PCR showed that alpha 6B is the major splice variant in embryonic kidney. During in vitro conversion of nephrogenic mesenchyme to epithelial tubules, a strong increase in the expression of the 6 kb mRNA for alpha 6 integrin subunit was seen by northern blotting at the onset of epithelial morphogenesis, on day two of culture. Immunoprecipitation of extracts from embryonic kidney with antibodies against alpha 6 subunit yielded bands corresponding to the expected size of beta 1 integrin subunit but not of beta 4 subunit. Monoclonal antibodies against either alpha 6 or beta 1 subunit but not against E-cadherin blocked kidney tubulogenesis in vitro. This suggests that integrin alpha 6B beta 1 is involved in kidney tubulogenesis in vitro. Another possibility is that the antibodies against integrin alpha 6 and beta 1 subunit cause abnormal signalling by the integrin.

Animals↗
PubMed1996

Expression levels of the insulin-like growth factor-II gene (IGF2) in the human liver: developmental relationships of the four promoters.

We have studied the insulin-like growth factor-II gene (IGF2) promoter usage in normal human liver from fetal to late adult life by quantifying the specific transcripts by RNase protection assays using exon-specific probes. While the fetal liver uses only three promoters (P2, P3, P4) for the transcription of IGF2, all four promoters can be used from the age of 2 months after birth. The levels of the individual promoter transcripts vary substantially during development and the P3 promoter, which is a highly active fetal promoter, was not used by all the investigated adult patients but was detected in 30% of the adult group as a whole. The P1 promoter, which has previously been considered as the only one responsible for IGF2 transcription in the postnatal/adult liver, displayed a trend of increasing relative and absolute activity throughout life, but in some adult cases it was found to be less active than the P4 promoter. The P4 promoter displayed an age-related trend of decreasing activity from a very high fetal level, but individual exceptions were apparent. The P2 promoter transcript, peaking at the age of 2 months, showed a relatively even absolute amount from 18 months onwards. Thus, while P2 and P3 were both found to reach their highest activity after birth, the P4 promoter displayed its highest transcription at the fetal stage. The total IGF2 transcription, primarily from P2, P3 and P4, was found to peak shortly after birth. After this age, the P3 promoter transcript declined most rapidly and a low or zero amount was detected in adulthood. From the age of 18 months to old adulthood the total IGF2 mRNA, derived primarily from P1, P2 and P4, displayed a relatively even amount (approximately one tenth) of that seen at the peak at 2 months. This data may be important in relation to translatability of the various IGF2 transcripts.

Adult↗
PubMed1996

Solid phase synthesis of two phosphorylated peptides related to casein using allyl phosphate protection, and their CD spectra.

Phosphoserine peptides related to the casein kinase II substrate consensus sequence ESLSSSEE have been synthesized using N-Boc-O-diallylphosphono-L-serine by solid-phase methods. The allyl groups were removed, while the peptide was still attached to the solid support, by Pd0 with azide as the nucleophile. Far UV circular dichroism measurements indicate that peptides phosphorylated at Ser 4 or Ser 5 have a somewhat higher content of ordered structure than the non-phosphorylated peptide.

Allyl Compounds↗
PubMed1996

Inducible and endothelial nitric oxide synthase expression during development of transplant arteriosclerosis in rat aortic grafts.

In the vascular system, distinct isoforms of nitric oxide synthase (NOS) generate nitric oxide (NO), which acts as a biological messenger. Its role in the development of transplant arteriosclerosis (TA) is still unclear. To investigate whether NO is involved in TA, we studied the expression of NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), by immunohistochemistry and in situ hybridization during the first two post-transplantation months and their relation with cold ischemia (1 to 24 hours) and reperfusion injury using an aortic transplantation model in the rat. We found an increased iNOS expression in the intima and adventitia and a decreased expression in the media, whereas eNOS expression was not significantly altered during the development of TA. Co-localization studies suggested that iNOS-positive cells were vascular smooth muscle cells, monocyte-derived macrophages, and endothelial cells. Prolonged ischemic storage time resulted in an increase in eNOS expression in the neointima. In situ hybridization showed iNOS mRNA expression by vascular cells in the neointima and media. NO produced by iNOS and eNOS may be involved, at least in part, in the pathogenesis of TA in aortic grafts. Additional studies are needed to confirm the modulatory mechanism of NO during the development of TA.

Amino Acid Sequence↗
PubMed1996

The expression of human endogenous retrovirus-3 in fetal cardiac tissue and antibodies in congenital heart block.

Endogenous retrovirus-3 (ERV-3) is an endogenous retrovirus encoding an open reading frame for an envelope protein expressed in placenta. In this study we also found high levels of expression in fetal heart, with peak expression occurring between 11 and 17 weeks of gestation. Antibodies to a peptide corresponding to a predicted epitope of ERV-3 were studied by ELISA in sera from 32 healthy women, 47 women during pregnancy, 19 post-partum, 34 with Sjogren's syndrome (SS), 28 with systemic lupus erythematosus (SLE) and 48 mothers of babies with congenital heart block (CHB). Elevated levels of antibodies to ERV-3 were found in normal pregnancy and in patients with SS or SLE. Compared with normal sera the highest levels occurred in mothers of CHB babies (P < 0.001). Antibodies from sera from three CHB mothers bound to recombinant transmembrane protein of ERV-3 on immunoblots, and to sections of fetal cardiac tissue and placenta. This study has shown evidence of autoimmunization to ERV-3 during pregnancy, with particularly high levels of antibodies in mothers of CHB babies. The expression of ERV-3 in fetal heart and the presence of antibodies in maternal sera suggest a possible role in the pathogenesis of CHB.

Adult↗
PubMed1995

Inhibition of transplant arteriosclerosis in rat aortic grafts by low molecular weight heparin derivatives.

The effects of low molecular weight heparin derivatives with a low anticoagulant activity on transplant arteriosclerosis (TA) in a rat aortic transplant model were investigated. TA was induced by ischemia in the syngeneic transplants and primarily by immunological mechanisms in the allogeneic transplants. Treatment with the heparin derivatives, OAM 71262 or LA-heparin, was administered in a dosage of 250 micrograms/kg/hr by mini-osmotic pumps during 8 weeks. No immunosuppressive regimen was given to the recipient rats in either model. All rats were killed 8 weeks after aortic grafting. The grafts were examined for intimal and medial changes using an image analysis system. Heparin derivatives had a beneficial effect on both the intimal thickening and the medial injury in the syngeneic transplants, but not in the allogeneic grafts. In the syngeneic LA-heparin treated grafts, the thickness of the intima was less than that in the syngeneic control grafts (P < 0.05). In the syngeneic transplants, a significant increase was observed in the media after treatment with OAM 71262 (P < 0.01) as well as those with LA-heparin (P < 0.001). In the syngeneic grafts treated with both heparin derivatives, a significant reduction in the antigen expression of alpha-actin-containing smooth muscle cells in the intima, transforming growth factor-beta 1 both in the media and adventitia, and platelet-derived growth factor-beta receptors in the adventitia was observed immunohistochemically. In summary, low molecular weight heparin derivatives with low anticoagulant activity partially inhibited ischemia-induced syngeneic TA, whereas no such effect could be demonstrated in nonimmunosuppressed recipients with allogeneic grafts.

Animals↗
PubMed1995

Fine-needle aspiration cytology of carcinosarcoma of the parotid gland: cytohistological and immunohistochemical findings.

Carcinosarcoma or true malignant mixed tumor of salivary glands is a very rare neoplasm which shows malignant features of the epithelial and mesenchymal components. We hereby present cytological, pathological, and immunohistochemical findings of one such case, first examined by fine-needle aspiration cytology. The aspirate was cell-rich and consisted of large cell clusters which at low magnification showed an arrangement reminiscent of a jigsaw puzzle. An amorphous substance was observed in the middle of some of these clusters. There were also numerous dissociated cells which often displayed marked atypia. Histology showed a tumor with malignant epithelial and mesenchymal components. The carcinomatous areas consisted of cells arranged in solid nests or glandular structures. The sarcomatous areas showed osteosarcoma, low-grade chondrosarcoma, and undifferentiated components. On immunohistochemistry, the tumor coexpressed epithelial and mesenchymal markers. Cytokeratin, keratin, and epithelial membrane antigen were mainly localized to the carcinomatous portion, whereas vimentin and neuron-specific enolase were restricted to the sarcomatous areas. S-100 protein was positive in both. Our findings support previous views that this tumor may be related to pleomorphic adenoma.

Aged↗
PubMed1995

Effects of angiopeptin on transplant arteriosclerosis in the rat.

The influence of the somatostatin analogue angiopeptin on transplant arteriosclerosis was investigated using two aortic transplantation rat models. One was characterized by ischemia/reperfusion-induced changes in syngeneic transplants while immunologically induced changes dominated in the other allogeneic model. Angiopeptin, 100 micrograms/kg per day, was administered continuously until the sacrifice of the rats after 8 weeks. No additional immunosuppression was used in either model. An image analysis system was used to quantify the intimal and medial thicknesses of the grafts. In the syngeneic grafts, the intimal thickness was less than 50% of that of control grafts (P < 0.05), but no difference was seen in the allogeneic model. The expression of selected cells, TGF-beta s, and PDGF and PDGF alpha-receptors was detected immunohistochemically and displayed a similar picture in control and angiopeptin-treated grafts in both models. We conclude that angiopeptin has no clear immunosuppressive properties but may counteract ischemia-induced transplant arteriosclerosis.

Animals↗
PubMed1995

Expression of CD11b and ICAM-1 in an in vivo model of transplant arteriosclerosis.

Adhesion molecules play a crucial role in transplant rejection in regulating the interaction of inflammatory cells with cells in the vascular wall. In an aortic transplantation model, we have previously analysed the early adhesion process (7.5 min to 24 h) and the impact of cold ischaemia time (1-24 h) upon transplant arteriosclerosis during the first 2 months after transplantation in the rat. The aim of this investigation was to study adhesion molecules in accelerated transplant arteriosclerosis in a rat model by analysing the immunohistochemical expression of CD11b and ICAM-1 up to 2 months and followed by a semiquantitative evaluation and multivariant analysis. Antigen expression of CD11b and ICAM-1 adhesion molecules was stronger in the aortic allografts than in the ischaemia-induced syngeneic aortic grafts in the whole vessel wall. Neither ICAM-1 nor CD11b antigen expression correlated significantly with time periods of ischaemia/reperfusion injury in allogeneic or syngeneic aortic transplants. CD11b and ICAM-1 are induced by allogeneic stimuli in transplanted aortas suggesting a role in the pathogenesis of transplant arteriosclerosis. Our findings have implications for understanding the role of cell adhesion activation in the vascular wall subject to chronic graft rejection.

Animals↗
PubMed1995

Non-muscle alpha-dystroglycan is involved in epithelial development.

The dystroglycan complex is a transmembrane linkage between the cytoskeleton and the basement membrane in muscle. One of the components of the complex, alpha-dystroglycan binds both laminin of muscle (laminin-2) and agrin of muscle basement membranes. Dystroglycan has been detected in nonmuscle tissues as well, but the physiological role in nonmuscle tissues has remained unknown. Here we show that dystroglycan during mouse development in nonmuscle tissues is expressed in epithelium. In situ hybridization revealed strong expression of dystroglycan mRNA in all studied epithelial sheets, but not in endothelium or mesenchyme. Conversion of mesenchyme to epithelium occurs during kidney development, and the embryonic kidney was used to study the role of alpha-dystroglycan for epithelial differentiation. During in vitro culture of the metanephric mesenchyme, the first morphological signs of epithelial differentiation can be seen on day two. Northern blots revealed a clear increase in dystroglycan mRNA on day two of in vitro development. A similar increase of expression on day two was previously shown for laminin alpha 1 chain. Immunofluorescence showed that dystroglycan is strictly located on the basal side of developing kidney epithelial cells. Monoclonal antibodies known to block binding of alpha-dystroglycan to laminin-1 perturbed development of epithelium in kidney organ culture, whereas control antibodies did not do so. We suggest that the dystroglycan complex acts as a receptor for basement membrane components during epithelial morphogenesis. It is likely that this involves binding of alpha-dystroglycan to E3 fragment of laminin-1.

Animals↗