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Biomedical subjects

E Larsson

Publications and source records attributed to E Larsson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Accelerated atherosclerosis in the transplant recipient: role of hypertension.

An accelerated atherosclerosis may occur in the native arteries of a transplant recipient as well as in arteries of transplanted kidneys or hearts. The dominating cause of patient mortality are cardiovascular diseases, where ischaemic heart disease is predominant. The accelerated form of arteriosclerosis which takes place in transplanted kidneys and hearts, has a complex pathogenesis, which includes both immunological and nonimmunological factors. Hypertension is one such factor which has been claimed to be an independent risk factor of chronic renal transplant dysfunction, usually characterised by transplant arteriosclerosis. Whether a more intense treatment of hypertension or a more selective use of antihypertensive drugs would have a beneficial effect upon the progression rate of chronic rejection is still an open question.

Arteriosclerosis↗
PubMed1998

Beneficial role of human endogenous retroviruses: facts and hypotheses.

Human endogenous retroviruses (HERVs) have recently been suggested as mediators of normal biological processes such as cellular differentiation and regulation of gene expression. Moreover, a direct role for HERVs in pathogenesis and the development of disease is now better appreciated. Elucidation of the mechanisms regulating HERV biology should provide information about fundamental cellular activities and the pathogenesis of multifactorial diseases such as cancer and autoimmune disease. The importance of understanding the roles of HERVs is underscored by the recently obtained insight that activation of endogenous retroviruses poses potential risks following xenotransplantation and in gene therapy using retroviral vectors. Furthermore, HERV-encoded superantigens have recently been implicated as causes of autoimmune disease. This review discusses the established and possible biological roles of HERVs, and proposes hypotheses concerning their involvement as mediators of fundamental cellular responses. We propose that the evolutionary persistence of endogenous retroviruses in the genomes of eukaryotic cells reflects their indispensability in important normal functions in specialized cellular environments. HERVs can also be potentially hazardous through their involvement in the development of disease. In addition, the creation of new retroviruses can occur through recombination, between different HERVs and between HERVs and exogenous retroviruses.

Cell Differentiation↗
PubMed1998

Demethylation of ERV3, an endogenous retrovirus regulating the Krüppel-related zinc finger gene H-plk, in several human cell lines arrested during early monocyte development.

The activation of H-plk (Human-proviral linked Krüppel), a human Krüppel-related zinc finger gene in organs such as placenta, adrenal cortex, and testis, is probably due to insertion of an endogenous retrovirus, ERV3, upstream of the gene. Several differently spliced transcripts originate from this locus, e.g., a transcript encoding the retroviral envelope protein and a few differentially spliced transcripts encoding both the env and the zinc finger protein. During a screening for zinc finger proteins expressed during monocyte differentiation, two H-plk encoding cDNA clones were isolated from the human monoblast cell line U-937. Northern blot analysis of a panel of human hematopoietic cell lines showed high levels of constitutive expression of this zinc finger transcript in two monocytic cell lines (U-937 and THP-1) but not in any of the other cell lines or tissues tested. In addition, the H-plk transcript was upregulated by the phorbolester PMA in U-937 and in an additional monocytic cell line, MonoMac 6. Genomic Southern blot analysis of a panel of hematopoietic cell lines, after cleavage with the methylation sensitive enzyme Xho I, led to the detection of tissue specific demethylation in all three monocytic cell lines. The Xho I site was mapped to a position just downstream of the regulatory region of the endogenous retrovirus. By analysis of the U-937 cell line with two additional restriction enzymes, Nar I and Sma I, the demethylation was shown to affect at least three independent CpG dinucleotides in this region of the gene. In summary, the present data provide evidence for specific demethylation of this genomic region, in cells of monocytic origin, resulting in enhanced transcription of the genetic regions derived from both the env region of the retrovirus and the Krüppel-related zinc finger gene.

Cell Cycle Proteins↗
PubMed1998

Experimental partial ureteric obstruction in newborn rats. X. Renal function and morphology after unobstruction.

Partial obstruction of the left ureter was created in newborn rats. Unobstruction was performed after 2 or 7 days. The investigations were carried out at 9 weeks of age--under slight hydropenia to institute an element of stress. Unobstruction was successful. On the unobstructed side, there were nevertheless impairments as compared to controls: urine osmolality (-32%), free water reabsorption (-44%), potassium excretion (-34%), renal blood flow (-36%) and glomerular filtration (-36%). On the intact contralateral side, tubular changes were the only signs of an attempt to compensate. Thus, consistent renal damage remained despite a very early unobstruction. Furthermore, the changes were similar to those we observed during long-term permanent obstruction. The injury seems to be established within a very short time and imitates the probable development seen in the affected fetus: after start of production, the urine is confronted by the preformed obstruction at the pyeloureteral junction. A high-pressure-prone system is built up and is not reversed, until the pelvis has become dilated and thus capable to buffer urinary flow peaks. Thereafter, no further deterioration occurs except in specific conditions. If clinically applicable, these observations implicate that there is no advantage with surgical intervention, even when performed early in fetal life, and there is no need for swift intervention, as the damage does not progress after its establishment. Most of the cases probably do not require surgery at all, unless pain, obvious functional impairment or urinary tract infection supervene.

Animals↗
PubMed1998

Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues.

We investigated the mRNA expression of the human endogenous retrovirus ERV3 (HERV-R) in several normal and corresponding tumor tissues. The env gene of ERV3 is expressed as mRNA in several tissues. Comparison of ERV3 mRNA expression by Northern analyses, revealed a non-systematic variation. Expression was shown to be particularly high in the adrenal gland and some cases of lung cancer. This tissue-tropism should be seen in relation to the high expression previously found in syncytiotrophoblasts in placenta and sebaceous glands of the skin, suggesting profound influences by steroid hormonal regulation.

Blotting, Northern↗
PubMed1998

Orthodontic aspects on feeding of young children. 1. A comparison between Swedish and Norwegian-Sami children.

1-18 months old Norwegian-Sami girls from Karasjok/Katokeino were compared with girls from Falköping in Sweden. All Karasjok/Kautokeino children were breastfed, usually until 1 year of age. Only a few developed a dummy- or fingersucking habit. They started eating porridge at 4-5 months of age. At about half a year of age they were fed dark, hard chewing bread to gnaw at. Cut and pulped adult food was introduced during the end of the first year of life. In almost all cases the children had dried reindeer meat to gnaw at. They were mostly fed by spoon and drank from a cup. The Falköping girls, on the other hand, were not so often breastfed and for a shorter time. They usually became dummysuckers. The Falköping girls got almost all their nutrition during the first one or two years by sucking or eating food with little chewing resistance. The differences in sucking and chewing behavior could influence on the transversal development of the jaws.

Bottle Feeding↗
PubMed1997

Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma.

Previous investigations have supported or indicated a stimulatory role of the insulin-like growth factor II gene (IGF2) in hepatocarcinogenesis. We have studied the transcript levels, promoter usage, and imprinting status of the ICF2 gene and its relationship to H19 in human hepatocellular carcinomas (HCCs) and liver tumor cell lines. The activity of the IGF2 promoter P1 was lost in about 70% of the cases (18 of 25). This is the most prominent abnormality regarding the IGF2 regulation in this study. Total IGF2 as well as promoter P3 transcription were up-regulated in a small group of the tumors. Twenty genetically informative cases were obtained from 26 cases, thus excluding the probability of loss of heterozygosity of the IGF2 gene. Among these, nine showed abnormal monoallelic expression of IGF2. One HCC and one HCC cell line proved loss of functional imprinting of IGF2. H19 and IGF2 were regulated in parallel, and expression levels were variable. Taken together, the disruption of the IGF2 promoter regulation, particularly the loss of P1 activity, is a common feature of human HCCs. The loss of P1 activity explains the frequent loss of biallelic IGF2 expression and may potentially be used as a diagnostic or monitoring marker for human HCC.

Alleles↗
PubMed1997

Antimicrobial effect of a chlorhexidine-thymol varnish (Cervitec) in orthodontic patients. A prospective, randomized clinical trial.

The aim of the present investigation was to study the effect of combined application of a fluoride varnish (Fluor Protector) and an antimicrobial varnish (Cervitec) on the oral microflora, caries and gingival condition in patients receiving treatment with fixed orthodontic appliances. A total of 198 individuals (12 to 15 years old), scheduled for fixed orthodontic treatment, were randomized into 2 groups. Prior to bonding, the Cervitec and the control group received one application with Cervitec or a placebo every week for 3 weeks, respectively. In the Cervitec group. Fluor Protector was applied at bonding and Cervitec at the next visit, 6 weeks later. Each varnish was then applied every 12 weeks for 24 weeks. In the control group, the fluoride varnish was applied only at bonding and every 12 weeks. The Visible Plaque Index (VPI), the Gingival Bleeding Index (GBI), the White Spot Lesion Index (WSL) and the level of mutans streptococci in plaque and saliva were recorded 3 weeks prior to bonding and after 24 weeks. At bonding and after 12 weeks, only VPI, GPI, plaque and salivary mutans streptococcus counts were recorded. During the 3-week prebonding period, the mean VPI, GBI and mutans streptococci in plaque decreased in both groups. At bonding, the mean level of mutans streptococci in plaque was significantly lower in the Cervitec group than in the control group. The mean level of mutans streptococci was significantly lower after 12 weeks' bonding in the Cervitec group than in the control group. No effects on the other parameters were found during the 24 weeks.

Adolescent↗
PubMed1997

Ischemia causes rapidly progressive nephropathy in the diabetic rat.

We examined the influence of renal ischemia in rats with diabetes mellitus (DM). Male Wistar rats were rendered diabetic by streptozotocin treatment. Two weeks later, 30 minutes of complete ischemia was induced in the left kidney of DM and non-DM animals. Both groups were evaluated functionally and morphologically four or eight weeks post-ischemia. In non-DM animals renal function and morphology showed almost complete recovery. In the DM animals, however, this comparatively short period of ischemia caused a substantial loss of renal function. Four weeks post-ischemia inulin clearance in the DM kidneys rendered ischemic was only 20% of that in the corresponding non-DM kidneys, and after eight weeks the DM kidneys were completely anuric. Extensive inflammation and tubulointerstitial fibrosis were evident in DM kidneys four weeks after ischemia and seemed to increase over time. After eight weeks, tubular atrophy was found in the ischemic DM kidneys, resulting in a substantial loss of kidney mass. We conclude that in diabetic rats renal ischemia causes rapidly progressive kidney damage that in several respects resembles diabetic nephropathy in humans. Since advanced renal lesions similar to those seen in human diabetic nephropathy never develop in the rat solely as a result of DM, the present study may provide an experimental model for further studies on renal failure in diabetes mellitus.

Animals↗
PubMed1997

Amelioration of collagen II-induced arthritis in rats by the type IV phosphodiesterase inhibitor Rolipram.

The effect of Rolipram, a selective inhibitor of the cyclic AMP specific phosphodiesterase (PDE IV) was evaluated in the rat collagen type II (RCII)-induced arthritis model in the DA rat. Rolipram was given either shortly before expected onset of disease (days 10-14) or shortly after the onset of clinically evident arthritis (days 15-19 after immunization). Administration at days 10-14 delayed the onset of arthritis for approximately 5 days, but the severity of arthritis was thereafter comparable to that seen in a non-treated control group. Rolipram treatment of animals with manifest arthritis inhibited further arthritis development and also tended to diminish its severity at a phase of disease where non-treated control animals showed a rapidly progressing disease development. Serum levels of antibodies to RCII were in all experiments similar between Rolipram-treated and control animals. An in situ hybridization method for determining cytokine mRNA synthesis in regional lymph nodes, after administration of Rolipram (at days 2-7), demonstrated a strong inhibitory effect on tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNA expression, whereas no effects were seen on IL-2 mRNA synthesis after in vivo challenge with native RCII emulsified in Freund's incomplete adjuvant. The results thus demonstrate strong preventive as well as therapeutic effects of Rolipram in a model for arthritis that is very similar to human rheumatoid arthritis with respect to cytokine regulation, and suggest that Rolipram has its major effects in the effector stage of the arthritogenic immune response.

Animals↗
PubMed1997

Increased serum levels of cartilage oligomeric matrix protein and bone sialoprotein in rats with collagen arthritis.

The aim of this study was to investigate whether serum levels of cartilage and bone macromolecules can be used to monitor tissue destruction in experimental arthritis in rats. Serum levels of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) were measured by novel immunoassays in the chronic and destructive arthritis induced in DA rats after immunization with autologous rat native collagen type II in Freund's incomplete adjuvant. Increased serum levels of COMP and BSP were seen on day 21 after immunization, and even higher levels were observed on day 28 at termination of the experiment, paralleling increases in the clinical joint score and histopathological signs of cartilage and bone erosions. Serum analyses of these markers may be a useful non-invasive way of monitoring tissue involvement in experimental arthritis and possibly the effects of therapeutic interventions aimed at retarding tissue destruction.

Animals↗
PubMed1997

Immunohistochemical detection of the melanocortin 1 receptor in human testis, ovary and placenta using specific monoclonal antibody.

We describe the immunohistochemical detection of the melanocortin 1 receptor (MC1R) protein in human gonadal tissues using a specific monoclonal antibody. The MC1R was found to be present in Leydig's cells in testis, in lutein cells in the corpus luteum and in the nucleus of the trophoblastic cells of the placenta. Though it has been speculated earlier that MC1R is present in gonadal tissues, this is the first report demonstrating the presence of MC1R protein in these cells.

Antibodies, Monoclonal↗
PubMed1997

Experimental partial ureteric obstruction in newborn rats. IX. Renal morphology and function after 1 year of obstruction.

Unfortunately, the nonoperative treatment of hydronephrosis, in wide use today, cannot be evaluated until after many decades. Long-term animal experiments offer a peekhole into the future. Partial obstruction of the left ureter was created in newborn rats. Its effects were studied after 1 year. In order to stress the system, the investigations were performed under hydropenic conditions. On the obstructed side, the renal pelvis was considerably enlarged; however, the microstructure of the kidney was only slightly affected. Renal blood flow was decreased (-17%) due to a rise in vascular resistance. Filtration was less affected (-9%), probably as a result of increased filtration fraction. Water excretion, including that of free water, was increased (+59%) due to a decreased reabsorption. Potassium excretion was decreased (-59%) either due to increased reabsorption and/or decreased secretion. Sodium excretion followed a similar pattern (-24%) although without statistical significance. The contralateral side compensated for the ipsilateral decreases in blood flow and filtration. Ipsilateral tubular functions were not compensated for, which indicates an acute situation that is reaffirmed by the finding of a normal hematocrit and serum osmolality/electrolytes. The changes in tubular functions were thus considered to be due to the hydropenic stress, but inescapably an incompetent concentration capacity exists. The changes in the obstructed kidney were thus moderate, some of which were fully compensated for, but, most important, all were nonprogressive. The study supports the nonoperative treatment of these patients, provided that the follow-up guarantees catch-up of the exceptional cases that deteriorate, especially during infancy.

Animals↗
PubMed1997

Tissue and differentiation specific expression on the endogenous retrovirus ERV3 (HERV-R) in normal human tissues and during induced monocytic differentiation in the U-937 cell line.

ERV3 (HERV-R) is a complete, single copy human endogenous retrovirus located on the long arm of chromosome 7. The open reading frame in its envelope gene has been conserved during evolution but the gag and pol genes contain in-frame termination codons. To find a suitable experimental model system for analysis of the functions of the ERV3 genome, an extensive screening study of different normal and neoplastic human tissues was performed. Most tissues express low levels of the ERV3 env mRNA although high expression levels are observed in placenta, sebaceous glands, adrenals, testis, bronchial, epithelium and the monocytic cell line U-937. In U-937 cells the ERV3 env expression varied in a manner related to the differentiation status of the cells; being highest in the terminally differentiated non proliferating cells. U-937 cells can be induced to differentiate from the monoblastic to the mature monocyte/macrophage stage upon stimulation by several substances such as phorbolesters (TPA), Vitamin D3, Retinoic Acid (RA) and combinations of some cytokines. We conclude that the ERV3 locus is expressed in a tissue and differentiation specific way and that the U-937 cell line is a suitable model system to further analyze the proposed functions of ERVs such as immunomodulation, cell fusion and protection against exogenous retroviral infections.

Cell Differentiation↗
PubMed1997

Interaction between infection and exercise with special reference to myocarditis and the increased frequency of sudden deaths among young Swedish orienteers 1979-92.

Infection and fever evoke a cytokine-mediated host response resulting in negative nitrogen balance, muscle protein degradation, which includes the skeletal muscles as well as the heart muscle, and deteriorated muscle function. Physical training has an opposite effect. Moderate physical training also stimulates the immune system, whereas exhaustive and longlasting exercise is followed by a temporary immunodeficiency and an increased susceptibility to respiratory tract infections. Exercise in the acute phase of an infection may promote complications including myocarditis. Exercise in myocarditis is associated with increased organism-associated as well as immune mediated tissue damage. An increased sudden death (SUD) rate among young Swedish male orienteers existed in 1979-92, suggesting (a) common underlying cause(s). Myocarditis was one of the most conspicuous histopathological features. Chlamydia pneumoniae, or a similar organism cross reacting in diagnostic tests, is hypothesized to be a factor causing this increased death rate. High frequency of intense exercise sessions, which was a common practice among the deceased, may have been immunosuppressive, promoting the development of severe myocardial disease.

Adolescent↗
PubMed1996

Smooth muscle cell migration into intima and adventitia during development of transplant vasculopathy.

Smooth muscle cell (SMC) migration from the medial layer into the intima is a characteristic feature of transplant vasculopathy and is thought to be regulated by locally produced cytokines. We studied the expression of smooth muscle alpha-actin, PDGF B-ligand and, PDGF alpha- and beta-receptors in rat aortic allografts with transplant vasculopathy using immunohistochemistry. At two weeks, an intense expression of PDGF B-ligand and, PDGF alpha- and beta-receptors was found in the neointima and adventitia. Medial SMC expression decreased with time in parallel with accumulation of smooth muscle alpha-actin in the neointima and adventitia. PDGF expression persisted in the adventitia. Prolonged ischemic storage time resulted in an increase in the number of alpha-actin-positive SMCs in the intima of syngeneic grafts. These data indicate that SMCs migrate into both the intima and adventitia. This migration may be induced, at least in part, by PDGF produced by graft invading monocyte-derived macrophages.

Actins↗
PubMed1996

Expression of the endogenous retrovirus ERV3 (HERV-R) during induced monocytic differentiation in the U-937 cell line.

ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. LTR-env-gene-spliced mRNA of 9 and 3.5 Kb is widely expressed in human tissues and cells, but gag-pol mRNA has not been found. Further, the env gp70 gene contains an open reading frame throughout its length and its expression has recently been detected as a full-length protein. The highest expression of ERV3 detected so far is in placenta and the lowest in cytotrophoblasts and choriocarcinoma cell lines. In this report we have studied ERV3 mRNA and protein expression in the human monoblastic cell line U-937 during differentiation into monocytes/macrophages. Differentiation of U-937 cells was induced by 1,25a-dihydroxyvitamin D3 (vitD3), retinoic acid (RA), gamma interferon (IFN-gamma) and phorbol-myristate-acetate (PMA-TPA). The expression of ERV3 env mRNA was found to be differentiation-associated, with high expression detected in the late stages of monocytic development. Using TPA, the expression of ERV3 env was detected as 9- and 3.5-kb transcripts by Northern blotting, as mRNA by in situ hybridization and as a cytoplasmic 65-kDa protein by immunofluorescence and Western blots. Low levels of basal expression were found, with up-regulation of both message and protein at 24 to 48 hr after addition of TPA. Induction with vitD3, IFN-gamma and RA produced higher levels of mRNA at earlier time points. It is concluded that the U-937 cell line represents an excellent model system for further studies to study the relationship between ERV3 expression and cellular differentiation.

Calcitriol↗