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Biomedical subjects

E Larsson

Publications and source records attributed to E Larsson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Deposition of eosinophil cationic protein in vascular lesions in temporal arteritis.

The possible role of the eosinophil and its cytotoxic granule proteins in the vascular lesions seen in temporal arteritis was elucidated. Sixteen sections of biopsy specimens from arteria temporalis showing giant cell arteritis were stained for eosinophil cationic protein (ECP) by polyclonal antibodies and the immunoperoxidase method. Activated eosinophils were identified by monoclonal antibodies linked to alkaline phosphatase. Activated eosinophils and secreted ECP were seen in all layers of the inflamed vessels and were most evident in necrotic lesions and thrombi. Only a small number of granulocytes seen in the adventitia were immunoreactive for cathepsin G, and no extracellular deposits of this neutrophil granule protein were seen. A few immunoreactive eosinophils were found in the adventitia in two of five negative temporal artery biopsy specimens from patients with polymyalgia rheumatica. All eight coronary artery biopsy specimens with atherosclerotic lesions showed no activated eosinophils or secreted ECP. These findings indicate that eosinophils are involved in the vascular lesion in temporal arteritis and suggest that cytotoxic eosinophil granule proteins may contribute to the necrotic lesions and the development of thrombi.

Aged↗
PubMed1991

Reaction to a media campaign focusing on delay in acute myocardial infarction.

A media campaign conducted to reduce delay time and to increase the use of ambulance transport in acute myocardial infarction was performed in an urban area with about half a million inhabitants during 1 year. The main message was that chest pain lasting more than 15 minutes might indicate acute myocardial infarction; dial 90,000 immediately for ambulance transport to the hospital. The target population was the general public. After 6 and 12 months 400 and 610 randomly chosen persons, respectively, were contacted by telephone to evaluate the reaction of the general public to the campaign. Of these, 60% and 71%, respectively, had heard of the campaign, and all parts of the message were spontaneously remembered by 15% and 19%, respectively. The reaction to the campaign was generally positive. Among all patients admitted to the coronary care unit of one of the two city hospitals, 65% were aware of the campaign and 31% of them were of the opinion that they came to the hospital faster because of the campaign. In conclusion, a media campaign aimed at reducing patient delay time in acute myocardial infarction was shown to reach a majority of people in the community and patients with ischemic heart disease. The reaction was positive and about one fifth of interviewed people spontaneously remembered the total message.

Adult↗
PubMed1990

500-Kilodalton calcium sensor regulating cytoplasmic Ca2+ in cytotrophoblast cells of human placenta.

Two monoclonal IgG antibodies E11 and G11, which react with parathyroid and kidney tubule cells, are in the present communication demonstrated to immunostain the surface of cytotrophoblast cells in human placenta. The G11 but not the E11 antibody has earlier been found to interfere with the sensing and gating of extracellular calcium in parathyroid cells. Microfluorometric measurement of the cytoplasmic calcium (Ca2+i) concentration was performed on suspended placental cells loaded with fura-2. The E11-positive placental cells displayed biphasic and parathyroid-like increases in Ca2+i in response to extracellular Ca2+. This increase was blocked by the G11 antibody and absent in the E11-negative placental cells. A sandwich enzyme-linked immunosorbent assay was constructed in which the G11 and E11 antibodies were shown to react with the same molecule. This calcium sensor was isolated and found to consist of a single, glycosylated polypeptide of approximately 500 kDa.

Antibodies, Monoclonal↗
PubMed1990

Localization of platelet-derived endothelial cell growth factor in human placenta and purification of an alternatively processed form.

Platelet-derived endothelial cell growth factor (PD-ECGF) was purified to homogeneity from human term placenta, an organ characterized by extensive angiogenesis. N-terminal amino acid sequencing revealed that placental PD-ECGF was proteolytically processed at Thr-6, in contrast to PD-ECGF purified from human platelets, which is processed at Ala-11. The purified factor stimulated porcine aortic endothelial cells as well as two choriocarcinoma cell lines. Immunohistochemical staining revealed that PD-ECGF was present in the connective tissue cells of the placenta. The possibility that PD-ECGF is involved in the development of the placenta is discussed.

Amino Acid Sequence↗
PubMed1990

The localization of hyaluronan in normal and rejected human kidneys.

Hyaluronan (HYA) is a large glycosaminoglycan with a high capacity to immobilize water. Increased levels of HYA have previously been observed in plasma as well as in affected tissues in various inflammatory conditions. The morphological localization of HYA has, however, not been described in normal or rejected human kidneys. Using a recently developed method for localization of HYA in tissue sections by means of a biotin-labeled hyaluronan binding protein used as a probe, we have now investigated the distribution of HYA in normal and irreversibly rejected human kidneys. In the normal kidney HYA was essentially confined to the medulla. In the rejected kidneys increased amounts of HYA were observed primarily in the cortex and in sclerotic vessels. Incubating tissue sections with hyaluronidase abolished the staining for HYA, showing the specificity of the staining procedure. The increased amounts of HYA of the rejected kidney may play a role in local edema formation, and thereby alter graft function.

Connective Tissue↗
PubMed1990

Rapidly proliferative arteriopathy in cyclosporin-induced permanently surviving rat cardiac allografts simulating chronic vascular rejection.

In an attempt to create a model of chronic rejection in rat, cardiac allograft transplantation was performed of hearts from PVG rats to DA rats treated with cyclosporin, 20 mg/kg body weight per day for 14 days and thereafter no immunosuppressive therapy. Experiments were made in 83 rats fed on a normal diet and in 24 rats fed on a diet containing an additional 0.5% cholesterol. Rats on the normal diet showed moderate signs of acute rejection during the first 20-40 days and grafts were lost in acute rejection during this period of time. However, after 2-3 months no signs of acute rejection were present. On the contrary, excessive proliferative changes of the vascular intima and endocardium along with fibrosis and fibrin deposition appeared and was progressive until 6 months post-transplantation. These morphological changes are similar to those found in chronically rejected organs like heart and kidney. In rats fed on a cholesterol diet after cessation of cyclosporin, development of the vascular and endocardial proliferative changes appeared three to four times as fast and were on average fully developed within 4-6 weeks post cessation of cyclosporin treatment. The recipients' own hearts showed no signs of vascular or endocardial damage. It is thus concluded that two models of vascular and endocardial proliferative changes in cardiac allografts have been developed showing distinct similarities to chronic vascular rejections seen in the clinical transplantation and with apparent similarities to severe arteriosclerosis. The models could be useful in the investigation of pathogenesis and therapeutical means for preventing chronic vascular damage in transplanted organs and arteriosclerosis.

Animals↗
PubMed1990

Characteristics of mouse to rat xenograft heart transplantation.

A simple technique for grafting a mouse heart heterotopically to rat neck vessels in experimental xenotransplantation is described. In this series, graft survival was tested with the following modes of immunomodulation: ciclosporin (Cy), athymic and nude rats, splenectomy, total lymphoid irradiation (TLI), 15-deoxyspergualin in two different doses and various combinations of these. The mean graft survival time, with Cy or athymic and nude rats as recipients, was 3 days as also seen in animals without treatment. With either irradiation, splenectomy or 15-deoxyspergualin, 10 mg/kg daily, the graft survival time was prolonged to 7.8, 4.7 and 6.8 days, respectively. In combination, TLI + splenectomy gave a graft survival of 9.7 days and Cy + splenectomy 7.2 days. With 15-deoxyspergualin at 10 mg/kg/day plus splenectomy, done 1 week prior to transplantation, graft survival was extended to 17.8 days.

Animals↗
PubMed1989

A retroviral gp70-related protein is expressed at specific stages during mouse oocyte maturation and in preimplantation embryos.

Mouse monoclonal antibodies directed against different epitopes of the murine leukemia virus envelope protein gp70 were used to study the expression of retroviral related env proteins during mouse oocyte maturation, fertilization and blastocyst formation. A gp70-related antigen was detected with immunohistochemistry in growing oocytes but not in primordial and primary non-growing oocytes. Atretic oocytes were also negative. Both parthenogenetically activated and fertilized oocytes were positive. Two-cell stages showed a patchy distribution of the antigen. Later preimplantation stages were negative except for a markedly positive period during compaction of the morula and adhesion of the blastocyst.

Animals↗
PubMed1989

Platelet-derived growth factor receptors in the kidney--upregulated expression in inflammation.

Major features of a long-standing inflammation in the kidney are vascular proliferation, glomerulosclerosis, interstitial fibrosis and tubular atrophy, leading to a gradual deterioration of the renal function. In this study we have investigated the expression of B-type receptors for platelet-derived growth factor (PDGF) in frozen sections from normal and inflamed kidneys. Immunohistochemical techniques, employing two monoclonal antibodies specific for PDGF B-type receptors, were used. The specimens investigated were 15 kidneys removed by transplantectomy because of chronic rejection, 20 cases of glomerulonephritis with crescent formation, mesangial proliferation or non-proliferative glomerulonephritis, and six normal kidneys. In parallel we characterized cellular infiltrates and class II transplantation antigen expression in the inflamed kidneys. An enhanced PDGF receptor expression was found on intimal cells and on smooth muscle cells of the proliferating vessels, on glomerular cells in glomeruli with mesangial proliferation, and on fibroblast-like cells in the proximity of clusters of infiltrating macrophages and T-lymphocytes of the interstitial tissue. Induction of PDGF receptor expression may render cells responsive to stimulation by PDGF, released from PDGF-producing cells, such as activated macrophages and from platelets. Our data suggest that PDGF is involved in the proliferation of mesenchymal cells that is seen in rejected kidney transplants and glomerulonephritis.

Antibodies, Monoclonal↗
PubMed1989

Abolition of the effect of cyclosporine on rat cardiac allograft rejection by the new immunomodulator LS-2616 (Linomide).

The effect of the quinoline-3-carboxamide LS-2616 (Linomide), given alone or together with cyclosporine, was studied in the first set cardiac allograft transplantation model in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto rat recipients on day 0. The recipients were given LS-2616 orally on day -1 to rejection and/or CsA orally on days 0-9. In untreated animals rejection occurred on days 8-9, as judged by the absence of palpable pulsations. Treatment with CsA (5 or 10 mg/kg) resulted in prolongation of graft survival to days 17-21, i.e., the rejection occurred 8-10 days after cessation of treatment. LS-2616 in a dose of 160 mg/kg did not in itself have any impact on graft survival, but when given in doses of 40 or 160 mg/kg simultaneously with CsA (10 mg/kg), the effect of CsA was totally abolished. Animals treated with LS-2616 together with CsA had slightly lower trough blood levels than those treated with CsA alone. This interaction with CsA pharmacokinetics does not explain the results, as doubling of the CsA dose to 20 mg/kg, which well compensated for the difference in blood levels, was not sufficient to reverse the effect of LS-2616. To our knowledge this is the first compound known to abolish the effect of CsA. The mechanism is unknown, but is is possible that studies on the interaction between these two drugs will shed further light on the molecular basis of their modes of action.

Adjuvants, Immunologic↗
PubMed1989

Immunologic diagnosis of kidney rejection using FACS analysis of graft-infiltrating functional and activated T and NK cell subsets.

In human organ transplantation, the correct diagnosis of rejection may be difficult using clinical and/or histopathologic criteria, and immunologic assays should therefore be considered. We have applied monoclonal antibodies in 2-color flow cytometric (FACS) analysis to study phenotypic patterns of kidney-infiltrating activated and functional T and NK cell subsets in 132 posttransplantation biopsies. Viable intragraft lymphocytes and kidney tubular cells were obtained by the use of medium-sized ultra-sound guided needle biopsy. In univariate analyses, highly significant differences were observed between rejecting and stable grafts. During rejection, the proportions of HLA-DR+ kidney tubular cells, total lymphocytes, T suppressor/cytotoxic cells, and natural killer (NK)-like cells increased; the fractions of phenotypically activated, HLA-DR+ cells within the latter 2 cell populations were elevated. Further, during rejection phenotypic T suppressor inducer and T suppressor effector cells were virtually absent in kidney tissue but reappeared rapidly upon successful antirejection therapy. Multivariate analyses revealed that combinations of antibodies in FACS analysis defining functional and activated subsubsets of T and NK cells allow a precise and rapid immunologic diagnosis of kidney rejection.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Blastocyst implantation precedes induction of insulin-like growth factor II gene expression in human trophoblasts.

The cytotrophoblast cell population of the human embryonic conceptus proliferates rapidly during the first month following blastocyst implantation. Since the trophectoderm lineage is established in preimplantation morula/blastocysts, the scenario underlying initiation and maintenance of the rapid proliferative phenotype of cytotrophoblasts is a central issue. The insulin-like growth factor II (IGF-II) gene is highly expressed in proliferative cytotrophoblasts of first trimester placenta and performs as a placenta growth factor. To establish a temporal correlation between IGF-II expression and initiation of highly proliferative trophoblasts in human development, we employed in situ hybridization analysis of the expression of the IGF-II and human chorionic gonadotropin beta-subunit (beta-HCG) genes in human pre- and postimplantation development. The data show that the appearance of high steady-state levels of IGF-II transcripts in trophoblasts is a postimplantation event, whereas beta-HCG transcripts can already be detected in preimplantation development. This observation makes a role for endogenously produced IGF-II in the normal development of preimplantation embryos unlikely, but suggests that endogenously produced IGF-II participates in the formation and subsequent expansion of the rapid proliferative phenotype of the trophoblastic shell, following implantation.

Blastocyst↗