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Biomedical subjects

E Larsson

Publications and source records attributed to E Larsson.

At least 109 records · Page 6Linked to original sources

Increased hyaluronan in acutely rejecting human kidney grafts.

The glycosaminoglycan hyaluronan is not only involved in cellular differentiation and migration but may also play a role in several inflammatory diseases. We have previously demonstrated an increased local production of hyaluronan in chronically rejected kidneys and the correspondingly affected renal vessels. In this report, we demonstrate the presence of hyaluronan in acutely rejecting kidneys. A total of 77 biopsies classified as either acute rejection or nonrejecting were analyzed using a biotin-labeled hyaluronan-binding protein in conjunction with an avidin-biotin peroxidase detection system and graded using an arbitrary scale from 0 to 3. Those biopsies classified as nonrejecting did not contain any peritubular hyaluronan in the cortex, with hyaluronan being localized only in the medulla. In contrast, those biopsies exhibiting acute rejection had an increase of hyaluronan both in the cortex and in the medulla. This increase was significantly different (P = 0.0001) and correlated with edema and interstitial inflammation. The detection of the local hyaluronan production may be a useful marker to measure acute rejection episodes.

Acute Disease↗

The influence of pretransplant lipoprotein abnormalities on the early results of renal transplantation.

Lipoprotein patterns were investigated before and after renal transplantation in a prospective study including 151 patients. Kidney graft losses during the first 6 months were associated with higher total cholesterol (P = 0.03), LDL cholesterol (P = 0.003) and LDL triglyceride levels (P = 0.01) before transplantation. Patients with serum cholesterol > or = 6.9 mmol l-1 before transplantation had more acute rejections (1.7 vs. 0.9), a worse graft function and more vascular intimal hyperplasia and glomerular mesangial changes in transplant biopsies at 6 months. Patients with serum creatinine levels exceeding 160 mumol l-1 at 6 months had more severe lipid disorders already before transplantation. Serum creatinine at 6 months was influenced by the number of acute rejection episodes (P = 0.0001) and the age of the donor (P = 0.009) while the number of acute rejections was found to be related to pretransplant total cholesterol levels (P = 0.0086) and the age of the recipient (P = 0.025). In conclusion, pretransplant lipoprotein disturbances have an impact on the early outcome of renal transplantation. Since there is a progression of hyperlipidaemia following transplantation, this may have an influence also on the cardiovascular morbidity and late graft dysfunction.

Adolescent↗

Pathogenesis and treatment perspectives of chronic graft rejection (CVR).

Chronic rejection is a major threat towards the long-term function and survival of transplanted hearts and kidneys. It is characterized by a proliferative remodelling of the graft vessels along with structural changes of the parenchyma and gradual deterioration of graft function. The pathogenesis is complex and multifactorial. Since grafts with chronic rejection are also subjected to a more or less intense invasion of immunoreactive cells, an important primary objective is to optimize the immunosuppressive treatment. There is no established means of prevention or treatment of chronic rejection. Pharmacological agents interfering with prostaglandin metabolism have been tried most frequently and preliminary results are also available from the use of polyunsaturated fatty acids of the omega-3 series and of heparin derivatives. Based on experimental studies the somatostatin analogue angiopeptin seems very promising today. There will certainly be an increased interest in the use of lipid-reducing agents in the future as well as antioxidant agents acting against the effects of reactive oxygen radicals and oxidative modification of LDL fractions. A strong novel candidate is carvedilol, exerting both antihypertensive, antioxidant and antiproliferative properties.

Animals↗

Rearing of Swedish, Norwegian, and Norwegian Sami children.

A total of 362 3-yr-old Swedish, Norwegian, and Norwegian Sami (Lapp) children were examined, and their parents were asked about their children's present and previous sucking habits and how long they had been breast-fed and bottle-fed. They were also asked what the children's age was when porridge or puréed food or food with a soft chewing resistance was introduced, and when more ordinary foods such as well-diced meat and potatoes were introduced. The study revealed that breast-feeding has increased greatly both in prevalence and in duration in Sweden during the last decades. Despite this, Swedish children were breast-fed for a significantly shorter time than Norwegian children. The longest breast-feeding times were noted for Sami children. Swedish children were bottle-fed two to three times longer than Norwegian children. Sucking habits were correlated to breast-feeding only for Sami children.

Bottle Feeding↗

Synthesis and function of an O-phosphorylated peptide corresponding to the cell adhesion sequence of bone sialoprotein (BSP).

Bone sialoprotein contains a cell-binding RGD sequence followed by a threonine residue. Since the protein is extensively phosphorylated, this threonine may also be modified. To study whether such a phosphorylation may alter cell-binding properties, the hexapeptide Pro-Arg-Gly-Asp-Thr(O-phosphoryl)-Tyr has been synthesized by the Fmoc technique using benzyl protective groups for Tyr and phosphate, tert-butyl ester for Asp and Pmc for Arg. Removal of Fmoc groups was effected by treatment with 20% morpholine in DMF. The phospho-peptide inhibited binding of R1 cells to BSP-coated surfaces 10 times less efficiently compared with the non-phosphorylated peptide, as did, surprisingly, also the fibronectin-derived peptide Gly-Arg-Gly-Asp-Ser-Pro.

Amino Acid Sequence↗

Hyaluronic acid accumulation; the mechanism behind graft rejection edema.

Hyaluronic acid (HA) is an important stabilizing consistuent of the loose connective tissue and regulates water homeostasis. Thus, excessive accumulation of HA in interstitial tissue immobilizes water and may thereby contribute to interstitial tissue edema. By the use of biotin labelled core protein and an avidin-enzyme system, we visualized HA in grafted rat kidney, rat heart, rat small bowel and also in human kidneys. By an extraction procedure the tissue amounts of HA were measured in the experimental grafts. Simple techniques for measuring water content were also employed. The extracellular amounts of HA increased between 100% and 350% in rejecting tissues as compared to syngeneic controls. The relative water content also increased and correlated well with the HA accumulation. The clinical value of these experimental observations was confirmed in human transplantation where rejecting kidney allografts demonstrated a highly significant increase in HA staining in the interstitium as compared to non-rejecting biopsy specimens. We therefore concluded that transplantation edema--a key features of graft rejection--is regulated by the accumulation of HA not only under experimental conditions but also in the clinical setting.

Animals↗

Rejection associated with early appearance of donor-reactive antibodies after kidney transplantation treated with plasmapheresis and administration of 15-deoxyspergualin. A report of two cases.

In two kidney transplant patients, one of whom had panel-reactive antibodies (PRA) before transplantation, a pretransplant negative donor-recipient crossmatch became positive within the 1st week after transplantation. Simultaneously, good graft function deteriorated to a state of anuria. One patient graft biopsy showed a vascular rejection, whilst the other patient biopsy was unrevealing. Both patients were treated with plasmapheresis and a new immunosuppressive drug, 15-deoxyspergualin (DSG). Plasmapheresis was performed for 6 and 9 days, respectively, and DSG was given for 5 days in a dosage of 6 mg/kg body weight per day. One of the patients received methylprednisolone i.v. in addition. During treatment the cross-match became negative and has since remained that way. In both patients the graft function was restored. No adverse effects were seen from the treatment, except for a slight leukocytopenia and thrombocytopenia.

Adult↗

Human oocytes express murine retroviral equivalents.

Unfertilized human oocytes expressed a gp70-related epitope as observed when staining section immunocytochemically with a panel of monoclonal antibodies against gp70 of murine leukemia virus. Some oocytes also expressed virus-like particles at the cell membrane. Follicular fluids, corresponding to these oocytes, contained p30- and gp70-related antigens, reverse transcriptase, and an increased titer of interferon. The three- to four-cell human cleavage stages did not contain the gp70-related epitope. It is concluded that human oocytes, but not early cleavage stages, express products that suggest the presence of an active endogenous retrovirus genome.

Antigens, Viral↗

Distribution of napin and cruciferin in developing rape seed embryos.

The distribution of napin and cruciferin, the two major storage proteins in rape seed, Brassica napus, has been visualized during seed development by antibody staining of paraffin-embedded and sectioned seeds. The results indicate that the synthesis of both proteins during embryogenesis is strictly regulated with respect to time and tissue. Although the synthesis of napin started a few days earlier than that of cruciferin, both proteins displayed similar patterns in their spatial distributions. They were first detected in the axis, then in the outer cotyledon, and finally in the cells of the inner cotyledon. Both proteins are also present in the endosperm, although in lower amounts. In germinating seeds, napin and cruciferin were rapidly degraded. Within 2 days the amounts had decreased dramatically, and after 4 days hardly any cells contained napin or cruciferin. Biochemical analyses of dissected embryos showed that, for napin as well as for cruciferin, similar levels of polypeptides were found in the axis and cotyledons.

Journal Article↗

Dummy- and finger-sucking habits in young Swedish and Norwegian children.

The prevalence of dummy- and finger-sucking habits in 3-yr-old children was registered in four different areas of Sweden and Norway. In Norway 245 children were examined and in Sweden 171 children. The Swedish children were more prone to develop a dummy-sucking habit as well as to prolong it. About 10-19% of the children in the different groups become finger-suckers. Very few of these finger-suckers had stopped sucking at 3 yr of age. The highest rate of non-suckers was found among the children from Karasjok/Kautokeino in northern Norway, who were mainly of Lappish origin.

Age Factors↗

Levels of cyclosporin-A (CsA) in saliva in children after oral administration of the drug in mixture or in capsule form.

The cyclosporin-A (CsA) level in human unstimulated whole saliva was studied in 5 children, aged 9-16 yr, receiving the immunosuppressive drug CsA following renal allograft transplantation. The time-concentration relationship of CsA in saliva was determined in the children who were taking the drug orally in mixture form (n = 3) as well as in capsule form (n = 3). For the mixture, the median maximal level of CsA in whole saliva was 2867 ng/ml compared to 5.4 ng/ml for the capsule. The oral mucosal exposure of CsA during the dosage interval was approximately 130 times higher when the drug was administered in mixture form than in capsule form. The study demonstrates that gingival tissue is exposed to a considerable concentration of CsA throughout the dosage interval in patients taking CsA in mixture form. Therefore the vehicle in which the drug is administered should be considered in the pathogenesis of CsA-induced gingival overgrowth.

Administration, Oral↗

Long-term partial ureteral obstruction and its effects on kidney function.

Previously it has been shown that partial ureteral obstruction present in young rats for 12 weeks results in small morphological changes in the kidney as well as slightly decreased kidney function. In the present study the aim was to examine whether rats obstructed for one year had more advanced changes in morphology and kidney function. The first group of animals examined after three weeks of obstruction showed only modest changes in kidney function with a reduced potassium concentration in the urine but no reduction in the glomerular filtration rate. After one year there was a reduction in urine flow as well as in the excretion of both potassium and sodium. Urine osmolality was also reduced. Glomerular filtration rate measured in this group of animals was reduced in the obstructed kidney by about 60% compared to the contralateral one. There were only small changes in the morphology with no loss in parenchymal weight or compensatory hypertrophy, but there was a significant deformation of the papilla and an increase in inflammatory cells in the parenchyma. In conclusion hydronephrosis during a shorter period is not harmful to kidney function but if sustained for an extended time period kidney function will deteriorate.

Animals↗

Safety aspects and diagnostic findings of serial renal allograft biopsies, obtained by an automatic technique with a midsize needle.

Percutaneous biopsy is an important diagnostic procedure in evaluating the renal allograft with compromised function. Graft losses and haemorrhagic complication are major risks. To minimize these problems we used a midsize TruCut needle, controlled by an automatic firing device (Biopty-Cut), fixed to an ultrasound guidance system. Core biopsies of 1.2 x 20 mm were obtained from 1,421 kidney grafts. On 5 occasions a haemorrhagic complication that required prolonged hospitalization or intervention occurred. No grafts were lost as a consequence of the biopsy procedure. Typical histological morphological parameters found during allograft rejection has earlier been established. Using a protocol with 27 histological parameters this study confirms that recognized criteria for rejection can be relied upon even with this smaller needle. The results showed that the degree of oedema and lymphocytic infiltration of the interstitium and in the arterial wall discriminated best between rejecting grafts and non-rejection grafts.

Adult↗