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Biomedical subjects

E Nordström

Publications and source records attributed to E Nordström.

At least 19 recordsLinked to original sources

ALOX5AP expression, but not gene haplotypes, is associated with obesity and insulin resistance.

OBJECTIVE: Inflammation in adipose tissue may link obesity to insulin resistance and atherosclerosis. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) gene is involved in the pathogenesis of atherosclerotic cardiovascular disease (CVD). We investigated ALOX5AP expression in adipose tissue, and association of gene polymorphisms with obesity and insulin resistance. DESIGN: For gene expression analysis in adipose tissue, we studied 12 lean and 36 obese women, eight lean and 13 obese men, and nine women before and 2-4 years after gastric banding surgery. For genetic analysis, we studied 231 nonobese and 350 obese men. RESULTS: The ALOX5AP protein, 5-lipoxygenase activating protein (FLAP), as well as 5-lipoxygenase (5LO) itself, were detected in adipocytes. The mRNA expression of ALOX5AP in subcutaneous adipose tissue was increased in obesity and normalized following weight reduction. High adipose tissue mRNA expression of ALOX5AP is associated with insulin resistance as measured by homeostasis model assessment (HOMA(IR)). ALOX5AP haplotypes that associate with CVD are not associated with obesity or insulin resistance. CONCLUSION: ALOX5AP is present in adipose tissue, where its expression is associated with body weight and HOMA(IR), and may provide a link between adipose tissue, inflammation and insulin resistance. Investigated ALOX5AP haplotypes are not major primary risk factors for obesity and insulin resistance.

5-Lipoxygenase-Activating Proteins↗

Recurrent varicose veins: incidence, risk factors and groin anatomy.

OBJECTIVES: To investigate the recurrence rate after sapheno-femoral junction (SFJ) ligation and great saphenous vein (GSV) stripping for varicose veins (VV), to evaluate risk factors for recurrence and to classify the anatomy of the recurrence in the groin. Design. Clinical follow-up study. METHODS: Eighty-nine consecutive patients with 100 operated legs were re-examined clinically and with duplex after 6-10 years. Fourteen groins were re-explored, 13 after varicography. The anatomy in the groin was classified according to the Edinburgh system. The original medical records were examined to check for risk factors which could lead to a recurrence. RESULTS: Fifty-seven legs had incompetent veins in the groin according to duplex. In 54 of them, it was possible to define whether the incompetent veins emanated from the former SFJ. Varicography and operative findings correlated well to duplex. The main difficulty was to distinguish neovascularization from residual branches. No significant risk factor for recurrence was found in the medical records. CONCLUSIONS: Recurrence of VV after SFJ ligation is common irrespective of perioperative difficulties or the surgeon's experience. The anatomy of recurrence in the groin is difficult to classify according to the Edinburgh system mainly because neovascularization is difficult to verify.

Adult↗

Human polyspecific immunoglobulin for therapeutic use induces p21/WAF-1 and Bcl-2, which may be responsible for G1 arrest and long-term survival.

High-dose intravenous immunoglobulin (IVIg) is used as therapy in an increasing number of immune mediated disorders including infections and autoimmune conditions. IVIg exerts profound effects both in vivo as well as in vitro on humoral and cell-mediated immunity. In this study we investigated whether IVIg could alter the pattern of apoptosis and apoptosis related proteins including Bcl-2, Bax, p53, CD95, and p21/WAF-1, a protein well known to arrest cells in G1 phase of the cell cycle and finally proliferation marker Ki-67 on peripheral blood mononuclear cells (PBMC). The cells were cultured either unstimulated or with mitogen in the presence or absence of different IVIg preparations. A dual effect by IVIg was found. The incidence of apoptosis was elevated in activated Ki-67 and CD95 positive PBMC, whereas it was lower in small, nonactivated cells. The cells that survived were associated with a striking increase in the expression of p21/WAF-1 suggesting G1 arrest. A concomitant upregulation of Bcl-2 was also obtained by IVIg exposition resulting in long-term survival. We suggest that these abilities of IVIg to alter cell cycle progression and apoptosis could explain some of the beneficial effects obtained in vivo with IVIg therapy.

Adult↗

Immune complex-induced chronic and intense IL-4 independent IgG1-rheumatoid factor production in NZB mice.

Immune complexes from the synovial fluid of rheumatoid arthritis (RA) patients, or artificial rheumatoid factors (RF)-like (antibody--antibody) immune complexes, induce a remarkably intense, sustained and selective immunoglobulin (Ig)G1 response under certain experimental conditions in mice. Because the IgG1 antibody response is extraordinarily strong, the role of interleukin (IL)-4, important for IgG1 synthesis, was investigated. Both C57BL/6 and NZB IL-4-deficient mice produced IgG1--RF antibodies after injection with RF-like immune complexes, although the antibody levels were slightly delayed compared to wild type mice. This shows that IL-4 is not obligatory in RF-like immune complex induced IgG1--RF production. A discrepancy in the decline of serum IgG1--RF was noted between NZB and C57Bl/6 mice. Serum IgG1-RF declined 43 days postinjection (p.i.), in C57BL/6 mice whereas high serum levels of IgG1--RF were maintained more than 100 days in the NZB mice, indicating different regulatory mechanisms in these mice. To study if the affinity for mouse IgG increased with time in NZB mice and thus become more directed against self, the cross-reactivity of the IgG1--RF antibodies with IgG from other species was investigated early and late after injection. It was, however, found that the cross-reactivity with IgG of human, goat and rabbit origin did not change between the two time points.

Animals↗

Longevity of immune complexes and abnormal germinal centre formation in NZB mice.

Rheumatoid factor (RF)-like (antibody-antibody) immune complexes induce a selective and intensive immunoglobulin (Ig)G1-RF response after a single injection in mice. However, the longevity of the response differs between mouse strains: serum IgG1-RF antibody titres decline 40 days after injection in C57Bl/6 mice whereas levels are maintained for more than 100 days in NZB mice. In order to elucidate whether this difference was owing to a lower ability of NZB mice to clear the injected immune complexes, sections of kidney, spleen, liver and mesenteric lymph nodes were harvested at different time points after injection with RF-like immune complexes. Immunohistochemical staining revealed that NZB mice have a delayed clearance of the injected immune complexes, because the immune complexes are retained for more than 40 days in their spleens and 100 days in their kidneys, compared to only 14 days in C57Bl/6 mice. Germinal centres were also present for a longer period in the spleens of the NZB mice, accompanying the presence of the immune complexes, and were abnormally large compared to C57Bl/6 mice. The clearance of immune complexes from the spleen coincided with the decline in serum levels of IgG1-RF, indicating that prolonged retention of immune complexes is responsible for the sustained IgG1-RF response.

Animals↗

Generation of a new protein purification matrix by loading ceramic hydroxyapatite with metal ions--demonstration with poly-histidine tagged green fluorescent protein.

The gene encoding the green fluorescent protein (GFP) from the jellyfish Aequorea victoria, was inserted under transcriptional control of the polyhedrin promoter of the Autographa californica nuclear polyhedrosis virus and expressed in the Spodoptera frugiperda insect cell line Sf9 during viral infection. The baculovirus transfervector pBlueBacHisB was used for constructing the recombinant baculovirus, so that the green fluorescent protein could be tagged with a poly-histidine tail. This fusion protein was utilized as a marker for evaluating the properties of metal ion loaded ceramic hydroxyapatite as a matrix in protein purification. Ceramic hydroxyapatite loaded with Zn(II) was the best choice for purifying this poly-histidine tagged GFP, followed by Fe(III) of the metal ions tested. Ni(II) that is superior especially in many poly-histidine purification systems did not, when loaded to hydroxyapatite, have binding properties comparable to Zn(II) or Fe(III). Elution of poly-histidine tagged GFP was best performed with phosphate buffers or EDTA that could compete with the phosphate molecules in hydroxyapatite or complexly bind the metal ions, respectively.

Animals↗

A microplate-based fluorometric assay for monitoring human cancer cell attachment to cortical bone.

A microplate-based fluorometric assay was developed for quantitation of cancer cell attachment to bone matrix. To evaluate this model system we used a panel of human cancer cell lines, including the human breast cancer cell line MDA-MB-231. For the assay, bovine cortical bone from the shaft of the femur was cut, turned, and sliced to 6-mm-diameter round 200-microm-thin disks and placed into the wells of a 96-well microplate. A fluorescent dye 2', 7'-bis(2-carboxyethyl-5(6)-carboxyfluorescein (BCECF-AM) and a microplate fluorometer equipped with a standard filter set for fluorescein isothiocyanate were used to detect the cells attached to the bone disks. The fluorescence was enhanced during the measurement step by using a K+ solution (pH 8.0) containing the H+/K+ ionophore nigericin, which equilibrates internal and external pH. By taking advantage of the pH sensitivity of BCECF, the fluorescence intensity in the assay was increased 2.5 times compared to cells loaded with calcein. The specificity of the assay was demonstrated with a specific immuneserum raised against the MDA-MB-231 cell line. The assay can be completed in 1 h and permits the use of a large number of samples and is therefore useful for screening potential drug candidates that could block cancer cell attachment to bone material. Moreover, the assay described can easily be used to characterize molecular structures involved in cell attachment to bone.

Animals↗

Sex differences in episodic memory: the impact of verbal and visuospatial ability.

The impact of verbal and visuospatial ability on sex differences in episodic memory was investigated. One hundred men and 100 women, 2040 years old, participated in a series of verbal and visuospatial tasks. Episodic memory was assessed in tasks that, to a greater or lesser extent, were verbal or visuospatial in nature. Results showed that women excelled in verbal production tasks and that men performed at a superior level on a mental rotation task. In addition, women tended to perform at a higher level than men on most episodic memory tasks. Taken together, the results demonstrated that (a) women perform at a higher level than men on most verbal episodic memory tasks and on some episodic memory tasks with a visuospatial component, and (b) women's higher performance on episodic memory tasks cannot fully be explained by their superior performance on verbal production tasks.

Adult↗

Osteogenic differentiation of cultured marrow stromal stem cells on surface of microporous hydroxyapatite based mica composite and macroporous synthetic hydroxyapatite.

In order to investigate the significance of hydroxyapatite based microporous composite (HA/mica composite) surfaces and a macroporous synthetic hydroxyapatite, rat marrow cell culture, which shows osteogenic differentiation, was carried out on six different culture substrata (two control culture dishes, two identical HA/mica composites, and two identical macroporous synthetic hydroxyapatites). A culture period of two weeks in the presence of beta-glycerophosphate (BGP), ascorbic acid, and dexamethasone resulted in abundant mineralized nodule formations that were positive for alkaline phosphatase (ALP) stain. The stain on the macroporous synthetic hydroxyapatite and the HA/mica composites were intense, the enzyme activity being about double that of control culture dishes. These data indicate that the synthetic macroporous hydroxyapatite surface and the HA/mica composite surface promotes osteoblastic differentiation.

Alkaline Phosphatase↗

Induction of IgG rheumatoid factor (RF) production by antibody-antibody (RF-like) immune complexes: the role of T cells, complement and Fc gamma receptors.

Rheumatoid factors (RF) are autoantibodies with specificity for the constant regions of IgG molecules. They are found in several immunopathological diseases. The mechanism(s) by which these autoantibodies are produced is largely unknown. We have previously shown that a single injection of RF-like immune complexes (ICs) into mice selectively induced an intense IgG1-antibody production with RF activity. This response was sustained for several months and did not resemble a conventional immune response to an antigen or other immune complexes. In the present study, we sought to elucidate the mechanism for the IgG1 RF response to RF-like ICs. Therefore, the roles of CD4+ T cells, complement and Fc gamma receptors were analysed. In order to characterize the role of CD4+ T cells, RF-like induced IgG1-RF production was analysed in NZB mice treated with a monoclonal antibody (mAb) against the CD4 molecule, which resulted in complete abrogation of IgG1 RF production. To evaluate the importance of Fc gamma Rs, the effect of RF-like ICs was tested in mice deficient for RF gamma RI/III. A significant decrease in the numbers of IgG1 antibody secreting cells, as well as in serum IgG1 RF levels, was found in the deficient mice, as compared with their normal outbred littermates. The role of complement in RF-like ICs mediated IgG1 RF was tested in complement depleted NZB mice, using Cobra venom factor. The IgG1 RF response in complement depleted and intact mice was comparable. Thus, our results demonstrate that RF-like immune complexes selectively induce an Fc gamma R-dependent, complement independent antibody response in mice.

Animals↗

Synovial fluid cytokines in patients with rheumatoid arthritis or other arthritic lesions.

The synovial fluid (SF) of rheumatoid arthritis (RA) patients contains a mixture of inflammatory mediators. In order to determine whether certain cytokine patterns locally in the joint are specifically related to the chronic inflammation in RA, the concentrations of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, transforming growth factor-beta (TGF-beta), tumour necrosis factor-alpha (TNF-alpha) and IgG2b-inducing factor (IgG2bIF) were measured in SF from 22 patients with RA and 22 patients with other types of arthritic lesions. High levels of IL-10, latent and active TGF-beta and the presence of IgG2bIF are significantly correlated with RA when corrected for age. As these factors have the capacity to promote antibody production, they might contribute to the maintenance of local antibody production in RA synovial tissues. All RA-SF samples contained detectable levels of IL-10 and all except one contained IL-1beta, while concentrations in several non-RA-SF samples were below detection limits. IL-6 and TGF-beta were present in all SF samples from both RA and non-RA patients. The presence of IgG2bIF was strongly correlated with high levels of IL-10 and IL-1beta in SF. However, no distinct cytokine profile specific for the chronic inflammation characteristic of RA was found.

Adult↗

Autoantibody patterns in synovial fluids from patients with rheumatoid arthritis or other arthritic lesions.

Patients with rheumatoid arthritis (RA) produce a variety of autoantibodies, not only demonstrable in the circulation, but also locally in the inflamed joint. We investigated the local production of several autoantibodies in the synovial fluid (SF) of 24 patients with RA and of 26 patients with other arthritic lesions. RA patients had higher titres of immunoglobulin M (IgM) and immunoglobulin G (IgG) rheumatoid factors (RFs) and of collagen type II antibodies in SF, whereas there were no demonstrable differences between groups with regard to antibodies against double-stranded (ds) DNA, C1q or the hapten 2,4,6-trinitrobenzene sulfonic acid (TNP). No differences were observed for total synovial levels of IgM or IgG. There was no autoantibody pattern that was typical of RA patients, except for the local presence of RF, primarily in seropositive RA patients. Our findings therefore support the notion that RF and collagen type II antibodies are induced by immunogenic material present in the local inflamed environment. In the accompanying paper we studied various synovial fluid cytokines in the same patient groups. Here we correlated the level of these cytokines with autoantibody titres in SF, but no specific cytokine associated with the production of RF was found. Hence, we conclude that several different inflammatory mediators might contribute to the chronic inflammation and autoantibody production in the joint of RA patients. An inverse correlation was established between concentrations of tumour necrosis factor-alpha (TNF-alpha) and levels of total IgG.

Adult↗

A prospective follow-up study of acute deep venous thrombosis using colour duplex ultrasound, phlebography and venous occlusion plethysmography.

OBJECTIVE: To study the extent of deep venous thrombosis (DVT) and thrombus regression over time and to compare the results obtained with different diagnostic techniques. EXPERIMENTAL DESIGN: A prospective follow-up study with repeated examinations during a 6-month period. SETTING: Patients studied at clinical vascular laboratories. PATIENTS: Forty patients hospitalised for acute DVT. Thirty-six of these completed the follow-up period. MEASURES: The diagnosis of DVT was confirmed with phlebographic and/or ultrasonographic techniques. The patient were then re-examined with colour duplex ultrasound and venous occlusion plethysmography after one week, 3 months and 6 months and with phlebography after 1 week and 6 months. The extent of DVT and number of occluded segments were determined with phlebographic and ultrasonographic techniques. Venous occlusion plethysmography was used to evaluate the functional degree of outflow obstruction. RESULTS: Colour duplex scanning at 3 months' and 6 months' follow-up showed that 55% and 74% of initially occlusive thrombi, respectively, were recanalized, with thrombus resolution occurring faster and more completely in those initially limited to popliteal and/or calf level. Discrepancies between phlebography and duplex scanning were found in 6% (26/441) of venous segments investigated by both methods, primarily concerning flow in the veins below the knee. CONCLUSIONS: In comparison with phlebography, colour duplex scanning is an accurate method for evaluation and follow-up of patients with DVT. The non-invasive nature of colour duplex scanning makes this method extremely suitable for repeated studies and thus a potentially very valuable tool for both clinical and research studies of circulatory changes involved in acute and chronic DVT.

Adult↗

A new model for evaluation of biocompatibility: combined determination of neoepitopes in blood and on artificial surfaces demonstrates reduced complement activation by immobilization of heparin.

An in vitro technique was developed for assessment of the biocompatibility of materials for use in clinical applications. Artificial materials were exposed to blood, and the resulting complement activation was quantified both in the plasma and on the material surface by enzyme immunoassays based on monoclonal antibodies specific for neoepitopes exposed in complement activation products. Several materials were evaluated, and the effect of surface modifications, including end-point immobilized heparin, was studied. The results revealed widely varying complement activation properties of the different materials and confirmed that heparin markedly improves biocompatibility. The present method is superior to analysis limited to either the fluid phase or solid phase since certain materials adsorb activation products (exemplified by Tecoflex) whereas others do not although activation was evident from fluid-phase assay (silicone). Furthermore, direct determination of activation-specific neoepitopes on the surface represents an improvement compared with previously described methods for detection of adsorbed components.

Biocompatible Materials↗

A combined electromyographic and cineradiologic investigation in patients with defecation disorders.

Records from 20 patients on whom defecography and electromyography were performed simultaneously because of defecation disorders were analyzed. According to the electromyographic investigation, the patients could be divided into three main groups: 1) normal sphincter reaction; 2) paradoxical sphincter reaction; and 3) combined reaction. Group A was characterized by a marked reduction of muscular activity during emptying and a pronounced closing reflex after emptying. This was followed by return of normal tonic activity. Patients in group B had no relaxation of the sphincters during emptying but a pronounced increased activity in the external sphincter and the puborectalis muscle. They also had severe emptying difficulties at defecography. No closing reflex was seen. In group C the electrical activity in the sphincters increased during moderate straining and when emptying was complete a clear closing reflex was seen. In this study, a dynamic visualization of the defecation together with a registration of electromyographic activity in the striated anal sphincters was performed. It was shown that patients with paradoxical sphincter reaction were lacking a closing reflex after emptying was complete. This has not been reported previously and is important evidence for the paradoxical defecation pattern. It was also shown that the patients with rectoceles had paradoxical sphincter reaction.

Adult↗

Assessment of deep venous incompetence: a prospective study comparing duplex scanning with descending phlebography.

In this prospective study duplex scanning was performed in 21 consecutive patients (23 lower extremities) referred for descending phlebography. The grade of deep venous insufficiency (Grades 1-4) was estimated in a blinded fashion with phlebography and duplex technique. Agreement occurred in 15 of 23 lower extremities. Discrepancies were found particularly in patients with minor degrees of reflux. The patients with reflux below the knee according to phlebography were also identified with ultrasonography. The authors found duplex scanning to be accurate method of evaluating deep venous valvular function. With duplex--but not with phlebography--it was also possible to diagnose isolated lower extremity valvular insufficiency.

Female↗

Severity and location of venous valvular insufficiency: the importance of distal valve function.

Venous calf pump function was evaluated with special reference to distribution and severity of deep venous reflux at different levels. A combination of ultrasonography, foot volumetry and venous plethysmography was used in 100 consecutive patients, 32 of whom were also studied with phlebography and intravenous pressure measurements. A clear relationship was found between clinical stage of chronic venous insufficiency and number of segments with reflux. Clinically important deep venous insufficiency was found particularly in patients with reflux in the distal posterior tibial veins, even in the presence of competent popliteal valves. The results demonstrated the calf pump to be functionally divided into a series of pumps, with the distal part more important than the proximal. The importance of evaluating venous valvular function at different levels for adequate assessment of venous calf pump function is emphasized.

Adult↗