Biomedical subjects

C Andersson

Publications and source records attributed to C Andersson.

At least 37 records · Page 2Linked to original sources

PubMed2002

Factor V Leiden (G1691A) and prothrombin gene G20210A mutations as potential risk factors for venous thromboembolism after total hip or total knee replacement surgery.

Patients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

Activated Protein C Resistance↗

PubMed2001

[Diabetic metabolism protective in severe acute intermittent porphyria].

In AIP attacks there is an escalating metabolic chain reaction leading to heme deficiency and increased levels of porphyrin precursors. This reaction is inhibited by treatment with glucose or heme arginate. In a population-based study in the two most northerly counties of Sweden (Norrbotten and Västerbotten), out of 319 patients > 18 years of age with DNA-verified AIP, 16 had type-2 diabetes. None of the 16 patients showed AIP symptoms after the onset of their diabetes. Three patients had suffered recurrent, severe attacks for many years, but after onset of diabetes their ALA and PBG levels decreased and the AIP symptoms resolved, to the relief of the patients. In a study of the 30 AIP patients with hepatocellular carcinoma (HCC) none had diabetes. This implies that diabetic metabolism may prevent the development of HCC in patients with AIP. The prevalence of AIP patients with diabetes was lower than the prevalence of diabetic patients in the general population. This study shows that diabetes mellitus may be beneficial for patients with severe AIP.

Adolescent↗

PubMed2001

[Neuropathy of the lower legs and feet in acute intermittent porphyria. A comparison of patients with type 1 diabetes and patients with AIP].

Distal neuropathy was assessed in 339 patients with acute intermittent porphyria (AIP). The chronic neurological signs were symmetrical and similar to those in Type 1 diabetic patients. Significant impairment was found concerning perception, extensor digitorum brevis test, lower leg pain, ankle and knee tendon reflexes but not concerning dry feet, loss of forefoot arch and hammer toes, when comparing patients with manifest vs. latent AIP. The neurological signs were more severe in the diabetic patients (n = 298). Five AIP patients had permanent quadriplegia and renal failure after severe attacks. Patients with manifest AIP had significantly more signs of distal chronic, symmetrical neuropathy of axonal type than had patients with latent AIP. More serious neurological lesions appear to develop after severe attacks.

Adult↗

PubMed2001

In vivo and in vitro lipidation of recombinant immunogens for direct iscom incorporation.

We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic tags to improve their capacity to be incorporated into an adjuvant formulation (J. Immunol. Methods 222 (1999) 171; 238 (2000) 181). Here, we have explored the possibility to use in vivo or in vitro lipidation of recombinant immunogens as means to achieve iscom incorporation through hydrophobic interaction. For the in vivo lipidation strategy, a general expression vector was constructed encoding a composite tag consisting of a sequence (lpp) of the major lipoprotein of E. coli, fused to a dual affinity fusion tag to allow efficient recovery by affinity chromatography. Upon expression in E. coli, fatty acids would be linked to the produced gene products. To achieve in vitro lipidation, the target immunogen would be expressed in frame with an N-terminal His6-ABP affinity tag, in which the hexahistidyl tag was utilized to obtain lipidation via a Cu2+-chelating lipid. A 238 amino acid segment DeltaSAG1, from the central region of the major surface antigen SAG1 of Toxoplasma gondii, served as model immunogen in this study. The two generated fusion proteins, lpp-His6-ABP-DeltaSAG1 and His6-ABP-DeltaSAG1, both expressed at high levels (approximately 5 and 100 mg/l, respectively), could be recovered to high purity by ABP-mediated affinity chromatography, and were evaluated in iscom-incorporation experiments. The His6-ABP-DeltaSAG1 fusion protein was associated to iscom matrix with pre-incorporated chelating lipid. Both fusion proteins were found in the iscom fractions after analytical ultracentrifugation in a sucrose gradient, indicating successful iscom incorporation/association. Iscom formation was further supported by electron microscopy analysis. In addition, these iscom preparations were demonstrated to induce high-titer antigen-specific antibody responses upon immunization of mice. For this particular target immunogen, DeltaSAG1, the induced antibodies demonstrated poor reactivity to the native antigen, although slightly better for the preparation employing the in vitro lipidation strategy, indicating that DeltaSAG1 was suboptimally folded or presented. Nevertheless, we believe that the presented strategies offer convenient alternative ways to achieve efficient adjuvant incorporation for recombinant immunogens.

Amino Acid Sequence↗

PubMed2001

[Female genital mutilation--a complex phenomenon].

As of today, more than 130 million girls and women worldwide are genitally mutilated. Female genital mutilation (FGM) exists primarily on the African continent (along and north of the equator), but the practice is also carried out elsewhere. Clitoridectomy was performed in medicine both in the United States and in Europe as late as in the 1950s. From a socioeconomic perspective FGM is understood as a practice that forms an important part of girls' socialization. FGM is practiced in societies where women's social acceptance and survival is secured through marriage and childbearing. Without FGM, the woman cannot get married, with the consequence that she has no status or access to resources. Her body practically becomes her only form of capital. From a psychosexual perspective FGM is interpreted as a practice that has been made possible in patriarchal societies where the sexuality of women has to be controlled and where unequal gender relationships are preserved. FGM is practiced by people from various religious denominations, among them Copts, Animists, Catholics, Protestants and Muslims, something that goes against the relatively common belief that FGM is practiced only among Muslims. The resistance to FGM found in countries where the practice is rife clearly demonstrates that patriarchal structures and what gets defined as "culture" are indeed possible to change and renegotiate.

Circumcision, Female↗

PubMed2001

[Female genital mutilation meets Swedish health care. Female genital mutilation is one of many forms of discrimination of women in the world].

About 27,000 women from countries in which female genital mutilation (FGM) is a common practice are presently living in Sweden. This means that FGM is a phenomenon that directly affects the Swedish health care system. Knowledge and understanding of the background, meaning and consequences of FGM are a prerequisite for effective prevention, proper clinical handling and supportive reception of the women. To avoid a stigmatizing reception it is also important to understand the situation of genitally mutilated women, and to become aware of the identity crisis many of them experience when they come to Sweden and lose their identity as "normal" women. It is essential to remember that female genital mutilation is one of many forms of discrimination affecting girls and women around the world. This discrimination knows no national or cultural borders and varies in expression and extent. In order to offer optimal care and reception of women who have been socialized into a gender role that is often seen as completely different from the gender role that Swedish society is said to embrace, it is of the utmost importance to first take a critical look beneath the veil of alleged gender equality of Swedish women.

Circumcision, Female↗

PubMed2001

Signaling properties of VEGF receptor-1 and -2 homo- and heterodimers.

Vascular endothelial growth factor (VEGF-A) exerts its effects through receptor tyrosine kinases VEGF receptor-1 (VEGFR-1) and VEGFR-2, which are expressed on most endothelial cell types in vitro and in vivo. We have examined VEGF-A-induced signal transduction in porcine aortic endothelial (PAE) cells individually expressing VEGFR-1 or VEGFR-2, and cells co-expressing both receptor types. We show that VEGF-A-stimulated PAE cells co-expressing VEGFR-1 and -2 contain receptor heterodimers. VEGF-A-stimulation of all three cell lines (expressing VEGFR-1, -2 and -1/2) resulted in signal transduction with different efficiencies. Thus, tyrosine phosphorylation of phospholipase Cgamma, and accumulation of inositol polyphosphates were efficiently transduced in the VEGFR-1/2 cells whereas cells expressing VEGFR-1 responded poorly in these assays. In contrast, VEGF-A-induced activation of phosphoinositide 3-kinase and induction of Ca2+ fluxes were transduced well by VEGFR-1 and VEGFR-2 homo- and heterodimers. The pattern of Ca2+ fluxes was unique for each type of VEGF receptor dimer. Our data show that signal transduction induced by VEGF-A is transduced in distinct manners by homo- and heterodimers of VEGF receptors.

Amino Acid Sequence↗

PubMed2001

Adults with cerebral palsy: a survey describing problems, needs, and resources, with special emphasis on locomotion.

The purpose of this study was to describe problems and resources of adults with cerebral palsy (CP) with special emphasis on locomotion. A questionnaire concerning demographic facts, locomotion, musculoskeletal problems, and present physical activity was mailed to 363 adults with CP. Two hundred and twenty-one adults, (125 male and 96 female; mean age 36 years, range 20 to 58 years) answered the questionnaire. Seventy-seven per cent reported problems with spasticity. Eighty-four per cent lived in their own apartments, with or without home services. Twenty-four per cent worked full-time and 18% had full disability pension. Twenty-seven per cent had never been able to walk, 64% could walk with or without walking aids, 35% reported decreased walking ability, and 9% had stopped walking. Eighty per cent reported contractures and 18% had pain every day. Approximately 60% were regularly physically active, and despite their disability, 54% considered that they were not limited in their ability to move about in the community.

Activities of Daily Living↗

PubMed2001

Autocrine growth factors in human periodontal ligament cells cultured on enamel matrix derivative.

OBJECTIVE: Enamel extracellular matrix proteins in the form of the enamel matrix derivative EMDOGAIN (EMD) have been successfully employed to mimic natural cementogenesis to restore fully functional periodontal ligament, cementum and alveolar bone in patients with severe periodontitis. When applied to denuded root surfaces EMD forms a matrix that locally facilitates regenerative responses in the adjacent periodontal tissues. The cellular mechanism(s), e.g. autocrine growth factors, extracellular matrix synthesis and cell growth, underlying PDL regeneration with EMD is however poorly investigated. MATERIAL AND METHODS: Human periodontal ligament (PDL) cells were cultured on EMD and monitored for cellular attachment rate, proliferation, DNA replication and metabolism. Furthermore, intracellular cyclic-AMP levels and autocrine production of selected growth factors were monitored by immunological assays. Controls included PDL and epithelial cells in parallel cultures. RESULTS: PDL cell attachment rate, growth and metabolism were all significantly increased when EMD was present in cultures. Also, cells exposed to EMD showed increased intracellular cAMP signalling and autocrine production of TGF-beta1, IL-6 and PDGF AB when compared to controls. Epithelial cells increased cAMP and PDGF AB secretion when EMD was present, but proliferation and growth were inhibited. CONCLUSION: Cultured PDL cells exposed to EMD increase attachment rate, growth rate and metabolism, and subsequently release several growth factors into the medium. The cellular interaction with EMD generates an intracellular cAMP signal, after which cells secrete TGF-beta1, IL-6 and PDGF AB. Epithelial cell growth however, is inhibited by the same signal. This suggest that EMD favours mesenchymal cell growth over epithelium, and that autocrine growth factors released by PDL cells exposed to EMD contribute to periodontal healing and regeneration in a process mimicking natural root development.

Cell Adhesion↗

PubMed2001

Mammalian cell production of a respiratory syncytial virus (RSV) candidate vaccine recovered using a product-specific affinity column.

The recombinant production of a respiratory syncytial virus (RSV) candidate vaccine BBG2Na in baby hamster kidney cells (BHK-21 cells) was investigated. BBG2Na consists of a serum-albumin-binding region (BB) fused to a 101-amino-acid fragment of the RSV G-protein. Semliki Forest virus-based expression vectors encoding both intracellular and secreted forms of BBG2Na were constructed and found to be functional. Affinity recovery of BBG2Na employing human serum albumin columns was found to be inefficient due to the abundance of BSA in the applied samples. Instead, a strategy using a tailor-made affinity ligand based on a combinatorially engineered Staphylococcus aureus protein A domain, showing specific binding to the G-protein part of the product, was evaluated. In conclusion, a strategy for production and successful recovery of BBG2Na in mammalian cells was created, through the development of a product-specific affinity column.

Animals↗

PubMed2001

Assessment of chloride secretion in human nasal epithelial cells by X-ray microanalysis.

The genetic disease cystic fibrosis (CF) is due to defective epithelial chloride transport. Different treatments have been proposed that could restore chloride transport in CF patients. A new method is proposed for measuring the chloride secretion in easily accessible epithelial cells. Fresh nasal epithelial cells were obtained by nasal brushing and made to attach to titanium grids for electron microscopy. Chloride efflux through the cystic fibrosis transmembrane regulator channel was stimulated by 20 microM forskolin and 100 microM isobutyl-methylxanthine (IBMX), in standard Ringer's solution (SR). Chloride efflux through the calcium-regulated channel was stimulated by 200 microM adenosine triphosphate (ATP) in SR. The cells were rinsed after the exposure, in order to remove the experimental medium, frozen and freeze-dried. The elemental composition of the cells was determined by X-ray microanalysis. Rinsing with distilled water or ammonium acetate appeared to cause damage to the cells, whereas rinsing with isotonic mannitol preserved the ionic composition. Stimulation of cells from healthy controls with forskolin and IBMX in a chloride-containing medium caused a significant (28 +/- 6%) decrease in chloride concentration, which is indicative of net chloride efflux. In similar conditions, stimulation with ATP induced a 29 +/- 5% decrease in the chloride concentration. Stimulation of cells from CF patients with forskolin and IBMX in a chloride-containing medium caused no significant change in the intracellular chloride concentration, whereas ATP stimulation induced a response similar to that obtained in cells from healthy controls. It is concluded that X-ray microanalysis of nasal epithelial cells may be used to determine chloride secretion in CF patients in an easily accessible cell type.

1-Methyl-3-isobutylxanthine↗

PubMed2001

A critical evaluation of the application of biomarkers in epidemiological studies on diet and health.

One of the problems which may beset epidemiological studies is the difficulty of accurately measuring the dietary intakes of participants. Biomarkers of diet promise to provide a more accurate measure of dietary intake and a more objective one in that they are not reliant on the subject's memory. This review considers some issues of importance in epidemiology when information is obtained from biomarkers. The approach taken is to use examples both of normal dietary constituents and of contaminants in relation to a range of diet and health questions to illustrate these points. A brief overview of the role of sample collection, processing and storage is given including some generic recommendations for maximising the reliability of subsequent analytical data. Using the examples of phytoestrogens and iodine the question of whether biomarkers can accurately reflect the intake of the dietary constituents of interest at the population level or at the individual level is considered. The relationship of the biomarker to the natural history of the disease is exemplified using the role of folate in neural tube defects. Finally, intakes of vitamin D and heterocyclic amines are used to illustrate the integration of biomarkers into epidemiological studies of prostate and colorectal cancer, respectively. It is concluded that biomarkers may provide a more accurate and objective measure of diet than estimates of current or usual intake but that this approach also has limitations. A combination of methods will probably prove to be most valuable and this approach is being taken in current large prospective studies.

Biomarkers↗

PubMed2001

Histopathological and cell biological factors of ductal carcinoma in situ before and after the introduction of mammographic screening.

With the introduction of mammographic screening the incidence of ductal carcinoma in situ (DCIS) has increased to 10-15% of all breast cancers. The aim of this study was to investigate whether there were any morphological and cell biological differences between DCIS detected during the pre-screening (n = 39) as opposed to the screening period (n = 120). We could not demonstrate any statistically significant differences between the pre-screening and the screening period with regard to nuclear grade, presence of necrosis, the Van Nuys classification system, growth pattern, or cell biological factors (estrogen and progesterone receptors, c-erbB-2, p53, DNA ploidy status, Ki67, and Auer classes). These findings suggest that DCIS tumors detected during the two time periods have a similar malignant potential. DCIS detected during the screening period was further divided into the prevalence period versus the period thereafter, and symptomatic versus screening-detected asymptomatic cases. More cases with diffuse growth patterns were seen during the prevalence period than after the prevalence period, and screening-detected asymptomatic DCISs were more often 15 mm or smaller in diameter than DCISs detected symptomatically.

Biomarkers, Tumor↗

PubMed2001

Immunocytochemical demonstration of oestrogen receptor beta in blood vessels of the female rat.

The role of oestrogen receptor (ER) beta in vascular function remains unclear. With the use of a specific ERbeta antibody we have now, using immunocytochemistry, visualized ERbeta in different parts of the vascular tree. In about 70% of medial smooth muscle cells of female rat aorta, tail artery and uterine artery, nuclear immunoreactivity to ERbeta was observed. In these vessels endothelial cells also expressed ERbeta. Vascular expression of the ERalpha subtype was lower than that of ERbeta. In aorta and tail artery, no immunoreactivity towards ERalpha was observed, while in uterine vessels occasional medial smooth muscle and endothelial cells expressed this ER subtype. ERbeta and alpha expression in uterine vessels was independent of the stage of the oestrous cycle, suggesting that variations in uterine blood flow occurring during the cycle are independent of ER density. The regional distribution of ERalpha, as determined by immunocytochemistry, was supported by measurements of ERalpha levels by enzyme immunoassay. In the uterine artery, the level of ERalpha was several times higher (P<0.001) than that of aorta and tail artery (10.1+/-1.7 fmol/mg protein in the uterine artery vs 3.3+/-1.0 and 0.5+/-0.5 fmol/mg protein in aorta and tail artery respectively). Thus, a prominent nuclear expression of ERbeta was observed in the vascular wall of several parts of the vascular tree, while ERalpha predominantly was expressed in uterine vessels, suggesting that ERbeta and alpha may have different roles in vascular function.

Analysis of Variance↗

PubMed2001

Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis.

BACKGROUND/AIMS: Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry, scaly skin. The effects on dryness and skin permeability of a new moisturising cream with 20% glycerine was compared with its placebo and with a medicinally authorised cream with 4% urea (combined with 4% sodium chloride) in the treatment of dry skin. METHODS: Patients (n=109) with atopic dermatitis were treated for 30 days with a moisturiser in a randomised, parallel and double-blind fashion. Transepidermal water loss (TEWL) and skin capacitance were assessed instrumentally, and changes in the dryness of the skin were assessed by the dermatologist. RESULTS: No difference in TEWL was found between glycerine treatment and its placebo, whereas a lower value was found in the urea-treated area compared to the glycerine-treated area. No difference in skin capacitance was found. The clinical assessment of dryness showed urea to be superior to glycerine in treating the condition. CONCLUSIONS: Moisturising creams are different, not only with respect to composition but also with respect to their influence on skin as a barrier to water in patients with atopic dermatitis.

Adult↗

PubMed2000

Improved systems for hydrophobic tagging of recombinant immunogens for efficient iscom incorporation.

We have previously reported a strategy for production in Escherichia coli of recombinant immunogens fused to a hydrophobic tag to improve their capacity to associate with an adjuvant formulation [Andersson et al., J. Immunol. Methods 222 (1999) 171]. Here, we describe a further development of the previous strategy and present significant improvements. In the novel system, the target immunogen is produced with an N-terminal affinity tag suitable for affinity purification, and a C-terminal hydrophobic tag, which should enable association through hydrophobic interactions of the immunogen with an adjuvant system, here being immunostimulating complexes (iscoms). Two different hydrophobic tags were evaluated: (i) a tag denoted M, derived from the membrane-spanning region of Staphylococcus aureus protein A (SpA), and (ii) a tag denoted MI consisting of the transmembrane region of hemagglutinin from influenza A virus. Furthermore, two alternative affinity tags were evaluated; the serum albumin-binding protein ABP, derived from streptococcal protein G, and the divalent IgG-binding ZZ-domains derived from SpA. A malaria peptide M5, derived from the central repeat region of the Plasmodium falciparum blood-stage antigen Pf155/RESA, served as model immunogen in this study. Four different fusion proteins, ABP-M5-M, ABP-M5-MI, ZZ-M5-M and ZZ-M5-MI, were thus produced, affinity purified and evaluated in iscom-incorporation experiments. All of the fusion proteins were found in the iscom fractions in analytical ultracentrifugation, indicating iscom incorporation. This was further supported by electron microscopy analysis showing that iscoms were formed. In addition, these iscom preparations were demonstrated to induce M5-specific antibody responses upon immunisation of mice, confirming the successful incorporation into iscoms. The novel system for hydrophobic tagging of immunogens, with optional affinity and hydrophobic tags, gave expression levels that were increased ten to fifty-fold, as compared to the earlier reported system. We believe that the presented strategy would be a convenient way to achieve efficient adjuvant association for recombinant immunogens.

Adjuvants, Immunologic↗

PubMed2000

[Risky alcohol drinking surveyed at a GP unit. Secondary prevention of alcohol problems in primary care patients].

This article describes an implementation of secondary prevention of alcohol abuse at a GP unit in southern Gothenburg, Sweden. During several periods between 1994 and 1996, screening for alcohol problems was performed using either AUDIT or a 4-item instrument called SWAG. In one part of the study, screening was simultaneously carried out using gamma-GT and MCV. The main object of screening efforts was to stimulate interest for alcohol-related conditions, and this goal was reached. The staff was trained in treatment techniques such as motivational interviewing (MI), bio-feedback using gamma-GT and delivery of concise information. Simple methods to determine level of motivation were used for treatment stratification. Some doctors reported that they had insufficient time for adequate MI treatment, and therefore a condensed model was sometimes used. A nurse-staffed treatment unit was started and successfully promoted work with alcohol problem. Attempts were made to spread these methods to other GP units in the region and this was partially successful, although support from the central primary care administration was not secured.

Adolescent↗

PubMed2000

CA(2+) mobilization in the human submandibular duct cell line A253.

Ca(2+)mobilization induced by ATP, isoproterenol and the Ca(2+)-ATPase inhibitor thapsigargin in the human submandibular duct cell line A253 was investigated using the Ca(2+)-sensitive fluorescent indicator fura-2. ATP and isoproterenol increased cytosolic free Ca(2+)([Ca(2+)](i)) and subsequent exposure to thapsigargin after ATP or isoproterenol stimulation caused a further increase in [Ca(2+)](i). However, ATP and isoproterenol were not able to elicit a further increase in [Ca(2+)](i)after exposure of the cells to thapsigargin. Relatively few cells reacted to isoproterenol stimulation, but nearly all cells reacted to isoproterenol if ATP was added together with, or prior to isoproterenol stimulation. Moreover, the effect of ATP was potentiated by prior or simultaneous addition of isoproterenol. Furthermore, ATP decreased [Ca(2+)](i)in the presence of thapsigargin probably due to agonist-induced export of intracellular calcium. The results may suggest the existence of three thapsigargin sensitive pools; one opened by ATP acting through P(2)-purinergic receptors and IP(3), one opened by isoproterenol acting through beta2-adrenergic receptors, and a third pool not sensitive to ATP or isoproterenol.

8-Bromo Cyclic Adenosine Monophosphate↗