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R Andersson

Publications and source records attributed to R Andersson.

At least 19 recordsLinked to original sources
PubMed1997

The serum albumin-binding region of streptococcal protein G: a bacterial fusion partner with carrier-related properties.

In this study, we have explored the use of the serum albumin-binding region (BB) from streptococcal protein G (SpG) as a bacterial fusion partner for production of peptide immunogens. The fusion protein BB-M3, containing BB and repeated structures from the Plasmodium falciparum malaria antigen Pf155/RESA, was efficiently purified from Escherichia coli culture supernatants by affinity chromatography using BB as an affinity tag. Rabbits immunized with BB-M3 in Freund's adjuvant produced high levels of antibodies which reacted with both M3 and BB in ELISA and stained intact Pf155/RESA in the membrane of infected erythrocytes. These antibody levels were sustained for more than 30 weeks. BB-M3 also induced antibody responses to M3, BB and intact Pf155/RESA in a number of mouse strains, including several strains which are non-responders to the malaria sequences. In the latter mice, however, BB-M3 only activated BB-specific T cells, suggesting that BB has ability to provide carrier-related T cell help for antibody production. Moreover, the minimal albumin-binding motif of SpG, containing only 46 amino acids, was immunogenic in both B10.BR, B10.D2 and C57BL/6 mice (H-2k, H-2d and H-2b, respectively). These results indicate that BB has both affinity tag and carrier-related properties and suggest that fusion proteins containing BB can be efficient tools for the generation of antibody responses to peptides which are weak immunogens.

Animals↗
PubMed1997

Results of adjuvant therapy in resected pancreatic cancer.

After an apparently curative resection, most patients develop local recurrence within the resection bed. In addition, almost all develop liver metastases. This implies that the surgical resection, even if extended, seldom is enough, and that an adjuvant treatment must be effective not only against systemic spread, but also against local recurrence. However, the time schedule may be different for different types of recurrence, resulting in different time frames for the adjuvant treatment. Although extended radical operations may increase the proportion of patients who can undergo resections, the incidence of local recurrences seems unchanged. There are, however, no randomized studies yet comparing the "Standard Whipple" with more extended resection. Intraoperative radiation (IORT) has failed to demonstrate a difference in long-term survival, but there have been reports of a decreased frequency of local progression at the site of the primary tumor. Therefore, it is encouraging that IORT seems to diminish the local recurrences after radical resections. However, randomized studies are also missing for this procedure. These are today only three published studies of adjuvant chemotherapy after radical pancreaticoduodenectomy, but a few more will be finished shortly. Still, the results have not convincingly shown that modern chemotherapy with or without radiotherapy prolongs the life of the patients, and there is little evidence for improving the quality of life. However, since the results are far from satisfactory after resection, more efforts should be made to find better treatment modalities, including adjuvant protocols.

Chemotherapy, Adjuvant↗
PubMed1997

Peripheral blood T cell expansions in patients with Behcet's disease.

Behçet's disease (BD) is a chronic multisystemic inflammatory disorder characterized mainly by recurrent oral and genital aphthous ulcerations and uveitis. Etiology and pathogenesis of BD remain unknown. T cell receptor (TCR) V alpha/V beta gene product expression as well as Jbeta gene segment expression in peripheral blood of BD patients were analysed to investigate the possible role of T lymphocytes in the etiopathogenesis of BD. Flow cytometry with 12 TCR V-specific MoAbs was used for TCRV analyses. Jbeta gene segment usage by T cell populations expressing certain V betas was determined by polymerase chain reaction (PCR) technique with V beta- and C beta-specific primers, Southern blotting of PCR products, and subsequent hybridization with radiolabelled Jbeta gene segment-specific probes. Although 13 of the 23 BD patients exhibited increases in expression of one or more TCR V-gene products, only expansions among the CD4+ T cell subset were significantly more frequent in BD patients (7/23) compared with healthy controls (0/15) (P = 0.019). Six out of eight cases followed for up to 20 months had at least one expansion correlated with disease activity. A strict preference for particular Jbeta gene segments implicating clonality was apparent in all analysed T cell expansions and correlated well with disease activity. These results suggest a possible involvement of antigen-specific T lymphocytes in the pathogenesis of BD.

Adolescent↗
PubMed1996

The role of transient mucosal ischemia in acetic acid-induced colitis in the rat.

The importance of early microcirculatory changes in the rat colon after exposure to acetic acid was investigated. Administration of 4% acetic acid for 15 sec into an exteriorized colonic segment induced a marked, transient (starting 2 min after the challenge with acetic acid and persisting for 15 min) decrease in the colonic blood flow as estimated by a laser-Doppler flowmeter. Four days after acetic acid administration, a uniform colitis had developed in the exteriorized colonic segment with a total morphological score (TMS) of 15.1 +/- 0.8, myeloperoxidase activity (MPO) increased more than threefold, and plasma exudation into the colonic lumen increased sevenfold. Administration of hydrochloric acid (HCl) with the same pH as the acetic acid or sodium acetate (pH 7.0) did not affect colonic blood flow or produce colitis. Mechanical colonic ischemia, induced by a controlled increase in the intraluminal pressure, resulted in several pathological features of colitis with a TMS of 7.3 +/- 0.2, combined with a significant increase in MPO activity. The TMS and MPO were further increased when mechanical colonic ischemia was combined with HCl or sodium acetate. Pretreatment with SOD and catalase 5 or 15 min before acetic acid administration did not affect the transient ischemia immediately following acetic acid administration. However, it partially prevented the development of colitis. It is concluded that immediate transient ischemia accompanied by the generation of oxygen free radicals might be of importance in the pathogenesis of acetic acid-induced colitis in the rat.

Acetic Acid↗
PubMed1996

Resection margins of 2 versus 5 cm for cutaneous malignant melanoma with a tumor thickness of 0.8 to 2.0 mm: randomized study by the Swedish Melanoma Study Group.

BACKGROUND: The traditional surgical treatment for primary malignant melanoma has often been a wide excision with a margin of about 5 cm. Since the risk of local recurrences is dependent on tumor thickness, thin tumors (<1 mm) have routinely been excised with a narrow margin. For thick tumors, the optimal resection margin is controversial, and can be determined only by prospective, randomized trials. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized multicenter study to evaluate an excision margin of 2 versus 5 cm for patients with cutaneous malignant melanoma with tumor thickness > 0.8 and < or = 2.0 mm. The trial includes 769 patients. Patients with melanomas of the skin of the head, neck, hands, feet, or vulva were not included in the trial. In the event of an excision biopsy for diagnosis, radical surgery was completed within 6 weeks. The median follow-up time was 5.8 years for estimation of survival and 4.0 years for diagnosis of recurrent disease. RESULTS: No significant differences have been observed between the treatment groups regarding local or regional recurrences or survival. CONCLUSIONS: We recommend an excision with a margin of 2 cm for cutaneous malignant melanoma with a tumor thickness > 0.8 and < or = 2.0 mm.

Biopsy↗
PubMed1996

Structural features of an arabinan fragment isolated from the water-soluble fraction of dehulled rapeseed.

A water-soluble polysaccharide fraction was prepared from dehulled rapeseed meal (winter rapeseed variety Casino). Further purification yielded two major fractions having a high content of arabinose and galactose residues, with Ara/Gal ratios of 5.4 (G1) and 1.8 (G2). The Ara/Gal ratio of the high molecular weight fraction G1 was stable over the whole gel filtration peak, indicating that the arabinose and galactose residues are part of the same polysaccharide. The high molecular weight fraction G1 was studied further by methylation analysis and several NMR techniques. Structural studies showed G1 to consist mainly of arabian fragments, which have terminal alpha-L-arabinofuranosyl groups with anomeric carbons bound (1-->5) (A) or (1-->2) (B), and 2,5-substituted arabinosyl residues with anomeric carbons bound (1-->5) (D) or (1-->2) (C) to adjacent arabinosyl residues. The A:B:C:D ratios were 2:1:1:1 according to results from NMR and methylation analysis.

Arabinose↗
PubMed1996

Repeated liver resection for recurrent liver cancer.

Patients with cancer recurrence limited to the liver alone after a first liver resection may be candidates for a repeat resection. Some 191 second and ten third liver resections for recurrent colorectal metastases, and 128 second and ten third liver resections for recurrent hepatocellular carcinoma (HCC), were evaluated after reviewing the literature. The 5-year survival rate after second liver resection for colorectal metastases was 26 per cent with a median survival time of 30 months. Mortality and morbidity rates were 1.2 and 27.4 per cent respectively. The 5-year survival rate after second resection for HCC was 40 per cent with a median survival time of 40 months. The operative mortality rate was 2.3 per cent; morbidity occurred in 13 per cent of patients with HCC. Survival after primary colorectal resection was significantly better for patients with metachronous metastases than for those with synchronous disease; survival correlated with a long interval between the first and second liver resection (in both colorectal liver cancer and HCC). Repeated liver resection may be performed in selected patients and yield a similar survival to that obtained after first liver resection.

Adult↗
PubMed1996

Alterations in intestinal function in acute pancreatitis in an experimental model.

Gastrointestinal tract failure may be involved in the development of systemic septic complications in acute pancreatitis. Systemic and intestinal circulation, intestinal permeability and absorptive function were evaluated in the early course of acute pancreatitis induced in rats by retrograde intraductal injection of 0.2 ml of 5 per cent sodium taurodeoxycholate and 0.4 nmol trypsin. A decrease in systemic arterial pressure and intestinal blood flow and an increase in intestinal permeability as measured by the leakage of 125I-labelled human serum albumin from blood to lumen were noted in the distal ileum and colon, reaching statistically significant differences 6 h after induction of pancreatitis. The transport of small molecular markers (sodium fluorescein and 51Cr-labelled ethylenediamine tetra-acetic acid) through the distal ileum and colon in vitro from the mucosal to the serosal site in Ussing chambers significantly increased in the early periodic (20-60 min) of incubation, while the passage of a macromolecular marker (ovalbumin) demonstrated a definite increase at 60-120 min of incubation. D-Xylose absorption from the gut lumen to the portal vein was significantly less in acute pancreatitis than after sham operation. Intravenous administration of the hydroxyl radical scavenger dimethylsulphoxide prevented the compromised intestinal permeability and gut absorptive capacity induced by acute pancreatitis, but did not affect the reduced arterial pressure and intestinal microcirculation. Cytotoxic oxygen-derived free radicals may contribute to the development of alterations in intestinal permeability and absorptive function found in the early stage of acute pancreatitis in the rat.

Acute Disease↗
PubMed1996

Protein adsorption and bacterial adhesion to biliary stent materials.

Four biliary stents inserted for relief of jaundice in patients with biliary obstruction due to carcinoma of pancreatic head were examined for the adsorption of biliary proteins and bacterial colonization. Fibronectin and vitronectin (S-protein) were found to be the two main proteins adsorbed on the inner surface of the stents. Biliary isolates included Escherichia coli, Enterococcus faecalis, and Candida albicans. In vitro studies were performed to clarify the kinetics of biliary protein and bacterial adhesion. Biliary drains of polytetrafluorethylene, polyethylene, polyurethane, and rubber were placed in a flow cell and perfused with human bile at 37% C for 24 hr. The materials were subjected to either detection of adsorbed biliary proteins or perfusion with 3 H-labeled E. coli cells (1 X 10 6 cfu/ml). The results show that the adsorbed biliary proteins were detectable on the surface of biliary stents and able to enhance bacterial adhesion to the surface in the first 24 hrs after the exposure of stent materials to bile, and that both the adsorption of biliary proteins and the adhesion of bacterial cells were material- and strain-dependent. Furthermore, there was a clear correlation between the amount of adsorbed fibronectin and the number of adherent bacteria. The results indicate that, in the clinical situation, biliary proteins may be adsorbed on the surface of inserted stents within a short time after insertion, and some of them may be used by bacterial cells as receptors for adhesion to the surface, and thus involved in the process of bacterial adhesion.

Adsorption↗
PubMed1996

Influence of colostomy on in vivo and in vitro permeability of the rat colon.

PURPOSE: Barrier properties of an isolated colon loop and the remnant colon in continuity with the gastrointestinal tract after colostomy were studied in the rat. METHODS: The in vivo absorption after colonic loop administration of the marker fluorescein sodium was measured as the urinary recovery. The in vitro permeability was measured in Ussing diffusion chambers as the transmucosal passage of [14C]mannitol and of human serum albumin in the isolated and the nonexcluded colonic segments and was compared with the corresponding colonic regions from sham-operated rats at 1 to 14 days after operation. RESULTS: Body weight gain of the rats decreased and diarrhea appeared from day 2 after colostomy. Histologic examination showed mucosal atrophy with decreased villus height in the isolated colonic loop and an increased villus height in the nonexcluded colon segment. Absorption of fluorescein sodium in the isolated loop was increased at 8 and 14 days. Moreover, permeability in the isolated loop was increased for both mannitol and human serum albumin from four days after colostomy compared with the corresponding colonic segments after the sham operation, whereas a decrease in the passage of mannitol was noted in the nonexcluded colon. CONCLUSIONS: Experimentally performed colostomy diversion in the rat induced alterations of the barrier function in both the isolated colonic loop and the nonexcluded colon in continuity with the fecal stream.

Animals↗
PubMed1996

Carbon dioxide transport in rats with acute pancreatitis.

CONCLUSION: The production, release, and transport of carbon dioxide from tissues to blood are facilitated both systemically and in the gastrointestinal tract in acute pancreatitis. Red blood cells are responsible for the major exchange and transport of this increase in CO2. The existence of arteriovenous shunting within the intestine is associated with tissue ischemia, which may be involved in the etiology of gut barrier failure in acute pancreatitis. BACKGROUND: Hemodynamic alterations in acute pancreatitis have been described, while little is known about CO2 metabolism. METHODS: Carbon dioxide metabolism was evaluated by virtual values of venoarterial CO2 concentration differences in the early phase after sham operation or induction of acute pancreatitis by intraductal injection of 5% sodium taurocholate in rats. RESULTS: In acute pancreatitis, virtual values of the CO2 concentration increased in arterial RBC at 6 and 12 h as well as in caval and portal vein RBC and plasma. Virtual values of the dissolved CO2 concentration were reduced in arterial and portal vein blood. The increment in blood CO2 concentration related to the increase in CO2 tension from arterial to caval or portal vein valves at constant CO2 tension. The total increment in CO2 concentration from arterial to caval or portal vein blood increased. Whole body oxygen extraction increased, whereas gut oxygen extraction decreased in pancreatitis.

Acute Disease↗
PubMed1996

Alterations in intestinal motility and microflora in experimental acute pancreatitis.

CONCLUSION: A delay in intestinal transit time appears as an early event in acute pancreatitis, preceding intestinal bacterial overgrowth and translocation. BACKGROUND: Septic complications, primarily caused by bacteria of enteric origin, are frequent in severe acute pancreatitis. Impairment in intestinal motility probably plays a pathophysiological role in the development of bacterial overgrowth and ensuing translocation. METHODS: In the present study, the influence of acute pancreatitis on intestinal motility was evaluated by measuring small intestinal transit time in the rat. Acute pancreatitis was induced by the retrograde intraductal infusion of 0.2 mL taurodeoxycholate. Intestinal transit time was studied by intraduodenal injection of Krebs' phosphate-buffered solution labeled with Na2(51)CrCO4, and 1 h small intestinal transit was measured at 1, 3, 12, and 24 h, after induction of pancreatitis. Bacterial overgrowth was evaluated by measuring Escherichia coli counts in the colon and distal small intestine, and bacterial translocation to mesenteric lymph nodes, the liver, spleen, and pancreas was determined. RESULTS: A delayed small intestinal transit time was noted from 3 h on after induction of acute pancreatitis, with most of the radioactivity retained in the first two intestinal segments. Overgrowth of E. coli was noted 12 h after induction of pancreatitis in both the colon and distal small intestine, and at the same time-point, a significant increase in the incidence of bacterial translocation to mesenteric lymph nodes was seen.

Acute Disease↗
PubMed1996

Enhanced prevalence of T cell receptor V beta 7 gene family expression in human intestine-associated T lymphocytes.

Relative levels of expression of T cell receptor variable (V) beta and joining (J) beta gene segments were determined in T cells derived from intestinal biopsies of healthy mucosal areas, mesenteric lymph nodes and peripheral blood of the same individuals. Samples taken from patients suffering from inflammatory (n = 8) and non-inflammatory (n = 8) bowel diseases were analyzed by semi-quantitative polymerase chain reaction-based methods. In the intestine, fewer (median = 3.5) V beta gene segments constituted more than 50% of the T cell receptor V beta repertoire compared to that of peripheral blood T cells (median = 7, P < 0.001). Interestingly, in all sixteen individuals studied, intestinal T lymphocytes (IL-T) expressed the V beta 7 gene family to a higher degree than did T cells in the paired peripheral blood and mesenteric lymph nodes (P < 0.001). T cell receptor J beta gene segment analyses of V beta 7+ T cells revealed no significant difference in oligoclonality rates between peripheral blood (4/16) and intestine (7/16) (P = 0.46). Hence, overexpression of intestinal TCR V beta 7 message does not seem to be due to oligoclonal expansions in the majority of the samples.

Adolescent↗
PubMed1996

Proliferation of distinct human T cell subsets in response to live, killed or soluble extracts of Mycobacterium tuberculosis and Myco. avium.

The proliferative responses of distinct cell subsets from healthy, bacille Calmette-Guérin (BCG)-vaccinated blood donors were assessed after in vitro stimulation with live or UV-killed Mycobacterium tuberculosis and Myco. avium or with soluble extracts obtained from either mycobacterial species. Proliferation of cell subsets was evaluated by flow cytometric determination of 5-bromo-2'-deoxy-uridine incorporation into DNA and simultaneous identification of surface phenotypic markers. In the presence of monocytes, the response to whole (live or killed) bacteria was characterized by a predominant proliferation of CD4+ alphabeta+ T cells and, to a lesser extent, of CD8+ alphabeta+ T cells. Proliferation of CD8+ alphabeta+ T cells was primarily elicited by live rather than killed bacilli (P < 0.05). Conversely, when soluble bacterial extracts were used as stimulators, a preferential proliferation of gammadelta+ T cells, expressing predominantly Vgamma9+ and Vdelta2+ T cell receptor chains, was recorded. Moreover, when monocyte-depleted cell populations were directly cultured with live bacteria, a marked proportion of CD3- CD16+ (natural killer (NK)) cells was detected among the responding cells. Although both alphabeta, gammadelta and NK cells have been previously shown to react with mycobacteria in vitro, their relative contributions to the response have been difficult to assess. Using a flow cytometric technique which allows direct identification of proliferating cells within complex cell populations, our study demonstrates significant differences in the ability of various mycobacterial antigen preparations to elicit proliferation of distinct cell subsets.

Antigens, Bacterial↗
PubMed1996

Immune responses in congenic mice to multiple antigen peptides based on defined epitopes from the malaria antigen Pf332.

Repeat sequences from the Plasmodium falciparum blood stage antigen Pf332 frequently comprise the pentapeptide VTEEI, an epitope recognized by certain parasite neutralizing antibodies. This B-cell epitope was assembled in an octavalent multiple antigen peptide (MAP) system either as trimers (VTEEI)3 (MAP1) or as an integral part of a naturally occurring Pf332 undecamer repeat sequence SVTEEIAEEDK (MAP2). Characteristics of the immunogenicity of these subunit constructs were evaluated in H-2 congenic mice. MAP1 generated antibody responses in mice of the H-2d, H-2k and H-2q haplotypes, but not in H-2b or H-2s mice, whereas MAP2 only induced antibodies in mice of H-2k haplotype. When analysing T-cell responses induced by the MAP, lymph node cells from responder strains primed in vivo with MAP1 proliferated in response to restimulation with both MAP1 and the peptide (VTEEI)3. MAP2, however, did not induce a detectable T-cell proliferation. Additionally, the lack of antibody response to MAP1 in H-2b mice could be circumvented by combining the MAP1 peptide and a H-2b-restricted T-cell epitope in a diepitope MAP construct. Despite the fact that the motif VTEEI has not been identified in Pf332 sequences in the form of a trimer, MAP1 did induce Pf332 protein-reactive antibodies. Assembly of multimers of short defined epitopes in MAP constitutes an interesting approach for the design of polyvalent subunit immunogens.

Amino Acid Sequence↗
PubMed1996

Biotransformation of the cyclopenta-fused polycyclic aromatic hydrocarbon benz[j]aceanthrylene in isolated rat liver cell: identification of nine new metabolites.

The biotransformation of benz[j]aceanthrylene (B[j]A) was studied in suspensions of hepatocytes isolated from Aroclor 1254-treated or untreated rats. Using radiolabeled cofactors and metabolic inhibitors combined with UV, mass and 1H-NMR spectroscopy, we have detected five known metabolites and characterized nine new metabolites: metabolite 1 was tentatively assigned as B[j]A-1,2-dihydrodiol-8-sulfate; metabolite 2, B[j]A-1,2,9,10-tetrahydrotetrol; metabolite 3, B[j]A-1,2-dihydrodiol-10-O-glucuronide; metabolite 4, B[j]A-1-one-8-sulfate; metabolite 5, B[j]A-1,2-dihydrodiol-10-sulfate; metabolite 6, the sulfate conjugate of B[j]A-dihydrodiol-phenol; peak 7 in the chromatogram is a mixture of one glutathione conjugate and two sulfate conjugates of a B[j]A-metabolite; metabolite 8, B[j]A-10-O-glucuronide; metabolite 8', B[j]A-1,2-dihydrodiol; metabolite 9, B[j]A-10-sulfate; metabolite 9', B[j]A-9,10-dihydrodiol and metabolite 10, B[j]A-9,10-dihydro-9-hydroxy-10-sulfate. The metabolites identified support the notion that epoxidation at the cyclopenta region is an important activation step of B[j]A. Furthermore, sulfation appears to play a very important role in the conversion of hydroxylated B[j]A metabolites into more polar excretable products.

Animals↗