Biomedical subjects

K Lundberg

Publications and source records attributed to K Lundberg.

At least 19 recordsLinked to original sources

PubMed2006

Arthritogenicity of collagen type II is increased by chlorination.

During inflammation, activated neutrophils, monocytes and macrophages produce and release myeloperoxidase (MPO). MPO converts hydrogen peroxide to hypochlorous acid, a highly reactive and oxidizing agent. Proteins subjected to hypochlorous acid become chlorinated. We analysed how chlorination of the cartilage antigen collagen type II (CII) affects its immunogenic and arthritogenic properties by studying immune responses to chlorinated CII in comparison to immune responses to CII and by studying the development of arthritis in rats immunized with CII-Cl. CII-Cl immunization of LEW.1AV1 rats caused a 100% incidence of arthritis with a mean maximum score of 9.2 (maximal score possible 16). The same dose of non-chlorinated CII did not induce arthritis at all. Rats immunized with CII-Cl developed high anti-CII-Cl IgG titres and also developed IgG antibodies recognizing the non-chlorinated form of CII. Analysis of cytokine mRNA expression in lymph nodes 10 days after immunzation revealed an increased expression of interferon (IFN)-gamma mRNA and interleukin (IL)-1beta mRNA in CII-Cl-immunized rats compared to CII-immunized rats. Thus, chlorination of CII increased its immunogenicity as well as its arthritogenicity. As neutrophils, monocytes and macrophages are abundant cells in arthritic joints of patients with rheumatoid arthritis, chlorination might be a mechanism by which immunoreactivity to CII is induced and by which chronic joint inflammation is supported.

Animals↗

PubMed2005

Inhibition by Artocarpus tonkinensis of the development of collagen-induced arthritis in rats.

Extracts of the leaves and roots from the tree Artocarpus tonkinensis A Cheval (family Moraceae) are used in traditional Vietnamese medicine in order to treat backache as well as rheumatic joint diseases. We prepared an ethyl acetate (EtOAc) extract from this plant and tested its anti-inflammatory properties in an experimental arthritis model, collagen-induced arthritis (CIA). CIA was induced in Dark Agouti rats by means of immunization with collagen type II (CII) emulsified in incomplete Freund's adjuvant. Starting at the day of immunization, the rats were treated daily with intraperitoneal injections of Artocarpus extract. Arthritis progression was measured by means of clinical scoring of paws and anti-CII antibody titres were measured by means of ELISA. In vitro, lymph node (LN) cell cultures were treated with Artocarpus extract and the apoptosis-inducing effect was determined with FACS staining by using annexin V and propidium iodide as well as the TUNEL method. Treatment of the rats with Artocarpus extract decreased arthritis incidence and severity and delayed disease onset. When treatment was started after the onset of arthritis, a tendency towards arthritis amelioration was observed. In vitro, Artocarpus extract acted as a T-cell modulator, inhibiting mitogen-induced T-cell proliferation and inducing apoptosis of activated LN-derived lymphocytes. Thus, we have demonstrated that an EtOAc extract of Artocarpus, a plant traditionally used in Vietnamese folk medicine for treating arthritic conditions, has beneficial effects in an experimental arthritis model. This effect is likely to be T cell-dependent and mediated through apoptosis induction in activated cells.

Animals↗

PubMed2003

Antigen inhibition of collagen-induced arthritis is associated with up-regulation of IL-4 mRNA and induction of Ox40 on T cells in draining lymph nodes.

The addition of a foreign antigen to an inoculum completely inhibits the development of collagen-induced arthritis (CIA). However, the mechanism of this phenomenon, antigen -inhibition, is incompletely understood. Previous studies have demonstrated that the inhibition of arthritis is not mediated through suppression of the antibody response to cartilage antigens. In this paper we investigated cytokine mRNA levels in lymph nodes cells recovered 3, 7 or 16 days from animals immunized with either collagen II in IFA or OVA + collagen II in IFA. At day 7, but not at other time-points, IL-4 mRNA was up-regulated in the lymph nodes of OVA-inhibited non-arthritic animals compared to control animals which all developed arthritis. No significant differences between the two groups could be detected when expression of IFN-gamma, IL-2, TNF-alpha, IL-1beta or IL-10 mRNA was analysed. Flow cytometry analysis of draining lymph node cells demonstrated that the T cell marker Ox40 was up-regulated in the OVA-inhibited group. Our results indicate that the complete inhibition of CIA caused by addition of OVA to the collagen II inoculum is due to the presence of a TH2 environment resulting from an increased production of IL-4 mRNA and a parallel increase in Ox40+ T cells.

Animals↗

PubMed2001

Clinical results of phacoemulsification with the use of Healon5 or Viscoat.

PURPOSE: To compare the ophthalmic viscosurgical devices Healon5 (viscoadaptive) and Viscoat (dispersive) regarding their overall clinical performance during phacoemulsification and posterior chamber intraocular lens (IOL) implantation as well as their influence on intraocular pressure (IOP). SETTING: Department of Ophthalmology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany. METHODS: In this prospective randomized patient- and observer-masked clinical study, the performance of Healon5 (sodium hyaluronate 2.3%) and Viscoat (sodium hyaluronate 3.0%-chondroitin sulfate 4.0%) was assessed by 3 surgeons during cataract surgery in 90 patients. Surgeons used a 5-point scale for the subjective assessment of the ease of injection, maintenance capacity during continuous curvilinear capsulorhexis, remaining capacity during phacoemulsification, facilitation of IOL implantation, removal from the eye, transparency, and overall performance throughout surgery. Intraocular pressure was measured preoperatively and 24 hours and 7 days postoperatively. Best corrected visual acuity was assessed preoperatively and 7 days postoperatively. RESULTS: Overall intraoperative product performance was assessed as good or very good in 34 of 44 patients (77%) in the Healon5 group and in 16 of 46 patients (35%) in the Viscoat group (P <.001). Retention in the anterior chamber was graded good or very good in 36 patients (82%) in the Healon5 group and in 23 (50%) in the Viscoat group (P =.001). There were no statistically significant between-group differences in mean IOP preoperatively and 24 hours postoperatively. CONCLUSIONS: Surgeons graded Healon5 better than Viscoat in overall surgical performance and retention in the anterior chamber during phacoemulsification. These data support that Healon5 adapts to each step during surgery.

Aged↗

PubMed2001

Immune-specific up-regulation of adseverin gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

To identify genes that are regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and possibly involved in TCDD-induced immunotoxicity, we used the differential display technique to screen for differentially expressed genes in the mouse thymus. Here we show that TCDD increased the expression of adseverin, a Ca(2+)-dependent, actin-severing protein. The induction of adseverin is dose- and time-dependent in parallel with the induction of CYP1A1, which is currently the most frequently used marker for TCDD exposure. A comparison between mouse strains with different TCDD responsiveness indicated that the induction of adseverin is dependent on the aryl hydrocarbon receptor, a transcription factor known to mediate most of TCDD's biological effects. Examination of additional organs revealed that the up-regulation of the adseverin gene expression is immune-specific. Using an anti-adseverin antibody, we confirmed the induction of adseverin by TCDD at the protein level and it was confined to the thymic cortex, which harbors immature thymocytes that are known target cells of TCDD. Considering adseverin's role in actin cytoskeletal reorganization, our observations reveal new mechanistic aspects of how TCDD might exert some of its immunotoxic effects.

Actins↗

PubMed1997

Specificity and function of "natural" antibodies in immunodeficient subjects: clues to B cell lineage and development.

The origin of natural antibodies has long been a subject of controversy. Polyreactive natural antibodies recognize multiple ligands and are thought to arise from B1 B cells. Natural antibodies against carbohydrate antigens such as Gal alpha 1-3Gal or against blood groups A and B are thought to be "elicited" by gut bacteria, but their origin is uncertain. To explore the origin of naturally occurring anticarbohydrate antibodies, the specificity and function of the xenoreactive antibodies and isohemagglutinins were investigated in immunodeficient subjects. Subjects with defects in T cell-dependent antibody synthesis had normal levels of xenoreactive natural antibodies, most of which, like xenoreactive antibodies from normal individuals, were specific for Gal alpha 1-3Gal. On the other hand, some subjects with hyper-IgM syndrome who were able to synthesize abundant quantities of xenoreactive antibodies and polyreactive antibodies were devoid of anti-Gal alpha 1-3Gal antibodies. These results suggest that the lineages of B cells giving rise to anti-Gal alpha 1-3Gal antibodies and isohemagglutinins are distinct from B1 B cells or at least exist at a more "advanced" stage of development than those B1 B cells that give rise to polyreactive antibodies. The findings also suggest that B cells which synthesize anti-Gal alpha 1-3Gal antibodies and isohemagglutinins may be distinct from B2 B cells or exist at a more "primitive" stage of development than B2 B cells that synthesize elicited antibodies in normal individuals.

Adolescent↗

PubMed1995

Intermediate steps in thymic positive selection. Generation of CD4-8+ T cells in culture from CD4+8+, CD4int8+, and CD4+8int thymocytes with up-regulated levels of TCR-CD3.

Minor thymus subpopulations representing possible intermediates in thymic positive selection were isolated by cell sorting from bcl-2 transgenic mice, and cultured 1 to 4 days in simple medium to assess their ability to spontaneously develop the surface phenotype of mature T cells. Recovery of cells was in the 60 to 80% range, and no cell proliferation occurred. Only cells originally expressing high, near mature T cell levels of CD3 developed further in culture by down-regulation of CD4 or CD8. The main mature cell product was CD4-8+, regardless of whether the starting phenotype of the CD3high intermediates was CD4+8+, CD4int8+, or CD4+8int; only an intermediate subpopulation expressing the highest levels of CD4 (CD4high8int) produced a dominance of CD4+8- mature progeny. Partial down-regulation of CD8 was therefore not a good indicator of CD4+ T lineage commitment. These and previous results indicate that maturation to the CD8+ T lineage involves a rapid up-regulation of the TCR-CD3 complex, but a relatively slow down-regulation of CD4; it may also involve a partial, transient reduction in surface CD8. In contrast, maturation to the CD4+ T lineage involves a relatively rapid down-regulation of CD8, with maintenance of high levels of CD4. There appears to be a marked asymmetry in the developmental steps leading from CD4+8+ thymocytes to the CD8+ or to the CD4+ T cell lineage.

Animals↗

PubMed1995

Intermediate steps in positive selection: differentiation of CD4+8int TCRint thymocytes into CD4-8+TCRhi thymocytes.

The differentiation potential of putative intermediates between CD4+8+ thymocytes and mature T cells has been examined. Such intermediate populations were sorted, in parallel with CD4+8+ thymocytes, from three types of C57BL/6 mice: major histocompatibility complex (MHC) class II-deficient mice, mice transgenic for an alpha/beta T cell receptor (TCR) restricted by class I MHC and normal mice. The sorted populations were then transferred into the thymus of nonirradiated C57BL/Ka mice differing in Thy 1 allotype, and the progeny of the transferred cells were analyzed 2 d later. Surprisingly, with all three types of donor mice, a major proportion of the CD4+8intTCRint-derived progeny were found to be CD4-8+TCRhi cells, thus delineating a new alternative pathway for development of the CD8 lineage. In contrast, the transfer of CD4int8+TCRint thymocytes produced CD4-8+TCRhi cells but no significant proportion of CD4+8-TCRhi cells, suggesting that there is no equivalent alternative pathway for the CD4 lineage. The results negate some of the evidence for a stochastic/selective model of lineage commitment, and point to an asymmetry in the steps leading to CD4-8+ versus CD4+8- T cells.

Animals↗

PubMed1994

Mercury levels in the hair of pregnant women in a polluted area in Sweden.

Total mercury concentration in hair, sampled at delivery, was determined in women living in an area polluted with atmospheric emissions of mercury from a metal smelter, (n = 122) and in a control area (n = 75). Information on fish consumption was obtained at the 10th week of pregnancy. The average mercury concentration in hair was 0.27 mg/kg (range 0.07-0.96 mg/kg), which is somewhat lower than previously reported for pregnant women in Sweden and very low compared with levels in fish-eating populations in other parts of the world. Women living in the polluted area had significantly lower mercury levels in hair than women in the control area when comparing groups with quantitatively similar consumption of freshwater fish. Possibly, the population in the smelter area does not catch fish in the neighbourhood and/or the fish in the control area has elevated mercury levels. Consumption of freshwater fish > or = once a week resulted in approximately twice as high hair mercury levels as in those who did not eat freshwater fish at all. Also consumption of saltwater fish > or = once a week resulted in significantly higher hair mercury levels than in those consuming saltwater fish < once a month. Hair levels from the 10th week of pregnancy were similar to the levels at delivery in women with high (> or = once a week) consumption of freshwater fish but decreased during this period in women who did not eat freshwater fish at all, which could be explained by decreased exposure during pregnancy and measurement in recently formed hair.

Adult↗

PubMed1994

Small cortical thymocytes are subject to positive selection.

To determine the developmental stages at which positive selection can act to produce mature T cells, CD4+8+3lo thymocytes of large dividing type and of small nondividing type were sorted and transferred into the thymus of nonirradiated Thy-1 congenic recipient mice. In contrast to earlier studies, the small as well as the large thymocytes produced mature CD4+8-3hi and CD4-8+3hi progeny, although production was less efficient from the small cells. The relative efficiency of small cells was increased and was close to that of large cells when bcl-2/anti-HY T cell receptor (TCR) alpha beta transgenic donors were used to improve cell survival, overcome stress effects of the transfer process, and increase the frequency of selectable cells. The results from transferring small CD4+8+3lo thymocytes expressing a TCR transgene from a nonselecting to a selecting thymic MHC environment also confirmed that the small cells were capable of being selected and maturing. Thus the developmental window available for positive selection includes the small CD4+8+3lo thymocytes. The results also showed a striking difference in the kinetics of production of mature progeny from the transferred CD4+8+3lo precursors. CD4+8-3hi cells appeared several days before CD4-8+3hi cells, apparently because the CD4-8+ lineage cells spent several days in transit as CD4+8+3hi intermediates before losing CD4. Most CD4+8- lineage cells on the other hand, either passed very rapidly through this intermediate stage, or lost CD8 before increasing the expression of CD3.

Animals↗

PubMed1994

Omeprazole or ranitidine in long-term treatment of reflux esophagitis. The Scandinavian Clinics for United Research Group.

BACKGROUND/AIMS: Patients with reflux esophagitis have rapid relapses after treatment withdrawal. This study was designed to investigate the relapse rate of symptomatic esophagitis during maintenance treatment with omeprazole or ranitidine. METHODS: Patients with endoscopically verified acute erosive or ulcerative esophagitis were initially treated with 20-40 mg omeprazole daily for 8-12 weeks. After healing, the patients were randomized to maintenance treatment with omeprazole (20 or 10 mg each morning) or ranitidine (150 mg twice daily). Control endoscopy was performed at the end of the healing phase and after 12 months of maintenance treatment or symptomatic relapse. RESULTS: Of 426 initially treated patients, 392 were healed and entered the maintenance study. The months of maintenance treatment with 20 mg omeprazole once daily (n = 131), 10 mg omeprazole once daily (n = 133), and 150 mg ranitidine twice daily (n = 128) were 72%, 62%, and 45%, respectively. Both the 10- and 20-mg doses of omeprazole were significantly better than the dose of ranitidine (P < 0.001 and P < 0.005, respectively). There was no significant difference between the 10- and 20-mg doses of omeprazole (P = 0.06). CONCLUSIONS: Maintenance treatment with omeprazole (20 or 10 mg once daily) is superior to ranitidine (150 mg twice daily) in keeping patients with erosive reflux esophagitis in remission over a 12-month period.

Adolescent↗

PubMed1992

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits the activation of antigen-specific T-cells in mice.

There are conflicting data in the literature regarding target cells in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity. In the present study, adult male C57BL/6 mice were exposed to TCDD (50 micrograms/kg) 4 days prior to immunization with ovalbumin (OVA). The effect of TCDD on the specific immune response in vivo was determined by T-cell proliferation and IL-2 production in response to either OVA or anti-mouse-CD3 antibodies plus PMA in vitro. The antigen-specific T-cell proliferation and IL-2 production in response to OVA were significantly suppressed by TCDD, while the polyclonal response to anti-CD3 antibodies plus PMA was not affected. This indicates that even at a high dose of TCDD the intra T-cell signalling pathways in resting cells are not disturbed, but TCDD selectively impairs the antigen-specific activation of T-cells. Since activated T-cells are required in antibody responses to T-dependent antigens, the low number of such cells observed in the present study, may well explain the suppressive effects of TCDD on humoral immunity reported previously.

Animals↗

PubMed1991

Dexamethasone and 2,3,7,8-tetrachlorodibenzo-p-dioxin can induce thymic atrophy by different mechanisms in mice.

The effects of in vivo exposure to dexamethasone (DEX) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thymocyte proliferation and thymocyte number were compared. In the thymus of DEX-treated mice (1 mg/kg) both proliferation and cell number had decreased by 70% one day after exposure. This decrease was, however, transient, and values returned to normal within 2 weeks. By contrast, in TCDD exposed mice (50 micrograms/kg), a reduction in proliferation was not observed until day 2 after exposure, and the degree of reduction was only about 50%. By this point in time, cell number had only decreased by 20%. Proliferation increased again on day 3 after TCDD administration, whereas cell number continued to decrease and remained low throughout the observation period (8 days). DEX had a direct and immediate effect on cells in all thymocyte subpopulations whereas TCDD initially only affected the immature double negative (DN) and double positive (DP) populations.

Animals↗

PubMed1991

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced suppression of the local immune response.

TCDD suppressed the normal immune response in popliteal and inguinal lymph nodes, when administered i.p. (50 micrograms/kg) to C57BL/6 mice, 4 days before immunization with the T-dependent antigen ovalbumin (10 micrograms/pad) in the hind foot pads. A hampered increase in lymph node cell number and a reduced frequency of antigen-specific B-cells were observed, despite the fact that cell proliferation in vivo was normal. While the restimulation of lymph node cells in vitro with ConA or LPS was normal, suggesting that the APC function was largely unaffected, the OVA-induced proliferation was greatly reduced. The anti-OVA antibody (ab) concentration both in serum and in supernatants of cultured lymph node cells was lower than in controls. In contrast, the production of anti-BSA ab upon LPS stimulation was normal. This indicates that the ability of the B-cells to produce ab and to proliferate was not disturbed. The DTH assay clearly showed an impaired T-cell function in TCDD-treated animals. Since APC or B-cells have appeared normal in their functions tested in this study, we propose that TCDD disturbed T-cell functions, leading to an impaired activation of B-cells.

Animals↗

PubMed1991

Effects of a technical PCB preparation and fractions thereof on ethoxyresorufin O-deethylase activity, vitamin A levels and thymic development in the mink (Mustela vison).

Clophen A50, a technical preparation of polychlorinated biphenyls (PCBs), was separated into four fractions; three containing chlorobiphenyls with 0, 1, or 2 to 4 ortho chlorines and one containing di- and tricyclic impurities such as naphthalenes and dibenzofurans. Clophen A50, the four fractions, and a synthetic mixture of the biologically most active non-ortho-chlorinated congeners (3,3',4,4'-tetra-, 3,3',4,4',5-penta-, and 3,3',4,4',5,5'-hexachlorobiphenyl), were separately mixed in the feed and given to female mink during the reproductive season. The concentration of a given compound in the feed mixture was equivalent to its concentration in the feed mixed with Clophen A50. Hepatic 7-ethoxyresorufin O-deethylase (EROD) activity in adults was enhanced 2-3 times by Clophen A50, the fractions containing non- or mono-ortho-chlorinated congeners, and the synthetic mixture. In neonatal kits delivered by females treated with non- or mono-ortho-chlorinated congeners, EROD was enhanced to about 30 times the control value. No live kits were delivered by the females treated with unfractionated Clophen A50. The fractions containing congeners with two to four ortho chlorines or di- and tricyclic compounds did not significantly induce EROD in either adults or kits. Clophen A50 reduced hepatic and pulmonary vitamin A contents in adult mink, while renal vitamin A was unaffected. Responses to the fractions containing the non- and mono-ortho-chlorinated congeners were similar to those obtained with Clophen A50. Their effects were, however, less pronounced, particularly with respect to the hepatic vitamin A reduction. The fractions containing congeners with two to four ortho chlorines and the di- and tricyclic compounds had no significant effects on tissue vitamin A contents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters intrathymic T-cell development in mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered to 2-4-week-old mice (5, 25, and 50 micrograms/kg body wt.) and to in vitro cultures (10(-9) M) of fetal thymi. By monitoring thymocyte populations with respect to the differentiation antigens CD4 and CD8, it was found that the cell number in all thymocyte populations except for CD8+ decreased significantly compared with controls. In vivo the most marked decrease occurred among double negative (DN) and double positive (DP) cells, whereas in vitro, the DP cells were most severely affected. The cell number had already decreased to some extent by day 1 after a dose of 50 micrograms/kg body wt. of TCDD, although a severe reduction did not become apparent until day 4. There was a clear dose/response relationship between 5 and 50 micrograms/kg body wt. Autoradiography and liquid scintillation counting studies showed that incorporation of [3H]thymidine in the thymus had already decreased 24 h after TCDD treatment, with the decrease being even more pronounced at 48 h. By 96 h, the rate of cell proliferation had returned to approximately normal values. The results show that TCDD has a long-lasting effect on thymocyte abundance together with a transient effect on cell proliferation. This indicates that in addition to the initial effects of TCDD on cell proliferation, it may also more permanently disturb the normal process of elimination by means of selection.

Aging↗

PubMed1990

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in vivo on thymocyte functions in mice after activation in vitro.

Thymocytes from 15-day old C57BL/6 mice, pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 4 days before sacrifice, showed an earlier response and a higher maximal cell proliferation than thymocytes from control mice upon stimulation by concanavalin A in vitro. This is partly in contrast to the conclusions from earlier published studies. IL-2 content--as measured by growth of CTLL cells--was equally high in TCDD and in control cultures at day 1. At day 2, TCDD cultures had decreased dramatically in IL-2 content, possibly due to a high rate of consumption. At this point in time, the controls still contained a high concentration of IL-2, although less than at day 1. In contrast to the increased sensitivity to mitogen stimulation, thymocytes from TCDD-treated mice induced B-cells less avidly with respect to antibody production, and could also inhibit the T-cell help of thymocytes from untreated animals, a phenomenon which could be reversed if TCDD-treated thymocytes were irradiated before culture.

Animals↗

PubMed1990

Accumulation of hyaluronan in bronchoalveolar lavage fluid is independent of iron-, complement- and granulocyte-depletion in bleomycin-induced alveolitis in the rat.

Previous studies on bleomycin-induced alveolitis in rats have demonstrated a transient histological accumulation of hyaluronan (hyaluronate or hyaluronic acid) in the alveolar interstitium, corresponding to increases in hyaluronan (HA) levels in bronchoalveolar lavage (BAL) fluid and lung tissue extracts. The accumulation of HA was related to the influx of inflammatory cells, especially polymorphonucleated cells (PMNs) in BAL fluid and the increase in lung water. In this study we have investigated the influence of iron, complement and PMN dependent mechanisms on the early connective response of the lung in the bleomycin rat model. Iron depletion had no effect on HA or the cellular composition of lavage fluid recovered on day 4 post bleomycin. Treatment of bleomycin-injured rats with cobra venom factor (CVF), totally neutralized complement haemolytic activity but had no effect on lavage HA or the cell invasion in BAL. Treatment with anti-neutrophil serum (ANS), reduced blood and lavage PMN by 70-80%, but had no influence on HA levels in BAL. These results suggest that regulatory mechanisms other than those dependent on iron, complement activation or PMN recruitment are responsible for HA accumulation in this fibrosing alveolitis animal model.

Animals↗