Nature of the type II collagen autoimmunity in mice susceptible to collagen-induced arthritis.
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Biomedical subjects
Publications and source records attributed to P Larsson.
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Arthritis induced with type II collagen in DBA/1 mice, was analyzed by immunohistochemical techniques. In the earliest detectable pathologic changes, before any macroscopic signs, an accumulation of Mac1+, macrophage-like cells, and an increased expression of major histocompatibility class II antigens were observed focally in the synovial lining layer. In these foci, CD4+ and interleukin 2 receptor expressing T lymphocytes were regularly detected, but not usually other sets of lymphocytes such as B lymphocytes and CD8+ lymphocytes. In clinically detectable arthritis, there was a prominent infiltration of Mac1+ cells, both polymorphonuclear-like and macrophage-like cells. T cells were relatively few, suggesting that they do not play a primary effector role, but rather that they may regulate or permit the self-perpetuative inflammation.
Flow cytofluorimetry identifies and quantifies cell markers of different leukocyte subpopulations by combining cytofluorimetry with the differences in the light scattering properties of the leukocytes in mixed populations. In the phagocytic assay, reported in this paper, the experimental conditions were selected in such a way that it was possible to analyse the phagocytic function of granulocytes in peripheral blood without time-consuming cell separation. The percentage of phagocytosing granulocytes was not dependent on the concentration of granulocytes at the selected incubation time and particle (yeast-C3b) concentration. Furthermore, it was possible to adapt a previously described fluorescence quenching technique (FQ method) to differentiate between attachment and ingestion. Crystal violet, originally used in the FQ method, could not be used in this assay due to its lysomotropic effect. Trypan blue at a concentration of 0.25 mg/ml or higher at pH 4.5 showed a plateau effect in fluorescence quenching indicating an effect on attached but not ingested particles. This assay offers a simple technique to screen the functional properties of phagocytic cells in peripheral blood.
Epidemiological studies suggest that urinary tract infection is an important risk factor in the development of bladder cancer. Chronic urinary tract infection in rats is associated with urothelial hyperplasia and papillomatosis. In the Sprague-Dawley strain, exposure to the 5-nitrofuran, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), is associated in particular with the development of renal pelvic tumors. The present study was designed to evaluate whether chronic urinary tract infection could enhance tumor development in FANFT-induced urinary tract carcinogenesis. One hundred forty-four female Sprague-Dawley rats were divided into the following groups. Group 1 received 0.2% FANFT in the diet for 7 wk followed by control diet. Group 2 received 0.2% FANFT in the diet for 7 wk followed by control diet. One wk after completion of FANFT administration, the suspension of 0.5 ml of Escherichia coli (06K13H1) was injected into the bladder through the urethra. Group 3 received 0.2% FANFT in the diet for 7 wk followed by control diet. One wk after completion of FANFT administration, a suspension of heat-killed E. coli (06K13H1) was injected into the bladder through the urethra. Group 4 received a suspension of 0.5 ml of E. coli (06K13H1) through the urethra and received control diet throughout the experiment. Group 5 was fed control diet only. The experiment continued for 104 wk. A significantly higher number of urinary tract tumors, particularly of the renal pelvis, was recorded in Group 2 compared to Groups 1, 3, 4, and 5. The majority of the rats in Groups 2 and 4 had morphological signs of urinary tract infections, particularly pyelitis and/or pyelonephritis. Thus, a single injection of E. coli (06K13H1) into the bladder results in an enhancement of FANFT-induced urinary tract carcinogenesis in the Sprague-Dawley rat, especially for renal pelvic tumors. The formation of dimethylnitrosamine or other nitroso compounds from nitrates in the urine or increased cell proliferation due to chronic inflammation or both may be important pathogenetic factors in the tumor development.
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After 25 years without any indigenous cases of diphtheria in Sweden, an outbreak occurred in the city of Göteborg, during 1984 to 1986. A group of alcoholics constituted the reservoir of Corynebacterium diphtheriae. The outbreak included 13 clinical cases and 65 carriers. The death-to-case ratio and the complication rate among the clinical cases was high, with three fatal cases and six patients developing reversible paralyses. The fatal cases had no history of previous immunization. The outbreak demonstrates the necessity of a good vaccination status to diphtheria, also in countries where the disease was thought to have been eradicated.
Monoclonal antibodies, specific for human cytomegalovirus, were conjugated to latex microspheres that were already labelled with rabbit anti-mouse immunoglobulin. The beads were then incubated with serum or urine from patients, and then collected on a filter surface, which was analyzed in a scanning electron microscope. Size, immunological specificity, and relative quantity of virus particles were determined within 2 h after serum or urine collection by the visualization of virus particles specifically bound to the latex-bead surface. No such binding of virus particles was detected in the various controls. This method was compared with conventional virus isolation by tissue culture. It enables identification of viruses within a few hours in different body fluids. Even without specific antibodies, the filtration method may permit the rapid detection of particles and the determination of their size in various body fluids.
Monoclonal antibodies specific for human cytomegalovirus were conjugated to latex microspheres that were already labelled with rabbit anti-mouse immunoglobulin. The beads were incubated with serum or urine from patients, and then collected on a filter surface, which was analyzed in a scanning electron microscope. Size, immunological specificity, and relative quantity of virus particles were determined within 2 h after serum or urine collection by the visualization of virus particles specifically bound to the latex bead surface. No such binding of virus particles were detected in the various controls. This method was compared with conventional virus isolation by tissue culture. It enables identification of viruses within a few hours in different body fluids. Even without specific antibodies, the filtration method may permit the rapid detection of particles and the determination of their size in various body fluids.
A total of 533 throat and nasopharyngeal cultures were obtained from 328 staff who nursed cases of diphtheria and carriers of Corynebacterium diphtheriae; none yielded C. diphtheriae. Only one out of 189 environmental samples relating to 22 patients and carriers was positive. In addition, one carrier with chronic skin disease was found to have widespread colonization with C. diphtheriae. Several samples both from his hospital room and home yielded C. diphtheriae, indicating that he was a 'disperser.'
A field sampling device to study the transport of aromatic, persistent chlorinated hydrocarbons from water to air was constructed. It was tested in large, outdoor artificial ponds contaminated with polychlorinated biphenyls (PCBs). The PCB compounds volatilised to air at a rate of 0.9 to 9.6 ng m(-2) h(-1) depending on levels of PCBs in the water and water temperature.
The levels of persistent, lipophilic pollutants in different organs and body-fluids of birds are governed by partitioning, i.e. the levels are correlated. This implies that it may be possible to estimate the total body-burden of chlorinated hydrocarbons, without sacrificing the animals, by examining the levels in secretory fluid. This hypothesis was tested on the goosander, a fish-eating waterfowl. We found that levels of PCB and DDE in secretions from the uropyginal gland were linearly related to levels in the breast muscle. Thus, by estimating the amounts of persistent pollutants in water-repellent secretions, the total body-burden could be calculated.
Epidemiological studies have demonstrated an association between urinary tract infection and the development of bladder cancer. The present study aimed at evaluating the influence of urinary tract infection in male Sprague-Dawley rats exposed to a sub-carcinogenic dose of N-[4-(nitro-2-furyl)-thiazolyl]formamide (FANFT). A single injection of Escherichia coli into the bladder resulted in a persistent upper urinary tract infection in a high percentage of the rats. Thirty-two percent of the rats exposed to FANFT and E. coli infection developed urinary tract tumors, all but one occurring in the renal pelvis. Urinary tract tumors were not found in rats treated with FANFT or E. coli alone. The present results support that inflammation resulting from infection is actively involved in urinary tract tumorigenesis and may support the epidemiological studies showing an association between infection and human urinary tract cancer. The formation of dimethylnitrosamine or other nitroso compounds from nitrates in the urine or increased cell proliferation due to chronic inflammation or both may be important pathogenetic factors in tumor development.
T cell subpopulations were studied in peripheral blood from 62 bone marrow recipients using monoclonal antibodies and flow cytometry. Patients with acute graft-versus-host disease (GVHD), patients with chronic GVHD, and patients with cytomegalovirus (CMV) infection had decreased OKT4/8 ratios. The data suggest that in GVHD this was due to reduced absolute numbers of OKT4-positive cells. CMV-infected patients had significantly increased numbers of OKT8-positive cells. Monitoring of T cell subpopulations was not informative for diagnosis or prognosis of acute GVHD in the single patient. CMV infection should be suspected at a sudden increase in the number of OKT8-positive cells.
Monoclonal antibodies reactive with different T lymphocyte antigens were administered to rats receiving heart allografts. Ox 19 antibodies (directed to the rat Ly 1 equivalent) and Ox 8 antibodies (directed to the rat CD8 equivalent) both prolonged graft survival, whereas W3/25 (anti-CD4), Ox 6 (anti-Ia), and W3/13 (anti-pan T) antibodies did not affect graft rejection. Immunohistological studies were carried out on spleen and graft specimens in order to analyse further the mechanisms behind the prolongation of graft survival. The observed almost complete absence of Ox 8-reactive cells in the spleen after treatment with Ox 8 antibodies corroborates earlier observations that injection of moderate amounts of Ox 8 antibodies leads to complete elimination of suppressor/cytotoxic T cells from peripheral lymphoid organs and blood. The present data on graft survival therefore both support the notion that suppressor/cytotoxic T cells are involved in graft rejection, and suggest that these cells are not the only ones involved. An unexpected and as yet unexplained finding was that Ox 8-reactive molecules were found in large numbers on various inflammatory cells as well as on certain myocytes in the grafted hearts that had experienced a prolonged graft survival due to treatment with Ox 8 or Ox 19 antibodies.
Immunization of female Lewis rats with bovine type II collagen induces a severe polyarthritis with an incomplete penetration. Castration of the rats increased the incidence to 94% compared with 50% among sham-operated controls. When castrated female rats were implanted with silicone capsules containing beta-oestradiol they developed arthritis with a delayed onset and a decreased severity compared with castrated rats implanted with empty Silastic capsules. The levels of anti-type II collagen auto-antibodies were not affected by castration or oestrogen treatment. These findings show that oestrogen suppresses the development of collagen arthritis in rats and that this effect is mediated by mechanisms other than anti-type II collagen auto-antibodies.
Epicutaneous sensitization with picrylchloride (PiCl) induced a strongly delayed hypersensitivity (DH) reaction in mice. Local challenge in the airways of these mice resulted in increased numbers of mononuclear cells, mast cells and mucus cells. Depletion of T helper cells in vivo by treatment with monoclonal antibody (GK 1.5) inhibited the DH reaction. This treatment also resulted in a decrease in the number of mononuclear and mucus cells in the lung after intranasal challenge. The DH reaction was transferred to recipients with immune lymph node cells and spleen cells from mice sensitized epicutaneously with PiCl. The recipient mice also showed a slight increase in the number of mononuclear cells in the lung after intranasal challenge. These results indicate that T cells are not only involved in the DH reaction but also in the accompanying lung reaction.
The antibacterial activity of erythromycin to 50 beta-hemolytic streptococci group A was assessed using disc diffusion and MIC techniques on solid media at pHs 6, 7 and 8 in CO2, aerobic and anaerobic atmospheres. The majority of the strains were only intermediately sensitive to erythromycin according to the disc diffusion method, whereas they were sensitive as judged by the MIC determination. This demonstrates that the regression line is invalid for the drug-bug combination of erythromycin and beta-hemolytic streptococci group A. It was also shown that the activity of erythromycin is reduced at a lower pH and in CO2 incubation.