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Biomedical subjects

P Larsson

Publications and source records attributed to P Larsson.

At least 145 records · Page 8Linked to original sources

Oestrogen-mediated suppression of collagen-induced arthritis in rats. Studies on the role of the thymus and of peripheral CD8+ T lymphocytes.

Administration of oestrogen to castrated female rats has previously been shown to exert a suppressive effect both on the development of collagen-induced arthritis (CIA) and on the delayed-type hypersensitivity (DTH) reaction to collagen II (CII). The present study is concerned with the mechanisms responsible for this suppression, particularly as to the role of the thymus and the CD8+ T lymphocytes; both the thymic epithelial cells and the CD8+ T cells have earlier been implicated as responsible for oestrogen-mediated immunomodulation on the basis of their expression of oestrogen receptors. Adult thymectomy alone did not affect either the incidence or severity of arthritis. Furthermore, adult thymectomy did not change the observed suppressive effects of oestrogen treatment on arthritis development or auto-anti-CII T-cell immunity. Elimination of CD8+ T cells was subsequently achieved in groups of thymectomized rats by utilizing the fact that efficient depletion of CD8+ T cells occurs after in vivo treatment with OX8 monoclonal antibodies; depletion of peripheral CD8+ T cells failed to influence the suppressive effect of oestrogen on CIA and on the in vitro proliferative response of lymph-node cells to CII. Depletion of CD8+ T cells did, however, in itself reduce the incidence of CIA in non-oestrogen-treated and thymectomized rats. We conclude that oestrogen may exert its suppressive effect on development of CIA and on T-cell responsiveness via mechanisms independent of both the thymus and the CD8+ T-cell subpopulation, but that CD8+ T cells are nevertheless involved in the regulation and/or effectuation of the immune reactions responsible for development of collagen arthritis in rats.

Animals↗

Quantitative rather than qualitative differences between monocytes with respect to IgE Fc receptor expression as studied by flow cytofluorometry.

In this study we have used aggregated human IgE, conjugated with fluoroisothiocyanate, as a ligand in flow cytofluorometry to detect the low-affinity Fc receptor for IgE on human leukocytes. The percentage of IgE-binding monocytes increased up to 44%, in a dose-related manner, as the concentration of aggregated IgE in the fluid phase increased to the highest concentration (300 micrograms/ml) used in this study. No such dose-related increase was shown for granulocytes (1.8% IgE-binding cells) or lymphocytes (2.1% IgE-binding cells). The IgE-binding was inhibited by IgE but not by IgG, whereas the opposite effect was obtained for IgG binding. We could not verify a distinct IgE-binding subpopulation of monocytes in peripheral blood. The results rather indicate that most monocytes bind IgE to a variable degree depending on the concentration of the ligand in the fluid phase.

Antigens, Differentiation, B-Lymphocyte↗

Pivmecillinam in long-term prophylaxis to girls with recurrent urinary tract infection.

Pivmecillinam in a single bed-time dose of 5-10 mg/kg was given as long-term prophylaxis to 20 girls with recurrent bacteriuria for a total of 228 months. Symptomatic recurrences occurred in 4 girls, i.e. 1.8 infections/100 months as compared to 17/100 months during the year preceding the study. The frequency of positive urine cultures during prophylaxis was 11%. 10 of the 15 isolates were enterococci, resistant to mecillinam. In rectal swabs examined for the presence of aerobic gram-negative bacteria, enterobacteria were isolated in 78% with a low rate of resistance to mecillinam (11%). Thus pivmecillinam offered effective protection against recurrent urinary tract infections, and did not tend to select resistant enterobacteria in the bowel, but allowed resistant enterococci to cause a few symptomatic infections.

Adolescent↗

Effects on rat T-helper cell proliferation by syngeneic epidermal cells exposed to IFN-gamma in vivo.

In several conditions in the skin, characterized by T-cell infiltration, keratinocytes are induced to synthesize and express class II transplantation antigens. The biological significance of this induced expression is still not understood. In this study, class II antigens were induced on rat ear keratinocytes by local intradermal injections into the ear of rat recombinant interferon-gamma (IFN-gamma). Epidermal cell suspensions prepared from these ears contained more than 50% class II-expressing cells, as judged by immunocytochemistry, compared with less than 5% in untreated epidermis. When comparing the capacity of these to different epidermal cell populations to stimulate a syngeneic PPD-specific T-helper cell line, it was found that IFN-gamma-exposed epidermal cells induced a lower T-cell response to PPD than did normal epidermal cells. This discrepancy could not be explained by either an infiltration of inflammatory cells into the epidermis of IFN-gamma-treated ears or by a difference in interleukin-1 production as determined in culture supernatants. The addition of indomethacin to cultures with IFN-gamma-exposed epidermal cells restored the T-cell response to PPD to that of normal epidermal cells, suggesting an inhibitory effect of prostaglandins. Our data indicate that epidermal cells exposed to IFN-gamma in vivo can suppress an antigen-specific T-cell proliferation.

Animals↗

Motor and sensory blockade after epidural injection of mepivacaine, bupivacaine, and etidocaine--a double-blind study.

In a double-blind study of epidural anesthesia, 30 young volunteers were given either 2% mepivacaine (400 mg), 0.5% bupivacaine (100 mg), or 1.5% etidocaine (300 mg), all solutions containing epinephrine (1:200,000). The spread of analgesia was equal in the groups, whereas the longest duration was noted in the etidocaine and bupivacaine groups. With use of a method for determining muscle force, motor blockade during anesthesia was recorded quantitatively for hip flexion, knee extension, and plantar flexion of the big toe. Onset of motor blockade was significantly more rapid with etidocaine than with bupivacaine and mepivacaine. All subjects given etidocaine developed complete motor blockade, but with the other local anesthetics 5%-33% of the initial muscle force remained. The least motor blockade was found in the L5-S2 segment (plantar flexion of the big toe). The duration of maximal motor blockade varied between 60 min (mepivacaine) and 360 min (etidocaine). With each of the three local anesthetics, motor function returned simultaneously in the three muscle groups tested. Complete restoration of muscle function occurred significantly later for etidocaine (600 min) than for bupivacaine (360 min) and mepivacaine (180 min). With etidocaine, the motor blockade outlasted the sensory blockade by 150 min. The Bromage scale corresponded to the motor blockade only during the first half of the regression phase. Not until 1-3 h after attainment of Bromage grade 0 was the muscle force of all movements restored (90% of control values).

Acetanilides↗

Linomide, a new immunomodulatory drug, shows different effects on homologous versus heterologous collagen-induced arthritis in rats.

The effects of the immunomodulatory drug Linomide (LS-2616) have been investigated on two variants of collagen-induced arthritis (CIA) in Lewis rats, i.e. arthritis induced either with heterologous (bovine) or with homologous (rat) collagen type II (CII). Treatment with Linomide from the day of immunization (prophylactic) had a mild ameliorative effect on the severity of arthritis in the heterologous CIA, while the homologous CIA was strongly augmented. In both models, Linomide treatment caused a more severe arthritis when given from onset of clinical signs of disease and onwards (therapeutic). Serum antibody levels to CII were significantly decreased by prophylactic Linomide treatment in rats immunized with heterologous CII, while elevated levels of anti-rat CII antibodies were seen in the homologous model. No effect on antibody levels was seen with the therapeutic treatment regime. The opposing effects of prophylactic treatment with Linomide in heterologous versus homologous CIA indicate that the immune response to an autoantigen may be regulated differently from that to a foreign antigen. These results further strengthen the view that heterologous and homologous CIA should be regarded as separate experimental models, and that the studies on homologous CIA may represent a novel approach for future studies of autoimmune responses and evaluation of anti-rheumatic drugs.

Adjuvants, Immunologic↗

Antibody response to pertussis toxin in patients with clinical pertussis measured by enzyme-linked immunosorbent assay.

Serum antibody response to pertussis toxin was measured by enzyme-linked immunosorbent assay in 172 patients with clinical symptoms typical of whooping cough. The diagnosis was verified by culture in 100 patients. Serum antibodies were either not detectable or present only at low levels in sera obtained in the early stage of disease. Significant changes in serum levels of IgG, IgM and/or IgA were demonstrated in 143 patients (83%). The lack of comparable increases in most of the other patients may be due to inappropriate timing of serum collection. Thus, detection of antibodies against pertussis toxin in paired serum samples can be used for serological diagnosis of pertussis. However, the presence of IgM and/or IgA in a single serum sample does not confirm a diagnosis of pertussis, since such antibodies were found in healthy adults as well as in patients two years after the disease. High levels of these antibodies are, however, suggestive of on-going or recent disease.

Adult↗

Tracing tissues with 4-ipomeanol-metabolizing capacity in rats.

Rats were given 3H-labelled 4-ipomeanol intravenously and whole-body autoradiography with freeze-dried sections, or with sections extracted with trichloroacetic acid, water and organic solvents, was performed to examine the disposition of unbound and bound radioactivity in various tissues. Microautoradiography with glutaraldehyde-fixed, resin-embedded material was used to investigate the cellular distribution of bound metabolites. Based on the data obtained from these experiments in vitro incubations with tissue-slices were carried out to examine the capacity by various tissues to form tissue-bound 3H from the 3H-labelled 4-ipomeanol and autoradiography of isolated organs after incubation with 3H-labelled 4-ipomeanol was performed to study the localization of radioactivity under in vitro conditions. The results showed a high formation of tissue-bound 3H in the lung in vitro and a localization of bound metabolites in several structures of the lung in vivo. In vitro formation of tissue-bound 3H was also found in the nasal olfactory and respiratory mucosa, the hard palate, the trachea, the liver and the kidney and this was also correlated with a localization of bound 3H in these tissues in vivo. Incubations of the lung, the nasal olfactory mucosa, the hard palate and the liver in CO- or N2-atmospheres or in the presence of the cytochrome P-450-inhibitor metyrapone showed decreased formation of tissue-bound 3H from the 3H-labelled 4-ipomeanol, indicating a role of cytochrome P-450 in the metabolism of 4-ipomeanol in the various tissues. The correlation between the in vitro capacity of various tissues to metabolize the 4-ipomeanol and the in vivo accumulation of tissue-bound metabolites in the same tissues indicate that a local bioactivation of the 4-ipomeanol takes place in these tissues in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Modulation of experimental allergic neuritis in rats by in vivo treatment with monoclonal anti T cell antibodies.

Monoclonal antibodies (MCA) to different T lymphocyte cell surface antigens have been used to treat rats during different phases of the development of experimental allergic neuritis (EAN). The effects of this treatment were followed by clinical evaluation and in some instances by immunohistochemical analysis of lymphoid organs and affected nerves of the antibody-treated rats. Several MCA, W3/13 (pan T cell reactive), W3/25 (anti-rat CD4), Ox 8 (anti-rat CD8) as well as Ox 6 (anti-Ia) partly prevented clinical signs of EAN when given shortly before expected onset of disease, whereas W3/13 and Ox 8 given at the height of disease did not further affect disease development. However, Ox 19 (anti-rat CD5) given at the same time as immunization partly prevented clinical signs of EAN, while Ox 19 given shortly before expected onset of disease or during height of disease drastically exaggerated disease symptoms. Immunohistochemical studies after Ox 8 or Ox 19 treatment showed a complete absence of staining for the respective antibodies, while staining was preserved with the other MCA. It is concluded that: (1) Ox 8 positive "suppressor/cytotoxic" T lymphocytes do not exert any suppressive effects on EAN during the now investigated phases of disease, and that (2) anti T lymphocyte antibodies (here Ox 19) may exert opposite effects on autoimmune disease when given at different phases of disease development. This may have implications for potential therapeutic trials of MCA therapy for putative autoimmune demyelinating diseases in man.

Animals↗

Binding of aflatoxin B1 to melanin.

Whole-body autoradiography of pigmented C57BL mice injected with 3H-labelled aflatoxin B1 (AFB1) showed a high degree of labelling of melanin-containing tissues, such as the melanin of eyes and hair follicles. The corresponding tissues in albino NMRI mice contained only low amounts of the label. Liquid chromatography of extracts of pigmented mouse eyes showed the presence of only non-metabolized AFB1. Analysis of the binding of AFB1 to melanin from bovine eyes using the method of Scatchard revealed two classes of binding sites. Incubations in the presence of metallic cations did not affect the binding, indicating that ionic forces play no role in the affinity. Comparisons of the binding of AFB1 to the bovine-eye pigment in media containing n-propanol, ethanol or methanol indicated that hydrophobic interactions play a role in the affinity. Apposition of the aromatic rings in AFB1 and the indole nuclei of the melanin may also result in van der Waals' forces, and the combination of these two types of forces may underly the binding of AFB1 to melanin. The melanin binding implies that AFB1 is retained in pigmented tissues at higher concentrations than in any other tissue of the body. The biological implication of this accumulation is now known, but the possibility that there may be an increased risk for the induction of melanomas is discussed.

Aflatoxin B1↗

Efficacy and safety of cefpirome (HR810).

Sixty adult patients with suspected systemic bacterial infections were treated with cefpirome 1 g or 2 g twice daily for 5-22 days. Forty-seven patients were evaluable for clinical efficacy. Diagnoses in evaluable patients were urinary tract infections (20), pneumonia (10), soft tissue infections (17), and bone and joint infections (4); four patients had two infections each. Nine patients were bacteraemic and all were cured; the responsible bacteria were Escherichia coli (6), Streptococcus pneumoniae (1), Pseudomonas aeruginosa (1), and Haemophilus influenzae (1). One patient with a soft tissue infection failed to respond clinically to cefpirome. Bacteriologically, 41 of 48 isolated pathogens (85%) were eradicated. In wound cultures, three strains of Staphylococcus aureus and one each of Ps. aeruginosa and Str. faecalis persisted. One Enterobacter sp. relapsed in urine. Of isolated strains, only Str. faecalis and methicillin resistant Staph, epidermidis were resistant to cefpirome. Staph, aureus strains were inhibited in vitro by 0.25 to 2 mg/l of cefpirome in agar dilution. Adverse effects, probably or possibly related to cefpirome, were skin reactions (3), fever (1), Clostridium difficile diarrhoea (2), and disturbed taste sensation (1). Tolerance was good. Cefpirome is suitable for large-scale comparative trials.

Adult↗

Elimination of CD8+ T cells in vivo does not break induced immunospecific tolerance to experimental allergic neuritis in rats.

The role of CD8+ T 'cytotoxic/suppressor' T cells in induced immunospecific tolerance and during recovery after actively induced disease was examined by means of elimination of CD8+ cells from Lewis rats using in vivo treatment by Ox8 monoclonal antibodies, in experimental allergic neuritis (EAN). Animals depleted of CD8+ T cells after recovery from EAN did not show any clinical signs of relapse. Other animals were pretreated with the peripheral nerve basic protein P2 and thereby rendered resistant to disease induction with a potentially neuritogenic emulsion. The elimination of CD8+ T cells did not result in EAN here either. Thus, the CD8+ T-cell population does not seem to participate in the suppression of this autoimmune disease under these experimental conditions.

Animals↗

Microbial degradation of xenobiotic, aromatic pollutants in humic water.

The microbial degradation of a number of 14C-labeled, recalcitrant, aromatic pollutants, including trichloroguaiacol and di-, tri-, and pentachlorophenol, was investigated in aquatic model systems in the laboratory. Natural, mixed cultures of microorganisms in the water from a brown-water lake with a high content of humic compounds mineralized all of the tested substances to a higher degree than did microorganisms in the water from a clear-water lake. Dichlorophenol was the most rapidly degraded pollutant.

Biodegradation, Environmental↗

Regulation by T cells of delayed hypersensitivity reaction in mouse lung as reflected by mononuclear cells, mast cells and mucus-producing cells.

The appearance of mononuclear cells, mast cells and mucus-producing cells in the lung and their linkage to the development of delayed hypersensitivity (DH) reactions were studied. Adoptive transfer of immune lymph node cells, spleen cells and serum and in vivo treatment with monoclonal antibodies to L3T4-positive T cells in Balb/c mice were performed to investigate the cellular regulation of the number of mononuclear cells, mast cells and mucus-producing cells in the lung. Immune lymph node cells and, to a lesser extent, immune spleen cells from mice sensitized epicutaneously with picrylchloride transferred DH reactions to the recipients as assessed by ear thickness increase after challenge. Serum from sensitized mice was not able to transfer a DH reaction. Cyclophosphamide treatment of donor mice increased the DH reaction in the recipient mice. Adoptive transfer of immune lymph node cells and spleen cells gave a slight increase in the number of mononuclear cells in the lung of recipient mice compared with controls. This weak accumulation of mononuclear cells in the lungs of recipient mice, however, was not accompanied by a consistent increase in the number of mucus-producing cells and mast cells. The number of spleen cells expressing the L3T4 antigen decreased after in vivo treatment with the monoclonal GK1.5 (anti-L3T4) antibody as assessed by immunohistochemistry. This antibody treatment also resulted in an inhibition of the DH reaction and a decrease in the number of mononuclear cells and mucus-producing cells, but not in mast cells in the lung of sensitized and challenged mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Erythromycin-resistant beta-hemolytic streptococci group A in Göteborg, Sweden.

A total of 21 erythromycin-resistant strains were found among 355 (5.9%) beta-hemolytic streptococci group A isolated in Göteborg during spring of 1987. T-typing showed 17 to be T12, 1 T4 and 3 nontypable. Spread of resistant strains could be demonstrated within 2 families and 1 day-care-center. Monitoring of erythromycin resistance among beta-hemolytic streptococci is advocated.

Anti-Bacterial Agents↗

Variable in vitro activity of cefaclor, cephalothin and cefadroxil against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis.

The in vitro activity of cefaclor, cephalothin and cefadroxil to 50 Escherichia coli, 23 Klebsiella pneumoniae and 20 Proteus mirabilis strains was tested with the disc diffusion and microdilution plate techniques. Cefaclor was more active than cefadroxil, while cephalothin was intermediate. The differences seriously affected the classification into the routine SIR system. For susceptibility testing we question the use of cephalothin as a class representative of oral cephalosporins.

Cefaclor↗

Susceptibility to beta-lactam antibiotics and gentamicin of gram-negative bacilli isolated from hospitalized patients: a Swedish multicenter study.

A total of 952 blood and 1543 urine isolates of gram-negative bacilli from hospitalized patients in 1986-1987 were consecutively collected by 10 Swedish laboratories and tested for susceptibility to 8 beta-lactam antibiotics and to gentamicin. The isolates were mostly Escherichia coli (58% and 44%, respectively) and Klebsiella sp. (17% and 18%). Resistance to ampicillin in blood and urine isolates was found in 35% and 45%, respectively, to piperacillin in 5% and 6%, to cephalothin in 26% and 34%, to cefuroxime in 12% and 22%, to cefotaxime in 3% and 5%, to ceftazidime in 1% and 1%, to imipenem in 0.5% and 0.1%, to aztreonam in 3% and 2%, and to gentamicin in 0.8% and 0%. Resistance of clinically important gram-negative bacilli to new beta-lactam antibiotics and to gentamicin is infrequent in Sweden.

Ampicillin↗