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Biomedical subjects

L A Nilsson

Publications and source records attributed to L A Nilsson.

At least 37 records · Page 2Linked to original sources
PubMed1990

Oestrogen is a potent disease accelerator in SLE-prone MRL lpr/lpr mice.

The influence of oestrogen on the lupus disease in MRL/l mice has been investigated. Adult, castrated male and female MRL/l mice were administered with s.c. injections of 3.2 micrograms of 17 beta-oestradiol twice a week. The results clearly demonstrate that a relatively small dose of oestrogen is a potent accelerator of the lupus disease in this mouse strain. Thus, administration of oestrogen accelerates glomerulonephritis, lymphoproliferation and mortality. Our results also indicate that oestrogen exerts a dual effect on the immune system of MRL/l mice by depression of antigen-specific and mitogen-induced T cell responses as well as enhancement of polyclonal B cell activation and autoantibody formation. In addition, even short-term administration of oestrogen in the preclinical phase of the disease resulted in long-lasting effects as evaluated by reduced longevity and aggravation of renal disease.

Animals↗
PubMed1990

Expression of heterozygous lpr gene in MRL mice. II. Acceleration of glomerulonephritis, sialadenitis, and autoantibody production.

Recently we showed that not only homozygous MRL lpr/lpr mice but also heterozygous MRL +/lpr mice display defective antigen- and mitogen-driven T-cell responses as well as polyclonal B-cell activation compared with congeneic MRL +/+ mice. In this study we examined the impact of the heterozygous lpr gene on organ pathology in kidneys, joints, and salivary glands, as well as serum levels of immunoglobulins and autoantibodies in young and old MRL mice. Only 1 out of 17 heterozygous lpr-bearing MRL mice developed clinically overt renal disease with significant proteinuria and haematuria during the first year of life. However, examination of Ig and C3 deposits in glomeruli of kidneys from these mice revealed that the expression of the heterozygous lpr gene in MRL mice accelerates glomerulonephritis. In addition, histological examination of the submandibular salivary glands showed an increased focus score in heterozygous MRL mice at 4-5 months of age compared with that of matched congeneic +/+ mice. In contrast, no signs of arthropathy were registered in the heterozygous lpr-bearing MRL mice. Heterozygous MRL mice displayed an expanding lymphoid system as evaluated by significantly increased spleen and lymph node weights compared with those of matched MRL +/+ mice. Further evidence for immunomodulatory properties of the heterozygous lpr gene was obtained when analysing serum levels of IgG, IgM, and autoantibodies. Thus, heterozygous MRL +/lpr mice produced significantly higher levels of both Ig and autoantibodies than matched MRL +/+ mice. We conclude that the expression of the heterozygous lpr gene in MRL mice results in acceleration of the autoimmune process, giving rise to precocious clinical disease.

Age Factors↗
PubMed1989

The effect of immunomodulating treatment on cutaneous delayed-type hypersensitivity in MRL lpr/lpr mice.

An autoimmune disease in MRL lpr/lpr (MRL/l) mice is associated with a plethora of T-cell abnormalities, one of them being impaired delayed-type hypersensitivity (DTH). Three immunomodulating drugs, cyclophosphamide (Cy), cyclosporin A (CsA) and LS 2616, all with beneficial effects on autoimmune diseases, have been examined with regard to their potential effects on DTH in female MRL/l mice and in healthy control mice. All three drugs, given as a single dose at the time of sensitization, increased DTH reactivity of oxazolone in healthy control mice, while only two of them, Cy and LS 2616, significantly augmented the defective DTH response in MRL/l mice.

Adjuvants, Immunologic↗
PubMed1989

Production of antibodies to gliadin in intestinal mucosa of patients with coeliac disease: a study at the single cell level.

Lymphocytes obtained after enzymatic digestion of intestinal biopsies from patients with coeliac disease were examined for the presence of gliadin specific antibody secreting cells by means of the ELISPOT technique. This technique permits enumeration of gliadin antibody secreting immunocytes, differentiated with regard to immunoglobulin class. Patients with coeliac disease were found to have high (834/10(6) cells) numbers of antigliadin spot forming cells (SFC) in gut mucosa. IgG and IgM antigliadin antibody secreting cells were infrequently shown whereas IgA antigliadin SFC predominated in all patients tested (average 68% of total SFC). Ten control patients were investigated in parallel with the coeliac patients and showed only low numbers of gliadin antibody secreting cells in gut mucosa (49/10(6) isolated cells). Antigliadin antibody secretion by peripheral blood mononuclear cells was shown in only two of six coeliac patients tested and in none of the control patients. The findings suggest that the intestinal mucosa is a major site for antigliadin antibody production and that IgA is the dominating Ig-class of these antibodies. The high sensitivity and accuracy of the ELISPOT technique may provide a useful instrument for future studies of antibody production and regulation of the gut immune response to gluten and other alimentary antigens in coeliac and other intestinal diseases.

Adult↗
PubMed1989

Kinetics and isotype distribution of parasite-specific antibody responses in the spleen of mice during primary infection with Schistosoma mansoni. Studies at the single-cell level.

The solid-phase enzyme-linked immunospot assay has been adapted for enumerating cells secreting antibodies to crude antigenic extracts from the main developmental stages of Schistosoma mansoni. The frequencies of splenocytes secreting antibodies reactive with soluble antigenic extracts from cercariae, adult worms, and eggs, were examined in C57BL/6 mice during the first 12 weeks of a primary infection with S. mansoni. Despite the existence of cross-reactive moieties present in these antigenic preparations, the characteristics of the responses monitored differed with regard to kinetics, magnitude, and/or isotype distribution. The responses peaked between 8 and 10 weeks of infection, were characterized by a predominance of cells secreting IgM antibodies against all three antigens, and followed the patterns IgM greater than IgA greater than IgG for cercariae, IgM greater than IgG greater than IgA for adult worms and IgM greater than IgG greater than IgA for egg extracts. On the other hand, these patterns were not always reflected in serum, especially for cercariae-reactive circulating IgG and IgA responses. When examined for numbers of total IgM-, IgG- and IgA-producing cells, the spleen of S. mansoni-infected mice was shown to display considerable numbers of immunoglobulin-producing cells in all three isotypes studied. The most spectacular increases were noted for IgG-secreting cells (more than 10-fold) and for IgM-secreting cells (up to 6-fold) 4 weeks after initial cercarial exposure. Taken together, these observations indicate that primary infection with S. mansoni results in early immunoregulatory alterations which may contribute to the maintenance of specific as well as nonspecific B cell hyperactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Oestradiol suppression of delayed-type hypersensitivity in autoimmune (NZB/NZW)F1 mice is a trait inherited from the healthy NZW parental strain.

In this paper we report that treatment with 17 beta-oestradiol depresses cutaneous delayed-type hypersensitivity (DTH) to oxazolone (OXA) in female oophorectomized NZB/W mice. Analysis of the parental strains revealed that this oestrogen-induced inhibition of DTH mice is a trait inherited from the healthy NZW and not from the autoimmune NZB strain. The down-regulating effect of oestradiol on DTH in female NZB/W mice was found both in the sensitization and effector phase of the DTH response. Decreased DTH reactivity to OXA was demonstrated in oophorectomized NZB/W and NZW mice after administration of both low, physiological doses (s.c. injections) and high, pharmacological doses (siliac tube implantation) of oestradiol. In addition, s.c. implantation of testosterone containing siliac tubes suppressed DTH reactivity to OXA in castrated male NZW mice. This down-regulating effect was not found in male NZB or NZB/W mice similarly treated. Serological analysis revealed that high doses of oestradiol increased whereas testosterone depressed the IgG anti-OXA antibody responses in female NZB/W mice. Our results indicate that one possible contribution of the NZW parental strain to the lupus disease in NZB/W mice is a trait of oestrogen sensitivity leading to the acceleration of the autoimmune disease, the latter feature being inherited from NZB mice.

Animals↗
PubMed1989

Oestradiol- and testosterone-mediated effects on the immune system in normal and autoimmune mice are genetically linked and inherited as dominant traits.

The influence of sex steroids on cutaneous delayed-type hypersensitivity (DTH) and antibody responses to oxazolone (OXA) in autoimmune and normal mouse strains has been investigated. The results show that: (i) treatment with 17 beta-oestradiol (E2) suppresses DTH responses and stimulates antibody responses in MRL, B6 and C3H mice, suppresses DTH in DBA/1 mice, while having no effects on DTH or antibody responses in BALB/c and NFR/N mice. (ii) Treatment with testosterone suppresses the antibody response in all studied strains (MRL, B6, BALB/c and DBA/1) while down-regulating the DTH response only in MRL and B6 but not in BALB/c or DBA/1. (iii) Neither the lympho-proliferative (lpr) gene, which accelerates autoimmune disease, nor the H-2 genes seem to be directly related to the effects of sex hormones on the immune system. (iv) Susceptibility to oestrogen- and testosterone-mediated suppression of DTH but not oestrogen-mediated enhancement of antibody response are inherited as dominant traits. The results are discussed in the context of certain autoimmune diseases known to be influenced by sex hormone manipulations.

Animals↗
PubMed1988

A novel two colour ELISPOT assay. I. Simultaneous detection of distinct types of antibody-secreting cells.

A novel assay system has been developed which is based on the ELISPOT methodology and employs a combination of two immunoenzyme visualization systems yielding distinct colour products. This variation permits the simultaneous enumeration of two different types of cell secreting antigenically distinct products. Optimal conditions for the concurrent detection of human mononuclear cells secreting IgG or IgA antibodies are described.

Adult↗
PubMed1988

Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells.

A reverse modification of ELISPOT assay using nitrocellulose membranes and epitope-specific monoclonal antibodies is described for the detection of single lymphokine-secreting cells. As a model, the production of gamma-interferon by mitogen stimulated human peripheral blood lymphocytes has been examined. The assay can also be modified to permit microscopic examination of spot-forming cells.

Antibodies, Monoclonal↗
PubMed1988

Linkage analysis of the properdin deficiency gene: suggestion of a locus in the proximal part of the short arm of the X chromosome.

Properdin is a component of the alternative pathway of complement activation. Inherited deficiency of the protein predisposes an individual to develop meningococcal disease. A family segregating for properdin deficiency (McKNo 31206), in a manner consistent with X-linked recessive inheritance, was studied by RFLP analysis using 24 X-chromosome-specific DNA probes of known regional assignments. Linkage was observed to the OTC locus and the DXS7 locus. These results suggest that the properdin gene is located on the short arm of the X chromosome in the region Xp21.1-Xcen.

Chromosome Mapping↗
PubMed1988

A second variant of properdin deficiency: the detection of properdin at low concentrations in affected males.

A selective deficiency of properdin (P) was identified in a 58-year-old male and in his 29-year-old nephew, both of whom were clinically healthy. As determined by different immunochemical methods P at low concentrations (about 2 mg/l) was detectable in serum and plasma. Three female relatives, including the mother and daughter of one of the P-deficient males showed moderately low P concentrations. The findings clearly suggested that the deficiency was inherited as an X-linked trait. Three males belonging to another family with P deficiency also showed detectable P concentrations. By contrast, no P (less than 0.1 mg/l) was found in 8 males belonging to three other families. We suggest that there are two variants of X-linked P deficiency: P deficiency type 1, characterized by extremely low P concentrations (less than 0.1 mg/l); and P deficiency type 2 recognizable by P concentrations of about 2 mg/l. The P detected in P deficiency type 2 had subunits of normal molecular weight (52 kilodaltons), but eluted in a lower molecular weight range than did the P of normal serum, either on gel filtration (Ultrogel AcA 22) or on size exclusion chromatography (TSK-4000). The evidence suggested that the P concentration may be one determinant of P oligomer formation. P-deficient serum type 2 did not support fluid phase C3 cleavage in the presence of such alternative pathway activators as inulin and zymosan, nor did it support efficient lysis of guinea pig erythrocytes in agarose gel. By contrast, rabbit erythrocytes were efficiently lyzed, but at a slow rate. P-deficient serum type 1 did not support lysis of rabbit erythrocytes in the assay system used. The reaction was clearly promoted by very low concentrations of purified P. Partially purified P from a male with P deficiency type 2 was shown to be hemolytically active. Further evidence of P function in P deficiency type 2 was obtained by using IgG-presensitized serogroup W-135 meningococci in an alternative pathway-mediated serum bactericidal assay.

Adult↗
PubMed1988

The predictive value of antimitochondrial antibodies in establishing the diagnosis of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) was diagnosed in 85% of patients with antimitochondrial antibodies (AMA) found in sera routinely analyzed for autoantibodies. In these patients and in those without PBC other autoimmune disorders were common, but the latter patients generally had a low AMA titer, 1:80 or less. It was concluded that a low AMA titer may occur in many patients without PBC. On the other hand, it appears very likely that PBC is present in patients with an AMA titer exceeding 1:80 and an increased activity of alkaline phosphatases without signs of extrahepatic biliary obstruction.

Autoantibodies↗
PubMed1987

Evaluation of a solid-phase immunoassay (DIG-ELISA) for the serodiagnosis of ovine toxoplasmosis.

The antibody response to Toxoplasma gondii was studied in 5 experimentally infected sheep by means of the indirect fluorescent antibody test (IFAT) and the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). A significant increase in the antibody levels was registered by both methods as early as one week after subcutaneous inoculation with the RH strain of T.gondii. Maximal antibody levels were recorded 4 to 8 weeks after the inoculation. Analysis of a total of 135 sera obtained during different stages of experimental or natural toxoplasma infection revealed close agreement between the results of the two methods used. The expediency of regular DIG-ELISA as well as of a modified procedure for the direct analysis of blood sampled onto filter paper discs was also demonstrated. There was a close correlation between the results obtained by analysis of serum and of blood adsorbed onto filter paper.

Animals↗
PubMed1987

Identification of basal cell carcinomas by means of monoclonal antibodies C50 and C241.

The monoclonal antibodies C50 and C241 with specificities for the carcinoma-associated carbohydrate structures sialylated Lea and sialosyllactotetraose, respectively, were used in the indirect immunofluorescent test for demonstration of malignant cells in patients with basal cell carcinoma (BCC). Among a total of 36 patients with BCC, 33 were positive with the MAb C50, and 30 with the MAb C241. All of five patients with premalignant conditions were positive with both antibodies, whereas none of 31 control individuals (biopsies from normal skin or from patients with non-malignant conditions) showed a positive reaction. It is suggested that the technique described may provide a convenient tool for evaluation of samples obtained by microscopically controlled surgery of BCC as well as being an adjunct to conventional light microscopy in pathologic-anatomic diagnosis of potentially malignant disease of the skin.

Antibodies, Monoclonal↗
PubMed1987

Serum antibodies to gliadin in coeliac disease after gluten withdrawal.

Serum gliadin antibodies of the IgA and IgG classes were determined by the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in 10 adult patients with villous atrophy of the small-intestinal mucosa. After introduction of a gluten-free diet a gradual decrease in serum gliadin antibody levels occurred, reaching statistical significance at 3 months of treatment for the IgA class (p less than 0.01) and at 6 months for the IgG class (p less than 0.05). A decrease of serum gliadin antibody levels after gluten withdrawal was related to an improvement of the intestinal mucosa and should thus be indicative of whether the patient is following the dietary recommendations. However, determination of gliadin antibody levels cannot replace small-intestinal biopsy, as there are a few patients in whom the antibody levels are not related to the morphology of the gut mucosa.

Adult↗
PubMed1987

Occurrence of sperm antibodies in adult rats after prefertile traumatic vas lesions.

The occurrence of sperm antibodies has been studied in adult rats, which at prefertile age had been subjected to unilateral vasectomy, unilateral or bilateral crush injury of the vas or bilateral resection of the ductal artery. By means of indirect immunofluorescence technique, circulating sperm antibodies could be demonstrated in the blood in all groups 13 weeks postoperatively: unilateral vasectomy 15/17 (88%), unilateral crush injury 14/20 (70%), bilateral crush injury 13/20 (65%) and vascular injury 14/20 (70%). Sperm granulomas were observed in the unilateral vasectomy group (14/17) and in the bilateral crush injury group (4/20), whereas no sperm granulomas were seen in the unilateral crush injury or the vascular injury group.

Animals↗
PubMed1986

Successful treatment of autoimmunity in MRL/1 mice with LS-2616, a new immunomodulator.

Autoimmune MRL/1 mice were treated with a recently developed substance with immunomodulating properties, LS-2616. Treatment was initiated at the age of 8 weeks, before the onset of clinically apparent disease, and at 16 weeks of age, after development of established lupus disease. Beneficial therapeutic effects were obtained, even when LS-2616 was administered at the lowest dose tested (1 mg/mouse/week) to 16-week-old mice. The effects of LS-2616 on longevity, as well as on development of lymphadenopathy, splenomegaly, glomerulonephritis, and vasculitis, were pronounced and were comparable with those of cyclophosphamide. The results obtained suggest a potential role for LS-2616 in the treatment of autoimmune disease in humans.

Adjuvants, Immunologic↗