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Biomedical subjects

M Fischbach

Publications and source records attributed to M Fischbach.

At least 127 records · Page 7Linked to original sources
PubMed1984

Defective T cell response to presented antigen in autoimmune mice.

The effect of the single autosomal recessive gene lpr on antigen presentation was studied. MRL/Mp-lpr/lpr, C3H/HeJ-lpr/lpr, C57BL/6J-lpr/lpr, and their normal congenic partners were investigated. Mice bearing the lpr gene were unable to respond to TNP-KLH when presented by syngeneic antigen-presenting cells. The congenic normal partners gave a brisk response. Mixing experiments demonstrated that the defect resided with the lpr responding T cell and not with the lpr antigen-presenting cell. Antigen-presenting cells from lpr mice were capable of inducing T cell proliferation in normal congenic partners, whereas antigen-presenting cells from normal mice failed to stimulate lpr T cells. This defect was intrinsic to an Lyt-1+2- cell. Pharmacologic restoration was attempted by in vivo and in vitro administration of interleukin 2. However, cells from lpr mice remained unaffected. The relationship of these findings to autoimmunity is discussed.

Animals↗
PubMed1984

Hemodiafiltration versus hemodialysis in children.

A total of 6 anuric children have been suitable treated with HD for 12 months and subsequently with HDF for 12 other months. Session time, tolerance and quality of epuration are compared in HD and HDF. Hemodiafiltration combining hemodialysis and hemofiltration in the same treatment time realizes in a short time (about 50% of hemodialysis session time) an optimal epuration with a good tolerance in children.

Anuria↗
PubMed1984

[Low caries activity and salivary pH in youngsters dialyzed for chronic renal failure].

Caries experience was studied in 18 young patients dialyzed for chronic renal failure and aged 7 to 17 years. The mean plaque index (Silness and Löe, 1964) was 1.89 +/- 0.15. Beside abundant plaque, these patients presented with poor oral hygiene and a food intake rich in sugars. Despite these unfavourable factors, caries experience was low. Of a total of 18 patients, ten (56%) had a DMF of 0. In addition, 11 subjects presented dental hypoplasias on more than two teeth. In these patients, the pH of whole saliva was determined at the beginning of the dialysis at time T and at the end of the dialysis at time To. The values at time T were always higher than those of time To. The mean pH at time T was 8.58 +/- 0.01 and the mean pH at time To was 8.09 +/- 0.01. These high salivary pH values are related to the low caries experience noted in these patients.

Adolescent↗
PubMed1984

Defective LN cell proliferative response to Sm antigen in mice bearing the lpr gene.

Several normal and lpr/lpr congenic mouse strains were immunized with an autoantigen (Sm) and a conventional antigen (PPD) and tested for their respective in vitro proliferative responses. All normal strains of mice demonstrated a brisk proliferative response to Sm and PPD on days 3 and 5 of culture. Two month old mice bearing the lpr gene demonstrated a proliferative response to the two antigens only on day 3, while by day 5 of culture, the proliferative response was markedly diminished. Mixing experiments between +/+ and lpr/lpr Sm primed lymph node cells ruled out the influence of a suppressor cell within the lpr/lpr population at day 5. The inability to sustain an in vitro proliferative response to antigen in young lpr/lpr mice was not due to an overall T cell defect nor to in vitro cell death since Con A stimulation and viability were the same in cultures containing lpr/lpr and +/+ LN, cells, respectively. The primary defect may be partly attributed to a defect in interleukin-2 (IL-2) production and response. By day 5 of culture, lpr/lpr supernatants contained much lower levels of IL-2 activity compared to supernatants from +/+ cultures. The addition of exogenous IL-2 was only moderately successful in improving the response falling far below that seen when IL-2 was added to +/+ cultures. This study demonstrates a decrease in autoantigen-induced T cell proliferation in mice that spontaneously produce autoantibodies to that antigen.

Animals↗
PubMed1983

Interleukins in experimental autoimmune disease.

New mouse models of SLE have been developed recently including strains bearing the lpr gene. The presence of this gene results in antibodies to nucleoproteins and DNA, immune complex glomerulonephritis, and proliferation of Lyt 1+23- T cells. A defect in Interleukin-2 (IL-2) production is a common abnormality in these autoimmune mice. We have utilized an antigen presentation system to study T cell proliferation in MRL/lpr, C57B16/lpr and C3H/He/lpr mice and their normal congenic counterparts. The normal mice proliferate well whereas there is little proliferation in the lpr variants. Mixing experiments demonstrate that the defect resides with the lpr responding T cells and not with the lpr macrophages. This abnormality could be due to defective IL-2 production by Lyt 1+23- T cells.

Animals↗
PubMed1983

Molecular and antigenic nature of isolated Sm.

The Sm antigen was isolated and purified from calf thymus nuclear extract by affinity chromatography. The affinity columns were made with serum antibodies from an SLE patient or an anti-Sm monoclonal antibody derived from a hybridoma cell line. Proteins eluted from these two columns had m.w. of 58,000 and 35,000 by SDS polyacrylamide gel electrophoresis. The natural conformation of this antigen appears to be 95,000 in m.w. with the 58,000 particle containing the Sm antigenic determinant. The affinity column-purified antigen detected by the human anti-Sm antibodies is also recognized by anti-Sm antibodies in murine lupus serum, as shown by solid-phase radioimmunoassay. This study 1) demonstrates the molecular and antigenic nature of the Sm antigen and 2) compares the anti-Sm binding capabilities of antibody populations present in sera from SLE patients and from MRL lpr/lpr mice.

Animals↗
PubMed1983

Impaired AMLR in autoimmunity.

A defective AMLR and impaired production and response to Interleukin 2 (IL-2) occur as a common feature of disease in several autoimmune-susceptible strains of mice and in patients with various autoimmune and lymphoproliferative disorders. We have studied the functional significance of these abnormalities and the cellular mechanism responsible by measuring specific antigen-induced proliferation following in vivo immunization with TNP25-KLH in three autoimmune strains bearing the lpr gene. The lpr mice manifest a decreased response in this assay system. Mixing experiments, in which T cells and macrophages from lpr mice and their normal congenic partners are allowed to interact, demonstrate that the defect resides with the responding Lyt 1+ T cells and not with lpr antigen-presenting macrophages. Flow cytofluorometry analysis using monoclonal antibodies to Thy 1.2, Lyt 1 and Lyt 2 reveals an abnormal distribution of these T cells reflecting a low antigen density on the cell surface. The actual number of Lyt 1+ cells is not diminished, but the pattern is displaced. These results suggest that the decreased AMLR, decreased IL-2 production, and decreased antigen-induced proliferation are not due to deficient numbers of responding cells but rather to functional impairment.

Animals↗
PubMed1982

[Renin-angiotensin-aldosterone system in obese children].

Plasma renin (PRA) and aldosterone activities were measured in 29 obese children and in 48 controls of the same age. Blood samples were taken at 8 AM after a night's sleep and after 3 days of a diet with normal sodium intake. The PRA in the obese children was lowered: m = 1.00 ng/ml/h (controls = 1.86 ng/ml/h; p = 0.01). The drop in plasma aldosterone activity was not significant: m = 134.1 pg/ml (controls: m = 167.5 pg/ml). Plasma aldosterone activity was positively correlated with PRA in controls (p less than 0.01): this correlation was not found in obese children. In obese children no dissociation could be found, in the resting state, between plasma aldosterone activity and PRA, contrary to obese adults under stimulation. In fact, 1) the aldosterone/PRA ratio did not differ significantly between obese children and controls, 2) the average value of plasma aldosterone activity that one could predict in the obese children from their average PRA level and the linear regression calculated from the controls exactly corresponded to the measured value. The elevated blood pressure found in the obese children could explain the drop in the PRA which would thus remain adapted to the blood pressure level.

Adolescent↗
PubMed1981

Comparison of different antinucleic acid antibody spectrotypes in spontaneous, induced, and murine lupus.

Sera from patients with systemic lupus erythematosus and from mice spontaneously developing lupus were subjected to isoelectric focusing by a microsucrose gradient method. The spectrotypes of human antibodies to native DNA, denatured DNA, and polyriboadenylic acid (poly A) were compared. Antibodies to native DNA and denatured DNA focused into two regions whose boundaries were pH 5.0-7.0 and pH 8.5-10.0. Antinative DNA antibodies were more homogeneous than antidenatured DNA antibodies. Anti-DNA antibodies in cryoglobulins showed more restriction than those present in serum. There was no relationship between spectrotype and pattern of disease expression. Murine antibodies to native DNA were more heterogeneous than human anti-DNA antibodies. The spectrotypes of antidenatured DNA antibodies from patients with systemic lupus erythematosus or drug induced lupus, or from an immunized rabbit, were similar. Likewise, antibodies to poly A were similar in both human and murine lupus. In contrast to anti-DNA, antibodies to poly A were restricted and focused only in the alkaline range (pH 9.5-10.0). The spectrotype of antipoly A antibodies induced by lipopolysaccharide were comparable but had an additional small band at pH 6.2. Our results suggest unique antibody spectrotypes with varying degrees of restriction for different nucleic acid antigens. Furthermore, spontaneous and induced autoantibodies have similar spectrotypes. Thus, the B cell clones producing antinucleic acid antibodies may be similar whether they are activated spontaneously, following immunization, or as a consequence of polyclonal stimulation.

Animals↗
PubMed1981

Genetic analysis of induction of anti-polyadenylic acid antibodies and xenotropic type-C viruses.

Normal mice can be induced by lipopolysaccharide to produce anti-polyadenylic acid (poly A) antibodies and xenotropic (X-tropic) type-C viruses. To determine whether these traits are genetically linked, high anti-poly A antibody, high virus-producing NZB mice were crossed with low anti-poly A antibody-producing, virus-negative SWR mice. All mice in the F1 generation could be induced by LPS to produce high levels of both anti-poly A antibodies and X-tropic virus. When F1 hybrids were back-crossed to the SWR parent, all offspring were high anti-poly A antibody producers, but one-third of the mice remained virus-negative. These results demonstrate that these two LPS responses of a B lymphocyte are not genetically-linked and the anti-poly A antibody response is multigenic.

Animals↗
PubMed1981

Antibodies to polyadenylic acid in patients with myasthenia gravis.

Sera from 100 patients with myasthenia gravis and 45 patients with non-myasthenia gravis neuromuscular diseases were studied for antibodies to poly rA, poly rA-rU, native and denatured DNA. All patients with myasthenia gravis had significant anti-acetylcholine receptor antibodies with a mean titre of 1.2 X 10(-7)M. Forty-eight per cent of the myasthenia gravis patients had anti-poly rA antibody levels which were greater than 3 standard deviations from the mean of 65 control patients by Millipore filter radioimmunoassay. The antibody was specific for poly rA and present in a much higher frequency than antibodies to the other nucleic acids tested. Sucrose-gradient ultracentrifugation demonstrated that the antibody was limited to the IgM class alone. Mechanisms relating these findings to a more generalized immunological dysfunction are discussed.

Antibodies↗
PubMed1980

Immune complexes in Sjögren's syndrome.

Sera from 48 patients with Sjögren's syndrome were examined for immune complexes by the Raji cell assay. There was no correlation between levels of immune complexes and the degree of lymphocytic infiltration of the labial salivary glands. Serum complement levels were normal. Five patients were serially followed during the development of pseudolymphoma or malignant lymphoma. Immune complex levels in 4 of the 5 patients were generally unchanged throughout the illness and did not parallel disease activity, rheumatoid factor, or SS-A and SS-B concentrations. Possible roles for immune complexes in Sjögren's syndrome are discussed.

Antibody Formation↗
PubMed1979

[Congenital carotid to jugular aneurysm].

A congenital carotid--jugular aneurysm was responsible for severe heart failure in a two day old baby. The child recovered after surgery. The signs suggesting an arteriovenous fistula (a continuous murmur and thrill, hyperdynamic circulation) may be absent, as in this case, when the child is in severe cardiac failure. The signs should be sought when the circulation improves.

Arteriovenous Malformations↗