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Biomedical subjects

L Jacob

Publications and source records attributed to L Jacob.

At least 91 records · Page 5Linked to original sources

Specificity of acebutolol-induced antinuclear antibodies.

Treatment with the beta blocker acebutolol may trigger antinuclear antibody (ANA) production. We retrospectively studied 97 sera from 47 patients who developed ANA during acebutolol treatment. Anti-histone and anti-denatured (ss) DNA antibodies were found in 53% and 66% respectively of the sera tested. The activities of these two antibodies correlated well with the total ANA titer. Anti-native (ds) DNA were absent or present at low titer. This immunochemical pattern of acebutolol-induced ANA is similar to that reported for other drug-induced ANA. To date, the presence such isolated ANA is not known to expose patients to any particular risk other than exceptional and minor clinical manifestations of lupus which are rapidly reversible following therapy cessation.

Acebutolol↗

Effects of H2-blocking agents on hepatocytes in vitro: correlation with potential for causing hepatic disease in patients.

The adverse effects on an in vitro model of oxmetidine, an H2-blocking agent which has been shown to produce hepatic injury in 1 to 4% of patients, were compared with those of cimetidine and ranitidine which have led to only rare instances of hepatic injury. Suspensions of hepatocytes, freshly isolated from Sprague-Dawley rats, were exposed to the three drugs. Oxmetidine, in concentrations of 3 X 10(-3) M or greater, led to leakage of AST into the medium after 4 hr of incubation. Ranitidine and cimetidine, in concentrations up to 5 X 10(-3) M, produced no identifiable leakage. Pretreatment of rats with phenobarbital, 3-methylcholanthrene, or SKF 525A resulted in no significant enhancement or inhibition of the oxmetidine effects. These results suggest that the adverse effects of oxmetidine on the hepatocytes are produced by the native compound, not a metabolite. The positive correlation between in vivo and in vitro toxicity supports the view that in vitro testing may prove to be of use in predicting the hepatotoxic potential of a drug.

Animals↗

[2 cases of AIDS in patients with hemophilia A].

The authors report the first two cases of lethal AIDS in haemophilia A in France. One French case of AIDS in haemophilia B has already been reported. The diagnosis was based on the observation of opportunist infections associated with severe depression of cell-mediated immunity in both cases. The possibility of active transmission of the LAV retrovirus by factor VII concentrate is discussed. This raises the problem of the signification of anti-LAV antibodies in haemophiliac patients and the control of products used for the treatment of haemophilia.

Acquired Immunodeficiency Syndrome↗

[Pathogenic antibodies in systemic lupus erythematosus: anti-LAMP antibodies].

We recently demonstrated that a monoclonal anti-DNA antibody, spontaneously produced in lupus B/W mice, recognizes the same protein(s) at the surface of several human cell types involved in lupus pathogenesis including normal human erythrocytes, normal platelets and rat neuronal tissue. This cell-surface protein(s) cross-react(s) with double-stranded DNA. We suggest to call this protein(s) LAMP [lupus associated membrane protein(s)]. Here we show that: immunoglobulins eluted from kidneys of autoimmune MRL/lpr/lpr mice strongly react with LAMP. Anti-LAMP antibodies are present in large amount in MRL/lpr and B/W mice sera. Anti-LAMP are present in 25 out of 25 human SLE sera ranged as SLE on the basis of revised American Rheumatism Associated classification. Interestingly, two of these sera did not display anti DNA anti-body activity. Taken together, these results strongly suggest a role of LAMP in the pathogeny of SLE.

Animals↗

Idiotypes of monoclonal anti-DNA antibodies produced in autoimmune B/W mice are expressed in normal mice.

An anti-idiotypic antiserum was prepared in a rabbit immunized against a pool of six monoclonal anti-DNA antibodies generated in B/W mice. This antiserum detected idiotypic determinants in four of the six monoclonal anti-DNA antibodies but also in the serum of several non autoimmune strains (BALB/c, NZB X BALB/c) F1 hybrids & CBA/LH). The antiserum also reacted, but only to a weak degree, with B/W mouse sera. These results indicate that some idiotypes of anti-DNA antibodies produced by autoimmune B/W mice are present in normal mouse sera.

Animals↗

[Myasthenia induced by D-penicillamine. Study of immuno-clinical correlations in 23 cases].

Sera from 23 patients with D-penicillamine-induced myasthenia gravis (MG) contained antibodies directed against the human muscle acetylcholine receptor (anti-AChR) in 83% of the cases at the onset of the disease. Twenty-one were patients with rheumatoid arthritis. The anti-AChR antibody titers were comparable to those of sera from ocular MG patients and were related to the presence of clinical signs but not to their severity. The anti-AChR antibodies persisted in autonomous MG (5 cases) and disappeared in the other cases. The same phenomenon occurred for antinuclear antibodies detected in sera from 13 patients at the onset of the disease: anti-ss DNA 9/13, antinuclear 4/13 and anti-histones 7/13. The latter antibodies seem to result from, and follow the D-penicillamine treatment.

Adult↗

Binding of a monoclonal anti-DNA autoantibody to identical protein(s) present at the surface of several human cell types involved in lupus pathogenesis.

A monoclonal anti-DNA antibody PME77, spontaneously produced in autoimmune B/W mice, has been found to recognize identical protein(s) present at the surface of several human cell types involved in the pathogenesis of systemic lupus erythematosus: glomeruli, platelets, erythrocytes, T and B cells, and neuronal tissue. Data indicate that protein(s) could represent a major stimulus or the target of anti-DNA autoimmunity and could account for tissue lesions observed in this disease.

Animals↗

Cefonicid kinetics in subjects with normal and impaired renal function.

Cefonicid is a cephalosporin with a longer t1/2 than currently available cephalosporins. Cefonicid kinetics after an intravenous dose of 7.5 mg/kg were followed in four groups of subjects: group 1, four subjects with normal creatinine clearance (Clcr greater than 80 ml/min); group II, seven subjects with mild renal insufficiency (Clcr 50 to 80 ml/min); group III, five subjects with moderate to severe renal impairment (Clcr 8 to 49 ml/min); and group IV, five subjects with end-stage renal disease who were receiving maintenance hemodialysis (Clcr less than 8 ml/ml). Cefonicid volume of distribution ranged from 6.9% to 17.6% body weight but was not related to Clcr. Elimination t1/2 was 4.6 +/- 0.7 hr in group 1,6.0 +/- 2.7 hr in group II, 25.6 +/- 14.0 hr in group III, and 65.3 +/- 43.6 hr in group IV. There was a strong correlation between plasma cefonicid clearance and Clcr. Nonrenal clearance did not change with decreasing Clcr. Hemodialysis clearance calculated from plasma concentrations and recovery in dialysate was 2.5 +/- 0.9 ml/min. These kinetic parameters were used to formulate dosage regimens for patients with renal impairment.

Cefamandole↗

A monoclonal anti-DNA antibody also binds to cell-surface protein(s).

A murine monoclonal anti-DNA antibody ( PME77 ) has been found to bind tightly to the plasma membrane of Raji cells. We show here that this monoclonal anti-DNA antibody reacts in a radioimmunoassay with the cell surface of a variety of mammalian cell types and that the antigenic determinant recognized by the monoclonal anti-DNA antibody at the surface of Raji cells is resistant to DNase. It belongs to polypeptides removed from the cell surface by a mild proteinase K treatment.

Animals↗

Induction of anti-DNA autoanti-idiotypic antibodies in (NZB X NZW)F1 mice: possible role for specific immune suppression.

(NZB X NZW)F1 (B/W) mice spontaneously produce anti-deoxyribonucleic (DNA) acid antibodies. PME77 anti-DNA monoclonal antibody (MoAb) is a syngeneic antibody bearing idiotype present in most B/W sera. In the present investigation the effect of immunization of B/W mice with the PME77 MoAb on the production of PME77 idiotypes and anti-DNA antibodies in B/W mouse sera was investigated. PME77 MoAb immunization regimen induced the production of autoanti-idiotypic antibodies and abrogated the expression of PME77 idiotype in B/W treated mice. In contrast, untreated mice and control B/W mice, receiving NZB polyclonal IgG2b which lacked detectable DNA binding capacity, expressed PME77 idiotopes. These results demonstrate that the expression of idiotype borne by autoantibodies may be modified through the induction of autoanti-idiotypic antibodies.

Animals↗

[A new specificity for anti-DNA antibodies].

A monoclonal antibody directed against double stranded DNA obtained by fusion between myeloma cells and spleen cells from auto-immune B/W Mice, binds to protein(s) at the plasma membrane of human B lymphoblastoid cell lines Raji.

Animals↗