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L Jacob

Publications and source records attributed to L Jacob.

At least 73 records · Page 4Linked to original sources
PubMed1987

Structure of the l(2)gl gene of Drosophila and delimitation of its tumor suppressor domain.

We have previously cloned lethal(2)giant larvae, a tumor-suppressor gene of Drosophila that normally controls cell proliferation and/or differentiation in the optic centers of the brain and the imaginal discs. Here we describe the structure of the l(2)gl genes as determined by sequencing genomic and cDNA clones. The structure of the cDNAs indicates the use of alternative splicing, either in the 5' untranslated exons or in the 3' coding exons. Thus the gene encodes two putative proteins of 1161 and 708 amino acids, p127 and p78, respectively, differing at their C termini. A 3'-truncated l(2)gl transposon that leaves the coding sequence of p78 intact but deletes 141 residues of p127 was capable of suppressing tumor formation in l(2)gl-deficient animals. These results suggest that the putative p78 protein is effective in controlling cell proliferation and/or differentiation.

Amino Acid Sequence↗
PubMed1987

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

A monoclonal anti-DNA autoantibody (EM85) produced in an autoimmune MRL/lpr/lpr mouse was studied. Its antigenic specificity was demonstrated to be directed against single-stranded DNA, double-stranded DNA, and also a variety of polynucleotides. We have recently reported that a murine monoclonal anti-DNA autoantibody produced in autoimmune B/W mice, with specificity for double-stranded DNA, also binds to cell-surface protein(s). We show here that EM85, which recognizes a variety of polynucleotides, also binds to protein(s) on the surface of Raji cells. These data indicate that the antigenic determinant, recognized by this monoclonal anti-DNA antibody, is common to a variety of polynucleotides and cell-surface protein(s).

Animals↗
PubMed1987

Splenocytes from MRL/Mp-lpr/lpr mice spontaneously produce antibodies against a cell-surface protein cross-reacting with DNA.

Anti-double-stranded (ds) DNA autoantibodies are considered as pathogenic in systemic lupus erythematosus (SLE). Anti-DNA antibodies have been shown to be released by B cells from lupus mice or patients in vitro. A monoclonal anti-DNA antibody (PME 77) specific for dsDNA has previously been shown to react with a cell-surface protein called LAMP (lupus-associated membrane protein), which is present on the cell surface of various cell types involved in SLE pathogenesis. Using an immunoreplica analysis technique, we show here that spleen cells from MRL/Mp-lpr/lpr lupus mice, cultured in vitro, spontaneously produce anti-LAMP IgG antibodies. Conversely, anti-LAMP antibodies were not detected in spleen-cell culture supernatants from nonautoimmune CBA/Ca mice. Taken together with our previous reports, this result adds a new argument for a pathogenic role of anti-LAMP autoantibodies in SLE.

Animals↗
PubMed1987

Altered cell-surface protein(s), crossreactive with DNA, on spleen cells of autoimmune lupic mice.

A murine monoclonal anti-DNA antibody, PME77, with specificity for double-stranded DNA, has previously been shown to react with a protein(s) present at the surface of such cells involved in lupus pathogenesis as human glomeruli, T and B lymphocytes, erythrocytes, and platelets. Mild elastase treatment of lymphoid cells from non-autoimmune (CBA/ca or BALB/c) mice releases a series of crossreactive polypeptides (34, 33, 17, 16, and 14 kDa) recognized by PME77. These polypeptides are not formed after treatment of the same cells with papain or trypsin. When lymphoid cells from autoimmune [MRL-lpr/lpr or (NZB X NZW)F1 B/W] mice are treated with elastase, trypsin, or papain, PME77 detects, in all supernatants, a single polypeptide of about 55 kDa. Antibodies present in the sera of autoimmune MRL-lpr/lpr and B/W mice and IgG eluted from kidneys of MRL-lpr/lpr mice react with the same polypeptides. Neither sera nor eluted IgG of normal BALB/c mice react with these polypeptides. These results suggest that an altered cell-surface protein(s), which we call LAMP [for lupus-associated membrane protein(s)], may be involved in lupus pathogenesis.

Animals↗
PubMed1987

Presence of antibodies against a cell-surface protein, cross-reactive with DNA, in systemic lupus erythematosus: a marker of the disease.

Antibodies against a cell-surface protein, cross-reactive with double-stranded DNA, were detected in the serum of 25 patients with active human systemic lupus erythematosus (SLE), defined on the basis of the revised American Rheumatism Association classification. Among these sera, two did not display anti-DNA antibodies, as shown by Farr assay, solid-phase radioimmunoassay, and Crithidia luciliae test. Five other SLE patients were consecutively studied in active and remission states. Antibodies against the protein were detected in the serum of the 5 SLE patients when they were in active phase but not in the serum of the same patients in inactive phase of the disease. The anti-protein antibodies were not found in the serum of 10 inactive SLE patients or in the sera of 10 normal human controls, 10 patients with rheumatoid arthritis, 5 patients with scleroderma, and 4 patients with primary sicca syndrome. Taken together, these results strongly suggest that antibodies against this cell-surface protein could provide a better diagnosis marker and activity index than anti-DNA antibodies in SLE.

Antigens, Surface↗
PubMed1987

[Lupus associated membrane protein. Changes in the sensitivity of proteases during the life span of mice with lupus].

A murine monoclonal anti-DNA antibody, PME77, spontaneously produced in autoimmune B/W mouse, has been shown to react with a protein present at the surface of several cells involved in lupus pathogenesis. We have called this cell-surface protein LAMP (Lupus Associated Membrane Protein). Mild elastase treatment of lymphoid cells from non autoimmune (BALB/c or CBA/ca) mice releases five polypeptides (34, 33, 17, 16 and 14 kDa) recognized by PME77. These polypeptides are not found after treatment of these cells with papain or trypsin. When lymphoid cells from autoimmune mice (MRL/lpr/lpr and B/W) are treated with elastase, trypsin or papain, PME77 detected in all supernatants a single polypeptide of 55 kDa. It is demonstrated in the present work that: (1) this 55 kDa polypeptide is also detected in the elastase supernatant of glomeruli from MRL/lpr/lpr and B/W mice but not from BALB/c and CBA/ca mice. These results suggest that LAMP expressed at the surface of lymphoid and glomerular cells from lupus mice displays altered sensitivity to proteases. (2) The change in sensitivity to proteolytic enzymes appears between 1 and 3 weeks after birth in MRL/lpr/lpr mice. Such modifications might results in the appearance of a non-self antigen and elicit an anti-LAMP immune response.

Animals↗
PubMed1987

Hormonal response to captopril pre-treatment during sodium nitroprusside-induced hypotension in man.

To assess the hormonal response to captopril pre-treatment during sodium nitroprusside (SNP) -induced hypotension, 12 patients were studied during a spinal surgical procedure. Haemodynamic data, plasma-renin activity, aldosterone, adrenaline and noradrenaline levels were measured. Patients were randomly allocated to two groups: Group I, control patients; Group II, 3 mg kg-1 captopril pre-treated patients. SNP requirement for the same level (mean arterial pressure (MAP) = 55 mmHg) and duration of hypotension (88.5 +/- 28.7 vs. 95.2 +/- 22.5 min) was significantly lower in Group II than in Group I (16.5 +/- 14.2 mg vs. 39.3 +/- 16.7 mg; P less than 0.05) and a lower SNP infusion rate was required to induce and to maintain hypotension. In Group II patients, MAP remained significantly lower than the control and Group I values for 30 min after SNP withdrawal. Cardiac index (CI) remained stable in both groups. Heart rate was not modified in Group II during hypotension. Plasma-renin activity rose more dramatically in Group II patients than in Group I both during hypotension (13.9 +/- 7.5 vs. 2.8 +/- 0.9 ng ml-1 h-1; P less than 0.05) and after hypotension (23.4 +/- 15.4 vs. 2.2 +/- 0.8 ng ml-1 h-1; P less than 0.05). Plasma catecholamine levels increased in both groups during hypotension and remained raised in captopril patients after SNP withdrawal. It can be concluded that recovery from hypotension may be delayed when using captopril and that sympathoadrenal activity induced by hypotension is not substantially altered by captopril pre-treatment, suggesting that sympathetic blockade might not be the mechanism by which captopril reduces SNP requirement during controlled hypotension for surgical procedure in man.

Adult↗
PubMed1986

Effects of three H2 antagonists on the isolated perfused rat liver. Correlation of bile flow changes with potential for causing hepatic disease in patients.

The adverse effects of oxmetidine, an H2 blocking agent which has been shown to produce hepatic injury in 1-4% of patients, on an in vitro model were compared with those of cimetidine and ranitidine which have led to only rare instances of hepatic injury. Bile flow was measured in the isolated perfused rat liver (Wistar rats), comparing the effects of each of the three drugs with control perfusions. Oxmetidine in concentrations of 3 X 10(-3) M or greater led to a decrease in bile flow within 15 min and, at a concentration of 5 X 10(-3) M, to complete cessation of flow within 5 min. Lower concentrations (5 X 10(-4) M) led to a marked choleresis. Ranitidine and cimetidine in concentrations up to 5 X 10(-3) M produced no decrease in bile flow. Ranitidine, however, led to a choleresis at a concentration of 5 X 10(-3) M. 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↗
PubMed1986

Human systemic lupus erythematosus sera contain antibodies against cell-surface protein(s) that share(s) epitope(s) with DNA.

In previous work, a murine monoclonal anti-DNA antibody (PME77) with specificity for double-stranded DNA has been found to bind five polypeptides (34, 33, 17, 16, and 14 kDa) that are expressed at the surface of several human cell types involved in lupus pathogenesis. To determine more precisely the nature of the antigens recognized by the PME77 monoclonal antibody, and to release cell-surface-accessible fragments, we used a mild, controlled elastase treatment. We isolated several of these polypeptides by immunoaffinity chromatography. A polyclonal antibody was prepared by immunizing a rabbit with a mixture of these polypeptides (17, 16, and 14 kDa) adsorbed on nitrocellulose. This antibody was shown to react with 17-, 16-, and 14-kDa polypeptides. This antibody does not bind to double-stranded DNA, suggesting that most of the immunogenic determinants of these polypeptides are not shared by double-stranded DNA. Of six human systemic lupus erythematosus sera tested, all contained antibodies that recognized this cell-surface protein(s) and crossreacted with double-stranded DNA. We suggest that this protein(s) be called LAMP [lupus-associated membrane protein(s)].

Antibodies↗
PubMed1986

The pharmacokinetics of droperidol in anesthetized patients.

A pharmacokinetic study of droperidol was performed in ten anesthetized patients receiving an intravenous bolus dose of 150 micrograms/kg of droperidol. Plasma concentrations were measured using a specific radioimmunoassay method. The pharmacokinetics of droperidol can be described according to a three-compartment open model. The mean (+/- SD) half-life for the rapid (t 1/2 pi) and slow distribution t 1/2 alpha) phases was 1.4 +/- 0.5 min and 14.3 +/- 6.5 min, respectively. The mean elimination half-life, t 1/2 beta was 103.8 +/- 20.2 min. The mean (+/- SD) total body clearance was 14.1 +/- 4.4 ml X min-1 X kg-1, and the total apparent volume of distribution (Vd beta) was 2.04 +/- 0.50 l/kg. The short terminal half-life of droperidol does not correlate with the well-known, relatively prolonged duration of its pharmacologic action.

Adult↗