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L Laurence

Publications and source records attributed to L Laurence.

11 recordsLinked to original sources
PubMed1987

Epitope design for the induction of antibodies which recognize a family of molecules: example of monoclonal antibodies to 2'-5' oligoadenylates.

Monoclonal antibodies directed against 2'-5' oligoadenylates (pxA(2'pA)n 0 less than or equal to x less than or equal to 3, n greater than or equal to 1) have been obtained with A2'pA-succinyl albumin as immunogen. A competition assay using 125I iodo succinyl A2'pA tyrosine methyl ester as a tracer and thirty chemically related analogs was used to investigate the molecular basis governing their reactivity. We show that the use of a hapten as small as A2'pA elicits antibodies of high affinity for this dinucleotide (Kd = 2 x 10(-11) M). The overall immunoreactivity is essentially shared between the first moiety (5'OH A2'p) and the 2'-5' phosphodiester bond; however, the second moiety is an integral part of the epitope which extends up to the spacer. Therefore, any modification at the 5'OH end or of the 2'-5' structure dramatically decreases the binding. Modifications at the 2' and/or 3' ends are favourable if they mimic the immunogen. Modifications of the ribose backbone reveal the part of antigenicity due to the different 3'OH groups. Substitution of the bases show that the second adenine is implicated in the antigenicity. We demonstrate how, with such requirements, these antibodies recognize A2'pA alone or at the 5' end of or else included in longer oligonucleotides.

Adenine Nucleotides↗
PubMed1985

Comparison of the effects of rabies virus infection and of combined interferon and poly(I).poly(C) treatment on the levels of 2',5'-adenyladenosine oligonucleotides in different organs of mice.

Intracellular levels of 2',5'-adenyladenosine oligonucleotides were analyzed in different organs of mice during the course of a rabies virus infection. Phosphorylated and nonphosphorylated 2',5'-adenyladenosine oligonucleotides were measured by radioimmunoassay and analyzed further by HPLC. As the infection progressed, concentrations of phosphorylated 2',5'-adenyladenosine oligonucleotides increased strongly, reaching their maxima late in the infection. In contrast, concentrations of the nonphosphorylated 2',5'-adenyladenosine oligonucleotides decreased. A similar phenomenon was observed in spleens analyzed at intervals after treatment of noninfected mice with interferon and poly(I).poly(C) and to a lesser extent after treatment of noninfected mice with interferon and poly(I).poly(C) and to a lesser extent after treatment with poly(I).poly(C) alone, but not after treatment with interferon alone. The products which accumulated during virus infection were primarily phosphorylated dimers whereas during combined interferon and poly(I).poly(C) treatment, the entire range of phosphorylated molecules from dimer to pentamer was present. These data show that infection of mice with rabies virus provokes both the induction and the activation of 2-5A synthetase, as does interferon and poly(I).poly(C) treatment. However, our data indicate that the intracellular products are different in the two situations: the species active on the nuclease were only detected in interferon- and poly(I).poly(C)-treated mice. The absence of molecules able to activate the 2-5A-dependent nuclease in virus-infected mice might well be one of the reasons why the interferon system is ineffective in rabies virus infection.

Adenine Nucleotides↗
PubMed1984

Immunological evidence for the in vivo occurrence of (2'-5')adenylyladenosine oligonucleotides in eukaryotes and prokaryotes.

A monoclonal antibody highly specific for (2'-5')adenylyladenosine oligonucleotides was used together with a 125I-labeled analog of this compound to detect and quantify phosphorylated and nonphosphorylated (2'-5')adenylyladenosine oligonucleotides in a variety of tissues and cells. These oligonucleotides were first assayed as a whole in perchloric acid extracts and then further individually characterized by HPLC analysis. Their sensitivity to alkaline phosphatase, snake venom phosphodiesterase, and T2 RNase was systematically checked. Nonphosphorylated (2'-5')adenylyladenosine oligonucleotides were found in mammalian tissues as well as in yeast and bacteria. In normal mouse brain, lung, heart, pancreas, spleen, kidney, and liver their concentrations ranged from 10 to 200 pmol/g wet weight, depending on tissue and strain. The oligonucleotides were mainly dimers, trimers, tetramers, and pentamers. In addition, phosphorylated (2'-5')adenylyladenosine oligonucleotides were shown in liver and kidney extracts.

Adenine Nucleotides↗
PubMed1981

A comparison of the MMPI results for psychiatric patients and male applicants for transsexual surgery.

Previous studies have been evenly divided in concluding that male sex change applicants do or do not evidence signs of psychopathology on Minnesota Multiphasic Personality Inventory testing. To clarify the discrepant findings, Minnesota Multiphasic Personality Inventory scale comparisons were made between sex change applicants who had been living continuously as women, applicants who had been living predominantly as men, and groups of psychiatric inpatients and outpatients. Findings revealed that members of both applicant groups were more likely than psychiatric patients to score high on a measure of femininity. However, applicants living as men were as disturbed as psychiatric patients on all other measures of psychopathology, whereas those living as women showed a notable absence of psychopathology. Like the psychiatric patients, applicants living as men produced significant elevations on the Depression, Psychopathic Deviate, Psychasthenia, and Schizophrenia Scales. A variety of group comparisons also revealed serious emotional disturbance in one sex change applicant group and none in the other. The results help to explain the previous discrepancies in the literature and underline the importance of the "living as female" variable for predicting disturbance in sex change applicants.

Adult↗
PubMed1976

Luminal eccentricity and deformity in atherosclerotic coronary arteries.

Detailed analyses of the configuration of lumina from one hundred (100) segments of severely atherosclerotic epicardial coronary arteries (at least 75 p. 100 of the area of their original lumina narrowed, determined by planimetry) were made. All lumina were distended by a standardized coronary injection technique. In contrast to the general impression, concentric lumina occurred as commonly as eccentric lumina and there were more arteries with an eccentric lumen and/or with significant luminal deformity, i.e. with their smallest diameter smaller than 50 p. 100 of their greatest diameter, than the concentric and more regular ones. The eccentricity and significant deformity of atherosclerotic lumina apparently cause difficulties in precise angiographic measurements of coronary stenosis. To solve the problem of the discrepancies between angiographic and anatomical estimation of coronary arterial stenosis, utilization of more than three different projection angles should be considered in clinical angiographic appraisal.

Angiography↗
PubMed1975

Atherosclerotic occlusions in anomalous left circumflex coronary arteries. A report of two unusual cases & a review of pertinent literature.

Two cases of atherosclerotic occlusion of anomalous left circumflex coronary arteries having origin from a common ostium with the left coronary artery are documented. The atheromatous lesion was found at the same site in each case, i.e. the junction of the segment bound to the posterior wall of the aorta and its freer course in the atrioventricular sulcus. It appears that these junctions have an increased susceptibility to atherosclerotic changes, to local hemodynamic factors and local trauma related to the sudden change from a fixed artery to one lying relatively unfixed in the fibro-fatty tissue of the atrioventricular sulcus.

Coronary Disease↗
PubMedDate not supplied

Enzyme immunoassay of 2'-5'-oligoadenylates at the femtomole level.

We have developed a competition enzyme immunoassay (EIA) for 2'-5'-oligoadenylates [p kappa(A2'p5')nA; 0 less than or equal to kappa less than or equal to 3; 1 less than or equal to n] based on an anti-A2'p5' A monoclonal antibody coated onto 96-well polystyrene plates and A2'p5' A peroxidase as a marker. It permits measurement of 5'OH(A2'p5')nA as such and p kappa(A2'p5')nA after alkaline phosphatase hydrolysis, with a detection threshold of 5 X 10(-12) M. All 2'-5'-oligomers were assayed with similar sensitivity. ATP and adenosine did not interfere at concentrations up to 10(6)-fold higher than those of 2'-5'-oligoadenylates. Reproducibility, stability of reagents and correlation with the radioimmunoassay were good. As such, this EIA is a suitable tool for studying the 2-5A system, particularly, in clinical investigations: the initial velocity of 2-5A synthetase can be determined on 10,000 cells without purification and the level of 2'-5'-oligoadenylates can be assayed on less than 1 ml of blood.

Adenine Nucleotides↗
PubMedDate not supplied

High concentrations of 2-5A, the interferon intracellular mediator, in the blood of children with acute viral infections.

We measured the concentration of 2-5A (2',5'-oligoadenylate), an intracellular mediator of the antiviral action of interferon, in the blood of children with acute viral and bacterial infectious diseases. 2-5A concentration was found to be elevated in several children with viral diseases. This elevation seemed transient and was not specific for viral infections. We provide arguments for the use of 2-5A as a marker of the evolution of diagnosed viral diseases.

Acute Disease↗