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Biomedical subjects

R Abraham

Publications and source records attributed to R Abraham.

At least 181 records · Page 10Linked to original sources

Pigmented gut.

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Animals↗

Determination of binding constants of diabodies directed against prostate-specific antigen using electrochemiluminescence-based immunoassays.

Two diabody molecules directed against the prostate-specific antigen (PSA) were generated from a combinatorial phage display library. The C-termini of diabodies incorporated the FLAG peptide epitope (P008D diabody) or the myc epitope (P001D). Both diabodies have the same antigen-binding site. Equilibrium-binding constants of these molecules were determined in two immunoassays using the ORIGEN detection system based on electrochemiluminescence. The binding of diabodies to biotinylated PSA was detected with either polyclonal antimouse Fab F(ab')2 or a monoclonal antibody directed against the FLAG epitope. Both detecting antibody preparations were covalently labeled with a ruthenium (II) tris (bipyridyl) moiety, Ru(bpy)3(2+), which allows quantification via an electrochemically triggered light reaction in an ORIGEN analyzer. The binding constants obtained by Scatchard analysis of non-linear curve fitting calculations from electrochemiluminescence immunoassays were compared with data derived from kinetic-binding studies using the BIAcore technology based on surface plasmon resonance. Depending on the detecting antibody, the dissociation constants KD determined at equilibrium with the ORIGEN technology are between 0.1 and 0.4 nM for both diabodies. From the kinetic constants kon and koff measured with the BIAcore instrument KD was calculated to be 0.2 nM for P001D and 0.6 nM for P008D. It is concluded that these two very different methods generate comparable affinity data for the diabodies.

Animals↗

EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF.

Cross-communication between different signalling systems allows the integration of the great diversity of stimuli that a cell receives under varying physiological situations. The transactivation of epidermal growth factor receptor (EGFR)-dependent signalling pathways upon stimulation of G-protein-coupled receptors (GPCRs), which are critical for the mitogenic activity of ligands such as lysophosphatidic acid, endothelin, thrombin, bombesin and carbachol, provides evidence for such an interconnected communication network. Here we show that EGFR transactivation upon GPCR stimulation involves proHB-EGF and a metalloproteinase activity that is rapidly induced upon GPCR-ligand interaction. We show that inhibition of proHB-EGF processing blocks GPCR-induced EGFR transactivation and downstream signals. The pathophysiological significance of this mechanism is demonstrated by inhibition of constitutive EGFR activity upon treatment of PC3 prostate carcinoma cells with the metalloproteinase inhibitor batimastat. Together, our results establish a new mechanistic concept for cross-communication among different signalling systems.

ADAM Proteins↗

Size and shape in dermatoglyphic analysis of palmar interdigital areas.

With very few exceptions, dermatoglyphic methodology either refers to shape (pattern) or to size (quantitative value). In this study, an attempt is made to consider simultaneously these two basic components of morphology in the analysis of the third palmar interdigital area. For this purpose, three criteria of shape and bc ridgecount (size) were studied in 150 male and 150 female Viennese pupils, and were each classified according to whether they could be interpreted as showing strong reduction, slight reduction or no reduction. Their frequencies alone and in combination were calculated. Their interrelation with the mean ridge counts and their comparison with the traditional reduction types of c-triradius or mainline C strongly suggest that the traditional notation is not sufficiently precise to evaluate criteria of reduction which are thought to indicate different embryonic growth patterns.

Child↗

Acute embryopathic effects of ethanol in the Long-Evans rat.

Thirty-two pregnant Long-Evans rats were divided into 10 groups of 3 or 4 pregnant rats, and each rat was given a single dose of 4 ml ethanol/kg (20 ml/kg of a 20% solution) between d 6 and 15 of gestation. An 11th group of 50 pregnant rats received distilled water and served as controls. Offspring body weights were decreased in groups of rats given ethanol as compared to controls (3.0-3.6 g, versus 3.9 g for controls). Total litter weight was decreased in dams given ethanol on d 6. Skeletal variants were seen in 13-78% of the offspring given ethanol, compared to 0.6% of the controls. Variations may be considered as additional signs of embryotoxicity. Malformations such as hydronephrosis, pelvic kidney, microcephalus, cranioschisis, and microphthalmia occurred in 72-100% of the ethanol treated offspring, as compared to 12% of controls. Hydronephrosis was most frequent on d 9 or 14, pelvic kidney on d 8 and 11, and microphthalmia from d 10-12. Cranioschisis was maximal on d 7, 11, and 15, and microcephalic offspring were most frequently born to dams given ethanol on d 7 or 14. Skeletal defects were usually single entities, while soft-tissue anomalies occurred in a consistent pattern. These results suggest that ethanol is a stage-specific teratogen in the rat at comparable exposure levels attained by many humans.

Abnormalities, Drug-Induced↗

Effects of various exposure levels of 2-phenylethanol on fetal development and survival in Long-Evans rats.

Phenylethanol was given at different levels (432, 43, or 4.3 mg/kg) by gavage to pregnant Long-Evans rats during the "critical period" of organogenesis. Examination of offspring revealed adverse reproductive and teratogenic effects in a dose-related manner. Intrauterine growth retardation occurred at levels of 432 and 4.3 mg/kg. Embryolethality was 18% at 43 mg/kg and 10% at 4.3 mg/kg. Malformations occurred in the following sequence: 100% at 432 mg/kg; 93% at 43 mg/kg, and 50% at 4.3 mg/kg. Noteworthy dose-related teratogenic effects of phenylethanol in offspring manifested themselves in increased incidences of malformed eyes, neural-tube defects, hydronephrosis, and limb defects.

Animals↗

Synthesis and biological behavior of a boronated analogue of the antiestrogen U 23,469-M.

A boronated analogue of the antiestrogen U 23,469-M (D. Lednicer, D. W. Emmert, S. C. Lyster, and G. W. Duncan, J. Med. Chem. 12, 881 (1969] was prepared, for possible use in neutron capture therapy of estrogen receptor-positive tumors. In this analogue, the terminal OH group was replaced by a B-decachloro-o-carboranyl residue. This compound showed a large, non-specific uptake in ZR 75-1 breast cancer-derived cells. It could partially inhibit the uptake of estradiol in these cells. Accumulation in the cells at physiologically obtainable concentrations was, however, too low to envisage a therapeutic effect following thermal neutron irradiation.

Boron↗