Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The orally active neutral metalloendopeptidase (NEP) inhibitor SCH34826 was given by oral gavage in a dose of 90 mg/kg twice daily for 3 days to rats with subtotal nephrectomy (n = 7) and effects were compared to a placebo group receiving phosphate buffer (n = 5). Inhibition of neutral endopeptidase in the remnant kidney was measured by in vitro autoradiography using the specific radioligand [125I]-SCH 47896. Treatment with the NEP inhibitor SCH34826 caused a 60% reduction in the neutral endopeptidase radioligand-binding site density in the kidneys of the SCH34826-treated animals compared to the placebo group (81.6+/-3.7 versus 214.5+/-4.2 dpm/mm2, p<0.01). This was associated with a marked increase in urinary atrial natriuretic peptide (ANP) from 3,930+/-295 to 9,094+/-1,089 pg/24 h in the SCH34826-treated group (p<0.01). Concomitantly there was a transient increase in natriuresis in the SCH34826-treated group [baseline 2.03+/-0.55 to 3.77+/-0.58 mmol/24 h on treatment day 1 (p = 0.02) and 2.58+/-0.19 mmol/24 h on treatment day 3 (p = 0.09)] which was not observed in the placebo group. Urinary protein excretion, glomerular filtration rate (determined by 99mTc-DTPA clearance), systemic blood pressure, plasma ANP concentration and urinary cyclic GMP excretion were not changed by SCH34826 treatment. These results suggest that oral administration of the NEP inhibitor SCH34826 inhibits renal neutral endopeptidase, increases urinary ANP and modulates natriuresis without alteration of systemic blood pressure, plasma ANP and renin level, glomerular filtration or protein excretion.
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PMID:Effects of neutral endopeptidase inhibition in the rat remnant kidney model. 993 26

Radioimmunotherapy recently afforded convincing results for B-cell non-Hodgkin's lymphoma treatment with antibody specific for B-cell differentiation antigens. High doses of unlabeled or labeled antibodies are necessary to saturate specific sites on normal B-cells. We thus developed a new targeting strategy, taking advantage of dual binding cooperativity, to enhance the specificity of the radioactive uptake by tumor cells. This approach was evaluated using human Burkitt lymphoma cells (Ramos) which express both CD10 and CD20 antigens. Most normal cells express at most one of these two differentiation antigens but many hematological tumors, including most human B type acute lymphoblastic leukemia cells, express both. Cells pretargeted with two bispecific antibodies, one recognizing CD10 and a histamine derivative (HSG), the other recognizing CD20 and the DTPA-indium complex, bind cooperatively radiolabeled mixed-haptens (DTPA-HSG). Increased binding (about 5-fold compared to binding to only one of CD10 or CD20 antigens) is observed at 37 degrees C, demonstrating the feasibility of the technique. This binding enhancement is a slow process, not observed at 4 degrees C. Such a binding enhancement will increase specificity for targeting isotopes to double antigen positive tumor cells compared to nontumor tissue cells bearing only one of them. This approach might be used to increase tumor irradiation with minimal irradiation of normal cells.
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PMID:Enhanced targeting specificity to tumor cells by simultaneous recognition of two antigens. 1089 65