Chronic one-kidney hypertension in rabbits. I. Treatment with kidney extracts.

An investigation into the mechanism that sustains the blood pressure in chronic one-kidney hypertension in rabbits was made using passive and active immunization with hog kidney extracts containing renin and with angiotensin antagonists. Seven hypertensive rabbits were passively immunized for extended periods with antiserum prepared in other rabbits. Antirenin levels were in the range of 1-3 units/ml. Control experiments demonstrated that antirenin concentrations of 1.0 unit/ml or more eliminated more than 99% of the pressor response to renin. There was no lowering of blood pressure that could be attributed to the antibodies. No decrease in blood pressure was observed in 13 experiments in 7 rabbits given the angiotensin II antagonist 1-Sar-8-Ile-angiotensin II; infusion rates of 0.09-87 mug/min kg-1 were used for periods of a few hours up to 3 days. A reduction in blood pressure occurred in 16 of 19 rabbits immunized directly with extracts containing renin with specific activities of 9.6-757 GU/mg. Plasma antirenin titers correlated poorly with reductions in blood pressure. The blood pressure of 22 rabbits given equal amounts of protein without renin was unaffected. It is concluded that the elevation of blood pressure in rabbits with chronic one-kidney hypertension is not dependent on ciculating renin or angiotensin; rather, it results from the presence of renin in an extravascular location or from an unknown pressor substance.     

Distribution of alpha-bungarotoxin binding sites over residues 173-204 of the alpha subunit of the acetylcholine receptor

The binding of alpha-bungarotoxin to several synthetic peptides comprising different segments of the region 173-204 of the alpha subunit of the Torpedo acetylcholine receptor was investigated to further localize the neurotoxin-binding site on the primary sequence. When tested in a solid phase microwell assay system, a 32-amino acid peptide corresponding to residues 173-204 (32-mer) bound 125I-alpha-bungarotoxin with the same affinity (4.2 x 10(-8) M as determined from IC50 values) as the isolated alpha subunit (4.6 x 10(-8) M). The relative affinities of other antagonists (alpha-cobratoxin, d-tubocurarine) maintained the same rank order in this assay system as has been demonstrated with the intact receptor. Agonists competed with binding of toxin at millimolar concentrations but lost all rank order of potency. These findings demonstrate that peptide 173-204 contains many of the antagonist-binding determinants present on denatured alpha subunit but has lost specificity of agonist binding. To further localize the toxin-binding site, alpha-bungarotoxin binding to seven shorter peptides corresponding to portions of the 32-mer was investigated. 125I-alpha-Bungarotoxin bound to alpha subunit peptides 179-192, 181-198, 185-196, 186-196, and 193-204, but not to alpha subunit peptides 173-180 and 194-204. In a second assay, all of the peptides competed with binding of 125I-acetylcholine receptor to immobilized alpha-bungarotoxin. The apparent affinity was highest for the 173-204 32-mer (1.4 x 10(-7) M) and lowest for peptides 173-180 and 194-204 (greater than 10(-4) M). The affinity of the other peptides was intermediate (approximately 10(-5) M) and about 100-fold less than that of the 32-mer. The affinity of alpha-bungarotoxin was 3.5 x 10(-10) M, of isolated, native acetylcholine receptor, 3.2 x 10(-9) M, and of isolated denatured subunit, 1.2 x 10(-8) M, with this assay. The retention of some toxin-binding capacity by the shorter peptides indicates toxin-binding determinants are distributed over the entire length of the 32-mer. The determinants with higher affinity are located in the central region of the 32-mer between residues 179 and 196.     

Association of factor V activity with membranous vesicles released from human platelets: requirement for platelet stimulation

The membrane-associated factor V-like activity (platelet factor 1, PF1) and the phospholipid-like catalytic surface activity (platelet factor 3, PF3) were studied in human platelets from normal and two factor V-deficient donors. Collagen stimulation or mechanical disruption of gel-filtered platelets was necessary for the expression of significant amounts of PF1 and PF3. Stimulation was also necessary for the uptake of factor V or Va by PF1-deficient platelets from the factor V-deficient donors. The activity of PF1 was also generated by association of factor V or Va with membrane-rich fractions obtained by gel filtration of the supernatant from collagen-stimulated or frozen-thawed PF1-deficient platelets. The amount of PF1 obtained by such all-or-none binding experiments was directly proportional to the amount of PF3 already expressed in the platelet preparation. These data have been summarized in terms of a hypothesis which views PF1 and PF3 to be activities associated with membranous vesicles released from platelets only after stimulation.     

Effectiveness of sampling-exposure procedures on facilities utilization by psychiatric hard-core chronic patients

Sampling-exposure procedures patterned on those of Ayllon and Azrin (1968 a, b) were systematically introduced, alternating with regular pass procedures, in an attempt to increase use of off unit facilities and services by residents of milieu and social-learning treatment units. Social-learning unit residents (for whom passes cost tokens) remained unaffected by the experimental conditions for 22-week duration of the study, using services at a frequency consistently and significantly below that of milieu unit residents (for whom passes were “free”). However, milieu unit residents' utilization was dramatically increased by the sampling-exposure procedures, generalized to alternating announce-only procedures, and continued at a significantly higher level at a final extended baseline.     

Indications, contra-indications, expected results and choice of neoadjuvant chemotherapy for operable breast cancer

Neoadjuvant chemotherapy in breast cancer corresponds to the use of a systemic treatment applied before loco-regional treatment (surgery and/or radiotherapy). Initiated in the seventies for treatment of the locally advanced and/or inflammatory breast cancers, induction chemotherapy has been extended in the beginning of eighties for cancers known as operable (size higher than 3 cm and/or in central position) in order to allow a more frequent conservating surgery. This objective is obtained in 75% of the cases approximately without increase in the risk of local relapse and without noxious effect on overall survival, in spite of the delay of the loco-regional treatment. Neo-adjuvant chemotherapy progressively moved with the advent of major drugs in breast cancer which are anthracyclins, vinorelbine and taxans. But to date, no protocol was essential like an uncontested standard. However, it seems that obtaining a complete clinical response is the best guarantor to avoid relapse. That seems to be observed only after 6 cycles, even 8 cycles of chemotherapy, each cycle combining the 2 major drugs for the treatment of breast cancer of which are anthracyclins and taxanes employed according a sequential scheme after a based-anthracyclins treatment, except any cardiac contra-indication. Moreover, the use of targeted therapeuticals like Herceptin, with a chemotherapy, seems to be promising and should be more studied. Finally, when a neoadjuvant chemotherapy is administered, the evaluation of the pre-treatment biopsy helps to establish key patient-management parameters such as tumour type, SBR grade and immunohistochemical parameters. This evaluation provides predictive parameters with regards to drug response (hormonal status, overexpression of Her2). The further studies realised in this way will permit to improve the results yet obtained.