Repulsive van der Waals Forces. I. Complete Dissociation of Antigen-Antibody Complexes by Means of Negative van der Waals Forces

When two types of particles and/or macromolecules with different inter- facial free energies are immersed (or dissolved) in a liquid medium with an interfacial free energy intermediate between those of the particles or macro- molecules, the net van der Waals forces between these particles or molecules are repulsive. Thus by lowering the interfacial free energy (proportional to the surface tension) of their liquid medium, antigen-antibody (Ag-Ab) complexes of the van der Waals type can be readily dissociated, as could be demonstrated with the antigen 3-azopyridine (P₃) coupled to rabbit serum albumin (P₃A) and rabbit anti-P₃ antiserum. As surface tension lowering agents, ethylene glycol (EG) and dimethyl sulfoxide (DMSO) were principally used. Prevention of the formation of P₃A-anti-P₃ complexes could be effected with the addition of less EG or DMSO than was needed for the dissociation of the precipitate, once formed. The reasons for this effect are discussed. P₃A-anti-P₃ complexes dissociated with EG, re-precipitated upon removal of the EG by dialysis. The mixed Coulombic-van der Waals system, bovine serum albumin (BSA)-goat anti-BSA antiserum, could be dissociated by lowering the pH (to pH 4.0) or raising it (to pH 9.5) while simultaneously lowering the surface tension.     

The anatomy of the laryngeal ventricle and its importance in carcinoma of the vocal cords (author's transl)

An anatomical study was made of the sinus of Morgagni (laryngeal ventricle) in 10 normal larynges and 15 larynges with vocal cord carcinoma. The most striking difference in those patients with malignancy was the relatively greater goblet cell population found. It is assumed that these anatomical changes reflect a disturbed function of the laryngeal ventricle. The epithelial metaplasia and the high goblet cell count probably indicate an increased risk of vocal cord carcinoma.     

Radionuclide renography predicts functional changes in patients with renal artery involvement by Takayasu's arteritis

Renovascular hypertension is a major complication of Takayasu's arteritis, which contributes to the high mortality associated with the disease. We studied 5 patients affected by different degrees of Takayasu's arteritis to assess the usefulness of radionuclide renography in evaluating renal perfusion and function, and to predict changes induced by the disease before and after therapeutic interventions. Computer-assisted dynamic renal imaging with Tc-99m diethylenetriaminepentaacetic acid (DPTA) and I-131 orthoiodohippurate (OIH), and renal arteriography were concurrently performed in all patients. Two patients with hemodynamically insignificant renal artery stenosis showed normal perfusion and function by renography. Three patients had significant renal artery stenosis and functional changes on renography. Subsequently, two of these patients had successful therapy (one had bilateral renal artery bypass grafts, and the other had renal artery angioplasty), and both showed functional improvement at renography. Our results demonstrate that radionuclide renography is valuable in the assessment of functional changes induced by Takayasu's arteritis as well as for determining the response to therapeutic interventions.     

Proton-mediated liberation of aldophosphamide from a nontoxic prodrug: a strategy for tumor-selective activation of cytocidal drugs

Based on the findings that the pH in malignant tumors can be preferentially decreased by stimulation of their aerobic glycolysis, acid-sensible prodrugs, which are nearly nontoxic at physiological pH, were synthesized. At lower pH, however, these compounds are cleaved with liberation of a cytotoxic species. The prototypic drug compound 2-hexenopyranoside of aldophosphamide was prepared, which releases aldophosphamide by acid-catalyzed hydrolysis. Exposure of cultured M1R rat mammary carcinoma cells to this agent at pH 7.4 only resulted in slight toxicity. However, when drug treatment was performed at pH 6.2, the mean pH in malignant tumors of hyperglycemic hosts, the colony-forming fraction of M1R cells decreased to 0.05 and 0.0001 of controls treated at pH 7.4 after exposure for 24 h and 48 h, respectively. The synthesis of the 2-hexenopyranoside of aldophosphamide is described in detail.     

The nematocyst extract of Hydra attenuata causes single channel events in lipid bilayers

The nematocyst extract of Hydra attenuata causes single conductance events in reconstituted planar lipid membranes as well as in inside-out patches derived from liposomes. The smallest single channel conductance level of the toxins is 110 pS. The conductance levels increase stepwise with time up to 2000 pS. These large conductance jumps indicate channel cooperativity. If the membrane-voltage is changed from positive to negative values, the single channel events become undefined and noisy, indicating major reorganizations of the proteins which form the channels. The molecular properties of the ionophoric component(s) of the nematocyst extract may help explain the observed macroscopic effects, such as hemolysis of human erythrocytes, after addition of the nematocyst extract.