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Initiation of protein synthesis in Escherichia coli is a catalytic process, provided that conditions for hydrolysis of GTP are present. This means that the initiation factors IF-1, IF-2 and IF-3 are released at a certain stage of initiation complex formation, whereafter they recycle and are reutilized in another round of initiation. Experiments presented in this paper provide evidence for the mechanism of recycling, in which the hydrolysis of GTP and IF-1 both play a predominant role. We demonstrate that binding of fMet-tRNA, which is dependent on IF-2, is a stoichiometric process in a system devoid of IF-1. Addition of IF-1 converts it into a catalytic process, however, only if GTP can be hydrolysed. No such conversion takes place with 5′-guanylylmethylenediphosphonate. The same observation is valid for the uncoupled IF-2 dependent GTPase activity. In the process of initiation IF-1 acts as a recycling promoting factor, which displays analogous properties to elongation factor EF-Ts. We postulate that a ribosomal-bound IF-2 · GDP complex is converted into an IF-2 · GTP complex, which is released and is capable of starting a new cycle of initiation. Furthermore, kinetic evidence is presented that IF-3 recycles even at the level of 30-S initiation complex formation, irrespective of whether conditions for hydrolysis of GTP are provided. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a conferences sponsored by the International Association for Dental Research is presented. Topics include the mechanism of action of sodium azide as an inhibitor of Candida and natural radioactivity found in human teeth, as well as information on anodic decalcification of teeth and dental surveys concerning the dental hygiene activities of grade school children in Seattle, Washington.

Kinetic studies were carried out in order to investigate the enzymic mechanism of a 1420-fold purified purine nucleoside : purine deoxyribosyl transferase fraction from Lactobacillus helveticus. Deoxyinosine and adenine were used as substrates. Initial velocity, product: inhibition and isotopic exchange studies are consistent with a ping-pong bi-bi mechanism (the first product is released before the second substrate combines with the enzyme). The numerical values of the Michaelis and dissociation constants, maximum Velocities and equilibrium constants for the forward and reverse reactions are derived graphically from secondary plots. A comparison with purine nucleoside phosphorylase is discussed. [ABSTRACT FROM AUTHOR]

Although systemic tetracycline remains the most frequent treatment for acne vulgaris, this report indicates that more effective antibacterial therapy can be achieved topically. The effective agent, benzoyl peroxide, produced a mild desquamation; while concommitantly reducing the fatty acids in sebum more dramatically than systemic tetracycline. Bacterial cultures demonstrated the potential of this peroxide to inhibit the growth of C acnes recovered from sebaceous follicles. Since the mechanism of benzoyl peroxide is different than topical vitamin A acid, combination therapy has been evaluated in over 1,000 acne patients. The clearing of acne lesions is now routine in the majority of these cases within the initial three months of therapy. [ABSTRACT FROM AUTHOR]

The kinetics of the exchange reactions between internal L-malate and external 2-oxoglutarate or malonate have been measured at 4 °C in the presence of external L-malate (external-product inhibitor), using preparations of rat-heart mitochondria under conditions where the oxoglutarate translocator is operating exclusively. Measurements of initial rates were made at three concentrations of the internal substrate (L-malate), three concentrations of the external substrate (2-oxoglutarate or malonate) and three concentrations of the external reaction product (L-malate). The Michaelis constant for the internal malate is unaffected by the presence of the external product whereas the apparent-maximum rate for each concentration of external substrate decreases when the concentration of external product increases. On the other hand the Michaelis constant for the external substrate, oxoglutarate or malonate, increases when the concentration of external malate increases. The external product inhibits the exchange in a competitive way when external substrate is varied and in a non-competitive way when internal substrate is varied. The inhibition constant determined for the external malate is equal to the previously determined dissociation constant of the corresponding external-malate · translocator complex. These results are in perfect agreement with the previously proposed mechanism (rapid-equilibrium random bi-bi) and a mixed dead-end and product inhibition. [ABSTRACT FROM AUTHOR]

The particulate antigen, polymerized fiagellin, was shown to be effective both in immunological priming and in inducing tolerance in newborn Wistar rats. The following results were obtained: (1) A single injection of 100 ng or more at birth caused priming without a primary responses A secondary response could be elicited 7 or more days after birth with a dose of 10–100 μg. (2) Daily injections of 100 ng to 1 μg/g body weight of polymerized flagellin during the first 2 weeks of life abrogated the priming effect and in fact gave rise to a state of high dosage-zone immunological tolerance. (3) The injection of 1 μg to 10-5 μg/g body weight/day into newborn rats for 2 weeks gave rise to two zones of tolerance separated by a slight ’immunity hump’, which suggested the presence of some primed cells but fewer virgin cells following these intermediate doses. (4) The low zone of tolerance was induced by a dose of 10-4 pg/g body weight/ day, which was equivalent to an initial antigen concentration in the animal of about 10-20 M, if one adopts the simplified assumption that polymerized flagellin has a molecular weight of 10×106, High zone tolerance was induced by doses of 100 ng/g body weight/day or more and the immunity region by 1 ng/body weight/ day. (5) In the low zone, polymerized fiagellin appears to induce tolerance even better in newborn rats than the lower molecular-weight monomeric fiagellin. The extremely small amounts which are effective are difficult to explain, but raise the possibility of some antigen concentrating mechanism.

Guinea-pigs injected with antigen in Freund's complete adjuvant develop delayed hypersensitivity to the antigen. This is reduced by the prior injection of the same antigen precipitated with alum. This may be termed immune deviation and has been shown to differ from immune tolerance. Four possible mechanisms for this phenomenon were considered: (a) that there was a specific defect in the cell population responsible for the passive transfer of delayed hypersensitivity; (b) that there was an antibody blocking the detection of delayed hypersensitivity; (c) that there was an antibody blocking the induction of delayed hypersensitivity; and (d) that the cells responsible for delayed hypersensitivity were desensitized in vivo. Experiments on the passive transfer of delayed hypersensitivity from deviated and control guinea-pigs showed that there was a defect in the cell population involved in the passive transfer of delayed hypersensitivity. Serum transfer failed to reveal evidence of antibody blocking the induction or detection of delayed hypersensitivity. Transfer of cells into recipients which had been pretreated with alum-precipitated antigen gave no evidence of desensitization in the PPD system. The findings with bovine γ-globulin were equivocal. It was concluded that there was a defect in the cell population involved in the passive transfer of delayed hypersensitivity and, in the absence of evidence for other mechanisms, this was attributed to a direct effect of the first injection of antigen on the cells responsible for the state of delayed hypersensitivity after the injection of the same antigen in Freund's complete adjuvant. [ABSTRACT FROM AUTHOR]