N-acetylation and N-formylation of m-aminobenzoic acid by cell suspension cultures of Solanum laciniatum.

Two new biotransformation products, N-acetyl-m-aminobenzoic acid and N-formyl-m-aminobenzoic acid were isolated from cell suspension cultures of Solanum laciniatum following administration of m-aminobenzoic acid, and their structures were elucidated using one- and two-dimensional 1H- and 13C-NMR data.

Clinical laboratory differentiation of Legionellaceae family members with pigment production and fluorescence on media supplemented with aromatic substrates.

A systematic study of pigment production (browning) and fluorescence (extracellular yellow-green and intracellular blue-white) by nine Legionellaceae species was performed. A total of 56 strains representing Tatlockia micdadei (Pittsburgh pneumonia agent), Legionella pneumophila, Legionella jordanis, Legionella longbeachae, Legionella oakridgensis, Legionella wadsworthii, Fluoribacter bozemanae, Fluoribacter gormanii, and Fluoribacter dumoffii could be separated on media supplemented with tyrosine plus cystine, 3,4-diaminobenzoic acid, 3,5-diaminobenzoic acid, and 3-aminotyrosine. Parallel testing by hippurate hydrolysis and the bromocresol purple spot test enabled the identification of Legionellaceae species 24 to 72 h after primary isolation. This schema may be a practical alternative to species-specific antisera methods (slide agglutination or direct immunofluorescence) in the identification of members of the family Legionellaceae.

The chemotherapy of rodent malaria, XXXII. The influence of p-aminobenzoic acid on the transmission of Plasmodium yoelii and P. berghei by Anopheles stephensi.

More oocysts of Plasmodium yoelii developed in Anopheles stephensi if the mosquitoes received a supplement of p-aminobenzoic acid (PABA) in their diet prior to their taking an infective blood meal, than in unsupplemented control insects. The optimum concentration was 0.05% PABA in 10% sucrose. This effect was not observed if the blood meal was taken prior to feeding with PABA. Similarly, PABA administered to gametocyte-carrying mice increased the numbers of oocysts developing in mosquitoes fed on them subsequently, the effect also being dose dependent, and not mediated through an increase in gametocyte numbers. Sulphadoxine (which blocks PABA uptake) had the opposite action, reducing the numbers of oocysts either when fed directly to the mosquitoes or to the donor mice. These results are compared with those reported in other host-parasite systems by earlier workers, and certain paradoxical observations are discussed with reference to a possible relationship between sulphonamides and contaminating microorganisms in the vector mosquitoes.

Potential anticancer agents. XVII. New developments in the benzoic acid nitrogen mustards area.

In order to obtain aromatic nitrogen mustards with improved therapeutic index against experimental neoplasms, greater than 75 new compounds were synthetized and studied. Their structure-activity relationship analysis led to the following conclusions: (a) the carboxylic group (especially when located in the meta position with respect to the nitrogen mustard group) exerts a favorable effect on the biologic properties of such compounds, probably by improving their transport characteristics; (b) a linear relationship was found between the chemical reactivity (expressed as alkylation rate, log k66) and toxicity (LD50) of 31 investigated compounds; and (c) the ortho effects also seem to be of importance in this area for a more accurate control of the nitrogen mustard activity. Other criteria (ie, log P, nucleophilicity of the target centers) involved in the rational design of aromatic nitrogen mustards are discussed. The design of new derivatives was oriented toward compounds which (a) were able to couple with selected proteins (ie, antibodies) leaving the cytotoxic moiety intact, and (b) were obtained by coupling of the 3-N,N-bis(2-chloroethyl)amino-4-methyl-benzoyl moiety with selected carriers (steroids, chromanones, etc) by way of an esteric bond.

Orthomolecular psychiatry. Varying the concentrations of substances normally present in the human body may control mental disease.

The functioning of the brain is affected by the molecular concentrations of many substances that are normally present in the brain. The optimum concentrations of these substances for a person may differ greatly from the concentrations provided by his normal diet and genetic machinery. Biochemical and genetic arguments support the idea that orthomolecular therapy, the provision for the individual person of the optimum concentrations of important normal constituents of the brain, may be the preferred treatment for many mentally ill patients. Mental symptoms of avitaminosis sometimes are observed long before any physical symptoms appear. It is likely that the brain is more sensitive to changes in concentration of vital substances than are other organs and tissues. Moreover, there is the possibility that for some persons the cerebrospinal concentration of a vital substance may be grossly low at the same time that the concentration in the blood and lymph is essentially normal. A physiological abnormality such as decreased permeability of the blood-brain barrier for the vital substance or increased rate of metabolism of the substance in the brain may lead to a cerebral deficiency and to a mental disease. Diseases of this sort may be called localized cerebral deficiency diseases. It is suggested that the genes responsible for abnormalities (deficiencies) in the concentration of vital substances in the brain may be responsible for increased penetrance of the postulated gene for schizophrenia, and that the so-called gene for schizophrenia may itself be a gene that leads to a localized cerebral deficiency in one or more vital substances.