Photocleavage coupling reactions between cyclohexa-2,4-dienone sulfone derivatives and amines by visible light irradiation.

A stable sulfone derivative of 2,4,6-trimethylcyclohexa-2,4-diene-1-one (7) undergoes facile ring cleavage under visible light to produce a ketene intermediate, which could be efficiently captured by amines to give amides even in the presence of competing nucleophiles such as water and ethanol.

Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis.

The preferred antitubercular drug isoniazid specifically targets a long-chain enoyl-acyl carrier protein reductase (InhA), an enzyme essential for mycolic acid biosynthesis in Mycobacterium tuberculosis. Despite the widespread use of this drug for more than 40 years, its precise mode of action has remained obscure. Data from x-ray crystallography and mass spectrometry reveal that the mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of InhA.

Progression of interproximal caries in the primary dentition.

While studies have addressed the diagnosis and progression of interproximal carious lesions within a primary tooth, few studies have addressed the development of proximal lesions in adjacent primary molars. The purpose of this study was to examine retrospectively the long term interproximal caries progression in primary molar teeth. Dental records of 150 children were retrospectively reviewed, 76 from a university pediatric dentistry clinic and 74 from a pediatric dentistry private practice. Out of the 387 teeth initially diagnosed with proximal caries, the combined university and private practice results for timing of the development of proximal lesions on adjacent tooth surfaces showed the following: simultaneous development-162 (41.9%); 1 to 24 months-65 (16.8%); 24 to 60 months-40 (10.3%); never-120 (31.0%). The combined results for formation of proximal caries in posterior quadrants showed that out of the 150 patients, the timing for development of additional quadrants with proximal caries was as follow: simultaneous development: 77 (51.3%); 1 to 24 months 31, (20.7%); 24 to 60 months 25, (16.7%); never 17 (11.3%). The conclusions of the study are that 69% of the primary molar teeth with proximal caries developed caries on the adjacent proximal surface and 89% of the patients who developed a proximal carious lesion on a primary molar tooth within one quadrant developed another primary molar proximal lesion in another quadrant.

A new procedure for the labeling of peptides and amino acids.

Several stable, water soluble cyclohexa-2,4-dien-1-ones have been prepared and their photolytic coupling reactions in aqueous solution at 28 degrees C with various amino acids and dipeptides investigated. This procedure represents a new and high yielding method for the labeling of the terminal amino functionality of peptides and amino acids.

The functionalisation of saturated hydrocarbons--XXX. Model studies on the mechanism of some oxygenases.

In harmony with our studies on the activation of hydrocarbons by Gif chemistry, we have, in the first part of this paper, studied the mechanism of the lipoxygenase enzymes using soybean lipoxygenase as a model. We have shown with trimethyl phosphite that no free radical is released by the enzyme. In a second part, we have studied the mechanism of the alpha-ketoglutarate dependent enzymes and shown evidence for a mechanism involving the reduction of an intermediate hydroperoxide by the alpha-ketoglutaric acid.

Oral-facial characteristics of circumscribed scleroderma: case report.

Scleroderma is a rare disorder of unknown etiology. Circumscribed scleroderma is a localized focal form. It may present as well defined elevated or depressed white or yellowish patches termed "morphea," or linear bands made up of a furrow with elevated ridges on the margins described as "coup de sabre." The oral-facial characteristics of circumscribed scleroderma in a ten year old afflicted female are described in detail.

Dental attitudes and memories: a study of the effects of hand over mouth/restraint.

The purpose of this study was to document whether there was a significant difference in the number and severity of generalized fears and dental fears between patients who did and patients who did not experience hand-over-mouth and/or restraint as children. Patient records in a dental school children's clinic and a private pediatric dental practice were examined to identify patients who had experienced hand-over-mouth and/or restraint. A set of verbal questions was designed, tested, and used to ascertain the differences between the HOM/restraint group and the comparison group. One hundred twenty-two subjects were interviewed, 61 who had experienced HOM/restraint and 61 who had not. When compared for generalized fears and specific dental fears, the two groups showed no statistically significant differences (P = 0.86 and P = 0.36 respectively). No statistically significant difference appeared between the two groups when asked how they felt about visiting the dental office (P = 0.41). When three different formats were used to question the subjects relative to their early dental memories, the two groups showed no statistical difference in negative or positive responses (P = 0.38, 0.75, and 0.25 respectively). More than two times as many HOM/restraint subjects as comparison subjects described negative experiences in a physician's office or hospital. This difference was statistically significant (P < 0.01).

Total synthesis of uracil analogues of sinefungin.

Analogues of sinefungin derivatives 18a and 18b have been prepared from uridine and L-aspartic acid. The key step in the synthesis was the coupling of the radical derived from 14 with the unsaturated amide 13. The latter was produced from the known N-hydroxy-2-thiopyridone ester of L-aspartic acid 12 with the olefin 11. Thus, the essential carbon skeleton was constructed by way of two radical coupling reactions. These analogues as well as 1a and 1b synthesized previously were tested for their antileishmanial effect in vivo and for their inhibitory activity of protein carboxymethylase (protein methylase II). The replacement of the adenine moiety by uracil or dihydrouracil considerably decreases the antiparasitic activity and the affinity for protein methylase II. The synthetic (S)-sinefungin was as active as the natural one. Interestingly, the C-6' epimer 1b was 50% less active in vitro than the natural sinefungin, but both had identical affinities for the target enzyme.

Mechanism of the selective functionalization of saturated hydrocarbons by Gif systems: relationship with methane monooxygenase.

Two intermediates, A and B, have been identified in the selective oxidation of saturated hydrocarbons to ketones by Gif-type systems. Intermediate A has been characterized as an Fev species with a secondary iron sigma-bond to carbon; it is captured by four different reagents or transformed into the second intermediate, B, which hydrolyzes to form a secondary alcohol. A mu-oxo Fe2III dimer is proposed as a basis for Gif-type reactivity. If the first iron is involved in the synthesis of intermediate A, the second is used to oxidize intermediate B intramolecularly to a ketal, which on hydrolysis yields a ketone. The enzyme methane monooxygenase shows a remarkable similarity to Gif-type systems in its selective hydrocarbon oxidation, particularly in the case of adamantane.

Evaluation of limonoids against the murine P388 lymphocytic leukemia cell line.

A structure/activity study of selected limonoids from two plant families (Meliaceae and Rutaceae) of the Rutales order against the murine P-388 lymphocytic leukemia system was undertaken. The presence of both a 19 leads to 28 lactol and a 14,15 beta-epoxide group was found especially important for pronounced inhibition of the PS in vitro cell line. Substitution of an A-ring alpha,beta-unsaturated ketone (3-oxo-1-ene) for the lactol led to diminished activity, while reduction of the olefin caused complete loss of activity. At the dose levels employed, even very good PS in vitro inhibition was not translated into PS in vivo antineoplastic effects.

Use of a continuing health history in dental practice: a survey.

The authors strongly recommend the routine use of a continual-health-update procedure at each recall appointment. The updated health-histories allow us to better evaluate the "whole" child. We have found that the parent appreciates not only the initial inquiry, but also the continuing concern about illnesses and injuries the child may have incurred since the last dental examination. The inquiries help build rapport between the families and the professional staff of our office. In addition, they upgrade the level of professional care provided.

Chemical and enzymic studies on the characterization of intermediates during the removal of the 14alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives.

By using cell-free preparations of rat liver it was shown that the removal of the 14alpha-methyl group (C-32) of steroids containing either a delta7(8) or a delta8(9) double bond is attended exclusively by the formation of the corresponding 7,14- and 8,14-dienes respectively (structures of types III and VIII). Cumulative evidence from a variety of experimental approaches had led to the deduction that delta8(14)-steroids are not involved as intermediates on the major pathway of cholesterol biosynthesis. The metabolism of [32-3H]lanost-7-ene-3beta,32-diol (structure of type I) results in the formation of radioactive formic acid, no labelled formaldehyde being formed. By using appropriately labelled species of the compound (I) it was found that the release of formic acid and the formation of 4,4-dimethylcholesta-7,14-dien-3beta-ol (strurcture of type III) were closely linked processes, and that in the conversion of compound (I) into compound (III), 3-beta-hydroxylanost-7-en-32-al (II) is an obligatory intermediate. Both the conversion of lanost-7-ene-3beta,32-diol (I) into 3beta-hydroxylanost-7-en-32-al (II) and the further metabolism of the latter (II) to 4,4-dimethylcholesta-7,14-dien-3beta-ol (III) exhibited a requirement for NADPH and O2. This suggests that the oxidation of the 32-hydroxy group of compound (I) to the aldehyde group of compound (II) does not occur by the conventional alcohol dehydrogenase type of reaction, but may proceed by a novel mechanism involving the intermediacy of a gem-diol. A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made.