Sapintoxin A. A fluorescent phorbol ester that is a potent activator of protein kinase C but is not a tumour promoter.

In this communication we report on the activity of the naturally occurring, highly fluorescent phorbol ester Sapintoxin A (12-o-[2-methylaminobenzoate]-4-deoxyphorbol 13-acetate). This compound potently activates the enzyme protein kinase C (PKC) (Ka 76 nM) but is neither a complete nor second-stage tumour promoter in traditional Berenblum tests. Sapintoxin A has properties in common with promoters such as 12-o-tetradecanoylphorbol 13-acetate (TPA) in that it will induce erythema in vivo, induce lymphocyte mitogenesis in vitro and cause aggregation of human and rabbit platelets.

Evaluation of a computerized version of the Diagnostic Interview Schedule.

An interactive, computerized version of the Diagnostic Interview Schedule (DIS) was completed by 135 randomly selected psychiatric inpatients and evaluated by the patients and their psychiatrists. The results showed that the majority of the patients interacted well with the computer and that the treating psychiatrists found the computer reports generally accurate and helpful. Analysis of the agreement between the computer and the psychiatrists' diagnoses yielded mixed results depending on the method of analysis chosen.

The stimulation of phosphorylation of intracellular proteins in GH3 rat pituitary tumour cells by phorbol esters of distinct biological activity.

Using a pituitary tumour cell line (GH3), we have studied the phosphorylation of intracellular proteins induced by phorbol esters of diverse biological activity. All the active phorbol esters, including the weakly tumour-promoting but non-platelet aggregatory compound DOPPA, stimulated the phosphorylation of a cytosolic 80 kDa protein. A protein of this molecular mass has been suggested to be a marker of PKC activity.

A probe for the mutagenic activity of the carcinogen 4-aminobiphenyl: synthesis and characterization of an M13mp10 genome containing the major carcinogen-DNA adduct at a unique site.

The duplex genome of Escherichia coli virus M13mp10 was modified at a unique site to contain N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG8-ABP), the major carcinogen-DNA adduct of the human bladder carcinogen 4-aminobiphenyl. A tetradeoxynucleotide containing a single dG8-ABP residue was synthesized by reacting 5'-d(TpGpCpA)-3' with N-acetoxy-N-(trifluoracetyl)-4-aminobiphenyl, followed by high-performance liquid chromatography purification of the principal reaction product 5'-d(TpG8-ABPpCpA)-3' (yield 15-30%). Characterization by fast atom bombardment mass spectrometry confirmed the structure as an intact 4-aminobiphenyl-modified tetranucleotide, while 1H nuclear magnetic resonance spectroscopy established the site of substitution and the existence of ring stacking between the carcinogen residue and DNA bases.

The potentiation of phorbol ester-induced aggregation of human platelets by the prostaglandin endoperoxide analogue, U46619.

It was not possible to desensitize human blood platelets to 12-deoxyphorbol-phenylacetate (DOPP) stimulation in a manner analogous with that to platelet aggregating factor (PAF), prostaglandin-endoperoxide analogue (U46619) or adenosine diphosphate (ADP). Platelets previously desensitized to U46619, when challenged with DOPP and ADP, showed an increased aggregation and release of 5-HT. Sub-threshold aggregating doses of U46619 also caused a potentiation of the platelet response and release reaction to DOPP.

Activation of phospholipase A2 by cannabinoids. Lack of correlation with CNS effects.

Cannabinoids delta 1-tetrahydrocannabinol, cannabinol, cannabidiol and cannabigerol have been shown to affect directly the activity of phospholipase A2 in a cell-free assay. The compounds produced a biphasic activation of the enzyme, with EC50 values in the range 6.0-20.

Toxic phorbol esters from Chinese tallow stimulate protein kinase C.

Phorbol esters were isolated from the seeds of Chinese tallow (Sapium sebiferum L. Roxb.).

High resolution mass spectrometric and high-field nuclear magnetic resonance spectroscopic studies of the herbicide propanil, its N-oxidative decomposition products and related compounds.

A number of compounds associated with dichloroaniline-based herbicides were examined by high resolution mass spectrometry and high-field nuclear magnetic resonance spectroscopy. These compounds included the herbicide propanil (N-propionyl-3,4-dichloroaniline) and the related compound N-acetyl-3,4-dichloroaniline. Several possible oxidative metabolic products, including N-hydroxy-3,4-dichloroaniline, nitroso-3,4-dichlorobenzene, N-hydroxy-N-propionyl-3,4-dichloroaniline and N-hydroxy-N-acetyl-3,4-dichloroaniline were also investigated.

Leukemia after radiotherapy for first primary cancers of various anatomic sites.

The authors conducted a case-control study designed to evaluate the association between radiotherapy for a first primary cancer and subsequent leukemia risk. Study subjects were selected from four tumor registries (California, Connecticut, Kansas, and Massachusetts). Cases were subjects with two primary cancers; the second cancer was a leukemia diagnosed one year or more after the diagnosis of the first primary cancer.

Cannflavin A and B, prenylated flavones from Cannabis sativa L.

Two novel prenylated flavones, termed Cannflavin A and B, were isolated from the cannabinoid free ethanolic extract of Cannabis sativa L. Both compounds inhibited prostaglandin E2 production by human rheumatoid synovial cells in culture.

1H NMR study of self-association and restricted internal rotation of the C8-substituted deoxyguanosine 5'-monophosphate adduct of the carcinogen 2-(acetylamino)fluorene.

The high-field 1H NMR spectra of a nucleotide-carcinogen adduct formed from 2-(acetylamino)fluorene (8-(N-fluoren-2-ylacetamido)-2'-deoxyguanosine 5'-monophosphate) have been examined in aqueous solution as a function of concentration at high and low temperatures. An anomalous concentration dependence of NMR spectra was observed at concentration levels over 1 mM. These spectral characteristics have been analyzed in terms of changes in self-association and in the interconversions between torsional diastereomers associated with the central nitrogen.

Conformation and configuration at the central amine nitrogen of a nucleotide adduct of the carcinogen 2-(acetylamino)fluorene as studied by 13C and 15N NMR spectroscopy.

The conformation and configuration at the central nitrogen of the adduct 8-(N-fluoren-2-ylamino)-2'-deoxyguanosine 5'-monophosphate has been investigated by high-field 13C and 15N NMR spectroscopy. One-bond nitrogen-hydrogen coupling constants and 13C chemical shifts for the adduct as well as for the model compounds diphenylamine, 4-nitrodiphenylamine and 2-aminofluorene have been measured in nonaqueous solutions. The data indicate a near planar configuration at the amine nitrogen that links the guanine and fluorene rings of the adduct.

Alcohol and drug abuse treatment in three different populations: is there improvement and is it predictable?

Prior research had shown that alcohol and drug abuse treatments were effective and that the results of treatments could be predicted from pretreatment information regarding the patient's employment, family, and especially psychiatric problems. However, this research had been conducted entirely with adult male service veterans, largely from lower socioeconomic strata. Three treatment centers were included in the present study to examine these conclusions with other populations containing adolescents, females, and patients from higher socioeconomic strata.

Pseudomalignant osseous tumor of the temporalis muscle.

A case is presented of a 10-year-old girl who had a benign osseous tumor of the temporalis muscle. The tumor appeared to be a variant of the so-called pseudomalignant osseous tumor of the soft tissues and could readily be distinguished from both osteogenic sarcoma and myositis ossificans.

New data from the Addiction Severity Index. Reliability and validity in three centers.

The Addiction Severity Index (ASI) is a clinical/research instrument which has been in wide use during the past 6 years to assess the treatment problems found in alcohol- and drug-abusing patients. In a study of male veterans, a preliminary evaluation of the ASI has indicated reliability and validity. The present report presents an expanded examination of these issues; 181 subjects from three treatment centers were studied.

Isolation from Cannabis sativa L. of cannflavin--a novel inhibitor of prostaglandin production.

The isolation from Cannabis sativa L. of an inhibitor of prostaglandin (PG) E2 production by cultured rheumatoid synovial cells is described. This agent, for which the name Cannflavin has been coined, is distinct from cannabinoids on the basis of isolation procedure, preliminary structural analysis and biological properties.

Mechanism of microsomal metabolism of benzene to phenol.

The mechanism of microsomal hydroxylation of benzene to phenol has been studied by examining the microsomal metabolism of the specifically deuterated derivative 1,3,5-[2H3]benzene. Evidence for the formation of the following four products was obtained: 2,3,5-[2H3]phenol, 3,5-[2H2]phenol, 2,4,6-[2H3]phenol, and 2,4-[2H2]phenol. The presence of 2,3,5-[2H3]phenol and 2,4-[2H2]phenol shows that, in the microsomal metabolism of benzene to phenol, a NIH shift had occurred.

Structural correlations of phorbol-ester-induced stimulation of PGE2 production by human rheumatoid synovial cells.

Eight phorbol esters were studied for their ability to stimulate prostaglandin production in human rheumatoid synovial cells over the dose range 0.1 ng to 1.0 micrograms.

Studies on the conformation and dynamics of the C8-substituted guanine adduct of the carcinogen acetylaminofluorene; model for a possible Z-DNA modified structure.

The structure of an adduct between guanine and the carcinogen acetylaminofluorene has been examined in the solid state by X-ray crystallography, and in solution by NMR techniques. The observed conformations have been compared with predictions from energy calculations and their relevance to models of adducts with DNA has been examined.

Needs assessment under the Maternal and Child Health Services Block Grant: Massachusetts.

The Massachusetts maternal and child health (MCH) agency has developed a needs assessment process which includes four components: a statistical measure of need based on indirect, proxy health and social indicators; clinical standards for services to be provided; an advisory process which guides decision making and involves constituency groups; and a management system for implementing funds distribution, namely open competitive bidding in response to a Request for Proposals. In Fiscal Years 1982 and 1983, the process was applied statewide in the distribution of primary prenatal (MIC) and pediatric (C&Y) care services and lead poisoning prevention projects. Both processes resulted in clearer definitions of services to be provided under contract to the state as well as redistribution of funds to serve localities that had previously received no resources.