Comparisons between autistic and nonautistic children on the Test for Auditory Comprehension of Language.

Expressive language differences between autistic and nonautistic populations have been a topic of research in the past decade, yet little information is available in regard to the receptive language performances based on standardized tests. Questions as to the existence of sex differences in language have also been raised. The study examines the performance of 19 matched pairs of autistic and nonautistic children on the Test for Auditory Comprehension of Language.

The effects of fenfluramine on communication skills in autistic children.

The effect of fenfluramine on communication skills in six autistic males was examined over a 9-month period. Communication behaviors were analyzed via standardized receptive and expressive measures, spontaneous speech samples gathered in the clinic, and videotaped observations of the numbers of noncommunicative utterances, immediate echolalia, and spontaneous initiations. The results demonstrated that fenfluramine had no significant effects on the communication behaviors of these six autistic males.

A pragmatic approach to increase expressive language skills in young autistic children.

This paper is a description of a pilot communication program for autistic children designed to increase communication skills in the context of establishing reciprocal communication exchanges. The methods involved intensive modeling of verbal responses within joint activity routines and using a reinforcement system based on fulfilling the intent of the child's communication. Five male subjects ranging in age from 36 to 68 months participated in the communication program for 6 weeks during an inpatient stay at the Iowa Autism Program, Child Psychiatry Service.

The development of sex differences in infantile autism.

Seventy-five autistic children, 52 males and 23 females, were admitted to the Iowa Autism Programme over a 3-year period. An overall male-female ratio of 2.26:1 was found, but in the patients with IQs less than 50, the ratio was 1.

Unfavourable left-right asymmetries of the brain and autism: a question of methodology.

Thirty-six patients with infantile autism and various neurological disorders underwent computerized tomographic (CT) scanning of the brain. All CT scans were assessed blindly and independently by a diagnostic radiologist. Two techniques modified from two previous studies were used for measuring parieto-occipital asymmetry.

Toxicity quantitative structure--activity relationships of colchicines.

A method for extracting LD50 values from antitumor test data is described. A quantitative structure--activity relationship (QSAR) for 7- and 10-substituted colchicines is presented. This correlation equation closely parallels that which had been derived earlier for potency.

Showdomycin analogues: synthesis and antitumor evaluation.

The synthesis of N-beta-D-ribofuranosyl derivatives of maleimide, 3-methylmaleimide, and 3-chloromaleimide was accomplished in three steps from ribosylamine. The synthetic ribosides can be considered N-nucleoside analogues of showdomycin, which is an antitumor antibiotic of the C-nucleoside type. Although the three analogues were cytotoxic to cultured L1210 cells, no in vivo antitumor activity was found with the murine P388 leukemia test system.

Quantitative structure-activity relationships of colchicines against P388 leukemia in mice.

A quantitative structure-activity relationship (QSAR) was derived for colchicine and 14 analogues acting against P388 lymphocytic leukemia in mice. Twelve additional compounds were synthesized to reinforce and confirm the correlation. The final correlation indicates that there is a parabolic dependence of antitumor potency on the partition coefficient with log P0=1.

Synthesis and antitumor activity of analogues of the antitumor antibiotic chartreusin.

First isolated in 1953 from a fermentation broth, chartreusin (1) has received renewed interest as a result of substantial antitumor activities recently demonstrated in several murine test systems. Poor water solubility frustrated formulation attempts, and rapid biliary excretion observed in mice made 1 an improbable candidate for clinical development but an excellent candidate for an analogue synthesis program. From a common intermediate, which was prepared from 1, three analogues were synthesized wherein the disaccharide moiety of 1 was systematically replaced with fucose (6), glucose (7), and the disaccharide maltose (8).

Synthesis of propranolol mustard as a possible lung-specific antitumor agent.

A nitrogen mustard analog of propranolol was synthesized as a potential lung-specific antitumor agent. Since dl-propranolol concentrates in lung tissue and beta-blocking activity resides only with the l-enantiomer, the d-modification could serve as a lung-directed carrier for a cytotoxic group. Reaction of 1-(1-naphthyloxy)-3-[bis(2-hydroxyethyl)amino]-2-propanol with thionyl chloride resulted in replacement of all three hydroxyl groups with chlorine.

Usnic acid derivatives as potential antineoplastic agents.

Usnic acid, a lichen antibiotic, showed low-level activity in the Lewis lung carcinoma test system. In an effort to produce new agents of potential use in the treatment of lung cancer, derivatives of the natural product were synthesized and evaluated with a cytotoxicity assay. Structure--activity analysis of the cytotoxicity data indicated the importance of the lipophilicity and the beta-triketone moiety of usnic acid on cytotoxicity.

Synthesis and antitumor activity of 5-azacytosine arabinoside.

5-Azacytosine arabinoside (ara-AC) can be considered a combination of structural elements derived from the antitumor nucleosides cytosine arabinoside (ara-C) and 5-azacytidine (5-AC). The synthesis of ara-AC, for which standard methods were inadequate, was accomplished using the stable dihydro derivative as a synthetic intermediate. A novel dehydrogenation of the latter through the application of a trimethylsilylation-oxidation procedure gave ara-AC in good yield.

Synthesis and antitumor properties of some isoindolylalkylphosphonium salts.

Antitumor evaluation of 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyltriphenylphosphonium bromide (1) revealed significant activity in P-388 lymphocytic leukemia (T/C = 160%). As a follow-up to this chemical lead, a series of closely related phosphonium salts was prepared in which the 1,3-dihydro-1,3-dioxo-2H-isoindole ring system was maintained or in which it was replaced by other moieties such as maleimido, bromo, methoxy, and isoindoline. Syntheses generally involved treatment of the appropriate N-(bromoalkyl)phthalimide with the required phosphine or condensation of the K salt of the substituted imide with beta-(bromoethyl)triphenylphosphonium bromide (12).

Isolation, characterization, and properties of a labile hydrolysis product of the antitumor nucleoside, 5-azacytidine.

The antitumor nucleoside, 5-azacytidine (5-AC), is best administered clinically by prolonged intravenous infusion to minimize toxic effects. In opposition to this administration technique is facile drug decomposition in aqueous formulations giving products of unknown toxicity. Analysis of 24-h-old water solutions of 5-AC with high-pressure liquid chromatography (HPLC) indicated a threefold mixture of 5-AC, N-(formylamidino)-N'-beta-D-ribofuranosylurea (RGU-CHO), and 1-beta-D-ribofuranosyl-3-guanylurea (RGU).

Comparative studies of the cytostatic action and metabolism of 5-azacytidine and 5,6-dihydro-5-azacytidine.

5,6-Dihydro-5-azacytidine hydrochloride, a chemically stable, soluble analog of 5-azacytidine, has cytostatic activity against mouse leukemic L1210 cells grown in culture, but concentrations on the order of 10 micronM, 10-fold higher, than the parent drug, are necessary to inhibit cell growth. The addition of either cytidine or uridine protected against growth inhibition by 5-azacytidine and 5,6-dihydro-5-azacytidine, whereas thymidine potentiated the cytostatic action of both drugs. Deoxycytidine also enhanced the action of 5-azacytidine but had no effect with the reduced analog.

Potential antitumor agents: procarbazine analogs and other methylhydrazine derivatives.

With the objective of developing new antitumor agents, two groups of hydrazine compounds, having structural features in common with the antitumor agents procarbazine and 1-acetyl-2-picolinoylhydrazine, were synthesized. The L-1210 leukemia system was used to evaluate compounds of both groups. The aliphatic procarbazines also were screened for antitumor activity as bis(benzyloxycarbonyl) derivatives and as derivatives having a phthalazine nucleus.

Antitumor agents II: nitrogen analogs of mycophenolic acid.

Mycophenolic acid, a novel antibiotic of low toxicity containing no nitrogen atoms in its structure, induces tumor regression in several murine solid tumor assays. It has been reported in extensive structure-activity studies that chemical modifications on the antibiotic itself reduce or eliminate antitumor activity. With the objective of antitumor activity enhancement, nitrogen-containing analogs of mycophenolic acid were synthesized according to a program directed toward the ultimate synthesis of close bioisosteres of the antibiotic.