Gesture development: a review for clinical and research practices.

The aim of this article is to provide clinicians and researchers a comprehensive overview of the development and functions of gesture in childhood and in select populations with developmental language impairments. Of significance is the growing body of evidence that gesture enhances, not hinders, language development. In both normal and impaired populations, gesture and language development parallel each other and share underlying symbolic abilities. Gesture serves several functions, including those of communication, compensation, and transition to spoken language. In clinical practice, gesture may play a valuable role in diagnosis, prognosis, goal selection, and intervention for children with language impairments. Where available, supporting evidence is presented. Needs for additional research on gesture are also highlighted.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

Prevalence of Chlamydia trachomatis and Mycoplasma pneumoniae in children with and without pharyngitis

The prevalence of Chlamydia trachomatis, Mycoplasma pneumoniae, group A beta-hemolytic streptococcus, and other treatable organisms was studied in children with and without pharyngitis. Children aged 2 to 12 years were evaluated between November 1985 and April 1986 in three family practice offices in the Salt Lake City area. Chlamydia trachomatis was not detected in the pharynx of any of the children studied. Mycoplasma pneumoniae was cultured from 5 percent of the 242 children studied, group A beta-hemolytic streptococcus from 30 percent, non-group A beta-hemolytic streptococcus from 5 percent, Hemophilus influenzae from 4 percent, and Staphylococcus aureus from 14 percent. The symptoms reported were not statistically associated with any organism isolated, and clinical signs of pharyngitis were associated only with the presence of group A beta-hemolytic streptococcus. Based on these results, management of pharyngitis in children should continue to be based on the detection and treatment of group A beta-hemolytic streptococcus.     

Protein components specifically associated with prespliceosome and spliceosome complexes.

We have carried out a systematic analysis of the protein composition of highly purified mammalian spliceosomes. We show that > 30 distinct proteins, including 20 previously unidentified components [designated spliceosome-associated proteins (SAPs)], are specifically associated with the spliceosome in a salt-resistant complex. In contrast to these spliceosome-specific proteins, we show that hnRNP proteins are not tightly associated with purified prespliceosome and spliceosome complexes. The splicing factor U2AF65, U1 snRNP-specific proteins, and several SAPs are present in the earliest prespliceosome complex (E). A set of 10 proteins is then added to the first ATP-dependent prespliceosome complex (A), and concomitantly, a significant decrease in the level of U2AF65 is observed. The fully assembled spliceosome is formed by the addition of 12 proteins in a reaction that requires ATP and both the 5' and 3' splice sites.