Cysteamine revisited: repair of arginine to cysteine mutations.

Cysteamine is a small aminothiol endogenously derived from coenzyme A degradation. For some decades, synthetic cysteamine has been employed for the treatment of cystinosis, and new uses of the drug continue to emerge. In this review, we discuss the role of cysteamine in cellular and extracellular homeostasis and focus on the potential use of aminothiols to reconstitute the function of proteins harboring arginine (Arg) to cysteine (Cys) mutations, via repair of the Cys residue into a moiety that introduces an amino group, as seen in basic amino acid residues Lys and Arg. Cysteamine has been utilized in vitro and ex vivo in four different genetic disorders, and thus provides "proof of principle" that aminothiols can modify Cys residues. Other aminothiols such as mercaptoethylguanidine (MEG) with closer structural resemblance to the guanidinium moiety of Arg are under examination for their predicted enhanced capacity to reconstitute loss of function. Although the use of aminothiols holds clinical potential, more studies are required to refine specificity and treatment design. The efficacy of aminothiols to target proteins may vary substantially depending on their specific extracellular and intracellular locations. Redox potential, pH, and specific aminothiol abundance in each physiological compartment are expected to influence the reactivity and turnover of cysteamine and analogous drugs. Upcoming research will require the use of suitable cell and animal models featuring Arg to Cys mutations. Since, in general, Arg to Cys changes comprise about 8% of missense mutations, repair of this specific mutation may provide promising avenues for many genetic diseases.

Enhanced detection of respiratory syncytial virus by shell vial in children hospitalised with respiratory illnesses in northern Jordan.

During the period between November 1997 and May 1998, a total of 350 nasopharyngeal aspirates were obtained from children admitted to the Respiratory Disease Unit at Princess Rahma Hospital, northern Jordan, and diagnosed clinically as suffering from respiratory tract infections. Nasopharyngeal aspirates were investigated for the presence of respiratory syncycial virus (RSV) by using shell vial (SV) culture assay, conventional culture assay, and direct immunofluorescence assay. Out of 350 nasopharyngeal aspirates, 101(28.9%) were found positive by any of SV, conventional culture, and immunofluorescence; 91 (90.1%) by SV, 87(86.1%) by culture, and 83(82.2%) by immunofluorescence. The maximum number of virus isolations was noted in children below the age of 1 year and was associated with bronchiolitis. SV assay showed the highest sensitivity (94.3%) and specificity (96.9%) for detecting RSV from nasopharyngeal aspirates. These results emphasise the importance of SV culture assay for diagnosis of RSV, although immunofluorescence is a valuable, rapid diagnostic assay.

Prevalence of parainfluenza and influenza viruses amongst children with upper respiratory tract infection.

OBJECTIVE: The objective of this study was to determine the prevalence of Parainfluenza and Influenza causing upper respiratory tract infections and to evaluate shell vial culture assay and direct immunofluorescence assay. METHODS: A retrospective study during the period between November 1997 and May 1998. A total of 350 nasopharyngeal aspirates were obtained from children suffering from respiratory tract infections. Nasopharyngeal aspirates were investigated for the presence of Parainfluenza 1, 2 and 3, Influenza A and B using shell vial culture assay, conventional culture assay and direct immunofluorescence assay. RESULTS: Parainfluenza 1 were identified in 3%, Parainfluenza 2 in 5% and Parainfluenza 3 in 6%. Influenza A were identified in 4% and Influenza B in 2%. Parainfluenza 1, 2 and 3 were isolated in children less than 5 years old. Most of Parainfluenza cases were associated with other upper respiratory infections. Shell vial assay showed a sensitivity of 90-93% and specificity of 99-100% for detecting Parainfluenza 1, 2 and 3. CONCLUSION: These results emphasize that shell vial assay is important for the diagnosis of Parainfluenza and Influenza, although direct immunofluorescence assay is the superior diagnostic assay.