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Thiols provide the major intracellular redox milieu and can undergo reversible oxidation and reduction. To understand the role of thiols in redox signaling events, we have studied the effect of N-ethylmaleimide, a specific thiol alkylating agent, on platelet-derived growth factor-BB (PDGF-BB)-induced mitogenesis in vascular smooth muscle cells (VSMC). Thiol alkylation inhibited PDGF-BB-induced expression of the Fos and Jun family proteins and AP-1 activity in VSMC. Thiol alkylation also inhibited PDGF-BB-induced expression of cyclin A and growth in these cells. In contrast, thiol alkylation enhanced and sustained the effect of PDGF-BB on the activation of the Jak STAT pathway, and this event was correlated with inhibition of protein tyrosine phosphatase lB activity. Thiol alkylation via inducing the expression of p21waf1/cip1 in a STAT1- and p53-dependent manner antagonized the downregulation of this cell cycle inhibitory molecule by PDGF-BB. The inhibition of AP-1 and activation of STATs, particularly STAT1, by thiol alkylation correlated with increased production of active caspase 1 and apoptosis in VSMC. Together, these findings suggest a role for thiols in mediating mitogenic and/or apoptotic signaling events in VSMC. These results also show that a sustained change in the intracellular thiol redox state can convert a mitogen into a death promoter.Oncogene (2003) 22, 117–130. doi:10.1038/sj.onc.1206065 [ABSTRACT FROM AUTHOR]

Presents several medical case studies. Association of water intoxication with carbamazepine treatment; Diagnosis of Miliary Crohn's disease; Effect of glibenclamide on antidiuretic hormones.

A three-year-old boy with positive diagnostic criteria for both Toxocara infection and active Toxoplasma infection was referred to the Pediatric Outpatient Department in Great Britain. He had a history of irregular fever, malaise, lethargy, occasional headache, and vomiting for two months. He was the fourth child in a family of five, of Indian parents, born in Wolverhampton, England following an uneventful full-term pregnancy and normal delivery. The medical history of the family was noncontributory. Treatment with diethylcarbamazine maintained for two weeks produced no appreciable improvement. A four weeks' course of pyrimethamine and sulphadiazine was then started, along with folic acid, iron, and vitamin supplements produced better results.

Thiols provide the major intracellular redox milieu and can undergo reversible oxidation and reduction. To understand the role of thiols in redox signaling events, we have studied the effect of N-ethylmaleimide, a specific thiol alkylating agent, on platelet-derived growth factor-BB (PDGF-BB)-induced mitogenesis in vascular smooth muscle cells (VSMC). Thiol alkylation inhibited PDGF-BB-induced expression of the Fos and Jun family proteins and AP-1 activity in VSMC. Thiol alkylation also inhibited PDGF-BB-induced expression of cyclin A and growth in these cells. In contrast, thiol alkylation enhanced and sustained the effect of PDGF-BB on the activation of the Jak STAT pathway, and this event was correlated with inhibition of protein tyrosine phosphatase lB activity. Thiol alkylation via inducing the expression of p21waf1/cip1 in a STAT1- and p53-dependent manner antagonized the downregulation of this cell cycle inhibitory molecule by PDGF-BB. The inhibition of AP-1 and activation of STATs, particularly STAT1, by thiol alkylation correlated with increased production of active caspase 1 and apoptosis in VSMC. Together, these findings suggest a role for thiols in mediating mitogenic and/or apoptotic signaling events in VSMC. These results also show that a sustained change in the intracellular thiol redox state can convert a mitogen into a death promoter.Oncogene (2003) 22, 117–130. doi:10.1038/sj.onc.1206065 [ABSTRACT FROM AUTHOR]