In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphory... more In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function.
Seventy-seven subjects infected with human immunodeficiency virus were randomized to switch from ... more Seventy-seven subjects infected with human immunodeficiency virus were randomized to switch from protease inhibitor (PI) therapy to nevirapine therapy (group A; n=26) or to efavirenz therapy (group B; n=25) or to continue PI therapy (group C; n=26). At month 12, viral suppression had been maintained in 96% of patients in group A, 92% of patients in group B, and 92% of patients in group C. A significant increase in the CD4(+) level was observed in all 3 groups. In group A, lipid profiles improved, whereas levels of gamma-glutamiltransferase and alanine aminotransferase significantly increased; 1 subject interrupted treatment because of hepatotoxicity. In group B, an increase in gamma-glutamiltransferase levels was also observed, and 3 patients interrupted treatment because of central nervous system symptoms. Two patients in group C withdrew therapy. Quality of life significantly improved for groups A and B. In patients receiving effective PI-based therapy, the replacement of the PI with either nevirapine or efavirenz is safe and virologically effective.
In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphory... more In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function.
Seventy-seven subjects infected with human immunodeficiency virus were randomized to switch from ... more Seventy-seven subjects infected with human immunodeficiency virus were randomized to switch from protease inhibitor (PI) therapy to nevirapine therapy (group A; n=26) or to efavirenz therapy (group B; n=25) or to continue PI therapy (group C; n=26). At month 12, viral suppression had been maintained in 96% of patients in group A, 92% of patients in group B, and 92% of patients in group C. A significant increase in the CD4(+) level was observed in all 3 groups. In group A, lipid profiles improved, whereas levels of gamma-glutamiltransferase and alanine aminotransferase significantly increased; 1 subject interrupted treatment because of hepatotoxicity. In group B, an increase in gamma-glutamiltransferase levels was also observed, and 3 patients interrupted treatment because of central nervous system symptoms. Two patients in group C withdrew therapy. Quality of life significantly improved for groups A and B. In patients receiving effective PI-based therapy, the replacement of the PI with either nevirapine or efavirenz is safe and virologically effective.
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Papers by Luis Cruz