Comparison of 12-hour urine protein and protein:creatinine ratio with 24-hour urine protein for the diagnosis of preeclampsia.

OBJECTIVE: The purpose of this study was to evaluate the performance of the 12-hour urine protein >165 mg and protein:creatinine ratio >0.15 for the prediction of 24-hour urine protein of ≥300 mg in patients with suspected preeclampsia. STUDY DESIGN: We performed a prospective observational study of 90 women who had been admitted with suspected preeclampsia. Protein:creatinine ratio and 12- and 24-hour urine specimens were collected for each patient. Test characteristics for the identification of 24-hour urine protein ≥300 mg were calculated. RESULTS: A 12-hour urine protein >165 mg and protein:creatinine ratio of >0.15 correlated significantly with 24-hour urine protein ≥300 mg (r = 0.99; P < .001; and r = 0.54; P < .001, respectively). A 12-hour urine protein >165 mg performed better than protein:creatinine ratio as a predictor of a 24-hour urine protein ≥300 mg (sensitivity, 96% and 89%; specificity, 100% and 49%; positive predictive value, 100% and 32%; negative predictive value, 98% and 91%, respectively). CONCLUSION: The high correlation of a 12-hour urine protein >165 mg with a 24-hour urine protein ≥300 mg (with the benefit of a shorter evaluation time) and the high negative predictive value of protein:creatinine ratio suggest that the use of both these tests have a role in the evaluation and treatment of women with suspected preeclampsia.

Activation of the extrinsic caspase pathway in cultured cortical neurons requires p53-mediated down-regulation of the X-linked inhibitor of apoptosis protein to induce apoptosis.

Cultured cortical neurons exposed to the Human Immunodeficiency Virus gp120 coat protein undergo apoptosis involving activation of both caspase-8 and caspase-9. Additionally, gp120-mediated neuronal apoptosis requires the pro-apoptotic transcription factor p53. As caspase-8-induced apoptosis does not typically require p53, we examined the possibility of a novel role for p53 in caspase-8 activation initiated by gp120. We observed that gp120 treatment of cultured cortical neurons induced caspase-8 activity and Bid cleavage independently of p53, but induction of caspase-3 enzymatic activity required p53 expression. These findings suggested the possibility that p53 down-regulates a caspase-3 inhibitor. We observed high-level expression of the caspase-3/9 inhibitor X-linked inhibitor of apoptosis protein (XIAP) in cultured cortical neurons. Adenoviral expression of p53 or induction of endogenous p53 by camptothecin treatment reduced XIAP protein in neurons. Infection with a p53 expressing adenovirus increased expression of the mRNA for Omi/HtrA2, a protease that cleaves and inactivates XIAP. These findings suggest that p53 regulates neuronal apoptosis, in part, by suppressing the anti-apoptotic protein XIAP via transcriptional activation of Omi/HtrA2.

HIV associated neurodegeneration requires p53 in neurons and microglia.

HIV infection of the central nervous system leads to HIV-associated dementia (HAD) in a substantial subset of infected individuals. The pathogenesis of neuronal dysfunction in HAD is not well understood, but previous studies have demonstrated evidence for activation of apoptotic pathways. The tumor suppressor transcription factor p53 is an apical mediator of neuronal apoptosis following a variety of injurious stimuli. To determine whether p53 participates in HAD, we exposed cerebrocortical cultures from wild-type and p53 deficient mice to the neurotoxic HIV envelope protein gp120. Using neuron/microglia co-culture of mixed p53 genotype, we observed that both neurons and microglia require p53 for gp120 induced neuronal apoptosis. Additionally, accumulation of p53 protein in neurons was recently reported in post-mortem cortical tissue from a small group of HAD patients. Using a much larger cohort of HAD cases, we extend this finding and report that p53 protein also increases in non-neuronal cells, including microglia. Taken together these findings demonstrate a novel role for p53 in the microglial response to gp120. Additionally, these findings, in conjunction with a recent report that monocytes expressing HIV-Tat also secrete neurotoxins that promote p53 activation, suggest that distinct HIV proteins may converge on the p53 pathway to promote neurotoxicity.