When antagonist-occupied steroid receptors have agonist-like effects, the clinical consequences are grave. We present evidence that human progesterone B-receptors (hPRB) when occupied by progesterone antagonists, inappropriately activate transcription by an unusual mechanism that does not require the canonical progesterone response element (PRE). In HeLa cells cotransfected with a PRE-tk-chloramphenicol acetyltransferase reporter and a hPRB expression vector, strong transcription is seen not only when receptors are activated by the agonist R5020, but also in the presence of the three antiprogestins, RU486, ZK112993, and ZK98299. Human PRB occupied by ZK98299 do not bind to a PRE, suggesting that the transcriptional stimulation is independent of DNA binding. Indeed, a tk-chloramphenicol acetyltransferase promoter-reporter lacking the PRE loses transcriptional activation by the agonist, but retains transactivation by the three antagonists. The PRE-independent antagonist-induced transcription requires that hPRB have an intact DNA-binding domain, but hPR target gene specificity is not required, because a hPRB mutant that binds an estrogen response element still activates transcription. It appears that antagonist-occupied hPR activate transcription without binding to a PRE, perhaps by interacting with tethering proteins instead. Even a gene that is not a normal progesterone target could be aberrantly activated. Human cells contain equimolar amounts of hPRB and the N-terminally truncated natural isotype, hPRA. Unlike hPRB, hPRA are not transcriptionally activated by progesterone antagonists. We, therefore, tested the effects of antagonists when the two receptor isotypes are coexpressed and found that A-receptors can annul the inappropriate transcription by B-receptors. Thus, when both receptor forms are present, the hPRA phenotype is dominant. Moreover, pure hPRB/hPRA heterodimers, produced by fos/jun leucine zipper domain-hPR chimeras, also have the inactive transcriptional phenotype of hPRA. Our studies suggest not only that the two hPR isotypes are functionally quite different, but also that some of the agonist-like transcriptional effects of antagonist-occupied B-receptors proceed through novel mechanisms.

Traumatic brain injury (TBI) is defined as a traumatically-induced structural brain injury or physiological disruption of brain function caused by an external force. Traumatic brain injury is a neuropsychiatric disorder that breaks down the remaining barriers between neurology and psychiatry. Several biomarkers have been developed to directly determine the pathology of the nerve cells in the central nervous system (CNS) when it is injured. This review recent research on brain injury biomarkers could be used for rapid and accurate diagnostics of TBI in easily accessible fluid. Objectives:The purpose of this study was to assess utility of GFAP-BDP for the diagnosis of intracranial injury in patients with a positive clinical screen for head injury across the spectrum of TBI typically presenting to ED in Kasr-Alainy hospital. Subjects & Methods:This prospective cohort study was based on the data collected from 90 cases presented to Kasr Al-Aini Hospitals Emergency Department, Cairo University, with history of traumatic brain injury through the period from April 2017 to Mars 2019. According to age, they were classified into 3 age groups; age group A (18-35 years), age group B (36-50 years) and age group C (> 50 years). Data were analyzed with respect to socio-demographic data, type of head injury, clinical presentations, radiological investigation, and management of TBI in relation to serum specific biomarkers level (GFAP, C-tau). Results:The most common age group was age group B (18-35 years) (70%). Males were more common than females (71.1% and 28.9% respectively). The most common cause of trauma was fall from height (33.3%). Serum GFAP level and C-tau levels in studied groups show high significant correlation between them (p value <0.001). Conclusion and Recommendations:The combination of the two biomarkers or more may be more useful than either biomarker in isolation for predicting intracranial lesions on CT scanning therefor decreases unwanted CT head scanning and radiological bad effect especially in young ages.