Splenic peliosis with spontaneous splenic rupture: report of two cases

BACKGROUND: Peliosis is a rare condition characterised by multiple cyst-like, blood-filled cavities within the parenchyma of solid organs. Most commonly affecting the liver, isolated splenic peliosis is an even more unique phenomenon. Patients with the condition are often asymptomatic. However, this potentially lethal condition can present with spontaneous organ rupture. We present two such cases, discuss their management and review what is currently known in the existing literature. CASE PRESENTATION: A previously well twenty-six year old woman presented with abdominal pain following a trivial episode of coughing. A diagnosis of spontaneous splenic rupture was made following clinical and radiological examination. She underwent emergency splenectomy and made a full, uneventful recovery. Histopathological examination confirmed splenic peliosis. The second case describes an eighty six year old lady who sustained a trivial fall and developed pain in her left side. A CT confirmed splenic rupture. She became haemodynamically unstable during her admission and underwent emergency splenectomy. Histopathological examination revealed splenic peliosis. She went on to make an uneventful recovery. CONCLUSION: Splenic peliosis is very rare. It has a number of associations including immunosuppression, drug therapy and infection. Although patients are often asymptomatic, life-threatening spontaneous organ rupture may occur. If the diagnosis of peliosis is confirmed, additional investigations should be considered to detect its presence in other organs. Furthermore, the presence of the condition may be relevant if further medical or surgical intervention is planned

Modeling the Basal Dynamics of P53 System

The tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis.Most previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses remain unchanged. Furthermore, the spontaneous pulses are filtered by ataxia telangiectasia mutated protein mediated posttranslational modifications and do not result in substantial p21 transcription. If challenged by externally severe DNA damage, cells generate synchronous p53 pulses and induce significantly high levels of p21. The high expression of p21 can also be partially induced by lowering the deacetylation rate.Our results demonstrated that the dynamics of p53 under nonstressed conditions is initiated by an excitable mechanism and cells become fully responsive only when cells are confronted with severe damage. These findings advance our understanding of the mechanism of p53 pulses and unlock many opportunities to p53-based therapy

SPO11-Independent DNA Repair Foci and Their Role in Meiotic Silencing

In mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs) are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chromatin of the sex chromosomes remain unsynapsed, contains persistent meiotic DSBs, and the whole so-called XY body undergoes meiotic sex chromosome inactivation (MSCI). A more general mechanism, named meiotic silencing of unsynapsed chromatin (MSUC), is activated when autosomes fail to synapse. In the absence of SPO11, many chromosomal regions remain unsynapsed, but MSUC takes place only on part of the unsynapsed chromatin. We asked if spontaneous DSBs occur in meiocytes that lack a functional SPO11 protein, and if these might be involved in targeting the MSUC response to part of the unsynapsed chromatin. We generated mice carrying a point mutation that disrupts the predicted catalytic site of SPO11 (Spo11YF/YF), and blocks its DSB-inducing activity. Interestingly, we observed foci of proteins involved in the processing of DNA damage, such as RAD51, DMC1, and RPA, both in Spo11YF/YFand Spo11 knockout meiocytes. These foci preferentially localized to the areas that undergo MSUC and form the so-called pseudo XY body. In SPO11-deficient oocytes, the number