Bleeding Gastric Heterotopic Polyp in the Duodenum of a Teenager with Severe Factor VII Deficiency.

Heterotopic gastric tissue can be found throughout the intestinal tract, and when it is present in the small intestine, it can present with symptoms that include gastrointestinal bleeding, chronic abdominal pain, diarrhea, and chronic dyspepsia. This finding is incredibly rare in pediatrics, but if present, it can lead to significant morbidity and mortality. This can be especially true if a patient presents with a comorbidity of a bleeding disorder. We here present the case of a teenage male with a history of severe factor VII deficiency who was found to have iron deficiency anemia resulting in multiple blood transfusions from an occult lower gastrointestinal bleed. He was ultimately found to have a bleeding gastric heterotopic polyp in his duodenum that was successfully removed via surgery.

Clostridium difficile Infection in a Very Young Infant with Pseudomembranous Colitis Noted on Endoscopy.

Clostridium difficile infection rates have been rising within the last decade and more pediatric patients have been suffering from this type of infection. However, this bacterium is a well-known contaminant in the normal flora of the colon in patients under the age of 2 years, and therefore consensus guidelines have recommended against routine testing for this infection, unless clinically indicated. We present here a case of a very young infant who presented with symptoms of food refusal, poor weight gain, abdominal distention, and colitis noted on imaging. Endoscopic evaluation demonstrated the presence of pseudomembranous colitis, so the patient was treated with antibiotics against C. difficile and recovered fully. This case demonstrates the importance of keeping C. difficile colitis in your differential diagnosis, even at a very young age.

The full spectrum of hepatic steatosis in children.

OBJECTIVE: We aim to identify the spectrum of etiologies of steatosis in pediatric liver biopsies. METHODS: Information was collected from 155 children with steatosis on liver biopsy, including anthropometrics, laboratory, and radiologic data. Biopsies were reviewed by a liver pathologist. RESULTS: The 4 major diagnoses associated with hepatic steatosis were nonalcoholic fatty liver disease (37%), metabolic disease (9%), oncologic disease (8%) and viral hepatitis (7%). Patients with nonalcoholic fatty liver disease were older (P = .0001) and more likely to have a body mass index z score >2 (P < .0001). Patients with a metabolic diagnosis were younger (P = .0002). Radiologic imaging of the liver yielded normal results in 44 of 108 of children (30%); 7 of these had >66% macrovesicular fatty change on biopsy, and 3 had severe fibrosis/cirrhosis. CONCLUSIONS: The range of causes of steatosis in pediatric liver biopsies is broad. Not all patients, even with advanced liver disease, had abnormalities with liver imaging, emphasizing the role for liver biopsy in certain cases.

Two Cases of Progressive Familial Intrahepatic Cholestasis Type 2 Presenting with Severe Coagulopathy without Jaundice.

Progressive familial intrahepatic cholestasis (PFIC) type 2 results from a mutation in the bile salt exporter pump, impeding bile acid transport. Patients usually present with jaundice, pruritus, growth failure, and fat soluble vitamin deficiencies. We present two patients diagnosed with PFIC type 2 due to severe coagulopathy and bleeding without jaundice.

Reversal of human cytomegalovirus major immediate-early enhancer/promoter silencing in quiescently infected cells via the cyclic AMP signaling pathway.

The human cytomegalovirus (HCMV) major immediate-early (MIE) enhancer contains five functional cyclic AMP (cAMP) response elements (CRE). Because the CRE in their native context do not contribute appreciably to MIE enhancer/promoter activity in lytically infected human fibroblasts and NTera2 (NT2)-derived neurons, we postulated that they might have a role in MIE enhancer/promoter reactivation in quiescently infected cells. Here, we show that stimulation of the cAMP signaling pathway by treatment with forskolin (FSK), an adenylyl cyclase activator, greatly alleviates MIE enhancer/promoter silencing in quiescently infected NT2 neuronal precursors. The effect is immediate, independent of de novo protein synthesis, associated with the phosphorylation of ATF-1 serine 63 and CREB serine 133, dependent on protein kinase A (PKA) and the enhancer's CRE, and linked to viral-lytic-cycle advancement. Coupling of FSK treatment with the inhibition of either histone deacetylases or protein synthesis synergistically activates MIE gene expression in a manner suggesting that MIE enhancer/promoter silencing is optimally relieved by an interplay of multiple regulatory mechanisms. In contrast, MIE enhancer/promoter silence is not overcome by stimulation of the gamma interferon (IFN-gamma) signaling pathway, despite the enhancer having two IFN-gamma-activated-site-like elements. We conclude that stimulation of the cAMP/PKA signaling pathway drives CRE-dependent MIE enhancer/promoter activation in quiescently infected cells, thus exposing a potential mode of regulation in HCMV reactivation.

The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis.

Mycobacterium tuberculosis (M.tb) survives in macrophages in part by limiting phagosome-lysosome (P-L) fusion. M.tb mannose-capped lipoarabinomannan (ManLAM) blocks phagosome maturation. The pattern recognition mannose receptor (MR) binds to the ManLAM mannose caps and mediates phagocytosis of bacilli by human macrophages. Using quantitative electron and confocal microscopy, we report that engagement of the MR by ManLAM during the phagocytic process is a key step in limiting P-L fusion. P-L fusion of ManLAM microspheres was significantly reduced in human macrophages and an MR-expressing cell line but not in monocytes that lack the receptor. Moreover, reversal of P-L fusion inhibition occurred with MR blockade. Inhibition of P-L fusion did not occur with entry via Fcgamma receptors or dendritic cell-specific intracellular adhesion molecule 3 grabbing nonintegrin, or with phosphatidylinositol-capped lipoarabinomannan. The ManLAM mannose cap structures were necessary in limiting P-L fusion, and the intact molecule was required to maintain this phenotype. Finally, MR blockade during phagocytosis of virulent M.tb led to a reversal of P-L fusion inhibition in human macrophages (84.0 +/- 5.1% vs. 38.6 +/- 0.6%). Thus, engagement of the MR by ManLAM during the phagocytic process directs M.tb to its initial phagosomal niche, thereby enhancing survival in human macrophages.

Pulmonary surfactant protein A activates a phosphatidylinositol 3-kinase/calcium signal transduction pathway in human macrophages: participation in the up-regulation of mannose receptor activity.

Surfactant protein A (SP-A), a major component of lung surfactant, binds to macrophages and has been shown to alter several macrophage biological functions, including up-regulation of macrophage mannose receptor (MR) activity. In the present study, we show that SP-A induces signal transduction pathway(s) that impact on MR expression. The addition of human, rat, or recombinant rat SP-A to human monocyte-derived macrophages significantly raised the level of cytosolic Ca2+ above baseline within 10 s of SP-A addition, as measured by spectrofluorometric analysis. SP-A induced a refractory state specific for SP-A consistent with homologous desensitization of a receptor(s) linked to calcium mobilization because a second application of SP-A did not induce a rise in cytosolic Ca2+ whereas the addition of platelet-activating factor did. Using site-directed mutations in SP-A, we determined that both the attached sugars and the collagen-like domain of SP-A are necessary to optimize Ca2+ mobilization. SP-A triggered the increase in cytosolic Ca2+ by inducing activation of phospholipase C, which leads to the hydrolysis of membrane phospholipids, yielding inositol 1,4,5-trisphosphate and mobilizing intracellularly stored Ca2+ by inositol triphosphate-sensitive channels. Finally, inhibition of PI3Ks, which appear to act upstream of phospholipase C in Ca2+ mobilization, decreased the SP-A-induced rise in MR expression, providing evidence that SP-A induction of MR activity involves the activation of a pathway in which PI3K is a component. These studies provide further evidence that SP-A produced in the lung plays a role in modulating macrophage biology, thereby contributing to the alternative activation state of the alveolar macrophage.