No indications for HPV involvement in the hypertrophic skin lesions of a Darier disease case without ATP2A2 gene mutations

Darier disease (DD) is a relatively common genodermatosis characterized by impaired differentiation and abnormal cell-to-cell adhesion. Haploinsufficiency of the ATP2A2 gene product, sarco/endoplasmic reticulum Ca²⁺ ATPase isoform 2 (SERCA2), is the underlying cause of most cases. Although DD may have a papillomatous appearance, few and controversial results have been reported about the role of human papillomavirus (HPV) in this disease. The aim of this study was to determine a possible correlation between development of hypertrophic lesions in DD and infection by HPV. We report the case of an 84-year-old woman with a hypertrophic DD variant that has been successfully treated with oral retinoids. HPV analysis for a broad spectrum of cutaneous and mucocutaneous genotypes was performed on surgical specimens obtained from the cutaneous lesions and snap-frozen plucked eyebrows. Genetic analysis of the ATP2A2 gene did not detect any mutations. Epidermal expression of SERCA2b was shown by immunohistochemistry. We describe a patient with DD lacking mutations of the ATP2A2 gene, but with reduced SERCA2b expression in the epidermal keratinocytes. The results obtained by polymerase chain reaction (PCR) genotyping, quantitative real-time PCR, and in situ hybridization indicate that HPV replication was very low and suggest no direct role of the virus in the development of the disease.     

A novel multimodal computational system using near-infrared spectroscopy predicts the need for ECMO initiation in neonates with congenital diaphragmatic hernia

Background/purpose

The purpose of this study was to develop a computational algorithm that would predict the need for ECMO in neonates with congenital diaphragmatic hernia (CDH).

Entamoeba histolytica calreticulin: an endoplasmic reticulum protein expressed by trophozoites into experimentally induced amoebic liver abscesses

Entamoeba histolytica calreticulin (EhCRT) is remarkably immunogenic in humans (90-100% of invasive amoebiasis patients). Nevertheless, the study of calreticulin in this protozoan is still in its early stages. The exact location, biological functions, and its role in pathogenesis are yet to be fully understood. The aim of the present work is to determine the location of EhCRT in virulent trophozoites in vivo and the expression of the Ehcrt gene during the development of experimentally induced amoebic liver abscesses (ALA) in hamsters. Antibodies against recombinant EhCRT were used for the immunolocalization of EhCRT in trophozoites through confocal microscopy; immunohistochemical assays were also performed on tissue sections of ALAs at different times after intrahepatic inoculation. The expression of the Ehcrt gene during the development of ALA was estimated through both in situ RT-PCR and real-time RT-PCR. Confocal assays of virulent trophozoites showed a distribution of EhCRT in the cytoplasmic vesicles of different sizes. Apparently, EhCRT is not exported into the hepatic tissue. Real-time RT-PCR demonstrated an over-expression of the Ehcrt gene at 30 min after trophozoite inoculation, reaching a peak at 1-2 h; thereafter, the expression fell sharply to its original levels. These results demonstrate for the first time in an in vivo model of ALA, the expression of Ehcrt gene in E. histolytica trophozoites and add evidence that support CRT as a resident protein of the ER in E. histolytica species. The in vivo experiments suggest that CRT may play an important role during the early stages of the host-parasite relationship, when the parasite is adapting to a new environment, although the protein seems to be constitutively synthesized. Moreover, trophozoites apparently do not export EhCRT into the hepatic tissue in ALA.     

D2 dopamine receptors recruit a GABA component for their attenuation of excitatory synaptic transmission in the adult rat prefrontal cortex

The dopamine modulation of neuronal excitability in the prefrontal cortex (PFC) changes during critical late periods of postnatal development. In particular, D2 receptors activate fast-spiking interneurons after, and not before, adolescence. To test the functional impact of this change, we investigated the effects of dopamine agonists on PFC excitatory synaptic transmission with whole-cell recordings from deep-layer pyramidal neurons in brain slices obtained from prepubertal [postnatal day (PD) 28-35] and postpubertal (PD>51) rats. Electrical stimulation of superficial layers elicited a fast AMPA/kainate excitatory postsynaptic potential (EPSP). In the adult PFC, the D2 agonist quinpirole decreased EPSP amplitude, an effect that lasted for at least 25 min after drug washout and was blocked by the D2 antagonist eticlopride. The late component of this effect was blocked by the GABA-A antagonist picrotoxin without affecting the early inhibition. Quinpirole also decreased EPSP amplitude in deep-layer pyramidal neurons from prepubertal rats, but this response was not affected by picrotoxin. A D1 agonist, on the other hand, did not affect the pyramidal neuron EPSP. These results indicate that D2, not D1, receptors attenuate local excitatory synaptic transmission in the adult PFC, and this effect of D2 involves a recruitment of local GABAergic activity.