Langerhans cell histiocytosis mimicking lichen nitidus with bone involvement

We report the case of a 6‐month‐old Hispanic boy with a 4‐month history of widespread pruritic hypopigmented papules mimicking lichen nitidus. The final diagnosis was multisystem non‐risk‐organ Langerhans cell histiocytosis (LCH), with cutaneous and multiple bone involvement. With this patient and others previously reported in the literature, we suggest an early biopsy of the hypopigmented rash in children.     

Multiple hereditary infundibulocystic basal cell carcinomas: a genodermatosis different from nevoid basal cell carcinoma syndrome.

BACKGROUND: Infundibulocystic basal cell carcinoma is a recently described distinctive clinicopathologic variant of basal cell carcinoma. Histopathologic differential diagnosis among infundibulocystic basal cell carcinoma, trichoepithelioma, and basaloid follicular hamartoma has generated controversy in the literature. OBSERVATIONS: Members of 2 families with multiple infundibulocystic basal cell carcinomas are described. Each patient showed multiple papular lesions, mostly located on the face. No patient showed palmar pits or jaw cysts. Forty-two cutaneous lesions from 5 patients were studied histopathologically. Thirty-nine lesions were infundibulocystic basal cell carcinomas. This clinicopathologic variant of basal cell carcinoma consists of a relatively well-circumscribed basaloid neoplasm composed of buds and cords of neoplastic cells arranged in anastomosing fashion and with scant stroma. Some of the neoplastic cords contain tiny infundibular cysts filled by cornified cells with abundant melanin. Linkage analysis in family 2 was performed using polymorphic markers (D9S196, D9S280, D9S287, and D9S180), and the affected members shared the same haplotype. Loss of heterozygosity analysis was performed in 2 affected members of this family from whom tumoral DNA was available, and although these individuals were constitutively heterozygous for D9S196, they did not show loss of heterozygosity for this marker in their neoplasms. CONCLUSIONS: Multiple hereditary infundibulocystic basal cell carcinomas represent a distinctive genodermatosis different from multiple hereditary trichoepitheliomas and nevoid basal cell carcinoma syndrome. We propose clinical and histopathologic criteria to distinguish infundibulocystic basal cell carcinoma from trichoepithelioma, basaloid follicular hamartoma, and folliculocentric basaloid proliferation.     

N400 and lexical decisions: automatic or controlled processing?

OBJECTIVE: To investigate whether the N400 effect is sensitive to automatic or controlled processes. METHODS: Two experiments were performed. In one experiment, directly related word pairs were used. In the other experiment, mediated-related word pairs were used. In order to reduce controlled processes, each experiment consisted of 3 tasks: Low- and high-proportion of related pairs, and single presentation lexical decision task. RESULTS: In the first experiment, the amount of priming was equivalent for the 3 tasks. The N400 effect appeared in the high and low proportion of directly related words, but not in the single presentation task. In the second experiment, behavioral priming was also found in the 3 tasks. However, the N400 effect was observed only in the task with low proportion of related pairs. CONCLUSION: These results suggest that the N400 effect may be related to controlled processes.     

Investigating the concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis

To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.2% and 98% concordance, respectively). In contrast, 40% to 70% of PT that were classified as mesenchymal-like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.8% and 76.5% concordance, respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95% CI = 1.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95% CI = 1.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC.     

Recombinant HCV NS3 and NS5B enzymes exhibit multiple posttranslational modifications for potential regulation

Posttranslational modification (PTM) of proteins is critical to modulate protein function and to improve the functional diversity of polypeptides. In this report, we have analyzed the PTM of both hepatitis C virus NS3 and NS5B enzyme proteins, upon their individual expression in insect cells under the baculovirus expression system. Using mass spectrometry, we present evidence that these recombinant proteins exhibit diverse covalent modifications on certain amino acid side chains, such as phosphorylation, ubiquitination, and acetylation. Although the functional implications of these PTM must be further addressed, these data may prove useful toward the understanding of the complex regulation of these key viral enzymes and to uncover novel potential targets for antiviral design.

     

Coronary collateral development during chronic ischemia: serial assessment using harmonic myocardial contrast echocardiography

OBJECTIVES: We sought to characterize collateral development in an experimental model of chronic myocardial ischemia by using myocardial contrast echocardiography (MCE). BACKGROUND: Coronary collaterals maintain myocyte viability during myocardial ischemia. The natural history and determinants of collateral development are difficult to study serially in vivo. METHODS: The left anterior descending coronary artery (LAD) in nine dogs was encircled (day 0) with a hydraulic occluder and ameroid constrictor to enable reversible and gradual total LAD occlusion, respectively. Myocardial contrast echocardiography was performed using intravenous injection of perfluorocarbon gas-containing microbubbles during two-dimensional harmonic echocardiographic imaging. Myocardial contrast echocardiography images and radiolabeled microsphere flow measurements were obtained during transient LAD occlusion on day 0. Over the ensuing six weeks, MCE imaging was performed during LAD occlusion at 10-day intervals. RESULTS: Myocardial contrast echocardiography risk area size (expressed as a percent of the left ventricular short axis slice) decreased over the course of six weeks (32%+/-3% on day 0, 21% +/-3% at day 10, 5+/-3% at day 20, 1%+/-1% at day 30 and 1%+/-1% at day 42, p< or =0.001 vs. day 0). Radiolabeled microsphere-derived LAD flow, normalized to left circumflex flow, correspondingly increased between day 0 and day 42 (0.14+/-0.02 to 0.90+/-0.07, p<0.02). CONCLUSIONS: Collateral development occurs relatively early and rapidly in this chronic canine model. Myocardial contrast echocardiography using harmonic imaging and intravenous injection of microbubbles can uniquely track the spatial and temporal course of collateral growth, and may be a powerful tool for noninvasively mapping the efficacy of therapeutic angiogenic strategies in vivo.