Not Your Typical Hyperammonemia: Non-hepatic Severe Hyperammonemia in an Adult.

Hyperammonemia in adults is most often due to cirrhosis. Ammonia is metabolized through the urea cycle. With liver disease, this pathway is altered, and urea is unable to be formed, creating a buildup of ammonia with numerous side effects, including encephalopathy. A less common presentation is hyperammonemia in the absence of liver disease. We present a rare case of non-cirrhotic hyperammonemia due to a splenogonadal shunt.

Unique N-linked glycosylation of CasBrE Env influences its stability, processing, and viral infectivity but not its neurotoxicity.

The envelope protein (Env) from the CasBrE murine leukemia virus (MLV) can cause acute spongiform neurodegeneration analogous to that induced by prions. Upon central nervous system (CNS) infection, Env is expressed as multiple isoforms owing to differential asparagine (N)-linked glycosylation. Because N-glycosylation can affect protein folding, stability, and quality control, we explored whether unique CasBrE Env glycosylation features could influence neurovirulence. CasBrE Env possesses 6/8 consensus MLV glycosylation sites (gs) but is missing gs3 and gs5 and contains a putative site (gs*). Twenty-nine mutants were generated by modifying these three sites, individually or in combination, to mimic the amino acid sequence in the nonneurovirulent Friend 57 MLV. Three basic viral phenotypes were observed: replication defective (dead; titer < 1 focus-forming unit [FFU]/ml), replication compromised (RC) (titer = 10(2) to 10(5) FFU/ml); and wild-type-like (WTL) (titer > 10(5) FFU/ml). Env protein was undetectable in dead mutants, while RC and WTL mutants showed variations in Env expression, processing, virus incorporation, virus entry, and virus spread. The newly introduced gs3 and gs5 sites were glycosylated, whereas gs* was not. Six WTL mutants tested in mice showed no clear attenuation in disease onset or severity versus controls. Furthermore, three RC viruses tested by neural stem cell (NSC)-mediated brainstem dissemination also induced acute spongiosis. Thus, while unique N-glycosylation affected structural features of Env involved in protein stability, proteolytic processing, and virus assembly and entry, these changes had minimal impact on CasBrE Env neurotoxicity. These findings suggest that the Env protein domains responsible for spongiogenesis represent highly stable elements upon which the more variable viral functional domains have evolved.

Onycholemmal carcinoma: a morphologic comparison of 6 reported cases.

BACKGROUND: We report 6 new cases of onycholemmal carcinoma, a rare, often misdiagnosed, subcategory of squamous cell carcinoma. All reported cases to date have been treated with amputation of the affected digit. OBJECTIVE: The purpose of this study was to present the clinical and pathological features of each new case and to discuss treatment options that spare digit functionality. METHODS: Hematoxylin-eosin stains were performed on tumor sections and examined using light microscopy. In situ hybridization using probes against human papillomavirus were examined in 1 case. RESULTS: The female to male ratio was 1:1 with involvement of fingers in 3, thumb in 1, and toe in 1. Among the symptoms were onycholysis, periungual erythema, and pain; symptom duration ranged from 6 months to 2 years. Histologically, all cases showed a well-differentiated atypical infiltrative squamous proliferative lesion exhibiting a lobulated and cystic pattern of growth in the dermis. Abrupt keratinization reminiscent of trichilemmal keratinization was noted. Mohs micrographic surgery and radiation therapy were used as primary treatment modalities, maintaining digit functionality and achieving remission. LIMITATIONS: Limitations of this study included the small number of cases, the infrequency with which this tumor has been reported in the literature, and the inability to obtain follow-up on an older archival case. CONCLUSIONS: Onycholemmal carcinoma is a distinct type of squamous cell carcinoma arising from the nail isthmus; its natural clinical course is indolent. In this regard less aggressive digit-sparing treatment modalities such as radiation or Mohs micrographic surgery should be considered.