Dataset Information

Soluble adenylyl cyclase antibody profile as a diagnostic adjunct in the assessment of pigmented lesions.

ABSTRACT: To investigate the usefulness of a novel marker for melanocytic proliferations.Using a novel monoclonal antibody against soluble adenylyl cyclase (sAC), various benign and malignant melanocytic proliferations were immunostained.Weill Medical College of Cornell University dermatopathology laboratory.The results were qualitative, not quantifiable.The sAC immunostaining produced distinctive patterns that paralleled melanomagenesis. At one pole of the spectrum were benign nevi, including atypical nevi of special sites and recurrent nevi showing a distinct pattern of dotlike Golgi staining, while at the opposite pole was melanoma, in which many cells demonstrated an intense pannuclear expression pattern, often accompanied by loss of the Golgi expression pattern. Melanomas of lentigo maligna and acral lentiginous subtypes exhibited the most striking pannuclear expression, while nodular melanomas showed the least, although with supervening enhanced diffuse cytoplasmic expression. Loss of the Golgi expression pattern was a feature of malignant melanoma.The sAC expression pattern is complex but seems discriminatory, with distinctive and variable staining patterns according to the nature of the lesion biopsied.

SUBMITTER: Magro CM

PROVIDER: S-EPMC3387488 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Soluble adenylyl cyclase antibody profile as a diagnostic adjunct in the assessment of pigmented lesions.

Magro Cynthia M CM Crowson A Neil AN Desman Garrett G Zippin Jonathan H JH

Archives of dermatology 20111121 3

<h4>Objective</h4>To investigate the usefulness of a novel marker for melanocytic proliferations.<h4>Design</h4>Using a novel monoclonal antibody against soluble adenylyl cyclase (sAC), various benign and malignant melanocytic proliferations were immunostained.<h4>Setting</h4>Weill Medical College of Cornell University dermatopathology laboratory.<h4>Main outcome measures</h4>The results were qualitative, not quantifiable.<h4>Results</h4>The sAC immunostaining produced distinctive patterns that ...[more]

PMID: 22105816

Similar Datasets

Project description:UnlabelledAnion exchanger 2 (AE2), the principal bicarbonate secretor in the human biliary tree, is down-regulated in primary biliary cholangitis. AE2 creates a "bicarbonate umbrella" that protects cholangiocytes from the proapoptotic effects of bile salts by maintaining them deprotonated. We observed that knockdown of AE2 sensitized immortalized H69 human cholangiocytes to not only bile salt-induced apoptosis (BSIA) but also etoposide-induced apoptosis. Because the toxicity of etoposide is pH-independent, there could be a more general mechanism for sensitization of AE2-depleted cholangiocytes to apoptotic stimuli. We found that AE2 deficiency led to intracellular bicarbonate accumulation and increased expression and activity of soluble adenylyl cyclase (sAC), an evolutionarily conserved bicarbonate sensor. Thus, we hypothesized that sAC regulates BSIA. H69 cholangiocytes and primary mouse cholangiocytes were used as models. The sAC-specific inhibitor KH7 not only reversed sensitization to BSIA in AE2-depleted H69 cholangiocytes but even completely prevented BSIA. sAC knockdown by tetracycline-inducible short hairpin RNA also prevented BSIA. In addition, sAC inhibition reversed BSIA membrane blebbing, nuclear condensation, and DNA fragmentation. Furthermore, sAC inhibition also prevented BSIA in primary mouse cholangiocytes. Mechanistically, sAC inhibition prevented Bax phosphorylation at Thr167 and mitochondrial translocation of Bax and cytochrome c release but not c-Jun N-terminal kinase activation during BSIA. Finally, BSIA in H69 cholangiocytes was inhibited by intracellular Ca(2+) chelation, aggravated by thapsigargin, and unaffected by removal of extracellular calcium.ConclusionsBSIA is regulated by sAC, depends on intracellular Ca(2+) stores, and is mediated by the intrinsic apoptotic pathway; down-regulation of AE2 in primary biliary cholangitis sensitizes cholangiocytes to apoptotic insults by activating sAC, which may play a crucial role in disease pathogenesis. (Hepatology 2016;64:522-534).

Dataset Information

Soluble adenylyl cyclase antibody profile as a diagnostic adjunct in the assessment of pigmented lesions.

Publications

Soluble adenylyl cyclase antibody profile as a diagnostic adjunct in the assessment of pigmented lesions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets