Increases in the intracellular concentration of calcium ([Ca 2+ ] i ) activate various signaling pathways that lead to the expression of genes that are essential for dendritic development, neuronal survival, and synaptic plasticity. The mode of Ca 2+ entry into a neuron plays a key role in determining which signaling pathways are activated and thus specifies the cellular response to Ca 2+ . Ca 2+ influx through L-type voltage-activated channels (LTCs) is particularly effective at activating transcription factors such as CREB and MEF-2. We developed a functional knock-in technique to investigate the features of LTCs that specifically couple them to the signaling pathways that regulate gene expression. We found that an isoleucine-glutamine (“IQ”) motif in the carboxyl terminus of the LTC that binds Ca 2+ -calmodulin (CaM) is critical for conveying the Ca 2+ signal to the nucleus. Ca 2+ -CaM binding to the LTC was necessary for activation of the Ras/mitogen-activated protein kinase (MAPK) pathway, which conveys local Ca 2+ signals from the mouth of the LTC to the nucleus. CaM functions as a local Ca 2+ sensor at the mouth of the LTC that activates the MAPK pathway and leads to the stimulation of genes that are essential for neuronal survival and plasticity.
We describe 5 cases of tick bite reactions with dermal necrosis and sparse interstitial to dense diffuse dermal neutrophilic infiltrates associated with thrombogenic vasculopathy. Tick bite reactions classically consist of moderately dense perivascular infiltrates composed of an admixture of inflammatory cells. Each of our patients had embedded tick parts, with interesting histologic features.
Ticks are ectoparasites that cause dermatologic disease both directly through physical trauma to the skin, salivary secretions, or remnant body parts, and indirectly through transmission of disease. Lyme disease, Rocky Mountain spotted fever, tularemia, and babesiosis are known tick‐transmitted diseases. The histopathology related to a primary tick bite, similar to other arthropod bites, classically consists of a perivascular infiltrate composed of lymphocytes, neutrophils, histiocytes, plasma cells, and eosinophils in varying amounts. We describe five patients with a novel histologic reaction to embedded tick parts., Each case demonstrates a thrombotic vasculopathy consisting of intraluminal eosinophilic deposits that stain strongly with Periodic acid Schiff stain. The adjacent tissue shows dermal necrosis with surrounding interstitial to diffuse dermal neutrophilic inflammation. We postulate that diffuse dermal nutrophilic infiltrates in association with thrombogenic vasculopathy is an unusual histologic picture of tick bite reactions that may be attributable to remnant tick parts.
Atypical fibroxanthoma is a fairly common dermal neoplasm that is characterized histologically by infiltrating pleomorphic spindle cells and atypical giant cells with numerous mitoses. Clinically, the lesion most commonly presents as a solitary ulcerated papule on the head or neck of elderly males. We report a patient with a rare granular cell variant of atypical fibroxanthoma. The patient was a seventy‐five‐year‐old male with a history of squamous cell carcinoma on the left scalp treated by Mohs surgery two years prior. In the vicinity of the previous squamous cell carcinoma site, the patient presented with a slow growing, approximately 1.0 by 1.0 cm red, violaceous, firm nodule on the left scalp. The clinical impression was recurrent squamous cell carcinoma. Biopsy of the lesion revealed a dermal tumor composed of pleomorphic cells with eosinophilic granular cytoplasm with numerous typical and atypical mitoses. The tumor stained focally with Factor VIII, CD 68, and SMA and 30% of the neoplastic cells stained with Ki 67. Staining for Keratin cocktail, High Molecular Weight Keratin, Melan A and S100 were negative. PAS strongly stained the granules. These features are consistent with a granular cell variant of atypical fibroxanthoma.
