Colocalization and distribution of HCN4 channels and a MAGUK protein in mammalian sinoatrial myocytes

The sinoatrial node is known as the pacemaker of the heart. It controls the rate at which action potentials are generated and propagate through the sinoatrial myocytes. This thesis is an attempt to identify the colocalization of a specific ion channel (HCN4 channel) with a class of scaffolding protein (MAGUK proteins) within the sinoatrial myocyte. The colocalization of these two variables was performed using immunocytochemistry on murine sinoatrial myocytes and experimental results revealed the existence of a strong colocalization between the two variables. Images collected from the confocal microscope and analyzed using ImageJ software revealed a strong dependent correlation between the pixel intensities (488 beam-green, 633 beam-blue). The colocalization of HCN4 channels with a specific MAGUK scaffolding protein could lead to further research into a possible complex among the HCN4 channels and β1ARs within the sinoatrial myocytes. Although automaticity of the heart has been identified, the precise molecular mechanisms involved in generating the involuntary contractions are still being investigated

Anti PD-1 immunotherapy related interstitial lung disease presenting as respiratory failure - A review with case series

Introduction: Lung cancer is one of the most common cancers in the world and it is the leading cause of cancer-related deaths, among men and women, in the United States. In advanced non-small cell lung cancers, immune checkpoint inhibitors such as programmed cell death protein-1 inhibitors (PD-1 inhibitors) have become second-line therapy and have revolutionized the management in selective cases conferring better overall response rates and progression free survival. Methods: We present a case series and review of literature emphasizing this immune-related adverse events (irAEs) in patients with metastatic non-small cell lung cancer and esophageal cancer who were treated with Nivolumab as a second line therapeutic option. Results: PD-1 inhibitors such as, Nivolumab and Pembrolizumab, have shown a stable regression of various malignancies, such as metastatic melanoma, renal cell carcinoma and metastatic non-small cell lung cancer. We describe 2 cases of such immune related adverse effects associated with immune check point inhibitors with recovery in one of the patients. Steroid therapy has been the cornerstone for treatment for such immune related adverse effects. Importance has also been laid on the typical radiographic patterns of pneumonitis and interstitial lung disease associated with immunotherapy. Conclusions: We attempt to raise awareness, discuss early management strategies and hypothesize an association between the incidence and development of these adverse events in cancer patients treated with anti-PD-1 immunotherapeutic agents