Primary biliary cholangitis presenting with granulomatous lung disease misdiagnosed as lung cancer: A case report.

BACKGROUND: There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis (PBC). No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported. CASE SUMMARY: A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography. She underwent left lobectomy, and the pathology of the nodules showed granulomatous inflammation, which was then treated with antibiotics. However, a new nodule appeared. Further investigation with lung biopsy and liver serology led to the diagnosis of PBC, and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid. CONCLUSION: Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.

Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes.

Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca(2+) overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca(2+) overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca(2+)](i) levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca(2+) stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca(2+)](i) in the absence of [Ca(2+)](o) and the subsequent restoration of [Ca(2+)](o) sustained the increased [Ca(2+)](i) for a few minutes, whereas, the persisting elevation of [Ca(2+)](i) was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl(3)) or spermine also resulted in the same effect and the duration of [Ca(2+)](i) increase was also shortened in the absence of [Ca(2+)](o). In adult and neonatal rat cardiomyocytes, GdCl(3) increased the expression of TRPC3 mRNA and protein, which were reversed by SKF96365 but not by inhibitors of the L-type channels and the Na(+)/Ca(2+) exchangers. However, GdCl(3) had no obvious effect on the expression of TRPC1 protein. These results suggested that CaR stimulation induced activation of TRP channels and promoted the expression of TRPC3, but not TRPC1, that sustained the increased [Ca(2+)](i).

Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes.

Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca(2+) stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium-sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca(2+) imaging, we found that the depletion of ER/SR Ca(2+) stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca(2+) ([Ca(2+)](i)), followed by sustained increase depending on extracellular Ca(2+). But, TRP channels inhibitor (SKF96365), not L-type channels or the Na(+)/Ca(2+) exchanger inhibitors, inhibited [Ca(2+)](i) relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl(3)) or by an increased extracellular Ca(2+)([Ca(2+)](o)) increased the concentration of intracelluar Ca(2+), whereas, the sustained elevation of [Ca(2+)](i) was reduced in the presence of SKF96365. Similarly, the duration of [Ca(2+)](i) increase was also shortened in the absence of extracellular Ca(2+). Western blot analysis showed that GdCl(3) increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl(3). Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca(2+)-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis.