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Cytosolic [Ca.sup.2+] ([Ca.sup.2+.sub.i]) flux within the pancreatic acinar cell is important both physiologically and pathologically. We examined the role of cAMP in shaping the apical-to-basal [Ca.sup.2+] wave generated by the [Ca.sup.2+]-activating agonist carbachol. We hypothesized that cAMP modulates intra-acinar [Ca.sup.2+] channel opening by affecting either cAMP-dependent protein kinase (PKA) or exchange protein directly activated by cAMP (Epac). Isolated pancreatic acinar cells from rats were stimulated with carbachol (1 [micro]M) with or without vasoactive intestinal polypeptide (VIP) or 8-bromo-cAMP (8-Br-cAMP), and then [Ca.sup.2+] was monitored by confocal laser-scanning microscopy. The apical-to-basal carbachol (1 [micro]M)-stimulated [Ca.sup.2+] wave was 8.63 [+ or -] 0.68 micro]m/s; it increased to 19.66 [+ or +] 2.22 [micro]m/s (*P < 0.0005) with VIP (100 nM), and similar increases were observed with 8-Br-cAMP (100 [micro]M). The [Ca.sup.2+] rise time after carbachol stimulation was reduced in both regions but to a greater degree in the basal. Lag time and maximal [Ca.sup.2+] elevation were not significantly affected by cAMP. The effect of cAMP on [Ca.sup.2+] waves also did not appear to depend on extracellular [Ca.sup.2+]. However, the ryanodine receptor (RyR) inhibitor dantrolene (100 [micro]M) reduced the cAMP-enhancement of wave speed. It was also reduced by the PKA inhibitor PKI (1 [micro]M). 8-(4-chlorophenylthio)-2'-O-Me-cAMP, a specific agonist of Epac, caused a similar increase as 8-Br-cAMP or VIP. These data suggest that cAMP accelerates the speed of the [Ca.sup.2+] wave in pancreatic acinar cells. A likely target of this modulation is the RyR, and these effects are mediated independently by PKA and Epac pathways. calcium signaling; pancreatitis: zymogen activation; exocrine pancreas

Abstract Background Cholestatic jaundice as a presenting symptom of Precursor T-lymphoblastic leukemia (T-ALL)/lymphoma (T-LBL) has never been reported in literature. Similarly, precursor T-ALL/T-LBL is characteristically negative for synaptophysin. We report the first case of a patient with precursor T-ALL/T-LBL who presented with cholestatic jaundice and aberrant tumor expression of synaptophysin. Case report 42 year old male presented with anorexia, nausea, jaundice, pale stools, dark urine and about 35 pound weight loss over the previous 3 weeks. The initial laboratory work was suggestive of cholestatic jaundice. Markedly elevated LDH (2025 U/L) and CA 19-9 (1778 u/ML) were also noticed. The CT scan of abdomen showed massive hepatomegaly with coarse echotexture with contracted gall bladder and normal sized common bile duct. Chest x-ray revealed a mediastinal mass with mediastinal widening. CT scan of the chest showed anterior mediastinal mass (16 cm × 10 cm). CT guided biopsy of the mass showed malignant lymphoma with diffuse proliferation of medium sized lymphoid cells. The neoplastic cells were positive for CD1a, CD3, CD4, CD5, CD8 and CD43 with aberrant expression of synaptophysin. PET CT scan again showed a large anterior mediastinal mass with diffuse liver involvement and abnormal activity in axial bones. CT guided liver biopsy and bone marrow biopsy revealed the same morphology and immunohistochemistry. Bone marrow aspirate showed 85% lymphoblasts. Thus, the diagnosis of precursor T-ALL/T-LBL was made and jaundice with elevated CA 19-9 were attributed to intrahepatic cholestasis. Conclusion Our case illustrates an unusual presentation of hematological malignancies as cholestatic jaundice. It also indicates the non-specific nature of CA 19-9 for pancreaticobiliary malignancies. It is the first case report of neoplastic precursor T cell lymphoblasts with unusual expression of synaptophysin. Tissue biopsy with thorough immunohistochemistry is required to differentiate precursor T-ALL/T-LBL from thymoma and small cell carcinoma.