Pancreatic acinar cystadenomas (ACAs) are rare cystic lesions showing acinar differentiation with benign outcome. Although debated, ACAs are favored to be neoplastic and potentially the benign counterpart of acinar cystadenocarcinoma. We present the largest single institution series to date comprising 10 cases. The mean age was 49 years with a female predominance (M:F=1:2.3). Abdominal/flank pain was the most common presentation (n=6). Serum amylase/lipase and cyst fluid amylase were often elevated. All lesions had a benign outcome on follow-up (5 to 67 mo). The lesions were unilocular (n=3) or multilocular (n=7) with mean size of 3.8 cm (range, 2.9 to 5.0 cm) and 5.1 cm (range, 2.0 to 7.5 cm), respectively. Eight lesions were unifocal with locations as follows: head (n=2), head/neck (n=2), body (n=1), tail (n=1), predominantly extrapancreatic with a microscopic intrapancreatic component (n=1), and unspecified location (n=1). Two lesions were multifocal, involving the head/uncinate/body and pancreatic head, respectively. Two aspects of ACAs that may represent a diagnostic pitfall include the propensity for acinar epithelium to appear as nondescript flat/cuboidal epithelium (trypsin/chymotrypsin immunopositive) and epithelial heterogeneity, with focal mucinous and squamous epithelium, the latter particularly in multilocular variants. In addition, 2 cases with intracystic nodules were observed. Array comparative genomic hybridization performed on 1 of these cases showed multiple chromosomal gains involving 1p, 3p, 5q, 6p, 7q, 8, 10q, 11, 14, 20, and X. These findings provide preliminary evidence that ACAs represent a cystic neoplastic lesion.

A recently described protein, metaxin 1, serves as a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion. A yeast two-hybrid screen with metaxin 1 as bait has now identified a novel protein, which we have termed metaxin 2, as a metaxin 1-binding protein. Metaxin 2 shares 29% identity with metaxin 1 at the amino acid level, but metaxin 2, unlike metaxin 1, lacks a C-terminal mitochondrial outer membrane signal-anchor domain. Two C. elegans hypothetical proteins, CelZC97.1 and CelF39B2.i, share high sequence similarity with metaxin 2 and metaxin 1, respectively, and likely represent the C. elegans orthologs. Affinity-purified antibodies against metaxin 2 were prepared against the recombinant protein produced in E. coli and were used to analyze the subcellular distribution of metaxin 2. In subcellular fractions of mouse liver, a 29 kD immunoreactive protein, consistent in size with the predicted translation product of metaxin 2 cDNA, was found solely in mitochondria. Alkali extraction of mitochondria indicated that metaxin 2 is peripherally associated with mitochondrial membranes. Metaxin 2 in intact mitochondria was susceptible to digestion with proteinase K, indicating that metaxin 2 is located on the cytosolic face of the mitochondrial outer membrane. Finally, baculoviruses encoding a His6-tagged metaxin 2 and an untagged metaxin 1 lacking its C-terminal transmembrane domain were produced and used separately or in combination to infect Sf21 insect cells. Metaxin 1 bound to a Ni2+-chelate affinity column only in the presence of metaxin 2, indicating that metaxin 1 and metaxin 2 interact when overexpressed in insect cells. These results suggest that metaxin 2 is bound to the cytosolic face of the mitochondrial outer membrane by means of its interaction with membrane-bound metaxin 1, and that this complex may play a role in protein import into mammalian mitochondria.

Recent data suggests the presence of cytotoxic (TIA-1 and granzyme B+) and regulatory T-cells (FOXP3+) in classical Hodgkin lymphoma (cHL) tissues has been shown to correlate with poor overall survival in mainly diagnostic biopsies. By tissue microarray analyses we extend this observation to a cohort of relapsed/refractory cHL tissue biopsies and analyze immunohistochemical expression of FOXP3, TIA-1 and granzyme B in the inflammatory background and the tumor microenvironment. High expression of TIA1 (>50%) correlated with poor overall survival (p<0.0001), low expression of FOXP3 (<25%) correlated with poor overall survival (p<0.01) and combined high TIA1 (>50%) and low FOXP3 (<25%) correlated with poor overall survival (p<0.0001). Expression of cytotoxic and regulatory T-cells shows prognostic significance in the relapsed/refractory clinical setting of cHL.

We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker panel (D-dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9], S-100 b, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon runners before and immediately after the 2005 Boston Marathon. Following competition, there was a statistically significant increase in MMP-9 (P < .001) and D dimer (P < .001). Nonsignificant changes in S-100 b and BNP were observed. Premarathon and postmarathon values for a multimarker stroke index increased from 0.97 (normal) to 3.5 (low risk or more; P < .001). Two subjects had index values more than the high-risk cutoff value. Mean TnT premarathon and postmarathon levels increased (from <0.01 to 0.03 ng/mL; P < .0001). After the marathon, with a cutoff value of 0.05 ng/mL, 7 runners (23%) had values above the manufacturer's recommended cutoff for myocardial damage. Although biochemical evidence of myocardial damage following strenuous exercise may reflect myocardial stunning or subclinical ischemia, the changes in the stroke index and values for individual stroke markers may reflect a systemic inflammatory response to exertional rhabdomyolysis which is common, but the possibility of subclinical central nervous system damage cannot be excluded.