Reovirus-associated meningoencephalomyelitis in baboons.

Baboon orthoreovirus (BRV) is associated with meningoencephalomyelitis (MEM) among captive baboons. Sporadic cases of suspected BRV-induced MEM have been observed at Southwest National Primate Research Center (SNPRC) for the past 20 years but could not be confirmed due to lack of diagnostic assays. An immunohistochemistry (IHC)-based assay using an antibody against BRV fusion-associated small transmembrane protein p15 and a conventional polymerase chain reaction (PCR)-based assay using primers specific for BRV were developed to detect BRV in archived tissues. Sixty-eight cases of suspected BRV-induced MEM from 1989 through 2010 were tested for BRV, alphavirus, and flavivirus by IHC. Fifty-nine of 68 cases (87%) were positive for BRV by immunohistochemistry; 1 tested positive for flavivirus (but was negative for West Nile virus and St Louis encephalitis virus by real-time PCR), and 1 virus isolation (VI) positive control tested negative for BRV. Sixteen cases (9 BRV-negative and 7 BRV-positive cases, by IHC), along with VI-positive and VI-negative controls, were tested by PCR for BRV. Three (of 9) IHC-negative cases tested positive, and 3 (of 7) IHC-positive cases tested negative by PCR for BRV. Both IHC and PCR assays tested 1 VI-positive control as negative (sensitivity: 75%). This study shows that most cases of viral MEM among baboons at SNPRC are associated with BRV infection, and the BRV should be considered a differential diagnosis for nonsuppurative MEM in baboons.

Promise and challenge: Markers of prostate cancer detection, diagnosis and prognosis.

Approximately 1 man in 6 will be diagnosed with prostate cancer during his life lifetime, and over 200,000 men in the U.S. are diagnosed with prostate cancer annually. Since the widespread adoption of PSA testing, about 60-70% of men at risk in the U.S. have had a blood test for prostate cancer. With this, prostate cancer death rates have decreased, yet only slightly. Thirty thousand men still die each year from this disease. PSA testing fails to identify a small but significant proportion of aggressive cancers, and only about 30% of men with a "positive" PSA have a positive biopsy. Additionally, of men who are treated for prostate cancer, about 25% require additional treatment, presumably due to disease recurrence. Also of concern is the growing evidence that there are some prostate cancers for which treatment may not be necessary. Very long-term studies from the U.S. and Europe, following men with prostate cancer have found that some tumors do not progress over time. In these individuals, prostate cancer treatment is unnecessary and harmful as these men do not benefit from treatment but will be at risk of treatment-related side effects and complications. They suggest a fundamental problem with prostate cancer: it is not possible, at this time, to predict the natural history of the disease. It is for these reasons that the most important challenge in prostate cancer today is the inability to predict the behavior of an individual tumor in an individual patient. Here we review issues related to performance and validation of biomarkers with a focus on "doing no harm", and bearing in mind that it is the ultimate goal of early detection to save lives. Improved diagnostic and prognostic biomarkers are needed for prostate cancer, and the use of these markers should ultimately translate into increased life span and quality of life. The ultimate goal would be to not only have accurate biomarkers suitable for early diagnosis, but also biomarkers that identify men at greatest risk of developing aggressive disease. Technology has been brought to bear on this problem, and the major approaches are genomics, expression analysis, and proteomics. Proteomics and DNA methylation assays may soon be used in sensitive and specific diagnostic testing of serum and tissues for cancer. Expression arrays may be used to establish both a more specific diagnosis and prognosis for a particular tumor. The proteome is only beginning to be understood, and alternative splicing and post-translational modifications of proteins such as glycosylation and phosphorylation are challenging areas of study. Finally, risk assessment and prognosis are being pursued through analysis of genomic polymorphisms (single nucleotide polymorphisms, SNPs). This huge task is only beginning, and requires the combined expertise of molecular epidemiologists, oncologists, surgeons, pathologists, and basic scientists.

Comparison of growth and development of the exocrine pancreas in pigs and rats during the immediate postnatal period.

This study compared pancreatic tissue growth and functional changes during the first 3 postnatal days in piglets and rat pups. In piglets the absolute weight and the relative weight per unit body weight of the pancreas increased by 97 and 70%, respectively, while in rat pups the same parameters decreased by 33 and 48%, respectively, during this period. The specific activity of pancreatic amylase rose by 336% while that of trypsin, chymotrypsin and lipase remained at newborn level in piglets. In rat pups the specific activities of all enzymes measured declined by 61 to 92% during the first 3 postnatal days. The rate of postnatal pancreatic growth in the two species coincide with the levels of epidermal growth factor and insulin-like growth factors in maternal milk as reported in the literature, suggesting that milk-borne growth factors may stimulate pancreatic development in newborn animals.

Growth and development of the exocrine pancreas in newborn pigs: the effect of colostrum feeding.

This study examined the growth and development of the pancreas in naturally suckled piglets during the first 3 postnatal days and the effects of colostrum feeding on the pancreatic development. The results showed that in naturally suckled piglets, the absolute weight of the pancreas increased 51% during the first day and 86% by the 3rd day, and the relative weight per unit body weight increased 37% during the first day and 47% by the 3rd day. Associated with the rapid weight gain was a significant increase in pancreatic DNA content and enlargement of pancreatic exocrine acinar units, the latter apparently resulted from an increase in number rather than size of acinar cells. It was further shown that the rapid pancreatic growth was related to colostrum ingestion as significant pancreatic weight gain was observed in piglets bottle-fed porcine colostrum or trypsinized porcine colostrum but not in piglets bottle-fed 5% lactose solution. Trypsinized porcine colostrum was apparently more potent than native porcine colostrum in stimulating pancreatic growth in newborn pigs. It is speculated that colostrum-borne growth factors and/or postnatal surge of gut hormones following onset of oral feeding are the major factors responsible for the rapid postnatal pancreatic growth in newborns.