Feeding distillers' grains, soybean hulls, or a mixture of both to cows as a forage replacement: Effects on intake, digestibility, and ruminal fermentation characteristics.

Coproduct feedstuffs offer a unique and potentially profitable avenue for cattle feeding strategies. However, research is lacking in the evaluation of varying coproducts on ruminal fermentation and digestive characteristics when included as the major component of the diet of cows. Our objective was to determine the effect of coproduct feedstuffs as a forage replacement on digestive and fermentative characteristics of cows. Eight ruminally fistulated cows (672 ± 32.0 kg initial BW and approximately 9 yr of age) were stratified by BW and randomly allocated to 1 of 4 diets (2 cows∙diet∙period) in a 2-period study: soybean hulls (SH), distillers' dried grains with solubles (DG), an isoenergetic mixture of soybean hulls and distillers' dried grains with solubles (MX), or ad libitum hay plus 0.9 kg/d of an isoenergetic mixture of soybean hulls and distillers' dried grains with solubles (HY). Diets were formulated to meet the ME requirements of a similar, companion study. Coproduct amounts were increased over a 14-d period. This was followed by a 14-d adaptation to diet and facilities and 5 d of total fecal collections. On the final day of fecal collections, rumen fluid was sampled immediately prior to feeding and 2, 4, 6, 8, 10 and 12 h after feeding for measurement of rumen VFA and ammonia concentrations. Intake of DM and OM was not different ( ≥ 0.28) among treatments, but digestibilities of DM, OM, NDF, and ADF were improved ( < 0.05) by coproduct feeding and by MX vs. the mean of SH and DG. Ruminal DM and OM fill were greater ( < 0.05) for cows offered HY than for cows offered the coproduct diets, greater for cows offered SH than for cows offered DG, and for the mean of SH and DG vs. MX. Ruminal retention time was greater ( < 0.05) for HY vs. the coproduct diets and for SH vs. DG. Apparent N absorption tended ( < 0.10) to be greater for cows offered the coproduct diets than for cows offered HY and greater for cows offered DG than for cows offered SH. Total VFA averaged across sampling times were greatest ( < 0.05) for cows offered SH, and ruminal ammonia N was greatest ( < 0.05) for cows offered either DG or MX at all sampling times. Based on these data, coproduct feedstuffs may be fed to meet the energy requirement of cows without negative effects on digestion or ruminal fermentation.

Storage characteristics, nutritive value, energy content, and in vivo digestibility of moist, large rectangular bales of alfalfa-orchardgrass hay treated with a propionic acid-based preservative.

Unstable weather, poor drying conditions, and unpredictable rainfall events often place valuable hay crops at risk. Recent research with large round bales composed of alfalfa (Medicago sativa L.) and orchardgrass (Dactylis glomerata L.) has shown that these large-bale packages are particularly sensitive to spontaneous heating and dry matter (DM) losses, as well as other undesirable changes with respect to forage fiber, protein, and energy density. Various formulations of organic acids have been marketed as preservatives, normally for use on hays that are not desiccated adequately in the field to facilitate safe bale storage. Our objectives for this study were to (1) evaluate the efficacy of applying a commercial (buffered) propionic acid-based preservative at 3 rates (0, 0.6, and 1.0% of wet-bale weight) to hays baled at 3 moisture concentrations (19.6, 23.8, and 27.4%) on the subsequent storage characteristics and poststorage nutritive value of alfalfa-orchardgrass forages packaged in large rectangular (285-kg) bales, and then (2) evaluate the in vivo digestibility of these hays in growing lambs. Over a 73-d storage period, the preservative was effective at limiting spontaneous heating in these hays, and a clear effect of application rate was observed for the wettest (27.4%) bales. For drier hays, both acid-application rates (1.0 and 0.6%) yielded comparable reductions in heating degree days >30°C relative to untreated controls. Reductions in spontaneous heating could not be associated with improved recovery of forage DM after storage. In this study, most changes in nutritive value during storage were related to measures of spontaneous heating in simple linear regression relationships; this suggests that the modest advantages in nutritive value resulting from acid treatment were largely associated with perturbations of normal heating patterns during bale storage. Although somewhat erratic, apparent digestibilities of both DM (Y=-0.0080x + 55.6; R(2)=0.45) and organic matter (Y=-0.0085x + 55.5; R(2)=0.53) evaluated in growing lambs were also directly related to heating degree days in simple linear relationships. Based on these data, applying propionic acid-based preservatives to large rectangular bales is likely to provide good insurance against spontaneous heating during storage, as well as modest benefits with respect to nutritive value and digestibility.

Performance by spring and fall-calving cows grazing with full, limited, or no access to toxic Neotyphodium coenophialum-infected tall fescue.

Replacing toxic, wild-type Neotyphodium coenophialum-infected tall fescue (E+) with nontoxic, N. coenophialum-infected tall fescue (NE+) has improved cow performance, but producer acceptance of NE+ has been slow. The objective was to compare performance by spring- and fall-calving cows grazing either E+ or NE+ at different percentages of the total pasture area. Gelbvieh×Angus crossbred cows (n=178) were stratified by BW and age within calving season and allocated randomly to 1 of 14 groups representing 5 treatments for a 3-yr study: i) Fall-calving on 100% E+ (F100); ii) Spring-calving on 100% E+ (S100); iii) Fall-calving on 75% E+ and 25% NE+ (F75); iv) Spring-calving on 75% E+ and 25% NE+ (S75); and v) Spring-calving on 100% NE+ (SNE100). Groups allocated to F75 and S75 grazed E+ until approximately 28 d before breeding and weaning, then were then moved to their respective NE+ pasture area for 4 to 6 wk; those allocated to F100, S100, and SNE100 grazed their pastures throughout the entire year. Samples of tall fescue were gathered from specific cells within each pasture at the time cows were moved into that particular cell (∼1 sample/mo). Blood samples were collected from the cows at the start and end of the breeding season. Stocking rate for each treatment was 1 cow/ha. Forage IVDMD, CP, and total ergot alkaloid concentrations were affected (P<0.05) by the treatment×sampling date interaction. Hay offered, cow BW, and BCS at breeding, end of breeding, and at weaning were greater (P<0.05) from fall-calving vs. spring-calving. Cow BW at weaning was greater (P<0.05) from F75 and S75 vs. F100 and S100. The calving season×NE+ % interaction affected (P<0.05) calving rates. Preweaning calf BW gain, actual and adjusted weaning BW, ADG, sale price, and calf value at weaning were greater (P<0.05) from fall-calving vs. spring-calving and from SNE100 vs. S75 except for sale price which was greater (P<0.05) from S75 vs. SNE100. Cow concentrations of serum prolactin at breeding and serum NEFA at the end of breeding were affected (P<0.05) by the calving season×NE+ % interaction. Serum Zn and Cu concentrations from cows were affected (P<0.05) by calving season. A fall-calving season may be more desirable for cows grazing E+, resulting in greater calving rates, cow performance, and calf BW at weaning, whereas limited access to NE+ may increase calving rates, serum prolactin, and NEFA concentrations during certain times in the production cycle, particularly in spring-calving cows.

Automated classification of renal cell carcinoma subtypes using bag-of-features.

Color variation in medical images degrades the classification performance of computer aided diagnosis systems. Traditionally, color segmentation algorithms mitigate this variability and improve performance. However, consistent and robust segmentation remains an open research problem. In this study, we avoid the tenuous phase of color segmentation by adapting a bag-of-features approach using scale invariant features for classification of renal cell carcinoma subtypes. Previous work shows that features from each subtype match those from expertly chosen template images. In this paper, we show that the performance of this match-based methodology greatly depends on the quality of the template images. To avoid this uncertainty, we propose a bag-of-features approach that does not require expert knowledge and instead learns a "vocabulary" of morphological characteristics from training data. We build a support vector machine using feature histograms and evaluate this method using 40 iterations of 3-fold cross validation. We achieve classification accuracy above 90% for a heterogeneous dataset labeled by an expert pathologist, showing its potential for future clinical applications.

Postoperative better than preoperative C-reactive protein at predicting outcome after potentially curative nephrectomy for renal cell carcinoma.

OBJECTIVES: Preoperative C-reactive protein (CRP) predicts metastasis and mortality in localized renal cell carcinoma (RCC). However, the predictive potential of after resection of localized RCC remains unclear. Therefore, we assessed the absolute ability of postoperative CRP to predict metastases and mortality as a continuous variable. METHODS: Patients with clinically localized (T1-T3N0M0) clear-cell RCC were followed for 1 year postoperatively. Metastases were identified radiologically and mortality by death certificate. Univariate and multivariate binary logistic regression analyses examined 1 year relapse-free survival (RFS) and overall survival (OS) across patient and disease characteristics. RESULTS: Of the 110 patients in this study, 16.4% developed metastases and 6.4% died. Mean (SD) postoperative CRP for patients who did and did not develop metastases were 69.06 (73.55) mg/L and 5.27 (7.80), respectively. Mean (SD) postoperative CRP for patients who did and did not die were 89.31 (69.51) mg/L and 10.88 (30.32), respectively. In multivariate analysis, T-stage (OR: 12.452, 95% CI: 2.889-53.660) and postoperative CRP ((B: .080, SE: .025; P < .001) were significant predictors of RFS. T-Stage (OR: 11.715; 95% CI: 1.102-124.519) and postoperative CRP (B: .017; SE: .007; P < .001) were also significant predictors of OS. After adjusting for postoperative CRP, preoperative CRP was not predictive of these outcomes. CONCLUSIONS: Postoperative, not preoperative, CRP is the better predictor of metastasis and mortality following nephrectomy for localized RCC. Clinicians should consider absolute postoperative CRP to identify high-risk patients for closer surveillance or additional therapy. Predictive algorithms should consider incorporating postoperative CRP as a continuous variable to maximize predictive ability.

Advances in molecular classification of renal neoplasms.

Kidney neoplasms are classified by light microscopy using the World Health Organization (WHO) system. The WHO system defines histopathologic tumor subtypes with distinct clinical behavior and underlying genetic mutations. In adults, the common malignant subtypes are variants of renal cell carcinoma (RCC). Histopathologic classification is critical for clinical management of RCC, but is becoming more complex with recognition of novel tumor subtypes, development of procedures yielding small diagnostic biopsies, and emergence of molecular therapies directed at tumor gene activity. Therefore, classification systems based on gene expression are likely to become essential for diagnosis, prognosis and treatment of kidney tumors. Recent DNA microarray studies have shown that clinically relevant renal tumor subtypes are characterized by distinct gene expression profiles, which are useful for discovery of novel diagnostic and prognostic biomarkers. In this review, we summarize the WHO classification system for renal tumors, general applications of microarray technology in cancer research, and specific microarray studies that have advanced knowledge of renal tumor diagnosis, prognosis, therapy and pathobiology.

Novel patterns of gene expression in pituitary adenomas identified by complementary deoxyribonucleic acid microarrays and quantitative reverse transcription-polymerase chain reaction.

Pituitary adenomas account for approximately 10% of intracranial tumors, but little is known of the oncogenesis of these tumors. The identification of tumor-specific genes may further elucidate the pathways of tumor formation. We used complementary DNA microarrays to examine gene expression profiles in nonfunctioning, PRL, GH, and ACTH secreting adenomas, compared with normal pituitary. Microarray analysis showed that 128 of 7075 genes examined were differentially expressed. We then analyzed three genes with unique expression patterns and oncogenic importance by RT-real time quantitative PCR in 37 pituitaries. Folate receptor gene was significantly overexpressed in nonfunctioning adenomas but was significantly underexpressed in PRL and GH adenomas, compared with controls and to other tumors. The ornithine decarboxylase gene was significantly overexpressed in GH adenomas, compared with other tumor subtypes but was significantly underexpressed in ACTH adenomas. C-mer proto-oncogene tyrosine kinase gene was significantly overexpressed in ACTH adenomas but was significantly underexpressed in PRL adenomas. We have shown that at least three genes involved in carcinogenesis in other tissues are also aberrantly regulated in the major types of pituitary tumors. The evaluation of candidate genes that emerge from these experiments provides a rational approach to investigate those genes significant in tumorigenesis.

Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers.

The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes-vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.

Nerve growth factor, but not epidermal growth factor, increases Fra-2 expression and alters Fra-2/JunD binding to AP-1 and CREB binding elements in pheochromocytoma (PC12) cells.

In pheochromocytoma (PC12) cells nerve growth factor (NGF) and epidermal growth factor (EGF) activate similar receptor tyrosine kinase signaling pathways but evoke strikingly different biological outcomes: NGF induces differentiation and EGF acts as a mitogen. A novel approach was developed for identifying transcription factor activities associated with NGF-activated, but not EGF-activated, signaling, using random oligonucleotide clones from a DNA recognition library to isolate specific DNA binding proteins from PC12 nuclear extracts. A protein complex from NGF-treated, but not EGF-treated, cells was identified that exhibits increased mobility and DNA binding activity in gel mobility shift assays. The binding complex was identified in supershift assays as Fra-2/JunD. The clones used as probes contain either AP-1 or cAMP response element binding (CREB) recognition elements. Time course experiments revealed further differences in NGF and EGF signaling in PC12 cells. NGF elicits a more delayed and sustained ERK phosphorylation than EGF, consistent with previous reports. Both growth factors transiently induce c-fos, but NGF evokes a greater response than EGF. NGF specifically increases Fra-1 and Fra-2 levels at 4 and 24 hr. The latter is represented in Western blots by bands in the 40-46 kDa range. NGF, but not EGF, enhances the upper bands, corresponding to phosphorylated Fra-2. These findings suggest that prolonged alterations in Fra-2 and subsequent increases in Fra-2/JunD binding to AP-1 and CREB response elements common among many gene promoters could serve to trigger broadly an NGF-specific program of gene expression.

Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination.

Epithelia of the vertebrate intestinal tract characteristically maintain an inflammatory hyporesponsiveness toward the lumenal prokaryotic microflora. We report the identification of enteric organisms (nonvirulent Salmonella strains) whose direct interaction with model human epithelia attenuate synthesis of inflammatory effector molecules elicited by diverse proinflammatory stimuli. This immunosuppressive effect involves inhibition of the inhibitor kappaB/nuclear factor kappaB (IkappaB/NF-kappaB) pathway by blockade of IkappaB-alpha degradation, which prevents subsequent nuclear translocation of active NF-kappaB dimer. Although phosphorylation of IkappaB-alpha occurs, subsequent polyubiquitination necessary for regulated IkappaB-alpha degradation is completely abrogated. These data suggest that prokaryotic determinants could be responsible for the unique tolerance of the gastrointestinal mucosa to proinflammatory stimuli.

Cellular aspects of trophic actions in the nervous system.

During the past three decades the number of molecules exhibiting trophic actions in the brain has increased drastically. These molecules promote and/or control proliferation, differentiation, migration, and survival (sometimes even the death) of their target cells. In this review a comprehensive overview of small diffusible factors showing trophic actions in the central nervous system (CNS) is given. The factors discussed are neurotrophins, epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, insulin-like growth factors, ciliary neurotrophic factor and related molecules, glial-derived growth factor and related molecules, transforming growth factor-beta and related molecules, neurotransmitters, and hormones. All factors are discussed with respect to their trophic actions, their expression patterns in the brain, and molecular aspects of their receptors and intracellular signaling pathways. It becomes evident that there does not exist "the" trophic factor in the CNS but rather a multitude of them interacting with each other in a complicated network of trophic actions forming and maintaining the adult nervous system.

Ewing's sarcoma presenting as a posterior mediastinal mass: a lesson learned.

Thoracic vertebral body hemicorpectomy and chest wall resection was performed in a 17-year-old male patient with a posterior mediastinal tumor thought to be neurogenic in origin. No preoperative tissue diagnostic endeavor was made. Final pathologic diagnosis showed this tumor to be Ewing's sarcoma. This communication alerts the thoracic surgeon to the need for definitive diagnosis of posterior mediastinal masses with vertebral body involvement, particularly in children. Induction chemotherapy is the accepted standard of management of these sarcomas.

Clonogenic potential of myeloid leukaemia cells in vitro is restricted to leukaemia cells expressing the CD34 antigen.

Cells from patients with acute myeloid leukaemia (AML) or chronic myeloid leukaemia (CML) were separated into CD34-enriched and CD34-depleted subpopulations. The clonogenic capacities of these two subpopulations were then compared to each other and to the original unseparated cell population. In every study, the CD34-enriched subpopulation demonstrated a substantial increase in clonogenicity in vitro in comparison with the original cell population, while the reverse was the case for the CD34-depleted subpopulations. For reasons not clear at present, the enrichment for clonogenic cells far exceeded the enrichment for cells expressing the CD34 antigen. Additionally, the clonogenic potential was found to be unrelated to the level of myc expression in the various cell populations.