253 research outputs found

    Constriction Behavior, a Key Innovation In Snake Evolution: The Integration of Ethology and Physiology

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    Among living tetrapod vertebrates, snakes exhibit the most radical shifts in feeding biology and among limbless squamate reptiles, only snakes have undergone a substantial adaptive radiation. The behavioral innovation, constriction, has been associated with the success of this clade. Constriction is a prey restraint behavior that enabled snakes to immobilize and subdue extremely large prey items relative to their own body mass. This behavior pattern is associated with the incredible shifts observed in snake feeding biology from consuming small meals frequently to less frequent feeding on large prey. Although constriction is an ethological homology for the majority of snakes, variations of constriction postures have been documented in many derived snake lineages. Nevertheless, the mechanisms driving behavioral variation are not well understood. In this dissertation, I attempt to use a comparative hierarchical approach to examine constriction behavior at both the ethological and physiological levels in order to better understand the behavioral variation of this key innovation. As reviewed in Part 1, derived snake lineages seem to have several methods with which to restrain prey. Prey restraint methods appear to vary with respect to prey characteristics (size, shape, activity level). On the other hand, intermediate taxa (boas and pythons) are thought to be less variable in the prey restraint phase of feeding. The kinematics of loop application pattern also appears to differ between intermediate and derived snake groups. Derived snakes use the lateral part of their body to wind prey whereas boas tend to bend ventrally around prey. The polarity for variable prey restraint behavior and loop application patterns have not been determined as observations on feeding behavior for basal snake taxa are lacking. I report on stimulus control studies evaluating prey restraint behavior and loop application pattern for basal and intermediate snake taxa in Part 2. Testing for the effects of prey size and status on the prey restraint behavior enabled me to polarize variable prey restraint behavior and loop application pattern. Prey size and status had varying effects on the capture position, prey restraint method, prey restraint time and swallowing time for basal and semi-fossorial boas while individuals of B. constrictor only constricted prey. Looping one or more times around prey was observed during the intraoral transport (swallowing) phase of feeding in the majority of trials for L. bicolor and Erycine snakes (Eryx muelleri, Charina bottae, Lichanura triviragata). Loop application patterns varied across snake taxa with basal and semi-fossorial boas applying loops laterally around prey. Individuals of B. constrictor bent ventrally around prey. The ability to vary prey restraint behavior, in response to prey characteristics and applying loops laterally around prey is probably the ancestral condition in snakes. Intermediate taxa, such a boas exhibit a derived simplified behavioral repertoire. Examining the underlying physiology of a complex motor pattern, such as constriction behavior, can provide a better understanding of the hierarchical structure of organisms in nature. As an ethological homology, constriction behavior provides us with the opportunity to trace evolutionary change at other levels of biological organization and to examine how various levels within a hierarchy relate to one another. Although constriction is an important key innovation associated with the adaptive radiation of snakes, few studies have examined the underlying physiological patterns of this complex motor pattern that may account for the kinematic variability of constriction postures among snakes. In Parts 3 & 4, I comparatively examine the muscle activity patterns during constriction for basal and intermediate snake lineages. I specifically investigated how the underlying physiological mechanisms of constriction correspond to the postural changes observed at the behavioral level using electromyography. Lateral bending and unilateral muscle activity patterns were predominant in the basal taxon, Loxocemus bicolor. Lateral bending and unilateral muscle activity patterns were also observed in derived snake taxa previously documented. Ventral bending and bilateral epaxial muscle activity patterns were predominant in intermediate lineages and present in derived snake lineages. Therefore, similar to prey restraint behaviors, three epaxial muscle activity patterns were observed: 1) mostly lateral bending with unilateral epaxial muscle activity, 2) mostly ventral bending with bilateral muscle activity and 3) mostly lateral and some bilateral bends associated with both unilateral and bilateral epaxial muscle activity, “mixed”. The kinematic and muscle activity patterns correspond with the ethological data in Part 2. Lateral bending and unilateral epaxial muscle activity support the more variable prey restraint behaviors observed in basal and derived snake taxa. Ventral bending and bilateral activity supports the highly stereotyped behavior patterns observed in intermediate snake taxa. A ‘mixed’ kinematic and epaxial activity pattern supports highly variable prey restraint methods as observed from previous research on gopher snakes and kingsnakes. Thus the patterns of epaxial muscle activity underlying constriction behavior can be correlated with the variability in prey restraint postures. In Part 5, I integrate the behavioral, physiological, and ecological differences reported for L. bicolor and Boid snakes, from the stimulus control data and the physiological data collected in this study, to further discuss the origin and evolution of feeding behavior among basal, intermediate and derived snake taxa

    An alternative flow cytometry strategy for peripheral blood dendritic cell enumeration in the setting of repetitive GM-CSF dosing

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    BACKGROUND: Enumeration of circulating peripheral blood dendritic cells (DCs) is complicated by the absence of a unique cell surface marker expressed on all DC subsets and by the use of various biological adjuvants to modulate the DC compartment, including granulocyte macrophage colony stimulating factor (GM-CSF). Common methods employ a cocktail of antibodies, typically including anti-CD14, to define a lineage negative, MHC class II positive, putative DC population. Reported flow cytometry protocols include highly variable gating strategies and DC identification criteria. Increasing appreciation of DC pleiomorphism, GM-CSF biology, and recognition of CD14 expression in some DC subsets led us to consider an alternative lineage cocktail to improve identification of the circulating DC pool. METHODS: Standard whole blood staining with appropriate fluorochrome conjugated antibodies to MHC class II and either standard CD14 containing, or an alternate CD66acde containing, lineage cocktail was performed on samples obtained from normal donors and breast cancer patients before and after administration of dose-dense, cytotoxic chemotherapy with daily GM-CSF hematopoetic growth factor support. Putative DCs were enumerated by standard flow cytometry. Data set differences were evaluated using two tailed Mann-Whitney or Wilcoxon signed rank tests. Cellular morphology was examined in cell-sorted populations from post GM-CSF samples. RESULTS: Use of either antibody cocktail defined comparably sized lineage negative, MHC class II positive populations in normal donors and at baseline in cancer patients. However, selection of lineage negative subsets with increasing MHC class II expression levels yielded larger putative DC populations identified with the alternate cocktail. Both cocktails yielded highly reproducible data. Use of the alternate cocktail: 1) yielded a putative DC population, post GM-CSF that was more homogenous and consistent with DCs, 2) resulted in less data variation across gating strategies, and 3) resulted in more uniform and concordant longitudinal data, consistent with established GM-CSF biological activity. CONCLUSION: An alternative lineage negative cocktail substituting anti-CD66 antibody for anti-CD14 is a viable option for enumerating the circulating DC population, potentially more accurately defining the circulating DC pool by including CD14 positive immature DCs, and thus, may give more reliable data, particularly in the setting of sustained GM-CSF administration

    Background Parenchymal Enhancement of the Contralateral Normal Breast: Association with Tumor Response in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

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    AbstractPURPOSE: This study investigated the association between background parenchymal enhancement (BPE) and pathologic response to neoadjuvant chemotherapy (NAC). METHODS: A total of 46 patients diagnosed with invasive breast cancer were analyzed. Each patient had three magnetic resonance imaging (MRI) studies, one pre-treatment and two follow-up (F/U) MRI studies. BPE was measured as the averaged enhancement of the whole fibroglandular tissues. The pre-treatment BPE and the changes in the F/U MRI were compared between patients achieving pathologic complete response (pCR) versus those not. Subgroup analyses based on age, estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) status of their cancers were also performed. RESULTS: The pre-treatment BPE was higher in the pCR group than that in the non-pCR group. Compared to baseline, BPE at F/U-1 was significantly decreased in the pCR group but not in the non-pCR group. In subgroup analysis based on age, these results were seen only in the younger group (<55 years old), not in the older group (≥55 years old). Older patients had a significantly lower pre-treatment BPE than younger patients. In analysis based on molecular biomarkers, a significantly decreased BPE at F/U-1 was only found in the ER-negative pCR group but not in the non-pCR, nor in the ER-positive groups. CONCLUSIONS: A higher pre-treatment BPE showing a significant decrease early after starting NAC was related to pCR in pre/peri-menopausal patients

    Characterization of Pure Ductal Carcinoma In Situ on Dynamic Contrast-Enhanced MR Imaging: Do Nonhigh Grade and High Grade Show Different Imaging Features?

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    To characterize imaging features of pure DCIS on dynamic contrast-enhanced MR imaging (DCE-MRI), 31 consecutive patients (37-81 years old, mean 56), including 2 Grade I, 16 Grade II, and 13 Grade III, were studied. MR images were reviewed retrospectively and the morphological appearances and kinetic features of breast lesions were categorized according to the ACR BI-RADS breast MRI lexicon. DCE-MRI was a sensitive imaging modality in detecting pure DCIS. MR imaging showed enhancing lesions in 29/31 (94%) cases. Pure DCIS appeared as mass type or non-mass lesions on MRI with nearly equal frequency. The 29 MR detected lesions include 15 mass lesions (52%), and 14 lesions showing non-mass-like lesions (48%). For the mass lesions, the most frequent presentations were irregular shape (50%), irregular margin (50%) and heterogeneous enhancement (67%). For the non-mass-like lesions, the clumped internal enhancement pattern was the dominate feature, seen in 9/14 cases (64%). Regarding enhancement kinetic curve, 21/29 (78%) lesions showed suspicious malignant type kinetics. No significant difference was found in morphology (P > .05), tumor size (P = 0.21), and kinetic characteristics (P = .38) between non-high grade (I+II) and high-grade (III) pure DCIS

    Tissue Oxygen Saturation Predicts Response to Breast Cancer Neoadjuvant Chemotherapy within 10 Days of Treatment

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    Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to healthy tissue, produced models with robust predictions. Notably, logistic regression based on z-score normalization using only tissue oxygen saturation (StO2) measured within 10 days of the initial therapy dose was found to be a significant predictor of pCR (AUC  =  0.92; 95% CI: 0.82 to 1). This observation suggests that patients who show rapid convergence of tumor tissue StO2 to surrounding tissue StO2 are more likely to achieve pCR. This early predictor of pCR occurs prior to reductions in tumor size and could enable dynamic feedback for optimization of chemotherapy strategies in breast cancer

    Prognostic impact of human epidermal growth factor-like receptor 2 and hormone receptor status in inflammatory breast cancer (IBC): analysis of 2,014 IBC patient cases from the California Cancer Registry

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    IntroductionInflammatory breast cancer (IBC) is an aggressive form of breast cancer associated with overexpression of Her2/Neu (human epidermal growth factor-like receptor 2 (HER2)) and poor survival. We investigated survival differences for IBC patient cases based on hormone receptor status and HER2 receptor status using data from the California Cancer Registry, as contrasted with locally advanced breast cancer (LABC), metastatic breast cancer (MBC) and non-T4 breast cancer.MethodsA case-only analysis of 80,099 incident female breast cancer patient cases in the California Cancer Registry during 1999 to 2003 was performed, with follow-up through March 2007. Overall survival (OS) and breast cancer-specific survival (BC-SS) were analyzed using Kaplan-Meier methods and Cox proportional hazards ratios.ResultsA total of 2,014 IBC, 1,268 LABC, 3,059 MBC, and 73,758 non-T4 breast cancer patient cases were identified. HER2+ was associated with advanced tumor stage (P &lt; 0.0001). IBC patient cases were more likely to be HER2+ (40%) and less likely to be hormone receptor-positive (HmR+) (59%) compared with LABC (35% and 69%, respectively), MBC (35% and 74%), and non-T4 patient cases (22% and 82%). HmR+ status was associated with improved OS and BC-SS for each breast cancer subtype after adjustment for clinically relevant factors. In multivariate analysis, HER2+ (versus HER2-) status was associated with poor BC-SS for non-T4 patient cases (hazards ratio = 1.16, 95% confidence interval 1.05 to 1.28) and had a borderline significant association with improved BC-SS for IBC (hazards ratio = 0.82, 95% confidence interval = 0.68 to 0.99).ConclusionsDespite an association with advanced tumor stage, HER2+ status is not an independent adverse prognostic factor for survival among IBC patient cases
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