Macroinfauna responses and recovery trajectories after an oil spill differ from those following saltmarsh restoration.

Given the severity of injuries to biota in coastal wetlands from the Deepwater Horizon oil spill (DWH) and the resulting availability of funding for restoration, information on impacted salt marshes and biotic development of restored marshes may both help inform marsh restoration planning in the near term and for future spills. Accordingly, we performed a meta-analysis to model a restoration trajectory of total macroinfauna density in constructed marshes (studied for ~30 y), and with a previously published restoration trajectory for amphipods, we compared these to recovery curves for total macroinfauna and amphipods from DWH impacted marshes (over 8.5 y). Total macroinfauna and amphipod densities in constructed marshes did not consistently reach equivalency with reference sites before 20 y, yet in heavily oiled marshes recovery occurred by 4.5 y post spill (although it is unlikely that macroinfaunal community composition fully recovered). These differences were probably due to initial conditions (e.g., higher initial levels of belowground organic matter in oiled marshes) that were more conducive to recovery as compared to constructed marshes. Furthermore, we found that amphipod trajectories were distinctly different in constructed and oiled marshes as densities at oiled sites exceeded that of reference sites by as much as 20x during much of the recovery period. Amphipods may have responded to the rapid increase and high biomass of benthic microalgae following the spill. These results indicate that biotic responses after an oil spill may be quantitatively different than those following restoration, even for heavily oiled marshes that were initially denuded of vegetation. Our dual trajectories for oil spill recovery and restoration development for macroinfauna should help guide restoration planning and assessment following the DWH as well as for restoration scaling for future spills.

Compensators for dose and scatter management in cone-beam computed tomography.

The ability of compensators (e.g., bow-tie filters) designed for kV cone-beam computed tomography (CT) to reduce both scatter reaching the detector and dose to the patient is investigated. Scattered x rays reaching the detector are widely recognized as one of the most significant challenges to cone-beam CT imaging performance. With cone-beam CT gaining popularity as a method of guiding treatments in radiation therapy, any methods that have the potential to reduce the dose to patients and/or improve image quality should be investigated. Simple compensators with a design that could realistically be implemented on a cone-beam CT imaging system have been constructed to determine the magnitude of reduction of scatter and/or dose for various cone-beam CT imaging conditions. Depending on the situation, the compensators were shown to reduce x-ray scatter at the detector and dose to the patient by more than a factor of 2. Further optimization of the compensators is a possibility to achieve greater reductions in both scatter and dose.

The feasibility of measuring silver concentrations in vivo with x-ray fluorescence.

X-ray fluorescence (XRF) has been demonstrated to be an extremely useful technique for measuring trace quantities of heavy metals in various tissues in the body. This study investigates the applicability of XRF to the measurement of silver concentrations in skin. The system chosen employs an 125I source to excite the silver K x-rays, with the source, sample and detector arranged in a 90 degrees geometry. Experiments with silver-doped skin phantoms indicate that a minimum detectable concentration of 3-4 ppm is possible in 10-20 min measurement periods. Based on estimates of silver concentrations in the skin of patients suffering from argyria, the proposed system has sufficient sensitivity to warrant further investigation into its usefulness for non-invasive monitoring of exposed populations. Specifically, such a measurement may well allow for the identification of individuals at risk of subsequently exhibiting argyria, an irreversible skin pigmentation arising from silver exposure.

The influence of shape similarity and shared labels on infants' inductive inferences about nonobvious object properties.

This study examined the influence of object labels and shape similarity on 16- to 21-month-old infants' inductive inferences. In three experiments, a total of 144 infants were presented with novel target objects with or without a nonobvious property, followed by test objects that varied in shape similarity to the target. When objects were not labeled, infants generalized the nonobvious property to test objects that were highly similar in shape (Experiment 1). When objects were labeled with novel nouns, infants relied both on shape similarity and shared labels to generalize properties (Experiment 2). Finally, when objects were labeled with familiar nouns, infants generalized the properties to those objects that shared the same label, regardless of shape similarity (Experiment 3). The results of these experiments delineate the role of perceptual similarity and conceptual information in guiding infants' inductive inferences.

Prevalence of risk factors in breast cancer patients at the University Hospital of the West Indies.

The records of one hundred and twenty consecutive patients diagnosed with carcinoma of the breast were examined between July 1996 and June 1999 in order to estimate the prevalence of established risk factors for this disease. Early menarche was present in 5.5% of patients, while 36 subjects (30%) were nulliparous and 6 (5%) had a first live birth after age 30 years. Four subjects had a previous biopsy with histological features of atypical hyperplasia. Fifteen subjects (12.5%) had one or more affected first degree relatives. Fifty-four per cent of subjects possessed none of the risk factors examined in this study while 36% had a single risk factor and 10% possessed two risk factors. There was no significant clustering of risk factors in the group of patients aged thirty-five years or less. Larger studies should be encouraged to identify the risk factors which operate in our population and the degree to which published predictive variables are applicable.

Prevalence of risk factors in breast cancer patients at the University Hospital of the West Indies

The records of 120 consecutive patients diagnosed with carcinoma of the breast were examined between July 1996 and June 1999 in order to estimate the prevalence of established risk factors for this disease. Early menarche was present in 5.5 percent of patients, while 36 subjects (30 percent) were mulliparous and 6 (5 percent) had a first live birth after age 30 years. Four subjects had a previous biopsy with histological features of atypical hyperplasia. Fifteen subjects (12.5 percent) had one or more affected first degree relatives. Fifty-four percent of subjects possessed none of the risk factors examined in this study while 36 percent had a single risk factor and 10 percent possessed two risk factors. There was no significant clustering of risk factors in the group of patients aged thirty-five years or less. Larger studies should be encouraged to identify the risk factors which operate in our population and the degree to which published predictive variables are applicable.(AU)

Prevalence of risk factors in breast cancer patients at the University Hospital of the West Indies

The records of 120 consecutive patients diagnosed with carcinoma of the breast were examined between July 1996 and June 1999 in order to estimate the prevalence of established risk factors for this disease. Early menarche was present in 5.5 percent of patients, while 36 subjects (30 percent) were mulliparous and 6 (5 percent) had a first live birth after age 30 years. Four subjects had a previous biopsy with histological features of atypical hyperplasia. Fifteen subjects (12.5 percent) had one or more affected first degree relatives. Fifty-four percent of subjects possessed none of the risk factors examined in this study while 36 percent had a single risk factor and 10 percent possessed two risk factors. There was no significant clustering of risk factors in the group of patients aged thirty-five years or less. Larger studies should be encouraged to identify the risk factors which operate in our population and the degree to which published predictive variables are applicable.

Preschoolers' and adults' reliance on object shape and object function for lexical extension.

We investigated the developmental progression of reliance on object function versus object shape to extend novel words. In 3 experiments, 3-year-olds, 5-year-olds, and adults were presented with sets of objects consisting of a target, a same-shape/different-function match, a different-shape/same-function match, and a distracter. In Experiments 1 and 2, function was emphasized during the word learning phase and participants were given direct experience with the functions of target and test objects. In Experiment 3, function was emphasized both during the learning phase and when requesting a referent of the novel labels. Across all 3 experiments, 3- and 5-year-olds focused on shape while adults focused on function when extending the novel words. These results suggest a developmental change in the consideration of shape and function in lexical extension.

Calcitonin driven v-Ha-ras induces multilineage pulmonary epithelial hyperplasias and neoplasms.

We initiated a transgenic model for primary pulmonary neuroendocrine cell (PNEC) hyperplasia/neoplasia using v-Ha-ras driven by the neural/neuroendocrine (NE)-specific calcitonin promoter (rascal). Previously, we showed that nitrosamine treated rodents develop PNEC hyperplasia but non-NE lung tumors, with variable outcomes presumably reflecting ras activation in multiple cell lineages. Interestingly, all rascal transgenic mouse lineages develop hyperplasias of NE and non-NE cells but mostly non-NE lung carcinomas, with rascal mRNA in differentiated PNECs and tumor cells. Analyses of embryonic lung demonstrate rascal mRNA in undifferentiated epithelium, consistent with expression in a common pluripotent precursor cell. These unexpected observations indicate that v-Ha-ras can lead to both NE and non-NE hyperplasia/neoplasia in vivo, opening new avenues for studies of lung carcinogenesis.

CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia.

In previous studies, we demonstrated that pulmonary neuroendocrine cell (PNEC) hyperplasia in hamsters treated with diethylnitrosamine (DEN) plus 65% hyperoxia (DEN/O2) reflects predominantly neuroendocrine cell differentiation. Several peptides implicated in non-neoplastic PNEC hyperplasia are hydrolyzed by CD10/neutral endopeptidase 24.11 (CD10/NEP), an enzyme known to downregulate neurogenic inflammation of the lung by modulating locally effective concentrations of multiple bioactive peptides. In fetal mice, we observed that CD10/NEP inhibition by SCH32615 potentiates cell proliferation and type II cell differentiation in the lung in utero. Further, CD10/NEP messenger RNA levels parallelled relative PNEC numbers in DEN/O2-treated hamster lung, suggesting that the enzyme might mediate spontaneous regression of PNEC hyperplasia. The goals of the present study were: (1) to determine whether CD10/NEP inhibition would alter the extent of PNEC hyperplasia occurring in these hamsters, and (2) to analyze cellular mechanisms potentially involved in altering numbers of PNECs in this model. We administered SCH32615 chronically to a subset of DEN/O2-treated hamsters. Immunostaining of lungs from the CD10/ NEP-inhibited subset demonstrated significant acceleration of the development of PNEC hyperplasia, increased PNEC proliferation, and diminished PNEC apoptosis as compared with animals receiving no SCH32615. These observations indicate that PNEC hyperplasia can occur as a result of multiple cellular processes, including increased neuroendocrine cell differentiation, proliferation, and survival. CD10/NEP modulates PNEC numbers primarily by promoting cell differentiation and proliferation during lung injury, probably via increasing the half-life of bioactive peptides in the lung.

Lexical form class information guides word-to-object mapping in preschoolers.

We demonstrate that lexical form class information can play a powerful role in directing the establishment of word-to-object mappings in referentially ambiguous situations. A total of 144 3- and 4-year-olds heard a novel label, modeled syntactically as either a proper name or an adjective, for a stuffed animal of a familiar kind. We then added a second object of the same kind and asked children (1) to choose one of the two objects as the referent of a second novel label, also presented syntactically as either a proper name or an adjective, and (2) to decide whether this second label could also apply to the object they did not choose. In each of three experiments, preschoolers were most likely to reject two words for the same object if both words were proper names (as if one dog could not be both "Fido" and "Rover"). They were significantly less likely to do so if both were adjectives (as if one dog could be both "spotted" and "furry") or if one was a proper name and the other was an adjective (as if one dog could be both "Fido" and "furry"). Information about lexical form class thus contributed significantly to the formation of linkages between words and objects.

Infants' reliance on shape to generalize novel labels to animate and inanimate objects.

Two experiments were conducted to examine infants' reliance on object shape versus colour for word generalization to animate and inanimate objects. A total of seventy-three infants aged 1;4 to 1;10 were taught labels for either novel vehicles or novel animals using a preferential looking procedure (Experiment 1) or an interactive procedure (Experiment 2). The results of both experiments indicated that infants limited their word generalization to those exemplars that shared shape similarity with the original referent for both animate and inanimate objects. These findings indicate that a strong reliance on shape is present earlier than previously shown. In Experiment 2, reliance on shape to generalize novel words did not vary as a function of vocabulary size. Thus reliance on shape versus colour for word generalization does not appear to increase in strength as a function of word learning during late infancy.

Infants' expectations about object label reference.

The aim of this research was to examine whether infants at the early stages of lexical development were sensitive to the word-category linkage. In Experiment 1, 16-to 19-month-old infants were requested to match a target with either a basic-level or a thematic match, with or without a novel label. Stimuli were presented using the preferential looking paradigm. Infants in the Novel Label condition looked significantly longer at the basic-level match than infants in the No Label condition. In Experiment 2, infants were presented with a target, followed by a basic-level match and a superordinate-level match with or without a novel label. Again, infants in the Novel Label condition looked significantly longer at the basic-level match than infants in the No Label condition. Taken together, these findings indicate that infants initially assume that novel words label basic-level categories and thereby do honour the word-category linkage.

Macrophage-stimulating protein and its receptor in non-small-cell lung tumors: induction of receptor tyrosine phosphorylation and cell migration.

Previously, we identified macrophage-stimulating protein (MSP) as being expressed during hamster lung injury induced by nitrosamine carcinogens. Transient, generalized epithelial-cell hyperplasia during the preneoplastic period, and eventually nonneuroendocrine (non-NE) lung tumors, are known to develop in these nitrosamine-treated hamsters. We wished to test the hypothesis that MSP and its tyrosine kinase receptor, RON, might represent an autocrine/paracrine system involved in the pathogenesis of human nonneuroendocrine lung tumors, the non-small-cell carcinomas (NSCLCs). We found that this occurred in a paracrine fashion in three of eight primary human NSCLCs that expressed messenger RNA (mRNA) for MSP at high levels in histologically normal lung adjacent to the tumor, but not in the primary tumor, together with mRNA for RON in both normal and tumor tissue. MSP and RON could also constitute an autocrine/paracrine system in human NSCLC cell lines: five of 16 cell lines (squamous and adenosquamous) expressed both MSP and RON; and an additional five of 16 cell lines expressed RON without detectable MSP. Although three cases of primary squamous-cell carcinomas expressed MSP (two of three in the tumor and one of three in nonneoplastic lung), mRNA for RON was not detectable in these cases. RON was functional in all tested RON mRNA-positive cell lines, with exogenous MSP inducing RON-mediated tyrosine phosphorylation. Treatment of a RON-positive adenosquamous carcinoma cell line with MSP additionally resulted in increased motility in a cell-migration assay, suggesting that MSP might promote cell migration of some NSCLCs. In conclusion, MSP and RON might represent an autocrine/paracrine system involved in the pathogenesis of lung cancer, although the nature of the biologic responses in different cell types might vary considerably.

Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival.

Transient pulmonary neuroendocrine cell hyperplasia and non-neuroendocrine lung tumors develop in nitrosaminetreated hamsters, which we hypothesized might modulate epithelial cell phenotype by expressing gene(s) homologous to human chromosome 3p gene(s) deleted in small cell carcinoma of the lung (SCLC). We differentially screened a chromosome 3 library using nitrosamine-treated versus normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) in injured lung. HGFL/MSP mRNA is low to undetectable in human SCLC and carcinoid tumors, but the HGFL/MSP tyrosine kinase receptor, RON, is present and functional on many of these neuroendocrine tumors. In H835, a pulmonary carcinoid cell line, and H187, a SCLC cell line, HGFL/ MSP induced adhesion/flattening and apoptosis. Using viable cell counts to assess proliferation after 14 d of treatment with HGFL/MSP, there is growth inhibition of H835 but not H187. Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/ MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia. These observations suggest that HGFL/MSP might regulate neuroendocrine cell survival during preneoplastic lung injury, which could influence the ultimate tumor cell phenotype.

Histochemical characterization of non-neuroendocrine tumors and neuroendocrine cell hyperplasia induced in hamster lung by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone with or without hyperoxia.

Lung tumors induced by 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) with or without hyperoxia have frequent K-ras mutations but only rare p53 mutations, suggesting that this may be a model for non-small cell lung cancers. The goals of the present study were (1) to characterize the histopathology of lung tumors induced in hamsters by NNK with or without O2 and (2) as a corollary, to quantitate the pulmonary neuroendocrine cell hyperplasia in the different treatment groups early and late in the treatment period. Lung tumors induced by NNK with or without O2 were 71% adenomas, 22% adenocarcinomas, approximately 4% bronchoalveolar carcinomas, and approximately 4% squamous/adenosquamous carcinomas. One-half of all tumors were positive for the Clara cell antigen CC10 and 21% of NNK-induced tumors were mucin positive, compared with 2% of NNK/O2-induced tumors (P = 0.003). Immunostaining for PGP9.5 was positive in 5% of tumors induced by NNK alone, but in none of NNK/O2-induced tumors (P = 0.024). Abundant proliferating cell nuclear antigen occurred in 55% of NNK-induced tumors, compared with 19% of NNK/O2-induced tumors (P = 0.009). These data indicate that NNK with or without O2 induces non-neuroendocrine lung tumors. Hyperoxia appears to inhibit cell proliferation and suppress mucinous and partial neuroendocrine differentiation in some of these tumors.

Quantification of mitral regurgitation by integrated Doppler backscatter power.

OBJECTIVES: We attempted to determine whether continuous wave Doppler backscatter power could be used to quantify mitral regurgitation. BACKGROUND: The power of a Doppler backscatter signal is proportional to the number of scatterers insonated and, hence, to the moving volume of blood. The relative power of the continuous wave Doppler signals from mitral inflow and aortic outflow is therefore proportional to the relative volumes of blood in motion. METHODS: Computer postprocessing was used to derive the relative power of the Doppler backscatter signal from the intensity of the pixels within the spectral display of anterograde aortic and mitral flow. The power ratio was used to calculate the regurgitant fraction in 20 patients (mean age 61.4 years) with mitral regurgitation. This Doppler regurgitant fraction was compared with that derived from angiographic left ventricular volume and thermodilution cardiac output. In addition, 12 normal control subjects were studied by the Doppler method. RESULTS: Mean (+/- SD) catheterization regurgitant fraction was 0.50 +/- 0.26, and mean Doppler regurgitant fraction was 0.47 +/- 0.25 (r = 0.89). The limits of agreement between the two methods by Bland-Altman analysis were -0.21 + 0.27. In normal control subjects with an expected regurgitant fraction of close to zero, mean Doppler regurgitant fraction was 0.03 +/- 0.05. CONCLUSIONS: Doppler backscatter power from mitral and aortic inflow provides a new and accurate method for quantifying mitral regurgitation.

Modulation of oncogene and tumor suppressor gene expression in a hamster model of chronic lung injury with varying degrees of pulmonary neuroendocrine cell hyperplasia.

BACKGROUND: Intense pulmonary neuroendocrine cell (PNEC) hyperplasia occurs during preneoplastic lung injury in hamsters treated with diethylnitrosamine (DEN) plus hyperoxia. Alterations in oncogene and tumor suppressor gene expression during this process have not been explored. EXPERIMENTAL DESIGN: Our goals were: (a) to analyze expression of genes potentially involved in growth and differentiation of PNECs and/or nonneuroendocrine pulmonary epithelial cells (non-PNECs) in hamsters treated for up to 20 weeks with hyperoxia and DEN or the major tobacco-derived nitrosamine, 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK); and (b) as a corollary, to determine which cells were most mitotically active by immunostaining for c-myc and proliferating cell nuclear antigen. RESULTS: Immunohistochemical analyses demonstrated intense PNEC hyperplasia after treatment with either DEN/O2 or NNK/O2. Whereas DEN/O2-induced PNEC hyperplasia spontaneously regressed, NNK/O2-induced PNEC hyperplasia continued to increase up to 20 weeks. Rb transcripts were decreased similarly in lungs from all treatment groups (NNK/O2 = DEN/O2 = DEN alone) in spite of large differences in PNEC hyperplasia between these groups. c-myc was overexpressed in lungs from animals treated with NNK/O2, DEN/O2 and DEN alone, in which c-myc protein immunostaining occurred predominantly in non-PNECs. Proliferating cell nuclear antigen immunostaining confirmed that non-PNECs were most mitotically active. CONCLUSIONS: These data indicate that PNEC hyperplasia is primarily due to PNEC differentiation, suggesting that this model is ideal for studying mechanisms of neuroendocrine differentiation. Paracrine effects of PNEC-derived growth factors may then contribute to dysregulation of non-PNEC growth preceding the ultimate development of non-neuroendocrine lung tumors in nitrosamine-treated hamsters.

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs.