bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Immunohistochemical Study of Morules in Endometrioid Lesions of the Female Genital Tract: CD10 Is a Characteristic Marker of Morular Metaplasia
Authors: Chiarelli Silvia , Buriticá Catalina , Litta Piero , Ciani Susana , Guarch Rosa , Nogales Francisco F. 
Published: July 2006

Abstract
Purpose: To analyze immunohistochemically morules in endometrioid lesions to show that CD10 is a sensitive marker for morular metaplasia.
Experimental Design: Immunohistochemical analysis of 53 instances of morular metaplasia comprising 1 cyclic endometrium and 52 endometrioid lesions associated with focal glandular complexity corresponding to 9 polyps, 4 atypical polypoid adenomyomas, 24 complex endometrial hyperplasias (18 with and 6 without atypia), 12 grade 1 endometrioid adenocarcinomas in early clinical stages of both uterus and ovary, and three ovarian adenofibromas. Immunohistochemistry in paraffin sections was done for CD10, β-catenin, estrogen and progesterone receptors, and cytokeratins 5-6, 7, 8, 13, 18, 19, 20, and 34β-E12.
Results: Morules were negative for estrogen and progesterone receptors and had β-catenin–positive nuclei. Cytokeratins 8, 18, 19 were positive; cytokeratins 7 and 20 were negative; and cytokeratins 5-6, 13, and 34β-E12 were weakly positive. All cases revealed strongly positive membranous CD10 staining in morules, which was absent in glands. CD10 positivity allowed easy identification of morules at low power in various types of surgical specimens and in curettings. CD10 also highlighted early morular metaplasia in glandular epithelium. In cases associated with squamous, keratinizing metaplasia, CD10 discriminated between both types of metaplasia.
Conclusions: CD10 staining represents a useful marker of morules in endometrioid neoplasms of the female genital tract, permitting identification of lesions usually associated with an attenuated malignancy. Considering the immunohistochemical and genetic similarities of morules in tumors of different organs, it is likely that this marker may be also useful to diagnose morular metaplasia in similar neoplasms of extragenital locations.
Rationale for a Phase II Trial of Pertuzumab, a HER-2 Dimerization Inhibitor, in Patients with Non–Small Cell Lung Cancer
Authors: Johnson Bruce E. , Jänne Pasi A. 
Published: July 2006

Abstract
Background and Rationale: In non–small cell lung cancer (NSCLC) HER-2 gene amplification and 3+ staining by immunohistochemistry are present in only 2% to 5% of the tumors. Therefore, relatively few patients with lung cancer are likely to benefit from treatment with trastuzumab, the humanized monoclonal antibody that is effective in the 20% of patients with breast cancer and HER-2 gene amplification and/or 3+ staining by immunohistochemistry. Pertuzumab (rhuMAb 2C4), a humanized HER2 antibody, represents a new class of targeted therapeutics that inhibit dimerization of HER2 with ligand-activated EGFR (HER1), HER3, and HER-4. Pertuzumab can have antitumor activity in patients with HER-2 present on the tumor without gene amplification or 3+ staining by immunohistochemistry. Preclinical xenograft studies have shown efficacy of pertuzumab in treating NSCLC. Therefore, a trial was undertaken for patients with relapsed NSCLC.
Materials and Methods: Subjects with advanced or recurrent NSCLC treated previously with chemotherapy were treated with pertuzumab (840 mg i.v. loading dose then 420 mg every 3 weeks). Mandatory fresh tumor biopsies before treatment were obtained for biomarker analysis including HER-2 phosphorylation. Computed tomography scans were obtained every two cycles to assess tumor response. Tumor response (response evaluation criteria in solid tumors criteria) was the primary end point.
Results: As reported in a previous abstract, none of the 33 patients with NSCLC and evaluable disease had a response to the treatment.
Conclusions: Pertuzumab has an appropriate rationale for therapeutic use in patients with NSCLC. A phase II trial in patients with NSCLC has completed enrollment, and the details of the trial will be presented in a future publication. This article will review the preclinical rationale for undertaking a study of pertuzumab for patients with relapsed NSCLC.
The Role of the ErbB Family Members in Non–Small Cell Lung Cancers Sensitive to Epidermal Growth Factor Receptor Kinase Inhibitors
Authors: Engelman Jeffrey A. , Cantley Lewis C. 
Published: July 2006

AbstractInhibitors targeting the epidermal growth factor receptor (EGFR) are effective in a subset of non–small cell lung cancers. Such cancers often harbor EGFR mutations and/or amplification. These cancers require EGFR activity for the maintenance of critical intracellular survival and growth signaling pathways. Evidence is now accruing that EGFR works in concert with other ErbB family members, particularly HER2 and ErbB3, to activate these signaling pathways in lung cancers. These findings have important implications regarding the biology of these cancers and may lead to improved methods for identifying tumors that are responsive to EGFR kinase inhibitors and alternative therapies to treat cancers driven by ErbB signaling.
Accuracy of commercial geocoding: assessment and implications
Authors: Whitsel Eric A , Quibrera P Miguel , Smith Richard L , Catellier Diane J , Liao Duanping , Henley Amanda C , Heiss Gerardo 
Published: July 2006

Abstract
Background
Published studies of geocoding accuracy often focus on a single geographic area, address source or vendor, do not adjust accuracy measures for address characteristics, and do not examine effects of inaccuracy on exposure measures. We addressed these issues in a Women's Health Initiative ancillary study, the Environmental Epidemiology of Arrhythmogenesis in WHI.

Results
Addresses in 49 U.S. states (n = 3,615) with established coordinates were geocoded by four vendors (A-D). There were important differences among vendors in address match rate (98%; 82%; 81%; 30%), concordance between established and vendor-assigned census tracts (85%; 88%; 87%; 98%) and distance between established and vendor-assigned coordinates (mean ρ [meters]: 1809; 748; 704; 228). Mean ρ was lowest among street-matched, complete, zip-coded, unedited and urban addresses, and addresses with North American Datum of 1983 or World Geodetic System of 1984 coordinates. In mixed models restricted to vendors with minimally acceptable match rates (A-C) and adjusted for address characteristics, within-address correlation, and among-vendor heteroscedasticity of ρ, differences in mean ρ were small for street-type matches (280; 268; 275), i.e. likely to bias results relying on them about equally for most applications. In contrast, differences between centroid-type matches were substantial in some vendor contrasts, but not others (5497; 4303; 4210) pinteraction < 10-4, i.e. more likely to bias results differently in many applications. The adjusted odds of an address match was higher for vendor A versus C (odds ratio = 66, 95% confidence interval: 47, 93), but not B versus C (OR = 1.1, 95% CI: 0.9, 1.3). That of census tract concordance was no higher for vendor A versus C (OR = 1.0, 95% CI: 0.9, 1.2) or B versus C (OR = 1.1, 95% CI: 0.9, 1.3). Misclassification of a related exposure measure – distance to the nearest highway – increased with mean ρ and in the absence of confounding, non-differential misclassification of this distance biased its hypothetical association with coronary heart disease mortality toward the null.

Conclusion
Geocoding error depends on measures used to evaluate it, address characteristics and vendor. Vendor selection presents a trade-off between potential for missing data and error in estimating spatially defined attributes. Informed selection is needed to control the trade-off and adjust analyses for its effects.
Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet
Authors: Tovar Alison , Ameho Clement K , Blumberg Jeffrey B , Peterson James W , Smith Donald , Booth Sarah L 
Published: July 2006

Abstract

Background
An adverse hematological interaction between vitamins E and K has been reported, primarily in patients on anticoagulants. However, little is known regarding circulating levels or tissue concentrations of vitamin K in response to vitamin E supplementation. The purpose of this study was to examine the effect of different levels of dietary α-tocopherol on phylloquinone and menaquinone-4 concentrations, while maintaining a constant intake of phylloquinone, in rat tissues.

Methods
Male 4-wk old Fischer 344 rats (n = 33) were fed one of 3 diets for 12 wk: control (n = 13) with 30 mg all-rac-α-tocopherol acetate/kg diet; vitamin E-supplemented (n = 10) with 100 mg all-rac-α-tocopherol acetate/kg diet; and vitamin E-restricted (n = 10) with <10 mg total tocopherols/kg diet. All 3 diets contained 470 ± 80 μg phylloquinone/kg diet.

Results
Phylloquinone concentrations were lower (P ≤ 0.05) in the vitamin E-supplemented compared to the vitamin E-restricted group (mean ± SD spleen: 531 ± 58 vs.735 ± 77; kidney: 20 ± 17 vs. 94 ± 31, brain: 53 ± 19 vs.136 ± 97 pmol/g protein respectively); no statistically significant differences between groups were found in plasma, liver or testis. Similar results were noted with menaquinone-4 concentrations in response to vitamin E supplementation.

Conclusion
There appears to be a tissue-specific interaction between vitamins E and K when vitamin E is supplemented in rat diets. Future research is required to elucidate the mechanism for this nutrient-nutrient interaction.
Expanding Your Coverage of Neuroscience: An Interview with Michael Gazzaniga
Authors: Rasmussen Erin B. 
Published: July 2006

Erin Rasmussen is an Assistant Professor in the Department of Psychology at Idaho State University where she teaches learning, behavioral pharmacology, senior seminar, and introductory psychology. She received her MS and PhD in experimental psychology (with a minor in behavioral pharmacology and toxicology) from Auburn University. She taught at the College of Charleston for 3 years before joining the faculty at Idaho State. Her past research involved examination of how prenatal exposure to heavy metals affects the behavior of offspring and the role of environmental enrichment in attenuating those effects. Currently, she is examining how prenatal food restriction affects food choices that lead to obesity. Michael Gazzaniga, the David T. McLaughlin Distinguished University Professor at Dartmouth College, is a pioneer in the field of cognitive neuroscience. He received his PhD from California Institute of Technology in psychobiology, where he conducted his famous work with Roger Sperry on the split-brain phenomenon. His research has provided insights on functional lateralization and how the cerebral hemispheres communicate with one another. He has written more than 20 books, many for the lay audience, and has well over 100 publications, including book chapters, interviews, and monographs. Currently, he serves as Director for the Center of Cognitive Neuroscience at Dartmouth. He was elected president of the American Psychological Society in 2004. He manages a summer school program in cognitive neuroscience and conducts many visiting professor seminars.
Microgravity-induced modifications of the vestibuloocular reflex inXenopus laevistadpoles are related to development and the occurrence of tail lordosis
Authors: Horn Eberhard R. 
Published: July 2006

SUMMARYDuring space flights, tadpoles of the clawed toad Xenopus laevisoccasionally develop upward bended tails (tail lordosis). The tail lordosis disappears after re-entry to 1g within a couple of days. The mechanisms responsible for the induction of the tail lordosis are unknown;physical conditions such as weight de-loading or physiological factors such as decreased vestibular activity in microgravity might contribute. Microgravity(μg) also exerts significant effects on the roll-induced vestibuloocular reflex (rVOR). The rVOR was used to clarify whether tail lordosis is caused by physiological factors, by correlating the occurrence ofμ g-induced tail lordosis with the extent of μg-induced rVOR modifications.Post-flight recordings from three space flights (D-2 Spacelab mission,STS-55 in 1993; Shuttle-to-Mir mission SMM-06, STS-84 in 1997; French Soyuz taxi flight Andromède to ISS in 2001) were analyzed in these experiments. At onset of microgravity, tadpoles were at stages 25-28, 33-36 or 45. Parameters tested were rVOR gain (ratio between the angular eye movement and the lateral 30° roll) and rVOR amplitude (maximal angular postural change of the eyes during a 360° lateral roll).A ratio of 22-84% of tadpoles developed lordotic tails, depending on the space flight. The overall observation was that the rVOR of tadpoles with normal tails was either not affected by microgravity, or it was enhanced. In contrast, the rVOR of lordotic animals always revealed a depression. In particular, during post-flight days 1-11, tadpoles with lordotic tails from all three groups (25-28, 33-36 and 45) showed a lower rVOR gain and amplitude than the 1g-controls. The rVOR gain and amplitude of tadpoles from the groups 25-28 and 33-36 that developed normal tails was not affected by microgravity while the rVOR of μg-tadpoles from the stage-45 group with normal tails revealed a significant rVOR augmentation. In conclusion: (1)the vestibular system of tadpoles with lordotic tails is developmentally retarded by microgravity; (2) after a critical status of vestibular maturation obtained during the appearance of first swimming, microgravity activates an adaptation mechanism that causes a sensitization of the vestibular system.
The influence of collagen fiber orientation and other histocompositional characteristics on the mechanical properties of equine cortical bone
Authors: Skedros John G. , Dayton Michael R. , Sybrowsky Christian L. , Bloebaum Roy D. , Bachus Kent N. 
Published: July 2006

SUMMARYThis study examined relative influences of predominant collagen fiber orientation (CFO), mineralization (% ash), and other microstructural characteristics on the mechanical properties of equine cortical bone. Using strain-mode-specific (S-M-S) testing (compression testing of bone habitually loaded in compression; tension testing of bone habitually loaded in tension),the relative mechanical importance of CFO and other material characteristics were examined in equine third metacarpals (MC3s). This model was chosen since it had a consistent non-uniform strain distribution estimated by finite element analysis (FEA) near mid-diaphysis of a thoroughbred horse, net tension in the dorsal/lateral cortices and net compression in the palmar/medial cortices. Bone specimens from regions habitually loaded in tension or compression were: (1) tested to failure in both axial compression and tension in order to contrast S-M-S vs non-S-M-S behavior, and (2) analyzed for CFO, % ash, porosity, fractional area of secondary osteonal bone, osteon cross-sectional area, and population densities of secondary osteons and osteocyte lacunae. Multivariate multiple regression analyses revealed that in S-M-S compression testing, CFO most strongly influenced total energy(pre-yield elastic energy plus post-yield plastic energy); in S-M-S tension testing CFO most strongly influenced post-yield energy and total energy. CFO was less important in explaining S-M-S elastic modulus, and yield and ultimate stress. Therefore, in S-M-S loading CFO appears to be important in influencing energy absorption, whereas the other characteristics have a more dominant influence in elastic modulus, pre-yield behavior and strength. These data generally support the hypothesis that differentially affecting S-M-S energy absorption may be an important consequence of regional histocompositional heterogeneity in the equine MC3. Data inconsistent with the hypothesis, including the lack of highly longitudinal collagen in the dorsal-lateral `tension' region, paradoxical histologic organization in some locations, and lack of significantly improved S-M-S properties in some locations, might reflect the absence of a similar habitual strain distribution in all bones. An alternative strain distribution based on in vivostrain measurements, without FEA, on non-Thoroughbreds showing net compression along the dorsal-palmar axis might be more characteristic of the habitual loading of some of the bones that we examined. In turn, some inconsistencies might also reflect the complex torsion/bending loading regime that the MC3 sustains when the animal undergoes a variety of gaits and activities, which may be representative of only a portion of our animals, again reflecting the possibility that not all of the bones examined had similar habitual loading histories.
Color discrimination at the spatial resolution limit in a swallowtail butterfly, Papilio xuthus
Authors: Takeuchi Yuichi , Arikawa Kentaro , Kinoshita Michiyo 
Published: July 2006

SUMMARY
Spatial resolution of insect compound eyes is much coarser than that of humans: a single pixel of the human visual system covers about 0.008°whereas that of diurnal insects is typically about 1.0°. Anatomically, the pixels correspond to single cone outer segments in humans and to single rhabdoms in insects. Although an outer segment and a rhabdom are equivalent organelles containing visual pigment molecules, they are strikingly different in spectral terms. The cone outer segment is the photoreceptor cell part that expresses a single type of visual pigment, and is therefore monochromatic. On the other hand, a rhabdom is composed of several photoreceptor cells with different spectral sensitivities and is therefore polychromatic. The polychromatic organization of the rhabdom suggests that insects can resolve wavelength information in a single pixel, which is an ability that humans do not have. We first trained the Japanese yellow swallowtail butterfly Papilio xuthus to feed on sucrose solution at a paper disk of certain color. We then let the trained butterflies discriminate disks of the training color and grey disks each presented in a Y-maze apparatus. Papiliocorrectly selected the colored disk when the visual angle was greater than 1.18° for blue, 1.53° for green or 0.96° for red: they appeared to see colors in single pixels to some extent. This ability may compensate their rather low spatial resolution.
Cloning and functional expression of voltage-gated ion channel subunits from cnidocytes of the Portuguese Man O'War Physalia physalis
Authors: Bouchard C. , Price R. B. , Moneypenny C. G. , Thompson L. F. , Zillhardt M. , Stalheim L. , Anderson P. A. V. 
Published: July 2006

SUMMARY
Cnidocytes were dissociated from the tentacles of the Portuguese Man O'War Physalia physalis using heat treatment, and purified using density centrifugation. Visual observation confirmed that these cnidocytes contained a nucleus, a cnidocyst and an apical stereocilium, confirming that the cells were intact. A cnidocyte-specific amplified cDNA library was then prepared using RNA isolated from the cnidocytes, and screened for voltage-gated ion channel subunits using conventional molecular cloning techniques. A variety of channel proteins were identified and full-length sequence obtained for two of them, a Ca2+ channel β subunit(PpCaVβ) and a Shaker-like K+channel (PpKV1). The location of the transcripts was confirmed by RT-PCR of total RNA isolated from individually selected and rinsed cnidocytes. The functional properties of these two channel proteins were characterized electrophysiologically using heterologous expression. PpCaVβ modulates currents carried by both cnidarian and mammalian α1 subunits although the specifics of the modulation differ. PpKV1 produces fast transient outward currents that have properties typical of other Shaker channels. The possible role of these channel proteins in the behavior of cnidocytes is discussed.
Effects of hypo- and hyperoxia on transcription levels of five stress genes and the glutathione system in liver of Atlantic cod Gadus morhua
Authors: Olsvik P. A. , Kristensen T. , Waagbø R. , Tollefsen K.-E. , Rosseland B. O. , Toften H. 
Published: July 2006

SUMMARY
The transcript levels of three genes coding for antioxidants, Cu/Zn superoxide dismutase (SOD), catalase and phospholipid hydroperoxide glutathione peroxidase (GSH-Px), and those of two stress proteins,metallothionein (MT) and CYP1A, were examined with real-time quantitative (q)RT-PCR in hepatic tissue of Atlantic cod exposed to 46% (hypoxia), 76%(normoxia) and 145% (hyperoxia) O2 saturation (tank outlet). To evaluate the oxidative stress state, the levels of total glutathione (tGSH),reduced glutathione (GSH) and oxidized glutathione (GSSG) and subsequently the oxidative stress index (OSI), were determined in the same tissue samples. The transcript level of GSH-Px was significantly upregulated in fish exposed to hyperoxia, and significantly downregulated in fish exposed to hypoxia,compared to the normoxia group. Significant downregulation was also found for SOD and CYP1A transcriptional levels in fish exposed to hypoxia. The transcript levels of catalase and MT did not change in liver of cod exposed to suboptimal oxygen levels. No significant differences were seen between the groups for tGSH, GSH, GSSG or OSI. Prolonged exposure to unfavourable oxygen saturation levels did not alter the OSI, indicating that the antioxidant glutathione system is maintained at an unchanged level in liver of the examined cod.
Feeding and osmoregulation: dual function of the marine teleost intestine
Authors: Taylor Josi R. , Grosell Martin 
Published: July 2006

SUMMARYExperiments on Gulf toadfish Opsanus beta demonstrate how feeding impacts osmoregulation in the marine teleost intestine. A high Ca2+diet of pilchards Sardina pilchardus ([Ca2+]=404.2 mmol kg-1) was compared to a low Ca2+ diet of common squid Loligo forbesi ([Ca2+]=1.3 mmol kg-1), as high[Ca2+] has been shown to stimulate intestinal anion exchange. Gastrointestinal fluids and blood plasma were collected over a time course from pre-feeding to 216 h post feeding. Following food intake, monovalent ions were largely absorbed across the intestinal epithelium, leaving a fluid rich in divalent ions, which have a lower osmotic coefficient and effectively reduce osmotic pressure in the lumen to allow for enhanced fluid absorption. Concentrations of Cl- and HCO -3 in fluid along the gastrointestinal tract of fish fed both diets, particularly 1 and 2 days post-feeding, demonstrate that apical Cl-/HCO -3 exchange plays a vital role in postprandial Cl- and water absorption. Postprandial acid-base balance disturbance as indicated by plasma alkalinization was limited or absent,indicating compensation for gastric acid secretion in this teleost fish. Plasma osmolality peaked 12 h post-feeding in toadfish fed squid, but was not accompanied by a significant increase in inorganic ion concentrations. Transient fluid secretion by the gastrointestinal tract was evident from reduced luminal Mg2+ and SO 2-4concentrations for 24-48 h post feeding. Discrepancy between the sum of inorganic osmolytes and measured osmotic pressure was attributed to organic osmolytes, which occurred at high concentrations in the stomach and anterior intestine for up to 24 h post feeding.