bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal Growth Factor Receptor Kinase Domain Mutations in Esophageal and Pancreatic Adenocarcinomas
Authors: Kwak Eunice L. , Jankowski Janusz , Thayer Sarah P. , Lauwers Gregory Y. , Brannigan Brian W. , Harris Patricia L. , Okimoto Ross A. , Haserlat Sara M. , Driscoll David R. , Ferry David , Muir Beth , Settleman Jeff , Fuchs Charles S. , Kulke Matthew H. , Ryan David P. , Clark Jeff W. , Sgroi Dennis C. , Haber Daniel A. , Bell Daphne W. 
Published: July 2006

AbstractPurpose: Specific activating mutations within the epidermal growth factor receptor (EGFR) identify a subset of non–small cell lung cancers with dramatic sensitivity to the specific tyrosine kinase inhibitors (TKI), gefitinib and erlotinib. Despite the abundant expression of EGFR protein in a broad range of epithelial cancers, EGFR mutations have not been reported in a substantial fraction of other cancers. Given recent reports of TKI-responsive cases of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers.Experimental Design: We sequenced exons 18 to 21 of EGFR from 21 cases of Barrett's esophagus, 5 cases of high-grade esophageal dysplasia, 17 cases of esophageal adenocarcinoma, and 55 cases of pancreatic adenocarcinoma. Subsets of esophageal (n = 7) and pancreatic cancer cases (n = 5) were obtained from patients who were subsequently treated with gefitinib or erlotinib-capecitabine, respectively.Results: Mutations of EGFR were identified in two esophageal cancers (11.7%), three cases of Barrett's esophagus (14.2%), and two pancreatic cancers (3.6%). The mutations consisted of the recurrent missense L858R and in-frame deletion delE746-A750, previously characterized as activating EGFR mutations in non–small cell lung cancer. We also identified the TKI drug resistance–associated EGFR T790M mutation in an untreated case of Barrett's esophagus and the corresponding adenocarcinoma.Conclusion: The presence of activating mutations within EGFR in both esophageal and pancreatic adenocarcinomas defines a previously unrecognized subset of gastrointestinal tumors in which EGFR signaling may play an important biological role. EGFR mutations in premalignant lesions of Barrett's esophagus also point to these as an early event in transformation of the esophageal epithelium. The role of genotype-directed TKI therapy should be tested in prospective clinical trials.
Inverse Effects of Mucin on Survival of Matched Hereditary Nonpolyposis Colorectal Cancer and Sporadic Colorectal Cancer Patients
Authors: You Jeng-Fu , Hsieh Ling-Ling , Changchien Chung Rong , Chen Jinn-Shiun , Chen Jim-Ray , Chiang Jy-Ming , Yeh Chien Yuh , Hsieh Pao-Shiu , Fan Chung-Wei , Liu Chun-Ting , Tang Reiping 
Published: July 2006

Abstract
Purpose: To compare survival and histologic features of hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) cases to well-matched sporadic colon cancers from the same patient population.
Experimental Design: Between January 1995 and March 2002, a total of 5,138 consecutive patients underwent resection of primary colorectal adenocarcinoma in a single institution. According to the Amsterdam criteria, 56 HNPCC patients were matched to 147 sporadic colorectal cancer (SCRC) with no family history of cancer and with the same gender, tumor location, and age within 3 years. Immunohistochemical analyses were done for MUC1, MUC2, MUC3, and MUC5AC.
Results: The HNPCC group had a marginally significantly better long-term outcome than the SCRC group (P = 0.058). The trend disappeared after adjustment by tumor-node-metastasis stage in a Cox model (P = 0.774). We noted a difference of &gt;50% in the 5-year cancer-specific survival rates of HNPCC- and SCRC-mucinous groups (92% versus 31%, P = 0.0003). Interaction between mucin and HNPCC and its effects on survival were further confirmed by comparing the Cox models with and without interaction terms (hazard ratio, 0.1; P = 0.034 with adjusting stage). Patients with tumors showing dual expression of mucin and MUC1, which appeared in 11% of those with HNPCC and 50% of those with SCRC, had a lower 5-year cancer-specific survival rate than patients without (30% versus 60%; P = 0.004 by log-rank test; P = 0.039 with adjustment for tumor-node-metastasis stage).
Conclusions: These results suggest that mucin has an inverse effect on survival in patients with HNPCC and SCRC, which might be partly explained by a lower prevalence of MUC1 expression in the mucinous HNPCC group than in the SCRC groups.
c-Met Ectodomain Shedding Rate Correlates with Malignant Potential
Authors: Athauda Gagani , Giubellino Alessio , Coleman Jonathan A. , Horak Christine , Steeg Patricia S. , Lee Ming-Jung , Trepel Jane , Wimberly Jennifer , Sun Jan , Coxon Angela , Burgess Teresa L. , Bottaro Donald P. 
Published: July 2006

Abstract
Purpose: Many proteins are proteolytically released from the cell surface by a process known as ectodomain shedding. Shedding occurs under normal physiologic conditions and can be increased in certain pathologies. Among the many receptors for which ectodomain shedding has been shown is c-Met, the hepatocyte growth factor (HGF) receptor tyrosine kinase. HGF stimulates mitogenesis, motogenesis, and morphogenesis in a variety of cellular targets during development, homeostasis, and tissue regeneration. Inappropriate HGF signaling resulting in unregulated cell proliferation, motility, and invasion occurs in several human malignancies. This can occur through paracrine signaling, autocrine loop formation, receptor mutation, gene amplification, or gene rearrangement, accompanied frequently with overexpression of ligand and/or receptor proteins. We hypothesized that c-Met overexpression in cancer might result in increased ectodomain shedding, and that its measure could be a useful biomarker of tumor progression.
Experimental Design: We developed a sensitive electrochemiluminescent immunoassay to quantitate c-Met protein in cell lysates, culture supernatants, and biological samples.
Results: A survey of cultured cell models of oncogenic transformation revealed significant direct correlations (P &lt; 0.001, t test or ANOVA) between malignant potential and the rate of c-Met ectodomain shedding that was independent of steady-state receptor expression level. Moreover, weekly plasma and urine samples from mice harboring s.c. human tumor xenografts (n = 4 per group) displayed soluble human c-Met levels that were measurable before tumors became palpable and that correlated directly with tumor volume (R2 &gt; 0.92, linear regression).
Conclusions: For a variety of human cancers, c-Met ectodomain shedding may provide a reliable and practical indicator of malignant potential and overall tumor burden.
Efflux pump genes of the resistance-nodulation-division family in Burkholderia cenocepacia genome
Authors: Guglierame Paola , Pasca Maria Rosalia , De Rossi Edda , Buroni Silvia , Arrigo Patrizio , Manina Giulia , Riccardi Giovanna 
Published: July 2006

Abstract

Background

Burkholderia cenocepacia is recognized as opportunistic pathogen that can cause lung infections in cystic fibrosis patients. A hallmark of B. cenocepacia infections is the inability to eradicate the organism because of multiple intrinsic antibiotic resistance. As Resistance-Nodulation-Division (RND) efflux systems are responsible for much of the intrinsic multidrug resistance in Gram-negative bacteria, this study aims to identify RND genes in the B. cenocepacia genome and start to investigate their involvement into antimicrobial resistance.

Results
Genome analysis and homology searches revealed 14 open reading frames encoding putative drug efflux pumps belonging to RND family in B. cenocepacia J2315 strain.
By reverse transcription (RT)-PCR analysis, it was found that orf3, orf9, orf11, and orf13 were expressed at detectable levels, while orf10 appeared to be weakly expressed in B. cenocepacia. Futhermore, orf3 was strongly induced by chloramphenicol. The orf2 conferred resistance to fluoroquinolones, tetraphenylphosphonium, streptomycin, and ethidium bromide when cloned and expressed in Escherichia coli KAM3, a strain lacking the multidrug efflux pump AcrAB. The orf2-overexpressing E. coli also accumulate low concentrations of ethidium bromide, which was restored to wild type level in the presence of CCCP, an energy uncoupler altering the energy of the drug efflux pump.

Conclusion
The 14 RND pumps gene we have identified in the genome of B. cenocepacia suggest that active efflux could be a major mechanism underlying antimicrobial resistance in this microorganism. We have characterized the ORF2 pump, one of these 14 potential RND efflux systems. Its overexpression in E. coli conferred resistance to several antibiotics and to ethidium bromide but it remains to be determined if this pump play a significant role in the antimicrobial intrinsic resistance of B. cenocepacia. The characterization of antibiotic efflux pumps in B. cenocepacia is an obligatory step prior to the design of specific, potent bacterial inhibitors for the improved control of infectious diseases. Consequently, the topic deserves to be further investigated and future studies will involve systematic investigation on the function and expression of each of the RND efflux pump homologs.
Free-flight responses ofDrosophila melanogasterto attractive odors
Authors: Budick Seth A. , Dickinson Michael H. 
Published: July 2006

SUMMARYMany motile organisms localize the source of attractive odorants by following plumes upwind. In the case of D. melanogaster, little is known of how individuals alter their flight trajectories after encountering and losing a plume of an attractive odorant. We have characterized the three-dimensional flight behavior of D. melanogaster in a wind tunnel under a variety of odor conditions. In the absence of olfactory cues, hungry flies initiate flight and display anemotactic orientation. Following contact with a narrow ribbon plume of an attractive odor, flies reduce their crosswind velocity while flying faster upwind, resulting in a surge directed toward the odor source. Following loss of odor contact due to plume truncation, flies frequently initiate a stereotyped crosswind casting response, a behavior rarely observed in a continuous odor plume. Similarly, within a homogeneous odor cloud, flies move fast while maintaining an upwind heading. These results indicate both similarities and differences between the behavior of D. melanogaster and the responses of male moths to pheromone plumes,suggesting possible differences in underlying neural mechanisms.
Cardiovascular and haematological responses of Atlantic cod (Gadus morhua) to acute temperature increase
Authors: Gollock M. J. , Currie S. , Petersen L. H. , Gamperl A. K. 
Published: July 2006

SUMMARYFor fish to survive large acute temperature increases (i.e. &gt;10.0°C)that may bring them close to their critical thermal maximum (CTM), oxygen uptake at the gills and distribution by the cardiovascular system must increase to match tissue oxygen demand. To examine the effects of an acute temperature increase (∼1.7°C h-1 to CTM) on the cardiorespiratory physiology of Atlantic cod, we (1) carried out respirometry on 10.0°C acclimated fish, while simultaneously measuring in vivocardiac parameters using Transonic® probes, and (2) constructed in vitro oxygen binding curves on whole blood from 7.0°C acclimated cod at a range of temperatures. Both cardiac output(Q̇) and heart rate(fh) increased until near the fish's CTM(22.2±0.2°C), and then declined rapidly. Q10 values for Q̇ and fh were 2.48 and 2.12, respectively, and increases in both parameters were tightly correlated with O2 consumption. The haemoglobin (Hb)-oxygen binding curve at 24.0°C showed pronounced downward and rightward shifts compared to 20.0°C and 7.0°C, indicating that both binding capacity and affinity decreased. Further, Hb levels were lower at 24.0°C than at 20.0°C and 7.0°C. This was likely to be due to cell swelling, as electrophoresis of Hb samples did not suggest protein denaturation, and at 24.0°C Hb samples showed peak absorbance at the expected wavelength (540 nm). Our results show that cardiac function is unlikely to limit metabolic rate in Atlantic cod from Newfoundland until close to their CTM, and we suggest that decreased blood oxygen binding capacity may contribute to the plateau in oxygen consumption.
Material properties and biochemical composition of mineralized vertebral cartilage in seven elasmobranch species (Chondrichthyes)
Authors: Porter Marianne E. , Beltrán Jennie L. , Koob Thomas J. , Summers Adam P. 
Published: July 2006

SUMMARY
Elasmobranchs, particularly sharks, function at speed and size extremes,exerting large forces on their cartilaginous skeletons while swimming. This casts doubt on the generalization that cartilaginous skeletons are mechanically inferior to bony skeletons, a proposition that has never been experimentally verified. We tested mineralized vertebral centra from seven species of elasmobranch fishes: six sharks and one axially undulating electric ray. Species were chosen to represent a variety of morphologies, inferred swimming speeds and ecological niches. We found vertebral cartilage to be as stiff and strong as mammalian trabecular bone. Inferred swimming speed was a good, but not infallible, predictor of stiffness and strength. Collagen content was also a good predictor of material stiffness and strength, although proteoglycan was not. The mineral fraction in vertebral cartilage was similar to that in mammalian trabecular bone and was a significant predictor of material properties.
Metabolic organization and effects of feeding on enzyme activities of the dogfish shark (Squalus acanthias) rectal gland
Authors: Walsh Patrick J. , Kajimura Makiko , Mommsen Thomas P. , Wood Chris M. 
Published: July 2006

SUMMARYIn order to investigate the metabolic poise of the elasmobranch rectal gland, we conducted two lines of experimentation. First, we examined the effects of feeding on plasma metabolites and enzyme activities from several metabolic pathways in several tissues of the dogfish shark, Squalus acanthias, after starvation and at 6, 20, 30 and 48 h post-feeding. We found a rapid and sustained ten-fold decrease in plasma β-hydroxybutyrate at 6 h and beyond compared with starved dogfish, suggesting an upregulation in the use of this substrate, a decrease in production, or both. Plasma acetoacetate levels remain unchanged, whereas there was a slight and transient decrease in plasma glucose levels at 6 h. Several enzymes showed a large increase in activity post-feeding, including β-hydroxybutyrate dehydrogenase in rectal gland and liver, and in rectal gland, isocitrate dehydrogenase, citrate synthase, lactate dehydrogenase, aspartate amino transferase, alanine amino transferase, glutamine synthetase and Na+/K+ ATPase. Also notable in these enzyme measurements was the overall high level of activity in the rectal gland in general. For example, activity of the Krebs' TCA cycle enzyme citrate synthase (over 30 U g-1) was similar to activities in muscle from other species of highly active fish. Surprisingly, lactate dehydrogenase activity in the gland was also high (over 150 U g-1), suggesting either an ability to produce lactate anaerobically or use lactate as an aerobic fuel. Given these interesting observations, in the second aspect of the study we examined the ability of several metabolic substrates (alone and in combination) to support chloride secretion by the rectal gland. Among the substrates tested at physiological concentrations (glucose, β-hydroxybutyrate, lactate,alanine, acetoacetate, and glutamate), only glucose could consistently maintain a viable preparation. Whereas β-hydroxybutyrate could enhance gland activity when presented in combination with glucose, surprisingly it could not sustain chloride secretion when used as a lone substrate. Our results are discussed in the context of the in vivo role of the gland and mechanisms of possible upregulation of enzyme activities.
Like a `rolling stone': quantitative analysis of the body movement and skeletal dynamics of the sponge Tethya wilhelma
Authors: Nickel Michael 
Published: July 2006

SUMMARY
Although sponges (Porifera) are basal Metazoa without muscles and a central nervous system, they are able to locomote, which is generally correlated to drastic morphological changes. This behaviour has been known for more almost 150 years, but it is only partly understood. The sponge T. wilhelmadisplays extraordinary movement and rhythmic body contractions, and is thus a valuable model for the investigation of sponge movement. The aims of the present study were to track T. wilhelma quantitatively on natural and artificial substrates, to test for a peristaltic movement mechanism and to check for the influence of morphological changes. T. wilhelmadisplays a unique mode of locomotion among sponges, without reorganizing the whole sponge body. The overall morphology was stable, and skeletal rotation during movement was shown; this is the first time that such movement has been demonstrated in a sponge. The stability of the skeletal superstructure arrangement during movement suggests that only the cortical tissue is involved in movement, with only local tissue rearrangements. The movement track followed a straight direction for long periods, but directions could be altered instantly. It is most likely that environmental conditions play an important roll in induction of movement. In summary, T. wilhelmaresembles the proverbial `rolling stone' that stays at a given location if the conditions are favourable and starts moving when conditions change for the worse.
Effects of different training protocols on Ca2+ handling and oxidative capacity in skeletal muscle of Atlantic salmon (Salmo salarL.)
Authors: Anttila Katja , Mänttäri Satu , Järvilehto Matti 
Published: July 2006

SUMMARYThe modulation of calcium channel density and oxidative capacity in skeletal muscle after different training protocols were studied in 3-year-old Atlantic salmon smolts. The effect of endurance exercise on dihydropyridine(DHP) and ryanodine (Ry) receptor densities as well as on muscle metabolism were determined by immunoblot and histochemical analysis from swimming muscles of fish subjected to nine different training protocols varying in duration and water current velocity.In general, exercise training caused a significant increase in the density of both DHP and Ry receptors in both muscle types studied. In red muscle, the most notable increase in DHP and Ry receptor expression was observed in muscle sections from fish swimming against intermediate current velocity for a 2-week period (182.3±16.3%, 234.6±30.3%, respectively). In white muscle, the expression of DHP and Ry receptors was most upregulated after a 6-week swimming period also at intermediate water current velocity(270.4±23.9%, 114.4±15.3%, respectively). As with the activity of enzymes involved in muscle energy supply, endurance exercise resulted in a significant increase in succinate dehydrogenase (SDH) activity, but a significant decrease in phosphorylase activity.We conclude that the expression of both DHP and Ry receptors was upregulated in the swimming muscles of salmon as a consequence of exercise training. This, along with the increased oxidative enzyme activity, provides benefits to the contraction efficiency of fish muscles while swimming. However, it was also observed that optimal oxidative swimming capacity is achieved only with a proper exercise program, since the most relevant changes in DHP and Ry receptor expression, as well as in oxidative capacity, were seen in the group training with the intermediate swimming velocity.
Sound production mechanism in carapid fish: first example with a slow sonic muscle
Authors: Parmentier Eric , Lagardère Jean-Paul , Braquegnier Jean-Baptiste , Vandewalle Pierre , Fine Michael L. 
Published: July 2006

SUMMARYFish sonic swimbladder muscles are the fastest muscles in vertebrates and have fibers with numerous biochemical and structural adaptations for speed. Carapid fishes produce sounds with a complex swimbladder mechanism, including skeletal components and extrinsic sonic muscle fibers with an exceptional helical myofibrillar structure. To study this system we stimulated the sonic muscles, described their insertion and action and generated sounds by slowly pulling the sonic muscles. We find the sonic muscles contract slowly, pulling the anterior bladder and thereby stretching a thin fenestra. Sound is generated when the tension trips a release system that causes the fenestra to snap back to its resting position. The sound frequency does not correspond to the calculated resonant frequency of the bladder, and we hypothesize that it is determined by the snapping fenestra interacting with an overlying bony swimbladder plate. To our knowledge this tension release mechanism is unique in animal sound generation.
The ESR Study of the Ion Pair Complexes of m-Iodonitrobenzene with Alkali and Alkaline Earth Metals
Authors: Nakamura Kazuo 
Published: July 2006

Abstract
The ESR spectra of the ion-pair complexes of the m-iodonitrobenzene anion with alkali and alkaline earth cations were measured. Cation-induced variations in the nitrogen and proton splitting constants were found. When the observed alkali metal splittings were related to the back-transferred charge, ρ, on the ns-shell of each metal, ρ increased in the sequence: Li&lt;Na&lt;K&lt;Rb&lt;Cs at 20°C. The solvent and the temperature effects on alkali-metal splitting varied with the alkali metal. The Cs and Rb splitting constants increased in the sequence: DME&lt;THF&lt;THP solutions, and were independent of the temperature. The Na and Li splitting constants decreased in the above sequence of solvents. With a lowering of the temperature, the Na splitting constant decreased while the Li splitting constant increased. The K splitting constant was independent of both the temperature and the solvent. These results were found in the ion pairs of other halogeno-nitrobenzenes, also.
A Classification of Polymerizations from a Kinetic Point of View
Authors: Kagiya Tsutomu , Izu Masatsugu , Fukui Kenichi 
Published: July 2006

Abstract
Polymerizations were classified from a kinetic point of view. The polymerizations were divided into those with a rapid initiation and those with a slow initiation, according to the magnitude of the initiation rate in relation to the propagation rate. Both of these groups were then divided into stationary and non-stationary polymerizations according to the change in the number of moles of the propagating species with the reaction time. The next sub-classification, into chain and successive polymerizations, was made by estimating the change, with the reaction time, in the number-average degree of the polymerization of the polymer formed. Each proposed class was shown to possess a characteristic kinetic feature. Several examples of each class were collected.
Studies of Diarylalkanes. IV. The Cleavage of Diphenylmethanes under the Influence of Aluminum Chloride in the Binary Mixture of Benzene with Chlorobenzene
Authors: Tsuge Otohiko , Tashiro Masashi 
Published: July 2006

Abstract
The reactions of DPM and its chloro derivatives with aluminum chloride in a mixture of benzene and chlorobenzene have been studied in order to obtain clearer information concerning the bond cleavage of the diarylmethanes. The constants or the activation energy of the cleavage reaction have been determined, and it has found that, in such reactions, a first-order dependence on the aromatic substrate exists; an equilibrium relationship consisting of four systems has been an equilibrium relationship consisting of four systems has been established among the products. The isomer distribution of the Cl-DPM which was formed by the cleavage of DPM or 4-Cl-DPM exhibited a marked variation with the reaction time. These results show that the cleavage reaction is closely connected with Friedel-Crafts benzylation.