bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidermal Growth Factor Facilitates Epinephrine Inhibition of P2X7-Receptor-Mediated Pore Formation and Apoptosis: A Novel Signaling Network
Authors: Wang Liqin , Feng Ying-Hong , Gorodeski George I.
Published: December 2004

Epidermal growth factor (EGF), epinephrine, and the P2X7 receptor system regulate growth of human uterine cervical epithelial cells, but little is known about how these systems intercommunicate in exerting their actions. The objective of this study was to understand the mechanisms of EGF and epinephrine regulation of growth of cervical cells. Treatment of cultured CaSki cells with 0.2 nm EGF increased cell number via a PD98059-sensitive pathway. Treatment with 2 nm epinephrine increased cell number, and the effect was facilitated by cotreatment with EGF. Whereas the effect of EGF alone involved up-regulation of [3H]-thymidine incorporation and an increase in cell proliferation, the effect of epinephrine was mediated by inhibition of apoptosis. Epinephrine inhibited apoptosis induced by the P2X7 receptor ligand 2′,3′-0-(4-benzoylbenzoyl)-ATP, by attenuation of P2X7 receptor plasma membrane pore formation. Cotreatment with EGF facilitated epinephrine effect via a phosphoinositide 3-kinase-dependent mechanism. CaSki cells express the β2-adrenoceptor, and the epinephrine antiapoptotic effect could be mimicked by β2-adrenoceptor agonists and by activators of adenylyl cyclase. Likewise, the effect could be blocked by β2-adrenoceptor blockers and by the inhibitor of protein kinase-A H-89. Western immunoblot analysis revealed that epinephrine decreased the levels of the glycosylated 85-kDa form of the P2X7 receptor and increased receptor degradation, and that EGF potentiated these effects of epinephrine. EGF did not affect cellular levels of the β2-adrenoceptor. In contrast, EGF, acting via the EGF receptor, augmented β2-adrenoceptor recycling, and it inhibited β2-adrenoceptor internalization via a phosphoinositide 3-kinase-dependent mechanism. We conclude that, in cervical epithelial cells, EGF has a dual role: as mitogen, acting via the MAPK/MAPK kinase pathway, and as an antiapoptotic factor by facilitating epinephrine effect and resulting in greater expression of β2-adrenoceptors in the plasma membrane. These findings underscore a novel signaling network of communication between the receptor tyrosine kinases, the G protein-coupled receptors, and the purinergic P2X7 receptor.
Comparison of the binding affinity of some newly synthesized phenylethanolamine and phenoxypropanolamine compounds at recombinant human β- and α1-adrenoceptor subtypes
Authors: Ahmed Maruf , Hanaoka Yoko , Kiso Tatsuya , Kakita Takao , Ohtsubo Yoshikazu , Muramatsu Ikunobu , Nagatomo Takafumi
Published: December 2004

We evaluated six new compounds, SWR-0065HA ([4-[2-[3-[[(3,4-dihydro-4-oxo-[1,2,4]-triazino(4,5-a)indol)-lyl]oxy]-2-hydroxypropylamino]ethoxy]phenyl]acetic acid methyl ester hydrochloride), SWR-0098NA ((R*R*-UE)-(E)-[4-[3-[(2-phenyl-2-hydroxyethyl)amino]-1-butenyl]phenoxy]acetic acid sodium salt), SWR-0315NA ((E, Z)-[4[[1-[2-[(3-phenoxy-2-hydroxy propyl)]amino]ethyl]-1-propenyl]phenoxy]acetic acid sodium), SWR-0338SA ((E)-[4-[5-[(2-phenyl-2-hydroxyethyl)amino]-2-pentene-3-yl]phenoxy] acetic acid ethanedioic acid), SWR-0342SA ((S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino] ethyl]-1-propenyl]phenoxy]acetic acid ethanedioic acid) and SWR-0345HA ((E)-2-methyl-3-[4-[2-(2-phenyl-2-hydroxyethylamino)ethoxy]phenyl]-2-propenoic acid ethyl ester hydrochloride) for their potencies as selective ligands at human β-adrenoceptors expressed in COS-7 cells and compared the binding affinities for human α1-adrenoceptors expressed in Chinese hamster ovary (CHO) cells using a radioligand-binding assay. Phenoxypropanolamine derivatives SWR-0315NA and SWR-0342SA showed higher binding affinities for β-adrenoceptor subtypes; SWR-0065HA, however, showed a higher affinity for only β2-adrenoceptors, accounting for 3-fold and 6-fold selectivity against β1- and β3-adrenoceptors. Compounds SWR-0315NA and SWR-0342SA did not show any binding selectivity for any of the subtypes. However, functionally these two compounds are selective for β3-adrenoceptors. Among the phenylethanolamine derivatives, SWR-0338SA and SWR-0345HA showed 9-fold and 16-fold higher binding selectivity for β3-adrenoceptors against β1-adrenoceptors, respectively, whereas they both showed a 7-fold higher binding selectivity for β3-adrenoceptors against β2-adrenoceptors. SWR-0098NA did not show any significant binding affinity for any of the β-adrenoceptor subtypes. These compounds, except for SWR-0098NA, were not found to possess any significant binding affinity for α1-adrenoceptor subtypes over that for β-adrenoceptor subtypes. However, SWR-0098NA has about a 3-fold to 22-fold higher binding selectivity for α1-adrenoceptor subtypes against β-adrenoceptor subtypes, making it difficult for use in a β-adrenoceptor receptor study. Compounds SWR-0315NA and SWR-0342SA have similar binding potency for α1-adrenoceptors as adrenaline (epinephrine), proving the finding of this manuscript that this phenoxypropanolamine group of β-adrenoceptor ligands could also be used as α1-adrenoceptor ligands. Functional assays have to be performed to confirm their agonistic activity.
Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment
Authors: Justo Oselys Rodriguez , Moraes Angela Maria
Published: December 2004

The primary goal of this study was the production of liposomes encapsulating kanamycin for drug administration by inhalation. The selected drug is indicated for multiresistant tuberculosis, and administration through inhalation allows both local delivery of the drug to the lungs and systemic therapy. The ethanol injection method used for the liposome production is easily scaled up and is characterized by simplicity and low cost. Vesicles were prepared using different lipid compositions, including hydrogenated soybean phosphatidylcholine and cholesterol (SPC/Chol), egg phosphatidylcholine and cholesterol (EPC/Chol), distearoyl phosphatidylcholine and cholesterol (DSPC/Chol), distearoyl phosphatidylcholine, dimyristoyl phosphatidylethanolamine and cholesterol (DSPC/DMPE/Chol), dipalmitoyl phosphatidylcholine and cholesterol (DPPC/Chol) and dipalmitoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol and cholesterol (DPPC/DPPG/Chol). The effects of different operational conditions for vesicle production and drug encapsulation were evaluated, aiming at a compromise between final process cost and suitable vesicle characteristics. The best performance concerning drug incorporation was achieved with the DSPC/Chol system, although its production cost was considerably larger than that of the natural lipids formulations. Encapsulation efficiencies up to 63% and final drug to lipid molar ratios up to 0.1 were obtained for SPC/Chol vesicles presenting mean diameters of 132 nm incubated at 60°C with the drug for 60 min at an initial drug-to-lipid molar ratio of 0.16.
Loperamide inhibits the biliary excretion of irinotecan (CPT-11) in the rat isolated perfused liver
Authors: Tobin Peter J , Hong Ying , Seale J Paul , Rivory Laurent P , McLachlan Andrew J
Published: December 2004

Patients treated with irinotecan (CPT-11) occasionally suffer from severe diarrhoea and aggressive treatment with loperamide at the first signs of loose stools is recommended. We have examined the effect of loperamide on the hepatic metabolism and biliary excretion of CPT-11 in the isolated perfused rat liver (IPRL). CPT-11 (0.5 μmol) was injected as a bolus into the IPRL reservoir, and perfusate and bile samples were collected over 3h. Experiments were conducted using loperamide-free perfusate (n = 5) or perfusate containing 10 μm loperamide (n = 6). Perfusate and bile concentrations of total CPT-11 and the major metabolites SN-38 (7-ethyl-10-hydroxy-camptothecin), SN-38G (7-ethyl-10-hydroxy-camptothecin glucuronide) and APC (7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidine] carbonyloxycamptothecin) were determined by HPLC. The unchanged parent drug was the predominant species in bile, with approximately 4% of the dose recovered over 180 min as compared with only 1% for the metabolites. Loperamide significantly reduced the biliary excretion of CPT-11 by approximately 50% (2.0 ± 0.9% dose compared with 3.8 ± 1.0% in the control group, P = 0.019) over the same period. In contrast, the biliary excretion of SN-38, SN-38G and APC was not significantly affected by loperamide (P > 0.05). Furthermore, bile flow rate was not affected by loperamide. Loperamide appeared to selectively inhibit the biliary excretion of CPT-11, although the extent to which loperamide altered the disposition of CPT-11 in the clinical setting remains to be determined.
Assessment of serum flecainide trough levels in patients with tachyarrhythmia
Authors: Homma Masato , Kuga Keisuke , Doki Kosuke , Katori Kumi , Yamaguchi Iwao , Sugibayashi Kenji , Kohda Yukinao
Published: December 2004

The reported therapeutic range for trough flecainide concentration is 200–1000 ng mL−1. Severe adverse events, such as ventricular arrhythmias, have occurred occasionally in patients whose serum flecainide exceeded 1000 ng mL−1. However, the lower limit remains controversial. We have evaluated blood flecainide concentrations in patients with tachyarrhythmia who received the drug to control palpitation. We measured the flecainide trough levels and incidence and frequency of palpitation of 44 outpatients receiving oral flecainide (150–300 mg daily). Mean serum flecainide trough concentrations differed significantly between patients with (n = 14) and without (n = 30) palpitation (259.5 ± 85.2 vs 462.2 ± 197.7 ng mL−1, P < 0.01). The frequency of palpitation decreased as the serum flecainide concentration increased. The incidence of palpitation was 65% at serum flecainide concentrations < 300 ng mL−1 and 11% at ≥ 300 ng mL−1. QRS values were increased significantly in patients with serum flecainide ≥ 300 ng mL−1 compared with < 300 ng mL−1 (0.110 ± 0.016s vs 0.093 ± 0.019s, P < 0.05). We concluded that to control paroxysm in patients receiving flecainide for tachyarrhythmia serum flecainide concentrations should be maintained at ≥ 300 ng mL−1.
Aqueous garlic extract alleviates ischaemia-reperfusion-induced oxidative hepatic injury in rats
Authors: Şener Göksel , Sehirli özer , Ipçi Yeşim , Ercan Feriha , şirvanci Serap , Gedik Nursal , Yeĝen Berrak Ç
Published: December 2004

This study was designed to examine the effects of aqueous garlic extract (AGE) on hepatic ischaemia-reperfusion (I/R) injury in rats. For this purpose, Wistar albino rats were subjected to 45 min of hepatic ischaemia, followed by a 60-min reperfusion period. AGE (1 mL kg−1, i.p., corresponding to 500 mg kg−1) or saline was administered twice, 15 min before ischaemia and immediately before the reperfusion period. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Liver tissues were taken for the determination of malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker, was also determined. Plasma ALT and AST activities were elevated in the I/R group as compared with the control group, while these increases were significantly decreased by AGE treatment. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in the AGE-treated I/R group. Increases in tissue MDA levels and MPO activity due to I/R injury were reduced back to control levels by AGE treatment. Similarly, increased hepatic collagen content in the I/R group was reduced to the control level with AGE treatment. Since AGE administration alleviated the I/R-induced injury of the liver and improved the hepatic structure and function, it seems likely that AGE, with its antioxidant and oxidant-scavenging properties, may be of potential therapeutic value in protecting the liver against oxidative injury due to ischaemia-reperfusion.
Low-frequency fatigue, post-tetanic potentiation and their interaction at different muscle lengths following eccentric exercise
Authors: Rijkelijkhuizen J. M. , de Ruiter C. J. , Huijing P. A. , de Haan A.
Published: December 2004

Low-frequency fatigue (LFF) and post-tetanic potentiation (PTP) were quantified at different muscle lengths in rat medial gastrocnemius (GM)muscle. In situ experiments were performed on GM muscle-tendon complexes of anaesthetised (urethane, 1.5 g kg-1 i.p.) Wistar rats(N=8). Force-length characteristics were determined at maximal (200 Hz) and submaximal (60 Hz) stimulation. Data for submaximally stimulated muscle were obtained in a non-potentiated and in a potentiated condition. LFF was induced by a series of 40 eccentric contractions. Post-exercise (40-80 min), data for the force-length relationships were obtained once more. Whereas force loss at 200 Hz-stimulation was least at optimum muscle length, L0,200Hz, (17.0±1.4%, mean ± s.e.m.), force loss at 60 Hz-stimulation was maximal near L0,200Hz (55.1±4.3% at L0,200Hz-1 mm). When the muscle was potentiated, force loss at 60 Hz-stimulation was maximal at short muscle length: L0,200Hz-4 mm (53.5±3.8%). The extent of LFF,quantified by a decrease in the 60:200 Hz force ratio, varied with muscle length: LFF increased with decreasing muscle lengths when muscles were potentiated. However, in the non-potentiated condition, LFF was maximal at a length just below L0,200Hz; the 60:200 Hz force ratio had decreased to 54.6±5.9% of the pre-exercise ratio at L0,200Hz-1 mm. Compared with the non-potentiated condition, LFF was less pronounced in the potentiated condition. PTP counteracted LFF particularly at long muscle lengths. However, at short muscle lengths, LFF was still observed in potentiated muscles.
Stress signaling: coregulation of hemoglobin and male sex determination through a terpenoid signaling pathway in a crustacean
Authors: Rider Cynthia V. , Gorr Thomas A. , Olmstead Allen W. , Wasilak Beth A. , LeBlanc Gerald A.
Published: December 2004

Environmental signals can activate neuro-endocrine cascades that regulate various physiological processes. In the present study, we demonstrate that two responses to environmental stress signaling in the crustacean Daphnia magna - hemoglobin accumulation and male offspring production - are co-elevated by the crustacean terpenoid hormone methyl farnesoate and several synthetic analogs. Potency of the hormones with respect to the induction of both hemoglobin and male offspring was highly correlated, suggesting that both processes are regulated by the same terpenoid signaling pathway. Six clones of the D. pulex/pulicaria species complex that were previously characterized as unable to produce male offspring and five clones that were capable of producing males were evaluated for both hemoglobin induction and male offspring production in response to methyl farnesoate. Four of the five male-producing clones produced both hemoglobin and male offspring in response to the hormone. Five of the six non-male-producing clones produced neither hemoglobin nor males in response to the hormone. These results provide additional evidence that both physiological processes are regulated by the same signaling pathway. Furthermore, the results indicate that the non-male-producing clones are largely defective in some methyl farnesoate signaling component, downstream from methyl farnesoate synthesis but upstream from the genes regulated by the hormone. A likely candidate for the site of the defect is the methyl farnesoate receptor. As a consequence of this defect,non-male-producing clones have lost their responsiveness to environmental signals that are transduced by this endocrine pathway. This defect in signaling would be likely to enhance population growth in stable environments due to the elimination of males from the population, assuming that other processes critical to population growth are not also compromised by this defect.
Stretching of supercontracted fibers: a link between spinning and the variability of spider silk
Authors: Guinea G. V. , Elices M. , Pérez-Rigueiro J. , Plaza G. R.
Published: December 2004

The spinning of spider silk requires a combination of aqueous environment and stretching, and the aim of this work was to explore the role of stretching silk fibers in an aqueous environment and its effect on the tensile properties of spider silk. In particular, the sensitivity of the spider silk tensile behaviour to wet-stretching could be relevant in the search for a relationship between processing and the variability of the tensile properties. Based on this idea and working with MAS silk from Argiope trifasciata orb-web building spiders, we developed a novel procedure that permits modification of the tensile properties of spider silk: silk fibers were allowed to supercontract and subsequently stretched in water. The ratio between the length after stretching and the initial supercontracted length was used to control the process. Tensile tests performed in air, after drying,demonstrated that this simple procedure allows to predictable reproduction of the stress-strain curves of either naturally spun or forcibly silked fibers. These results suggest that the supercontracted state has a critical biological function during the spinning process of spider silk.
The interplay of cutaneous water loss, gas exchange and blood flow in the toad,Bufo woodhousei:adaptations in a terrestrially adapted amphibian
Authors: Burggren Warren W. , Vitalis Timothy Z.
Published: December 2004

Toads experiencing dehydrating conditions exhibit complex physiological and behavioral responses, some of which can potentially impact cutaneous gas exchange, an important component of total gas exchange. We measured the effect of dehydration on cutaneous gas exchange in the xeric-adapted toad Bufo woodhousei. First, two pharmacological agents were used to stimulate cutaneous blood flow - phentolamine (an α-blocker) and isoproterenol, aβ-stimulant and powerful cardio-accelerator - to determine a relationship between cutaneous blood flow and water loss. Both drugs increased heart rate and blood pressure, and caused visually evident extensive vasodilation of the skin. Untreated toads in a dry air stream took an average of 10.1±0.7 h to dehydrate to 80% body mass, while animals treated with isoproterenol and phentolamine requires only 7.2±0.8 h and 7.4±0.9 h,respectively. Rehydration, which was more rapid than dehydration, was similarly accelerated in pharmacologically treated toads.

Cutaneous gas exchange(ṀO, ṀCO) and C18O diffusing capacity (DSkinC18O) were then examined in unanesthetized toads under different states of body hydration. Blood gases and hematocrit were measured separately but under identical conditions. In fully hydrated toads at 23-25°C, cutaneous gas exchange values were: ṀO =1.43±0.47 μmol g-1 h-1, ṀCO = 1.75±0.85μmol g-1 h-1, and the respiratory exchange ratio R =1.36±0.56 (N=6, mean + 1s.d.). DSkinC18O was 0.48±0.03 μmol g body mass-1 h-1 kPa. Following an enforced 20-25% loss of body water, DSkinC18O fell by nearly 50% to 0.28±0.09 μmol g-1 h-1 kPa. However, cutaneous ṀO, ṀCO and R were unchanged at 1.48±0.15 μmol g-1 h-1, 1.72±0.29μmol g-1 h-1 and 1.13±0.08 μmol g-1 h-1, respectively. Partial pressure of arterial(sciatic) oxygen, PaO2, normally about 12-13 kPa, remained unchanged by dehydration, but PaCO2 increased about 250% from 0.93±0.27 up to 2.27±0.93 kPa. The fall in DSkinC18O during dehydration presumably results at least in part from decreased cutaneous blood flow, possibly in an attempt to reduce the transcutaneous water loss that would otherwise result during dehydrating conditions. Concurrently, cutaneous ṀCO is maintained under dehyrdating conditions by a greatly increased PaCO2 diffusion gradient across the skin. Thus, Bufo woodhousei appears able to restrict cutaneous blood flow without compromising vital cutaneous CO2 loss.
Dendritic spike back propagation in the electrosensory lobe of Gnathonemus petersii
Authors: Gómez Leonel , Kanneworff Morten , Budelli Ruben , Grant Kirsty
Published: December 2004

Spike timing-dependent plasticity that follows anti-Hebbian rules has been demonstrated at synapses between parallel fibers and inhibitory interneurons known as medium ganglionic layer (MG) neurons in the cerebellum-like electrosensory lobe of mormyrid fish. This plasticity is expressed when presynaptic activation is associated with a characteristically broad,postsynaptic action potential, lasting 7-15 ms, occurring within a window of up to 60-80 ms following synaptic activation. Since the site of plastic change is presumably in the apical dendrites, it is important to know where, when and how this broad spike is generated and the manner in which such events propagate within the intrinsic network of the electrosensory lobe.

The electrosensory lobe has a strict layered organization that makes the preparation suitable for one dimension current source density analysis. Using this technique in an `in vitro' interface slice preparation, we found that following either parallel fiber stimulation or an orthogonal field stimulus, a sink appeared in the ganglionic layer and propagated into the molecular layer. Intracellular records from MG somata showed these stimuli evoked broad action potentials whose timing corresponds to this sink. TTX application in the deep fiber layer blocked the synaptically evoked ganglionic layer field potential and the `N3' wave of the outer molecular layer field potential simultaneously, while the molecular layer`N1' and `N2' waves corresponding to synaptic activation of the apical dendrites remained intact. These results confirm the hypothesis that the broad spikes of MG cells originate in the soma and propagate through the molecular layer in the apical dendritic tree, and suggest the possibility that this backpropagation may contribute to `boosting' of the synaptic response in distal apical dendrites in certain circumstances.
Tolerance of endolithic algae to elevated temperature and light in the coralMontipora monasteriatafrom the southern Great Barrier Reef
Authors: Fine Maoz , Meroz-Fine Efrat , Hoegh-Guldberg Ove
Published: December 2004

Photosynthetic endolithic algae and cyanobacteria live within the skeletons of many scleractinians. Under normal conditions, less than 5% of the photosynthetically active radiation (PAR) reaches the green endolithic algae because of the absorbance of light by the endosymbiotic dinoflagellates and the carbonate skeleton. When corals bleach (loose dinoflagellate symbionts),however, the tissue of the corals become highly transparent and photosynthetic microendoliths may be exposed to high levels of both thermal and solar stress. This study explores the consequence of these combined stresses on the phototrophic endoliths inhabiting the skeleton of Montipora monasteriata, growing at Heron Island, on the southern Great Barrier Reef. Endoliths that were exposed to sun after tissue removal were by far more susceptible to thermal photoinhibition and photo-damage than endoliths under coral tissue that contained high concentrations of brown dinoflagellate symbionts. While temperature or light alone did not result in decreased photosynthetic efficiency of the endoliths, combined thermal and solar stress caused a major decrease and delayed recovery. Endoliths protected under intact tissue recovered rapidly and photoacclimated soon after exposure to elevated sea temperatures. Endoliths under naturally occurring bleached tissue of M. monasteriata colonies (bleaching event in March 2004 at Heron Island) acclimated to increased irradiance as the brown symbionts disappeared. We suggest that two major factors determine the outcome of thermal bleaching to the endolith community. The first is the microhabitat and light levels under which a coral grows, and the second is the susceptibility of the coral-dinoflagellates symbiosis to thermal stress. More resistant corals may take longer to bleach allowing endoliths time to acclimate to a new light environment. This in turn may have implications for coral survival.
On steering wobble oscillations of motorcycles
Authors: Sharp R S , Limebeer D J N
Published: December 2004

The paper is aimed at an improved understanding of steering wobble oscillations of motorcycles through simulation. The background to the problem is discussed first. Then, an existing mathematical model of a manoeuvring motorcycle and rider is extended to include a yaw freedom for the upper body of the rider. The rider upper body and arm structural parameters are chosen in the light of newly published results from the testing of human subjects in a driving simulator, with forced motion of the steering wheel by means of an electric motor. Results show that steering wobble oscillations grow more vigorously as their amplitude increases beyond a few degrees of steering and that the stabilizing influence of the rider's tensing his/her muscles in response to a growing wobble problem is small. The work supports the idea that any machine which has a very lightly damped wobble mode at some operating condition may be made unstable by an unusual set of initial conditions and that the natural response of the rider to the problem will be largely ineffective. This idea is closely aligned with anecdotal accounts from general motorcycle usage.
Mathmathematical models, meshing analysis and transmission design for a robust cylindrical gear set generated by two blade-discs with parabolic cutting edges
Authors: Lee C-K , Chen C-K
Published: December 2004

This paper proposes mathematical models for analysing meshing characteristics and controlling a parabolic-like kinematic error function for a newly developed cylindrical gear set generated by two blade-discs with parabolic cutting edges. Unlike the former design, the proposed gear set is robust against assembly errors owing to its localized bearing contact and parabolic-like kinematic error function. Based on the proposed systematic mathematical procedures, the dimension of major axis of contact ellipse and magnitude of kinematic error can be controlled by the parameters of the blade-discs. To avoid gear undercutting, explicit functions of minimum numbers of teeth of non-undercutting for gear and pinion are derived. Equations for analysing tooth contact status, specific slide and contact ellipse are created. Based on the proposed mathematical models, a computer program has been established to analyse the effects of variation in parameters for cutting tools on meshing characteristics. The robustness of the developed gear set against various assembly errors is verified through numerical examples. With the proposed mathematical models and the computer program, gear designers can quickly determine the values of parameters for cutting tools without manual trial-and-error procedures.
Scanning electron microscope and energy dispersive X-ray spectrometry studies on the material surface of extruded Polycel® ossicular prostheses
Authors: Jang Chul Ho , Wang Pa-Chun
Published: December 2004

Background: The cause of ossicular prosthesis extrusion remains an issue of interest to many otologists. This study evaluated the change in material surfaces and chemical elements of extruded total ossicular replacement prostheses (TORPs) and partial ossicular replacement prostheses (PORPs).

Methods: A total of nine extruded Polycel® ossicular prostheses (four TORPs, five PORPs) from nine patients was investigated using scanning electron microscope and energy dispersive X-ray spectrometry (EDX). Three prostheses (TORPs) obtained during revision surgery
for hearing restoration were used as control subjects for EDX study.

Results: All subjects from the study group showed loss of fibrous capsule at both platform and shaft in the extruded prostheses. In comparison with the control group, the extruded prostheses had a lower level of carbon element (Wilcoxon signed-rank test, p < 0.05).

Conclusion: Loss of fibrous capsule and micro-degradation are probably two of the many factors that contribute to the extrusion of ossicular prostheses.
Nerve injury and the laryngeal mask airway
Authors: Bruce I.A. , Ellis R. , Kay N.J.
Published: December 2004

The laryngeal mask airway is a widely used, non-invasive, general purpose airway. We report the case of a temporary vocal cord palsy following the use of such an airway. The development of inappropriately high cuff pressures secondary to nitrous oxide diffusion into the cuff is proposed as the most likely cause. Knowledge of the existence of nerve injuries complicating laryngeal mask use is particularly important when counselling certain patients. Mandatory intraoperative cuff pressure monitoring should lower the risk of subsequent voice problems.
Post-transplant lymphoproliferative disorder presenting as epistaxis
Authors: Clarke Jonathan D. , Stock David , Singh Vijay
Published: December 2004

An unusual case of epistaxis resulting from post-transplant lymphoproliferative disorder is described.

A 30-year-old woman who had undergone renal transplantation 12 years previously presented with profuse, posterior, unilateral epistaxis. The initial findings, workup and treatment are presented. A post-nasal space (PNS) mass was detected and biopsy showed this to be an Epstein-Barrvirus-positive polymorphous B-cell post-transplant lymphoproliferative disorder. Computed tomography findings showed a polypoid lesion protruding from the sphenoethmoidal recess and filling
the left PNS.

Post-transplant lymphoproliferative disorder is well known to involve tonsil tissue. Commonly, this is the first presentation of the disease in children. However, until now post-transplant lymphoproliferative disorder has not been described in the PNS or nasal cavity presenting
as epistaxis. We conclude that all transplant patients presenting with epistaxis should be followed up for an accurate examination of the PNS and nasal cavity after the acute episode.
Sensorineural hearing loss associated with psoriatic arthritis
Authors: Srikumar S. , Deepak M.K. , Basu S. , Kumar B.N.
Published: December 2004

Autoimmune inner ear disease is a well described entity. We report a case of sudden-onset sensorineural hearing loss in association with psoriatic arthritis, which has not been reported in the literature. The case satisfies the criteria for the presumptive diagnosis of autoimmune hearing loss. A high index of suspicion, with early diagnosis and aggressive treatment with steroids and/or immunosuppressive agents, is essential to prevent irreversible hearing loss. The condition of psoriatic arthritis must be added to the pantheon of autoimmune diseases that can lead to sensorineural hearing loss.
Pharmacokinetics and Pharmacodynamics of Meropenem in Febrile Neutropenic Patients with Bacteremia
Authors: Ariano Robert E , Nyhlén Anna , Donnelly J Peter , Sitar Daniel S , Harding Godfrey KM , Zelenitsky Sheryl A
Published: December 2004

BACKGROUND:

Pharmacodynamic investigations with antimicrobials define the relationship between the infecting organism and achievable drug concentrations with clinical outcome.

OBJECTIVE:

To examine this relationship for meropenem in a population of patients who are at high risk of infection-related morbidity and mortality.

METHODS:

The study was a retrospective analysis of a multicenter, randomized, blinded clinical trial. A population-based predictive model was created using data from adults with febrile neutropenia and the nonparametric modeling program, NPEM. Patient age, body weight, and serum creatinine level were covariates in the model used to predict unbound concentrations for each patient. Pathogen susceptibility was estimated using product literature minimum inhibitory concentrations for effectiveness against 50% of microorganisms (MIC50) for specific organisms. The pharmacodynamic index of percent time above MIC (% T>MIC) was analyzed for its association with clinical outcome.

RESULTS:

A 2-compartment pharmacokinetic model using patient covariates of body weight and renal function best described the pharmacokinetics of meropenem in febrile neutropenic patients. Sixty patients with confirmed gram-positive or -negative bacteremia were studied. An average of 83% T>MIC was identified for the 42 clinical responders compared with 59% T>MIC for the 18 nonresponders (p = 0.04). An 80% clinical response rate was evident when the % T>MIC for meropenem exceeded 75% of the dosing interval (p = 0.01).

CONCLUSIONS:

To our knowledge, this is the first published report of a relationship between a pharmacodynamic index and clinical outcome in a febrile neutropenic population. Based on this relationship, dosing with intravenous meropenem 500 mg every 6 hours is predicted to be comparable to the currently recommended 1 g every 8 hours for serious infections. Our model provides further justification for a prospective clinical trial to evaluate a pharmacodynamically targeted meropenem dosing schedule as to its ability to improve clinical outcome in these patients.
Precise Localization of α7 Nicotinic Acetylcholine Receptors on Glutamatergic Axon Terminals in the Rat Ventral Tegmental Area
Authors: Jones Ian W. , Wonnacott Susan
Published: December 2004

α7 neuronal nicotinic acetylcholine receptors (nAChRs) constitute one of the predominant nAChR subtypes in the mammalian brain. Within the ventral tegmental area (VTA), nicotine application, paired with postsynaptic stimulation, contributes to a form of long-term potentiation, an effect attributed to presynaptic α7 nAChRs on glutamatergic afferents (Mansvelder and McGehee, 2000). The aim of this study was to examine the precise subcellular distribution of α7 nAChRs in the adult rat VTA to establish whether these receptors are indeed present on glutamatergic axon terminals and to determine their relationship with cholinergic afferents. The spatial relationship between α7 nAChRs, labeled using the α7 nAChR-specific antagonist α-bungarotoxin, and the local neurochemical environment was investigated by the application of multiple labeling strategies with antibodies against tyrosine hydroxylase, vesicular glutamate transporters (VGluTs), vesicular acetylcholine transporter, and glial fibrillary acidic protein. α7 nAChRs were localized at both somatodendritic and presynaptic loci within the VTA: on subpopulations of dopaminergic and nondopaminergic neurons and glutamatergic and nonglutamatergic terminals. There was no detectable α7 nAChR expression within astrocytes in the VTA. Most α7 nAChRs were cytoplasmic (82%), and the remainder were associated with the plasma membrane. Most presynaptic receptors (75%) were on glutamatergic axon terminals, with similar levels of α-bungarotoxin binding present on both VGluT1- and VGluT2-immunoreactive boutons. Both preembedding and postembedding electron microscopy revealed that presynaptic α7 nAChRs are often located at extrasynaptic (27%) and perisynaptic (61%) loci. α7 nAChRs were not associated with cholinergic synapses, consistent with their activation by a paracrine mode of acetylcholine or choline delivery.
Molecular Dissection of the Semaphorin 4D Receptor Plexin-B1-Stimulated R-Ras GTPase-Activating Protein Activity and Neurite Remodeling in Hippocampal Neurons
Authors: Oinuma Izumi , Katoh Hironori , Negishi Manabu
Published: December 2004

Plexins serve as receptors for repulsive axonal guidance molecules semaphorins. The cytoplasmic domain of the semaphorin 4D (Sema4D) receptor, Plexin-B1 has two separated Ras GTPase-activating protein (GAP)-homologous domains, C1 and C2. Recently, we reported that the Rho family small GTPase Rnd1 associates with Plexin-B1, and the Plexin-B1-Rnd1 complex stimulates GTPase activity of R-Ras, inducing growth cone collapse in hippocampal neurons in response to Sema4D. However, the molecular mechanisms by which Plexin-B1 exhibits the GAP activity remain unclear. In this report, critical roles of Rnd1 and Sema4D in Plexin-B1-stimulated R-Ras GAP activity and neurite remodeling were examined. The N-terminal region of the cytoplasmic domain of Plexin-B1 containing the C1 domain interacts with the C-terminal region containing the C2 domain, and Rnd1 disrupts this interaction. On the other hand, Sema4D induces clustering of Rnd1-bound Plexin-B1, in parallel with inactivation of R-Ras in cells. Antibody clustering of the recombinant cytoplasmic domain of Plexin-B1 in the presence of Rnd1 triggers the R-Ras GAP activity. Deletion of the extracellular domain of Plexin-B1 causes ligand-independent clustering of the receptor, rendering the receptor constitutively active in the presence of Rnd1, and induces contraction of COS-7 cells and inhibition of neurite outgrowth in hippocampal neurons. These results indicate that Rnd1 opens the two R-Ras GAP domains of Plexin-B1, and Sema4D-induced receptor clustering stimulates R-Ras GAP activity and neurite remodeling in hippocampal neurons.
Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response
Authors: Winsky-Sommerer Raphaëlle , Yamanaka Akihiro , Diano Sabrina , Borok Erzsebet , Roberts Amanda J. , Sakurai Takeshi , Kilduff Thomas S. , Horvath Tamas L. , de Lecea Luis
Published: December 2004

The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. We tested whether the hypocretinergic system is a critical component of the stress response activated by the corticotropin-releasing factor (CRF). Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. We also demonstrate that application of CRF to hypothalamic slices containing identified hypocretin neurons depolarizes membrane potential and increases firing rate in a subpopulation of hypocretinergic cells. CRF-induced depolarization was tetrodotoxin insensitive and was blocked by the peptidergic CRF-R1 antagonist astressin. Moreover, activation of hypocretinergic neurons in response to acute stress was severely impaired in CRF-R1 knock-out mice. Together, our data provide evidence of a direct neuroanatomical and physiological input from CRF peptidergic system onto hypocretin neurons. We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response.
CNS Myelin Paranodes Require Nkx6-2 Homeoprotein Transcriptional Activity for Normal Structure
Authors: Southwood Cherie , He Chris , Garbern James , Kamholz John , Arroyo Edgardo , Gow Alexander
Published: December 2004

Homeodomain proteins play critical roles during development in cell fate determination and proliferation, but few studies have defined gene regulatory networks for this class of transcription factors in differentiated cells. Using alacZ-knock-in strategy to ablate Nkx6-2, we find that theNkx6-2promoter is active embryonically in neuroblasts and postnatally in oligodendrocytes. In addition to neurological deficits, we find widespread ultrastructural abnormalities in CNS white matter and aberrant expression of three genes encoding a paranodal microtubule destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules neurofascin and contactin. The involvement of these downstream proteins in cytoskeletal function and cell adhesion reveals mechanisms whereby Nkx6-2 directly or indirectly regulates axon- glial interactions at myelin paranodes. Nkx6-2 does not appear to be the central regulator of axoglial junction assembly; nonetheless, our data constitute the first evidence of such a regulatory network and provide novel insights into the mechanism and effector molecules that are involved.
Peopling the Portholes: National Identity and Maritime Museums in the U.S. and U.K.
Authors: Leffler Phyllis
Published: December 2004

This research essay explores both the substance and style of exhibits at maritime museums in Britain and the United States. The museums selected reflect how social history concerns affect representations of national identities and national values on both sides of the Atlantic. Issues of social inclusion and diversity prevail, but are treated in substantially different ways in Britain and the U.S. Representations of life at sea, relocation and travel, and commerce provide focal points for exploring these differences. Issues of class, race, loss and guilt, social mobility, and national identity are woven into the analysis.
Catalytic partial oxidation of methane in a high‐temperature reverse‐flow reactor
Authors: Neumann Dirk , Veser Götz
Published: December 2004

The production of hydrogen and synthesis gas (syngas) from methane is a key technology for the twenty‐first century. It is currently performed predominantly by steam reforming of methane. An alternative reaction route is the direct catalytic partial oxidation of methane (CPOM) at high‐temperature, short contact time conditions, which proceeds autothermally over noble metal catalysts. However, syngas yields are limited at autothermal operation by a complex interplay of total and partial oxidation reactions. We demonstrate that these limitations can be overcome through dynamic heat integration in a catalytic reverse‐flow reactor. The efficient heat integration in this reactor type leads to strongly increased syngas yields; that is, it effectively converts sensible heat into chemical energy. Furthermore, even shorter contact times can be achieved without yield losses, allowing for even more compact reactors or further increased reactor throughput. The combination of short contact time catalysis with dynamic heat integration therefore appears ideally suited for small‐scale and decentralized syngas and hydrogen production. © 2004 American Institute of Chemical Engineers AIChE J, 51: 210–223, 2005
Precipitation of CuS and ZnS in a bubble column reactor
Authors: Al‐Tarazi Mousa , Heesink A. Bert M. , Versteeg Geert F. , Azzam Mohammed O. J. , Azzam Khalid
Published: December 2004

This work presents an experimental study into the precipitation of CuS and ZnS in a semibatch‐wise operated bubble column. First the applied bubble column was characterized with respect to mass transfer phenomena. The influences of ionic strength and superficial gas velocity on volumetric mass transfer coefficient and gas holdup, respectively, were determined using both CO2 and H2S gas. Increasing the ionic strength was found to increase the gas holdup and volumetric mass‐transfer coefficient. Although the gas holdup with H2S was found to be higher than that with CO2 at the same ionic strength and superficial gas velocity, the measured volumetric mass transfer coefficient was for CO2 absorption. In the second part of the study the influences of the H2S gas concentration, initial metal concentration and gas pressure on the precipitation of ZnS and CuS were investigated. With increasing H2S concentration, the initial concentration or pressure of Zn ions yields a decrease in the average size of produced ZnS particles. No significant effects could be observed when producing CuS particles. This was probably a result of the surface activity of such particles, causing them to cluster and form agglomerates. The results are useful for scale‐up and design of similar types of precipitator. © 2004 American Institute of Chemical Engineers AIChE J, 51: 235–246, 2005
Supporting user‐subjective categorization with self‐organizing maps and learning vector quantization
Authors: Goren‐Bar Dina , Kuflik Tsvi
Published: December 2004

Today, most document categorization in organizations is done manually. We save at work hundreds of files and e‐mail messages in folders every day. While automatic document categorization has been widely studied, much challenging research still remains to support user‐subjective categorization. This study evaluates and compares the application of self‐organizing maps (SOMs) and learning vector quantization (LVQ) with automatic document classification, using a set of documents from an organization, in a specific domain, manually classified by a domain expert. After running the SOM and LVQ we requested the user to reclassify documents that were misclassified by the system. Results show that despite the subjective nature of human categorization, automatic document categorization methods correlate well with subjective, personal categorization, and the LVQ method outperforms the SOM. The reclassification process revealed an interesting pattern: About 40% of the documents were classified according to their original categorization, about 35% according to the system's categorization (the users changed the original categorization), and the remainder received a different (new) categorization. Based on these results we conclude that automatic support for subjective categorization is feasible; however, an exact match is probably impossible due to the users' changing categorization behavior.
Interaction between the ADH1C polymorphism and maternal alcohol intake in the risk of nonsyndromic oral clefts: An evaluation of the contribution of child and maternal genotypes
Authors: Chevrier Cécile , Perret Claire , Bahuau Michel , Nelva Agnès , Herman Christine , Francannet Christine , Robert‐Gnansia Elisabeth , Cordier Sylvaine
Published: December 2004

BACKGROUND

Maternal alcohol consumption has been associated with an increased risk of nonsyndromic oral clefts in some studies. Study of gene‐environment interaction may provide insight into the reasons for their discrepancies observed. We focused on a polymorphism of the ADH1C gene (third gene of the class I alcohol dehydrogenase family), involved in the metabolism of ethanol and other alcohols.

METHODS

Data come from a French case‐control study (1998–2001), which tested the association between maternal alcohol consumption during the first trimester of pregnancy and the risk of nonsyndromic oral clefts (240 cases, 236 controls). A case‐parent study design looked at the association with an ADH1C polymorphism (Ile349Val site) and potential gene‐environment interaction effects. A log‐linear model was used to distinguish the direct effect of the child's genotype from the maternally mediated effects.

RESULTS

An increased risk of nonsyndromic oral clefts was observed for women who reported drinking alcohol during the first trimester, compared with women who did not. The mutated ADH1C allele carried by the child seemed to have a protective effect against the risk of oral clefts (RRone copy, 0.71; 95% confidence interval [CI], 0.50–1.02; RRtwo copies, 0.63; 95% CI, 0.3–1.3). The maternal genotype played a less important role than the child's, and its action remains unclear. No significant evidence of interaction effects between the ADH1C genotype and maternal alcohol consumption was observed.

CONCLUSIONS

Because the ADH1C gene is involved in the metabolic pathways of many alcohols, we propose several hypotheses about the causal pathway, including ethanol oxidation activity and, more probably, retinol oxidation. Birth Defects Research (Part A), 2005. © 2005 Wiley‐Liss, Inc.