bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 8 Can Affect Inner Ear Function
Authors: Iguchi Hiroyoshi , Anniko Matti 
Published: April 2003

The chemokine interleukin 8 (IL-8) was instilled into the round window niche of rats through a small perforation in the tympanic membrane in order to study its effect on inner ear function by electrophysiological and morphological techniques. The frequency-specific auditory brainstem response (ABR) was recorded at the frequencies 4, 8, 10, 12, 16 and 20 kHz just before and 1, 2, 5 and 14 days after instilling IL-8 to ascertain the hearing level during each interval. Morphological examination by light microscopy was performed during the same interval following the instillation of IL-8. On day 1, the rise in ABR threshold was within 5 dB SPL (non-significant elevation). However, a significant threshold elevation (above 5 dB SPL) occurred in high-frequency areas (16 and 20 kHz) on day 2, and in middle frequency areas (10 and 12 kHz) on day 5 with sensorineural hearing loss type intensity-latency curves. By day 14, the elevated thresholds had returned to pre-instillation levels. In the lowest areas (4 and 8 kHz), no significant threshold elevation was detected at any time during the observation period. By light microscopy, on day 1, clusters of inflammatory cells (predominantly neutrophils) were observed just outside the round window membrane (RWM), while only a few neutrophils were detected in the cochlea. These cells were still present outside the RWM on day 2. The neutrophils had disappeared by day 5 and only macrophages were present on the middle ear side of the RWM. However, throughout the observation period, the organ of Corti and stria vascularis appeared to be intact. These results suggest that IL-8 in the middle ear cavity is able to influence inner ear function.
Indication and Technique of Transnasal Microscopic Orbital Decompression for Endocrine Ophthalmopathy
Authors: May A. , Fries U. , von Ilberg C. , Weber A. 
Published: April 2003

If endocrine ophthalmopathy progresses despite conservative treatment then indications for surgical decompression are: loss of visual acuity, increasing strabism, and severe keratopathy. Endonasal microsurgery ensures a binocular view onto the intranasal landmarks of the orbital walls and allows simultaneous decompression of the medial and inferior wall as well as a good relief of pressure at the orbital apex. Surgical decompressions were performed on 29 orbits in 19 patients, 16 by using the endonasal microsurgical, 3 via external approach. The microscopic approach was entirely comparable with regard to the reduction of proptosis with a mean improvement of 4.2 mm against a mean of 4.7 mm by external approach and a mean 0.2 of better visual acuity in both procedures. The microsurgical technique is considered superior to an external approach avoiding external scars, neural pain, and reportedly less diplopia. The healing phase and the hospitalization time are shorter.
Regulation of Cytokine-Induced Neutrophil Chemoattractant in Rat Bone Marrow-Derived Macrophages by Inflammatory Mediators
Authors: Crippen Tawni L. , Klasing Kirk C. , Hyde Dallas M. 
Published: April 2003

During the course of inflammation, macrophages are highly influenced by their local environment and changes in the cytokine milieu. Exposure of macrophages to various factors during different phases of the inflammatory response may have a strong influence on the pattern of gene expression, which a macrophage exhibits. We examined how these mediators affect the regulation of the expression and production of cytokine-induced neutrophil chemoattractant (CINC). Our study demonstrates that CINC can be induced in bone marrow-derived macrophages by lipopolysaccharide, interleukin-1β, tumor necrosis factor-α (TNFα), and interferon-γ/TNFα. These mediators are factors which a macrophage would be expected to encounter early in an inflammatory process. In contrast, transforming growth factor-β (TGFβ), which is expressed late in the inflammatory process during mesenchymal cell proliferation and tissue repair, did not induce detectable amounts of CINC and functioned to suppress CINC production stimulated by early inflammatory mediators. Suppression of CINC production occurred whether TGFβ was added simultaneously, 12 or 24 h prior to the stimulus.
Transforming Growth Factor-β-Mediated Proliferation of Renal Tubular Epithelial Cells Involves Pertussis Toxin-Sensitive G Protein- and Protein Kinase C-Dependent Pathways
Authors: Wu Hsiao-Ling , Nambi Ponnal 
Published: April 2003

Exposure of LLCPK-1 cells to transforming growth factor (TGF)-β<sub>1</sub> resulted in an increase in [<sup>3</sup>H]thymidine incorporation. This increase depended on the concentration of TGF-β<sub>1</sub> used with an EC<sub>50</sub> value of 0.3–1 pmol/l. Concentrations >10 pmol/l were inhibitory. Similar effects occurred with TGF-β<sub>3</sub>. Addition of both TGF-β<sub>1</sub> and TGF-β<sub>3</sub> together had no additive effect. Pretreatment of cells with 10 µmol/l genestein exerted no effect on TGF-β-mediated response, whereas pretreatment with 10 µmol/l Ro-32-0432 inhibited TGF-β-mediated [<sup>3</sup>H]thymidine incorporation. In addition, pretreatment of cells with pertussis toxin attenuated TGF-β-mediated proliferation of LLCPK-1 cells. These data indicate that in LLCPK-1 cells, TGF-β<sub>1</sub> and TGF-β<sub>3</sub> mediate their responses through the same receptor. This pathway involves protein kinase C and pertussis toxin-sensitive G protein.
Pyrazinoylguanidine in End-Stage Renal Disease: A Prospective, Placebo-Controlled Pilot Study
Authors: Ahsan Nasimul , Korsunsky Zhanna , Beyer Jr. Karl H. , Vesell Elliot S. 
Published: April 2003

Cardiovascular disease is the leading cause of mortality in end-stage renal disease (ESRD) patients receiving dialysis. In these patients, hypertriglyceridemia appears to increase the risk of accelerated atherosclerosis. The present placebo-controlled study evaluated prospectively lipid-lowering effects of pyrazinoylguanidine (PZG) in 6 ESRD patients undergoing maintenance hemodialysis. The design of the study entailed a placebo phase of 1 week followed by 3 weeks of PZG, 400 mg three times a day. Compared to placebo, PZG reduced serum triglycerides (PZG vs. placebo 370 ± 171 vs. 414 ± 182 mg/dl; p = 0.01). PZG also tended to decrease total cholesterol. In addition, PZG selectively lowered blood glucose in hyperglycemic patients. PZG was well tolerated; it did not interfere with hemodynamic parameters or alter liver function tests, nutritional parameters or dialysis clearance.
In vitro and in vivo Activity of Two Pt(IV) Salts against <i>Leishmania donovani</i>
Authors: Mesa-Valle C.M. , Rodriguez-Cabezas M.N. , Moraleda-Lindez V. , Craciunescu D. , Sanchez-Moreno M. , Osuna A. 
Published: April 2003

The activities of 8 platinum drug complex salts were determined against <i>Leishmania donovani</i> promastigotes. The three most active salts were selected: [Pt<sup>IV</sup>Br<sub>6</sub>]H<sub>2</sub> (pentamidine); [Pt<sup>IV</sup>Br<sub>6</sub>]H<sub>2</sub> (stilbamidine), and [Pt<sup>IV</sup>Cl<sub>6</sub>]H<sub>2</sub> (2-piperazinyl(1) ethyl amine), which induced growth-inhibition rates of more than 50% at 24 h of treatment and at the maximum dosage tested. The cytotoxicity assays on the macrophage cell line J-774 showed high cytotoxicity for the salt [Pt<sup>IV</sup>Br<sub>6</sub>]H<sub>2</sub> (stilbamidine) with a percentage of specific <sup>51</sup>Cr release of 58.2% at 24 h of incubation and 100 µg/ml. Meanwhile, assays of the other compounds showed practically no cytotoxicity. The salt [Pt<sup>IV</sup>Br<sub>6</sub>]H<sub>2</sub> (pentamidine) notably inhibited the incorporation of <sup>3</sup>H-thymidine in the treated parasites. The ultrastructural alterations observed in the flagellates treated with the salts [Pt<sup>IV</sup>Cl<sub>6</sub>]H<sub>2</sub> (2-piperazinyl(1)ethyl amine) and [Pt<sup>IV</sup>Br<sub>6</sub>]H<sub>2</sub> (pentamidine) suggest that both act preferentially at the nuclear level and at the kinetoplast-mitochondrion complex. Both compounds showed a high in vivo activity in parasitized Wistar rats.
Ca<sup>2+</sup>-Induced Inhibition of Adenylyl Cyclase in Turkey Erythrocyte Membranes
Authors: Demirel Emine , Ugur Özlem , Onaran H. Ongun 
Published: April 2003

We investigated the effects of calcium ions (Ca<sup>2+</sup>) on the adenylyl cyclase activity in purified turkey erythrocyte membranes. Results showed the following: (i) Ca<sup>2+</sup> inhibits cAMP accumulation stimulated by isoproterenol (1 µmol/l), NaF + AlCl<sub>3</sub> (10 mmol/l + 20 µmol/l) or forskolin (10 µmol/l) in EGTA-washed turkey erythrocyte membranes. IC<sub>50</sub> of free [Ca<sup>2+</sup>] is approximately 0.1 mmol/l in the presence of Mg<sup>2+</sup> (2.5 mmol/l) and isobutylmethylxanthine (1 mmol/l). (ii) The potency of Ca<sup>2+</sup> to inhibit cAMP accumulation is independent of the type of stimulus used to activate the adenylyl cyclase. We also evaluated the calcium sensitivity of the basal cAMP accumulation in the presence of GTP (10 µmol/l) and Mg<sup>2+</sup> (2.5 mmol/l) which was also inhibited by Ca<sup>2+</sup> with the same potency. (iii) The inhibition pattern of cAMP accumulation is not affected by the presence of added calmodulin (100 nmol/l). (iv) Ca<sup>2+</sup> is ineffective on the binding of isoproterenol to the β-adrenoceptors. (v) Increasing the concentration of Ca<sup>2+</sup> does not induce an observable activation of cyclic nucleotide phosphodiesterase in the present experimental conditions. Thus, we concluded that the inhibition of cAMP accumulation is due to an inhibition of the adenylyl cyclase rather than the activation of phosphodiesterase(s). The presence of a yet unidentified isoform of adenylyl cyclase that can be directly inhibited by Ca<sup>2+</sup> or a G<sub>i</sub> protein that can be activated by Ca<sup>2+</sup> seems to explain these results. In either case, these results provide an additional mode of cross-talk that can take place between the Ca<sup>2+</sup>- and cAMP-signaling systems.
Pharmacological Characteristics of MJ-451, a New Benzopyran- Derived ATP-Sensitive Potassium Channel Opener, in Guinea Pig Isolated Trachea
Authors: Lin Chien-Huang , Lee Yen-Mei , Sheu Joen-Rong , Cheng Chen-Yu , Chang Ming-Jyh , Yen Mao-Hsiung 
Published: April 2003

In this study, we determined the pharmacological activities of MJ-451 (6-cyano-3S,4R-dihydro-2,2-dimethyl-2H-3-hydroxy-4-[2-oxo-5S-1-hydroxmethyl)-1-pyrrolidinyl]-1-benzopyran) in guinea pig isolated trachea and compared its effects with those of cromakalim. MJ-451 (0.1–10 µmol/l) and cromakalim (0.01–1 µmol/l) produced concentration-dependent relaxation of guinea pig isolated trachea precontracted with carbachol (0.5 µmol/l) or histamine (1 µmol/l). MJ-451 (0.03–30 µmol/l), as well as cromakalim (0.03–30 µmol/l), caused a complete and concentration-dependent relaxation of guinea pig isolated trachea precontracted with 20 mmol/l KCl, but did not inhibit the spasmogenic effect of 80 mmol/l KCl. However, theophylline (30–3,000 µmol/l) caused a complete and concentration-dependent relaxation of guinea pig isolated trachea precontracted with either 20 or 80 mmol/l KCl. Propranolol (0.1 µmol/l) markedly antagonized the relaxant action of isoprenaline, but not that of MJ-451 in carbachol-contracted isolated trachea. 8-(p)-sulfophenyltheophylline (150 µmol/l), a selective P<sub>1</sub> purinoceptor antagonist, had no effect against the tracheal relaxation induced by MJ-451, but markedly depressed the concentration-response curve of 5′-N-ethylcarboxamidoadenosine. Charybdotoxin (10 µmol/l), a large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel blocker, failed to modify the relaxant activity of MJ-451 in carbachol-contracted isolated trachea. The ATP-sensitive K<sup>+</sup> channel blocker, glibenclamide (0.1, 1 and 10 µmol/l) concentration-dependently antagonized the relaxant activity of MJ-451 in carbachol-contracted isolated trachea. It is concluded that MJ-451 is a selective ATP-sensitive K<sup>+</sup> channel opener in the tracheal smooth muscle of the guinea pig.
Prostaglandin E<sub>2</sub> in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E<sub>2</sub> Formation by Nicotine and Cotinine
Authors: Sastry B.V. Rama , Hemontolor M.E. , Olenick Molly 
Published: April 2003

Tobacco smoking by pregnant women increases the frequency of spontaneous abortions and preterm births. Human labor is associated with enhanced intrauterine phospholipid metabolism and production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) which induces labor, initiates uterine contractions and maintains the homeostasis of placental blood flow. Therefore, we studied: (a) the influence of nicotine and cotinine on the effects of PGE<sub>2</sub> on placental vasculature in perfused human placental cotyledon, and (b) the activation of placental phospholipase A<sub>2</sub> (PLA<sub>2</sub>) by nicotine and cotinine using 1-palmitoyl-2-[1-<sup>14</sup>C]arachidonyl-phosphatidylethanolamine (PE, 2.2 nmol) as substrate. These studies revealed that: (1) increasing concentrations of PGE<sub>2</sub> (10– 150 ng/ml) increased umbilical perfusion pressure by 170 ± 10% (n = 6) of control (100%). Cotinine (2 µg/ml) enhanced this effect at all concentrations of PGE<sub>2</sub>. Nicotine (2 µg/ml) prevented the effect of PGE<sub>2</sub>; (2) both cotinine (EC<sub>50</sub> 470–500 fmol/l) and nicotine (EC<sub>50</sub> 18–32 pmol/l) activated PLA<sub>2</sub> in human placental tissues. These observations indicated that cotinine was more potent than in nicotine activating PLA<sub>2</sub> and potentiating the vasoconstrictive effects of PGE<sub>2</sub> on fetal placental circulation. Nicotine activates nicotinic receptors and releases placental acetylcholine, a vasodilator of placental arteries. Acetylcholine stimulates muscarinic receptors of endothelial cells resulting in the release of endothelium-derived relaxing factor (EDRF), and possibly nitric oxide. Therefore, nicotine prevents or abolishes the vasoconstrictive effects of PGE<sub>2</sub> through the release of EDRF. Cotinine is inactive at nicotinic and muscarinic receptors. Therefore, accumulation of cotinine, the major metabolite of nicotine, in fetal circulation may contribute to production of PGE<sub>2</sub> and induction of preterm labor and spontaneous abortions.
Captopril Inhibits Peptidylglycine- α-Hydroxylating Monooxygenase: Implications for Therapeutic Effects
Authors: Mueller S.Alyssa , Driscoll WilliamJ. , Mueller GregoryP. 
Published: April 2003

The therapeutic actions of captopril are facilitated by its sulfhydryl moiety which interacts with the metal (Zn<sup>2+</sup>) prosthetic groups of angiotensin-converting enzyme (ACE; EC 3.4.15.1). This study focused on captopril as an inhibitor of another metal-dependent (Cu<sup>2+</sup>) enzyme, peptidylglycine-α-hydroxylating monooxygenase (PHM; EC 1.14.17.3). PHM is rate limiting in α-amidation, a COOH-terminal modification that bioactivates several pressor peptides. Captopril inhibited PHM in vitro in a dose-dependent manner with an IC<sub>50</sub> of approximately 100 μmol/l. This inhibition was partially reversed by increased concentrations of Cu<sup>2+</sup>. Structurally similar nonsulfhydryl ACE inhibitors did not affect the activity of PHM. The present findings indicate that the therapeutic effectiveness of captopril may result from actions on a range of metalloenzymes including ACE and PHM.
Inhibition of T-Type and L-Type Ca<sup>2+</sup> Currents by Aranidipine, a Novel Dihydropyridine Ca<sup>2+</sup> Antagonist
Authors: Masumiya Haruko , Tanaka Yoshio , Tanaka Hikaru , Shigenobu Koki 
Published: April 2003

The effects of aranidipine, a novel dihydropyridine Ca<sup>2+</sup> channel antagonist, on membrane currents in guinea pig ventricular myocytes and on action potentials in rabbit sinoatrial node tissue were examined. In myocytes, aranidipine (10 nmol/l to 1 μmol/l) concentration-dependently decreased T-type and L-type Ca<sup>2+</sup> currents. Aranidipine (1 μmol/l) had little effect on K<sup>+</sup> currents. In the sinoatrial node, 0.1 μmol/l aranidipine increased cycle length, and decreased +&#118;&#775;<sub>max</sub> and the slope of the phase 4 depolarization. Thus, inhibition of both T-type and L-type Ca<sup>2+</sup> currents by aranidipine may partly explain its potent negative chronotropic activity.
Do Airstream Mechanisms Influence Tongue Movement Paths?
Authors: Hoole Philip 
Published: April 2003

Abstract
Velar consonants often show an elliptical pattern of tongue movement in symmetrical vowel contexts, but the forces responsible for this remain unclear. We here consider the role of overpressure (increased intraoral air pressure) behind the constriction by examining how movement patterns are modified when speakers change from an egressive to ingressive airstream. Tongue movement and respiratory data were obtained from 3 speakers. The two airstream conditions were additionally combined with two levels of speech volume. The results showed consistent reductions in forward tongue movement during consonant closure in the ingressive conditions. Thus, overpressure behind the constriction may partly determine preferred movement patterns, but it cannot be the only influence since forward movement during closure is usually reduced but not eliminated in ingressive speech.
Relationship between Rhythmic Behavior and Canonical Babbling in Infant Vocal Development
Authors: Ejiri Keiko 
Published: April 2003

Abstract
The onset of canonical babbling (CB) is a landmark event in infants’ vocal development for spoken language. Previous research has suggested that the onset of CB coincides with the peak period of rhythmic activities. To examine this phenomenon in detail, 28 Japanese infants (14 girls, 14 boys) were observed longitudinally from the age of 5 to 9 months. In the experimental sessions, an audible or an inaudible rattle was placed into a hand of each tested infant. Then the number of times that the infant shook the rattle was counted. In the observational sessions, infants’ spontaneous rhythmic activities under natural conditions were observed. The result shows that rhythmic activities reached their peak around the onset of CB. When the infants began to babble, they shook whichever rattle was in their hand, regardless of its audibility. After this period, they shook the audible rattles more frequently than the inaudible ones. These findings suggest that, around the onset of CB, infants learn to control their motor activities based on auditory feedback.
Investigating Unscripted Speech: Implications for Phonetics and Phonology
Authors: Kohler K.J. 
Published: April 2003

Abstract
This paper looks at patterns of reduction and elaboration in speech production, taking the phenomenon of plosive-related glottalization in German spontaneous speech, on the basis of the ‘Kiel Corpus’, as its point of departure, and proposes general principles of human speech to explain them. This is followed by an enquiry into the nature of a production-perception link, based on complementary data from perceptual experiments. A hypothesis is put forward as to how listeners cope with the enormous phonetic variability of spoken language and how this ability may be acquired. Finally, the need for a new paradigm of phonetic analysis and phonological systematization is stressed, as a prerequisite to dealing adequately and in an insightful way with the production and perception of spontaneous speech.
Language Acquisition as Complex Category Formation
Authors: Lotto Andrew J. 
Published: April 2003

AbstractPurported units of speech, e.g. phonemes or features, are essentially categories. The assignment of phonemic (or phonetic) identity is a process of categorization: potentially discriminable speech sounds are treated in an equivalent manner. Unfortunately the extensive literature on human categorization has typically focused on simple visual categories that are defined by the presence or absence of discrete features. Speech categories are much more complex. They are often defined by continuous values across a variety of imperfectly valid features. In this paper, several kinds of categories are distinguished and studies using human subjects, animal subjects and computational models are presented that endeavor to describe the structure and development of the sort of complex categories underlying speech perception.
Dynamic Simulation of Human Movement Using Large-Scale Models of the Body
Authors: Pandy Marcus G. , Anderson Frank C. 
Published: April 2003

Abstract
A three-dimensional model of the body was used to simulate two different motor tasks: vertical jumping and normal walking on level ground. The pattern of muscle excitations, body motions, and ground-reaction forces for each task were calculated using dynamic optimization theory. For jumping, the performance criterion was to maximize the height reached by the center of mass of the body; for walking, the measure of performance was metabolic energy consumed per meter walked. Quantitative comparisons of the simulation results with experimental data obtained from people indicate that the model reproduces the salient features of maximum-height jumping and normal walking on the level. Analyses of the model solutions will allow detailed explanations to be given about the actions of specific muscles during each of these tasks.
An Embodiment Perspective on the Acquisition of Speech Perception
Authors: Davis Barbara L. , MacNeilage Peter F. 
Published: April 2003

Abstract
Understanding the potential relationships between perception and production is crucial to explanation of the nature of early speech acquisition. The ‘embodiment’ perspective suggests that mental activity in general cannot be understood outside of the context of body activities. Indeed, universal motor factors seem to be more responsible for the distribution of early production preferences regarding consonant place and manner, and use of the vowel space than the often considerable cross-language differences in input available to the perceptual system. However, there is evidence for a perceptual basis to the establishment of a language-appropriate balance of oral-to-nasal output by the beginning of babbling, illustrating the necessary contribution of ‘extrinsic’ perceptual information to acquisition. In terms of representations, at least one assumption that segmental units underlying either perception or production in early phases of acquisition may be inappropriate. Our work on production has shown that the dominant early organizational structure is a relatively unitary open-close ‘frame’ produced by mandibular oscillation. Consideration of the role of ‘intrinsic’ (self-produced) perceptual information suggests that this frame may be an important basis for perceptual as well as production organization.