bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Th1/Th2 Cytokine Responses to Paternal and Vaccination Antigens in Preeclampsia: No Differences Compared with Normal Pregnancy
Authors: Jonsson Yvonne , Ekerfelt Christina , Berg Göran , Nieminen Katri , Sharma Surendra , Ernerudh Jan , Matthiesen Leif
Published: March 2004

Problem:  A Th1‐shift has been suggested to be involved in the pathogenesis of preeclampsia. This study was designed to compare Th1/Th2 related cytokine secretion in blood between women with preeclampsia (n = 15) and normal pregnancies (n = 15), using a high‐sensitivity technique for cytokine detection.

Methods of study:  Spontaneous as well as ‘fetus‐specific’ and recall antigen‐specific (purified protein derivate of Mycobacterium tuberculosis, tetanus toxoid and lipopolysaccharide) secretion of interferon‐γ, interleukin (IL)‐4, IL‐10 and IL‐12 in peripheral blood mononuclear cells (PBMC) was detected by enzyme‐linked immunosorbent spot‐forming cell assay (ELISPOT). Fetus‐specific secretion was induced by stimulation with paternal PBMC in a mixed leukocyte culture assay.

Results:  All cytokines were secreted by PBMCs both from women with preeclampsia and women with normal pregnancies. No differences in the number of cytokine‐secreting cells were found between the two groups.

Conclusions:  No evidence was found for a shift in the systemic Th1/Th2 responses, in preeclampsia compared with normal pregnancy. This does, however, not exclude differences in the local immune responses related to the fetoplacental unit.
IFN‐γ‐Mediated Inhibition of COX‐2 Expression in the Placenta from Term and Preterm Labor Pregnancies
Authors: Hanna Nazeeh , Bonifacio Lea , Reddy Pradeep , Hanna Iman , Weinberger Barry , Murphy Shaun , Laskin Debra , Sharma Surendra
Published: March 2004

Problem:  The inflammatory‐anti‐inflammatory cytokine network is thought to play a critical role in regulated progression and termination of pregnancy. The aim of this study was to evaluate the effects of interferon (IFN)‐γ on the expression of Cyclooxygenase (COX)‐2 and production of prostaglandin E2 (PGE2) in the human placenta from term and preterm labor deliveries.

Method of study:  Placental explant culture system was used. COX‐2 expression was determined by complementary techniques of immunohistochemistry and Western blotting. Released IFN‐γ and PGE2 by placental explants were measured by enzyme‐linked immunosorbent assay. Signal transducer and activator of transcription 1 (STAT1) phosphorylation was evaluated by Western blotting using a specific antibody.

Results:  IFN‐γ was poorly detected in the placenta but was significantly expressed in decidual tissues from both term and preterm pregnancies as detected by immunohistochemistry. IFN‐γ significantly inhibited COX‐2 expression and PGE2 release in cultured placental explants from term and preterm labor deliveries. This effect most likely occurred in a STAT1‐dependent manner as this regulatory protein was phosphorylated in response to IFN‐γ. IFN‐γ receptor (IFN‐γR) was expressed in normal early pregnancy placental samples. However, its expression was significantly reduced in placental samples from term and preterm deliveries. Of interest, IFN‐γR was expressed in placentas from term and preterm labor deliveries after 24 hr in culture.

Conclusions:  Our data suggest that the human placenta is an important site for IFN‐γ‐mediated repression of COX‐2 expression and PGE2 production, implying that functional withdrawal of IFN‐γ may be involved in the onset of term or preterm labor.
Tooth replantation after traumatic avulsion: a 27‐year follow up
Authors: Martins Wilson Denis , Westphalen Vania Portela Ditzel , Westphalen Fernando Henrique
Published: March 2004

Abstract  – This report presents a case of replantation of a traumatically avulsed central incisor in a 32‐year‐old woman. The tooth was replanted after a 30‐min extra‐alveolar period. Emergency unconventional immobilization was performed, using 2–0 chromic gut, and a restorative composite made Gunning‐type splint. The tooth is still in place 27 years after replantation (1976 to date) without marked resorption.
Pulp revascularization of replanted immature dog teeth after treatment with minocycline and doxycycline assessed by laser Doppler flowmetry, radiography, and histology
Authors: Ritter Alessandra Luisa de Souza , Ritter André Vicente , Murrah Valerie , Sigurdsson Asgeir , Trope Martin
Published: March 2004

Abstract –  This study investigated the effect of topical antibiotic treatment on pulp revascularization in replanted teeth. Thirty‐four immature teeth were selected from three young dogs. Baseline radiographs and laser Doppler flowmetry (LDF) readings were obtained. Specimens were randomly divided into four groups: Thirty‐eight teeth were extracted, kept dry for 5 min, and either (Group 1) covered with minocycline mixture (G1, n = 11), (Group 2) soaked in doxycycline (G2, n = 11), or (Group 3) soaked in saline (G3‐negative control, n = 6), and replanted. Teeth in Group 4 were not extracted (positive control, n = 6). Postoperative radiographs and LDF readings were obtained for 2 months after replantation. After sacrifice, the jaws were collected and processed for light microscopy. Pre‐ and postreplantation LDF readings and radiographs, and histologic findings were analyzed to assess revascularization. Pulp revascularization occurred in 91% (G1), 73% (G2), and 33% (G3) of the specimens. In conclusion, minocycline facilitates pulp revascularization in replanted immature teeth after replantation.
Chronic osteomyelitis: 20 years after mandible fracture
Authors: Ertas Umit , Tozoglu Sinan , Gursan Nesrin
Published: March 2004

Abstract  – Chronic osteomyelitis is a persistent abscess of the bone that is characterized by the usual complex of inflammatory processes, including necrosis of mineralized and marrow tissues, suppuration, resorption, sclerosis, and hyperplasia. The purpose of this paper is to report a case of chronic osteomyelitis seen 20 years after mandible fracture.
Prevalence of traumatic injuries to the permanent incisors in candidates for orthodontic treatment
Authors: Bauss Oskar , Röhling Johannes , Schwestka‐Polly Rainer
Published: March 2004

Abstract  – The dental records made on presentation of 1367 consecutive patients (731 females and 636 males) for orthodontic treatment at a private orthodontic practice between 1998 and 2002 were examined for data relating to trauma to the permanent incisors. The results showed that 10.3% of these patients had suffered from dental trauma before the onset of orthodontic treatment. The highest prevalence of dental trauma was determined in the 11–15 years age group, corresponding to the dental developmental stage of the late mixed dentition. The most frequently affected teeth were the maxillary central incisors (79.6%), and the most common types of trauma were fracture of enamel–dentin without pulpal involvement (42.7%) and fracture of enamel (33.8%). Compared to patients with normal overjet and adequate lip coverage, the frequency of dental trauma was significantly higher in patients with increased overjet and adequate lip coverage (P = 0.028) or with increased overjet and inadequate lip coverage (P = 0.003). The results of the present study indicate that a significant percentage of candidates for orthodontic treatment, and especially those with increased overjet and inadequate lip coverage, suffer trauma to their permanent incisors before the onset of orthodontic treatment. It might also be concluded that preventive orthodontic treatment of such patients should be initiated and completed before the age of 11, i.e. in the early to middle mixed dentition.
A quantitative analysis of Propolis: a promising new storage media following avulsion
Authors: Martin Margaret P. , Pileggi Roberta
Published: March 2004

Abstract –  Both length of extra‐alveolar time and type of storage media are significant factors that can affect the long‐term prognosis of replanted teeth. Numerous studies have examined various media in an attempt to determine the ideal material for storage of the avulsed tooth. The purpose of this study was to use a Collagenase–Dispase assay to investigate the potential of a new storage media, Propolis, in maintaining viable periodontal ligament (PDL) cells on simulated avulsed teeth. Seventy freshly extracted human teeth were divided into five experimental groups and two control groups. The positive and negative controls corresponded to 0‐min and an 8‐h dry time, respectively. The experimental teeth were stored dry for 30 min and then immersed in one of the five media (Hank's balanced salt solution (HBSS), milk, saline, Propolis 50%, and Propolis 100% for 45 min). The teeth were then treated with dispase grade II and collagenase for 30 min. The number of viable PDL cells were counted with a hemocytometer and analyzed. Statistical analysis demonstrated that both Propolis groups kept significantly more PDL cells viable compared to either milk, saline, or HBSS. Within the parameters of this study, it appears that Propolis may be a better alternative to HBSS, milk, or saline in terms of maintaining PDL cell viability after avulsion and storage.
The association between incisor trauma and occlusal characteristics in individuals 8–50 years of age
Authors: Shulman Jay D. , Peterson Jill
Published: March 2004

Abstract –  To explore the association between incisal trauma and occlusal characteristics using oral examination and health interview data from the Third National Health and Nutrition Examination Survey 1988–1994 (NHANES III). Incisal trauma examinations were performed on 15 364 individuals 6–50 years of age using an ordinal scale developed by the National Institute of Dental and Craniofacial Research. Occlusal examinations were performed on 13 057 individuals 8–50 years of age. We fitted separate multivariate logistic regression models for maxillary and mandibular incisor trauma adjusting for socio‐demographic variables (age, gender, race‐ethnicity) and occlusal characteristics (overbite, overjet, open bite). 23.45% of all individuals evidenced trauma on at least one incisor, with trauma more than four times more prevalent on maxillary (22.59%) than on mandibular incisors (4.78%). Males (OR = 1.67) had greater odds of trauma than females; Whites (OR = 1.37) and non‐Hispanic Blacks (OR = 1.37) had greater odds of trauma than Mexican–Americans. The odds of trauma increased with age, peaked from age 21 to 30 (OR = 2.92), and declined. As overjet increased, so did the odds of trauma. Compared to individuals with ≤0‐mm overjet, odds of trauma increased from 1–3 mm (OR = 1.42) to 4–6 mm (OR = 2.42) to 7–8 mm (OR = 3.24) to >8 mm (OR = 12.47). Trauma to incisors is prevalent but mostly limited to enamel. Trauma to maxillary incisors is associated with overjet, gender, race‐ethnicity, and age, while trauma to mandibular incisors is associated with gender, age, and overbite.
Stress–strain response in human dentine: rethinking fracture predilection in postcore restored teeth
Authors: Kishen Anil , Kumar Ganesh V. , Chen Nah‐Nah
Published: March 2004

Abstract –  In this study, the biomechanical perspective of fracture predilection in post‐core restored teeth is investigated using computational, experimental, and fractographic analyses. The computational finite element analysis and the experimental tensile testing are used to evaluate the stress–strain response in structural dentine. The fractographic evaluations are conducted using laser scanning confocal microscopy and scanning electron microscopy to examine the topography of dentine from experimentally fractured specimens, and clinically fractured post‐core restored teeth specimens. These experiments aided in correlating the stress–strain response in structural dentine with cracks and catastrophic fractures in post‐core restored teeth. It was observed from these experiments that the inner dentine displayed distinctly high strains (deformations), while the outer dentine demonstrated high stresses during tensile loading. This implies that the energy fed into the material as it is extended will be spread throughout the inner dentine, and there is less possibility of local increase in stress at the outer dentine, which can lead to the failure of dentine structure. During post‐endodontic restoration with increase in loss of inner dentine, the fracture resistance factor contributed by the inner dentine is compromised, and this in turn predisposes the tooth to catastrophic fracture.
Lumbar sympathetic nerve activity and hindquarter blood flow during REM sleep in rats
Authors: Miki Kenju , Oda Michiyo , Kamijyo Nozomi , Kawahara Kazumi , Yoshimoto Misa
Published: March 2004

The present study aimed to investigate the response of lumbar sympathetic nerve activity (LSNA) to the onset of rapid eye movement (REM) sleep and its contribution to the regulation of muscle blood flow during REM sleep in rats. Electrodes for the measurements of LSNA, electroencephalogram, electromyogram and electrocardiogram and a Doppler flow cuff for the measurements of blood flow in the common iliac and mesenteric arteries, also catheters for the measurements of systemic arterial and central venous pressures were implanted chronically. REM sleep resulted in a step increase in LSNA, by 22 ± 9% (mean ±s.e.m., P < 0.05), a reduction of iliac vascular conductance, by −16 ± 3% (P < 0.05) and a gradual increase in systemic arterial pressure, reaching a maximum value of 8.1 ± 2.0 mmHg (P < 0.05) at 89 s after onset of REM sleep, while mesenteric vascular conductance increased simultaneously by 5 ± 2% (P < 0.05). There was a significant (Pearson's correlation coefficient = 0.94, P < 0.05) inverse linear relationship between LSNA and the iliac blood flow. Unilateral lumbar sympathectomy blunted the reduction of iliac blood flow induced by the onset of REM sleep. The present observations suggest that the onset of REM sleep appears to be associated with a vasodilation in viscera and a vasoconstriction in skeletal muscle, such that systemic arterial pressure increases during REM sleep in rats.
Patch clamp study of the UNC‐105 degenerin and its interaction with the LET‐2 collagen in Caenorhabditis elegans muscle
Authors: Jospin Maëlle , Mariol Marie‐Christine , Segalat Laurent , Allard Bruno
Published: March 2004

Degenerins have emerged from genetic studies in Caenorhabditis elegans as candidate mechanically gated amiloride‐sensitive ion channels for transducing mechanical stimuli into cellular responses. In C. elegans muscle, the existence of a genetic interaction between the unc‐105 degenerin gene and let‐2, a gene encoding an α2(IV) collagen, raised the possibility that UNC‐105 may function as a mechanically gated channel in a stretch receptor complex. However, to date, ion channel activity of UNC‐105 has only been recorded in a gain‐of‐function mutant form in heterologous expression systems. In this study we investigated the in situ properties of UNC‐105 using the whole cell configuration of the patch clamp technique on body wall muscle cells from acutely dissected C. elegans. Amiloride was found to be without effect on membrane potential of wild‐type muscle cells, suggesting that the UNC‐105 degenerin is electrically silent in resting muscle. Hypo‐osmotic shocks induced a reversible depolarization of muscle cells but which was not affected by amiloride. Deformation of the cells by applying tension to the filamentous complex on which muscle cells remained attached or by ejecting external solution under pressure failed to induce any change of membrane potential. In gain‐of‐function unc‐105(n506) mutant cells, an amiloride‐sensitive inward Na+ current was found to be constitutively active, leading to maintained muscle depolarization. An associated mutation in the α2(IV) collagen LET‐2 led to the closure of the mutant UNC‐105(n506) channel while a collagenase treatment of these double mutant cells caused it to re‐open, giving evidence for a functional interaction between LET‐2 collagen and mutant UNC‐105 channel.
Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle
Authors: Jensen L. , Bangsbo J. , Hellsten Y.
Published: March 2004

The effect of intense training on endothelial proliferation, capillary growth and distribution of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was examined in human skeletal muscle. Two intermittent knee extensor training protocols (at ∼150% (Study 1) versus∼90% (Study 2) of leg V̇O2 max) were conducted. Muscle biopsies were obtained throughout the training periods for immunohistochemical assessment of capillarization, cell proliferation (Ki‐67‐positive cells), VEGF and bFGF. In Study 1, microdialysis samples were collected from the trained and untrained leg at rest and during exercise and added to endothelial cells to measure the proliferative effect. After 4 weeks of training there was a higher (P < 0.05) capillary‐to‐fibre ratio (Study 1: 2.4 ± 0.1 versus 1.7 ± 0.1) and number of Ki‐67‐positive cells (Study 1: 0.18 ± 0.05 versus 0.00 ± 0.01) than before training. Neither the location of proliferating endothelial cells nor capillarization was related to muscle fibre type. The endothelial cell proliferative effect of the muscle microdialysate increased from rest to exercise in both the untrained leg (from 262 ± 60 to 573 ± 87% of control perfusate) and the trained leg (from 303 ± 75 to 415 ± 108% of perfusate). VEGF and bFGF were localized in endothelial and skeletal muscle cells and training induced no changes in distribution. The results demonstrate that intense intermittent endurance training induces capillary growth and a transient proliferation of endothelial cells within 4 weeks, with a similar growth occurring around type I versus type II muscle fibres.
Multiple mechanisms govern the dynamics of depression at neocortical synapses of young rats
Authors: Fuhrmann Galit , Cowan Anna , Segev Idan , Tsodyks Misha , Stricker Christian
Published: March 2004

Synaptic transmission between pairs of excitatory neurones in layers V (N= 38) or IV (N= 6) of somatosensory cortex was examined in a parasagittal slice preparation obtained from young Wistar rats (14–18 days old). A combined experimental and theoretical approach reveals two characteristics of short‐term synaptic depression. Firstly, as well as a release‐dependent depression, there is a release‐independent component that is evident in smaller postsynaptic responses even following failure to release transmitter. Secondly, recovery from depression is activity dependent and is faster at higher input frequencies. Frequency‐dependent recovery is a Ca2+‐dependent process and does not reflect an underlying augmentation. Frequency‐dependent recovery and release‐independent depression are correlated, such that at those connections with a large amount of release‐independent depression, recovery from depression is faster. In addition, both are more pronounced in experiments performed at physiological temperatures. Simulations demonstrate that these homeostatic properties allow the transfer of rate information at all frequencies, essentially linearizing synaptic responses at high input frequencies.
Effects of aerobic training on pyruvate dehydrogenase and pyruvate dehydrogenase kinase in human skeletal muscle
Authors: LeBlanc Paul J. , Peters Sandra J. , Tunstall Rebecca J. , Cameron‐Smith David , Heigenhauser George J. F.
Published: March 2004

This study examined the effects of short‐ and long‐term aerobic training on the stable up‐regulation of pyruvate dehydrogenase (PDH) and PDH kinase (PDK) in human skeletal muscle. We hypothesized that 8 weeks, but not 1 week, of aerobic training would increase total PDH (PDHt) and PDK activities compared to pretraining, and this would be detectable at the level of gene transcription (mRNA) and/or gene translation (protein). Resting muscle biopsies were taken before and after 1 and 8 weeks of aerobic cycle exercise training. PDHt and PDK activities, and their respective protein and mRNA expression, did not differ after 1 week of aerobic training. PDHt activity increased 31% after 8 weeks and this may be partially due to a 1.3‐fold increase in PDH‐E1α protein expression. PDK activity approximately doubled after 8 weeks of aerobic training and this was attributed to a 1.3‐fold increase in PDK2 isoform protein expression. Similar to 1 week, no changes were observed at the mRNA level after 8 weeks of training. These findings suggest that aerobically trained human skeletal muscle has an increased maximal capacity to utilize carbohydrates, evident by increased PDHt, but increased metabolic control sensitivity to pyruvate through increased contribution of PDK2 to total PDK activity.
A voltage‐dependent K+ current contributes to membrane potential of acutely isolated canine articular chondrocytes
Authors: Wilson Jim R. , Duncan Neil A. , Giles Wayne R. , Clark Robert B.
Published: March 2004

The electrophysiological properties of acutely isolated canine articular chondrocytes have been characterized using patch‐clamp methods. The ‘steady‐state’ current–voltage relationship (I–V) of single chondrocytes over the range of potentials from −100 to +40 mV was highly non‐linear, showing strong outward rectification positive to the zero‐current potential. Currents activated at membrane potentials negative to −50 mV were time independent, and the I–V from −100 to −60 mV was linear, corresponding to an apparent input resistance of 9.3 ± 1.4 GΩ (n= 23). The outwardly rectifying current was sensitive to the K+ channel blocking ion tetraethylammonium (TEA), which had a 50% blocking concentration of 0.66 mm (at +50 mV). The ‘TEA‐sensitive’ component of the outwardly rectifying current had time‐ and membrane potential‐dependent properties, activated near −45 mV and was half‐activated at −25 mV. The reversal potential of the ‘TEA‐sensitive’ current with external K+ concentration of 5 mm and internal concentration of 145 mm, was −84 mV, indicating that the current was primarily carried by K+ ions. The resting membrane potential of isolated chondrocytes (−38.1 ± 1.4 mV; n= 19) was depolarized by 14.8 ± 0.9 mV by 25 mm TEA, which completely blocked the K+ current of these cells. These data suggest that this voltage‐sensitive K+ channel has an important role in regulating the membrane potential of canine articular chondrocytes.
Altered properties of volume‐sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3‐/‐ mice
Authors: Yamamoto‐Mizuma Shintaro , Wang Ge‐Xin , Liu Luis L. , Schegg Kathleen , Hatton William J. , Duan Dayue , Horowitz Burton , Lamb Fred S. , Hume Joseph R.
Published: March 2004

ClC‐3, a member of the large superfamily of ClC voltage‐dependent Cl– channels, has been proposed as a molecular candidate responsible for volume‐sensitive osmolyte and anion channels (VSOACs) in some cells, including heart and vascular smooth muscle. However, the reported presence of native VSOACs in at least two cell types from transgenic ClC‐3 disrupted (Clcn3−/−) mice casts considerable doubt on this proposed role for ClC‐3. We compared several properties of native VSOACs and examined mRNA transcripts and membrane protein expression profiles in cardiac and pulmonary arterial smooth muscle cells from Clcn3+/+ and Clcn3−/− mice to: (1) test the hypothesis that native VSOACs are unaltered in cells from Clcn3−/− mice, and (2) test the possibility that targeted inactivation of the Clcn3 gene using a conventional murine global knock‐out approach may result in compensatory changes in expression of other membrane proteins. Our experiments demonstrate that VSOAC currents in myocytes from Clcn3+/+ and Clcn3−/− mice are remarkably similar in terms of activation and inactivation kinetics, steady‐state current densities, rectification, anion selectivity (I− > Cl−≫ Asp−) and sensitivity to block by glibenclamide, niflumic acid, DIDS and extracellular ATP. However, additional experiments revealed several significant differences in other fundamental properties of native VSOACs recorded from atrial and smooth muscle cells from Clcn3−/− mice, including: differences in regulation by endogenous protein kinase C, differential sensitivity to block by anti‐ClC‐3 antibodies, and differential sensitivities to [ATP]i and free [Mg2+]i. These results suggest that in response to Clcn3 gene deletion, there may be compensatory changes in expression of other proteins that alter VSOAC channel subunit composition or associated regulatory subunits that give rise to VSOACs with different properties. Consistent with this hypothesis, in atria from Clcn3−/− mice compared to Clcn3+/+ mice, quantitative analysis of ClC mRNA expression levels revealed significant increases in transcripts for ClC‐1, ClC‐2, and ClC‐3, and protein expression profiles obtained using two‐dimensional polyacrylamide gel electrophoresis revealed complex changes in at least 35 different unidentified membrane proteins in cells from Clcn3−/− mice. These findings emphasize that caution needs to be exercised in simple attempts to interpret the phenotypic consequences of conventional global Clcn3 gene inactivation.
Physiological mechanisms of lysophosphatidylcholine‐induced de‐ramification of murine microglia
Authors: Schilling Tom , Lehmann Frank , Rückert Berit , Eder Claudia
Published: March 2004

Activation of microglial cells, the resident macrophages of the brain, occurs rapidly following brain injury. De‐ramification, i.e. transformation from ramified into amoeboid morphology is one of the earliest manifestations of microglial activation. In the present study, we identified the physiological mechanisms underlying microglial de‐ramification induced by lysophosphatidylcholine (LPC). Patch‐clamp experiments revealed activation of non‐selective cation currents and Ca2+‐dependent K+ currents by extracellular LPC. LPC‐activated non‐selective cation channels were permeable for monovalent and divalent cations. They were inhibited by Gd3+, La3+, Zn2+ and Grammostola spatulata venom, but were unaffected by diltiazem, LOE908MS, amiloride and DIDS. Ca2+ influx through non‐selective cation channels caused sustained increases in intracellular Ca2+ concentration. These Ca2+ increases were sufficient to elicit charybdotoxin‐sensitive Ca2+‐dependent K+ currents. However, increased [Ca2+]i was not required for LPC‐induced morphological changes. In LPC‐stimulated microglial cells, non‐selective cation currents caused transient membrane depolarization, which was followed by sustained membrane hyperpolarization induced by Ca2+‐dependent K+ currents. Furthermore, LPC elicited K+ efflux by stimulating electroneutral K+–Cl− cotransporters, which were inhibited by furosemide and DIOA. LPC‐induced microglial de‐ramification was prevented by simultaneous inhibition of non‐selective cation channels and K+–Cl− cotransporters, suggesting their functional importance for microglial activation.
Characterization of a hyperpolarization‐activated time‐dependent potassium current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium
Authors: Ehrlich Joachim R. , Cha Tae‐Joon , Zhang Liming , Chartier Denis , Villeneuve Louis , Hébert Terence E. , Nattel Stanley
Published: March 2004

Cardiomyocytes from the pulmonary vein sleeves (PVs) are known to play an important role in atrial fibrillation. PVs have been shown to exhibit time‐dependent hyperpolarization‐induced inward currents of uncertain nature. We observed a time‐dependent K+ current upon hyperpolarization of PV and left atrial (LA) cardiomyocytes (IKH) and characterized its biophysical and pharmacological properties. The activation time constant was weakly voltage dependent, ranging from 386 ± 14 to 427 ± 37 ms between −120 and −90 mV, and the half‐activation voltage averaged −93 ± 4 mV. IKH was larger in PV than LA cells (e.g. at −120 mV: −2.8 ± 0.3 versus−1.9 ± 0.2 pA pF−1, respectively, P < 0.01). The reversal potential was ∼−84 mV with 5.4 mm[K+]o and changed by 55.7 ± 2.4 mV per decade [K+]o change. IKH was exquisitely Ba2+ sensitive, with a 50% inhibitory concentration (IC50) of 2.0 ± 0.3 μm (versus 76.0 ± 17.9 μm for instantaneous inward‐rectifier current, P < 0.01), and showed similar Cs+ sensitivity to instantaneous current. IKH was potently blocked by tertiapin‐Q, a selective Kir3‐subunit channel blocker (IC50 10.0 ± 2.1 nm), was unaffected by atropine and was significantly increased by isoproterenol (isoprenaline), carbachol and the non‐hydrolysable guanosine triphosphate analogue GTPγS. IKH activation by carbachol required GTP in the pipette and was prevented by pertussis toxin pretreatment. Tertiapin‐Q delayed repolarization in atropine‐exposed multicellular atrial preparations studied with standard microelectrodes (action potential duration pre‐ versus post‐tertiapin‐Q: 190.4 ± 4.3 versus 234.2 ± 9.9 ms, PV; 202.6 ± 2.6 versus 242.7 ± 6.2 ms, LA; 2 Hz, P < 0.05 each). Seven‐day atrial tachypacing significantly increased IKH (e.g. at −120 mV in PV: from −2.8 ± 0.3 to −4.5 ± 0.5 pA pF−1, P < 0.01). We conclude that IKH is a time‐dependent, hyperpolarization‐activated K+ current that likely involves Kir3 subunits and appears to play a significant role in atrial physiology.
Developmental plasticity of the hypoxic ventilatory response in rats induced by neonatal hypoxia
Authors: Bavis R. W. , Olson E. B. , Vidruk E. H. , Fuller D. D. , Mitchell G. S.
Published: March 2004

Neonatal hypoxia alters the development of the hypoxic ventilatory response in rats and other mammals. Here we demonstrate that neonatal hypoxia impairs the hypoxic ventilatory response in adult male, but not adult female, rats. Rats were raised in 10% O2 for the first postnatal week, beginning within 12 h after birth. Subsequently, ventilatory responses were assessed in 7‐ to 9‐week‐old unanaesthetized rats via whole‐body plethysmography. In response to 12% O2, male rats exposed to neonatal hypoxia increased ventilation less than untreated control rats (mean ±s.e.m. 35.2 ± 7.7%versus 67.4 ± 9.1%, respectively; P= 0.01). In contrast, neonatal hypoxia had no lasting effect on hypoxic ventilatory responses in female rats (67.9 ± 12.6%versus 61.2 ± 11.7% increase in hypoxia‐treated and control rats, respectively; P > 0.05). Normoxic ventilation was unaffected by neonatal hypoxia in either sex at 7–9 weeks of age (P > 0.05). Since we hypothesized that neonatal hypoxia alters the hypoxic ventilatory response at the level of peripheral chemoreceptors or the central neural integration of chemoafferent activity, integrated phrenic responses to isocapnic hypoxia were investigated in urethane‐anaesthetized, paralysed and ventilated rats. Phrenic responses were unaffected by neonatal hypoxia in rats of either sex (P > 0.05), suggesting that neonatal hypoxia‐induced plasticity occurs between the phrenic nerve and the generation of airflow (e.g. neuromuscular junction, respiratory muscles or respiratory mechanics) and is not due to persistent changes in hypoxic chemosensitivity or central neural integration. The basis of sex differences in this developmental plasticity is unknown.
SUR2A C‐terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes
Authors: Rainbow R. D. , Lodwick D. , Hudman D. , Davies N. W. , Norman R. I. , Standen N. B.
Published: March 2004

C‐terminal fragments of the sulphonylurea receptor SUR2A can alter the functional expression of cloned ATP‐sensitive K+ channels (KATP). To investigate the protective role of KATP channels during metabolic stress we transfected SUR2A fragments into adult rat cardiac myocytes. A fragment comprising residues 1294–1358, the A‐fragment, reduced sarcolemmal KATP currents by over 85% after 2 days (pinacidil‐activated current densities were: vector alone 7.04 ± 1.22; and A‐fragment 0.94 ± 0.07 pA pF−1, n= 6,6, P < 0.001). An inactive fragment (1358–1545, current density 6.30 ± 0.85 pA pF−1, n= 6) was used as a control. During metabolic inhibition (CN and iodoacetate) of isolated myocytes stimulated at 1 Hz, the A‐fragment delayed action potential shortening and contractile failure, but accelerated rigor contraction and increased Ca2+ loading. On reperfusion, A‐fragment‐transfected cells also showed increased intracellular Ca2+ and the proportion of cells recovering contractile function was reduced from 40.0 to 9.5% (P < 0.01). The protective effect of pretreatment with 2,4‐dinitrophenol, measured from increased functional recovery and reduced Ca2+ loading, was abolished by the A‐fragment. Our data are consistent with a role for KATP channels in causing action potential failure and reduced Ca2+ loading during metabolic stress, and with a major role in protection by preconditioning. The effects of the A‐fragment may arise entirely from reduced expression of the sarcolemmal KATP channel, but we also discuss the possibility of mitochondrial effects.
Direct evidence for the contribution of the superior colliculus in the control of visually guided reaching movements in the cat
Authors: Courjon Jean‐Hubert , Olivier Etienne , Pélisson Denis
Published: March 2004

The production of visually guided reaching movements relies on a large neural network. Based on indirect experimental evidence, it has been suggested that the superior colliculus, a subcortical centre known for its key role in controlling rapid orienting gaze shifts, also belongs to this network. The aim of the present study was to investigate the role of the cat superior colliculus (SC) in the control of visually guided reaching movements. To address this issue, we studied the effect of SC electrical stimulation on forelimb reaching movements in two cats trained to catch a piece of food. Electrical stimulation delivered just after the movement onset yielded a consistent perturbation of the movement trajectory of the forelimb extremity. This perturbation followed stimulation onset by 56 ± 11 ms on average, and consisted of a deviation of the spatial path and a deceleration of the movement. The forelimb perturbation was elicited in the absence of concomitant gaze or head displacement in 52% of the stimulation trials. Forelimb perturbations were followed by in‐flight adjustments so that reaching movements reliably ended on the target. The present results constitute the first behavioural evidence for a contribution of the cat SC to the control of visually guided forelimb movements.
Cyclooxygenase‐2 contributes to dysmotility and enhanced excitability of myenteric AH neurones in the inflamed guinea pig distal colon
Authors: Linden David R. , Sharkey Keith A. , Ho Winnie , Mawe Gary M.
Published: March 2004

We have previously demonstrated that trinitrobenzene sulphonic acid (TNBS)‐induced colitis in guinea pig is associated with hyperexcitability of myenteric AH neurones, enhanced synaptic activity in the myenteric plexus, increased serotonin (5‐HT) availability in the mucosa, and decreased propulsive motor activity. The current study tested the hypothesis that the activation of cyclooxygenase (COX) contributes to these alterations in bowel functions. DFU inhibition of COX‐2, but not SC‐560 inhibition of COX‐1, restored to normal levels the electrical properties of myenteric AH neurones, the proportion of S neurones exhibiting slow EPSPs, and the rate of propulsive motor activity. Neither inhibitor was effective in altering the level of inflammation, the increased availability of mucosal 5‐HT, or the enhanced fast EPSPs in myenteric AH and S neurones. COX‐2 expression is enhanced in the myenteric plexus and cells within the smooth muscle layers during colitis, possibly reflecting the site at which COX‐2 inhibition acts to allow recovery of motor function. In support of this concept, COX‐1, but not COX‐2, inhibition was effective in restoring normal mucosal prostaglandin levels. These results indicate that the various changes that occur in the motor neural pathways of the distal colon in TNBS‐induced colitis do not involve a single neuroimmune mechanism. COX‐2 activation is a critical step in the enhanced excitability of AH neurones as well as diminished propulsive motility in TNBS colitis, whereas other yet to be resolved pathways, that do not involve COX‐1 or COX‐2 activation, lead to altered 5‐HT content in the mucosa and an augmentation of fast EPSPs.
CaT1 knock‐down strategies fail to affect CRAC channels in mucosal‐type mast cells
Authors: Kahr Heike , Schindl Rainer , Fritsch Reinhard , Heinze Barbara , Hofbauer Michael , Hack Marlene E. , Mörtelmaier Manuel A. , Groschner Klaus , Peng Ji‐Bin , Takanaga Hitomi , Hediger Matthias A. , Romanin Christoph
Published: March 2004

CaT1, the calcium transport protein 1 encoded by TRPV6, is able to generate a Ca2+ conductance similar but not identical to the classical CRAC current in mucosal‐type mast cells. Here we show that CaT1‐derived Ca2+ entry into HEK293 cells is effectively inhibited either by expression of various dominant negative N‐terminal fragments of CaT1 (N334‐CaT1, N198‐CaT1 and N154‐CaT1) or by antisense suppression. By contrast, the endogenous CRAC current of the mast cells was unaffected by CaT1 antisense and siRNA knockdown but markedly suppressed by two (N334‐CaT1, N198‐CaT1) of the dominant negative N‐CaT1 fragments. Inhibition of CRAC current was not an unspecific, toxic effect, as inward rectifier K+ and MagNuM currents of the mast cells were not significantly affected by these N‐CaT1 fragments. The shortest N154‐CaT1 fragment inhibited CaT1‐derived currents in mast cells, but failed to inhibit CRAC currents. Thus, the structural requirements of rCaT N‐terminal fragments for inhibition of rCaT1 and CRAC channels are different. These results together with the lack of CaT1 antisense and siRNA effects on currents render it unlikely that CaT1 is a component of native CRAC channels in mast cells. The data further demonstrate a novel strategy for CRAC current inhibition by an N‐terminal structure of CaT1.
Design of a Lightweight Hyper-Redundant Deployable Binary Manipulator
Authors: Sujan Vivek A. , Dubowsky Steven
Published: March 2004

This paper presents the design of a new lightweight, hyper-redundant, deployable Binary Robotic Articulated Intelligent Device (BRAID), for space robotic systems. The BRAID is intended to meet the challenges of future space robotic systems that need to perform more complex tasks than are currently feasible. It is lightweight, has a high degree of freedom, and has a large workspace. The device is based on embedded muscle type binary actuators and flexure linkages. Such a system may be used for a wide range of tasks, and requires minimal control computation and power resources.
Mobility Analysis of a Class of RPSPR Kinematic Chains
Authors: DasGupta Anirvan
Published: March 2004

This paper presents mobility analysis and type identification of a class of RPSPR kinematic chains with zero twist on any one of the links carrying a revolute and prismatic pairs. Conditions for detecting the presence of crank at any of the revolute pairs of the chain are derived. The mobility conditions have very interesting geometric interpretations which are used to identify the mechanism type. Based on the geometric conditions, sufficient conditions of rotatability have also been derived.
On the Determination of Basic Dimensions of a Cam With a Translating Roller-Follower
Authors: DasGupta Anirvan , Ghosh Amitabha
Published: March 2004

The problem of determination of basic dimensions from the point of view of follower jamming of a cam with translating roller-follower is addressed. Departing from the common practice of using only a constant pressure angle to assess jamming of the follower in its guide, this paper presents a detailed analysis of the problem taking into consideration the follower-guide friction. This leads to new bounds on the pressure angle. Based on the bounds obtained, a graphical method for determination of the optimal values of the basic dimensions is proposed. A numerical example is presented for the purpose of illustration.
Mobility Analysis of a Novel 3-5R Parallel Mechanism Family
Authors: Li Q. C. , Huang Z.
Published: March 2004

Mobility analysis of a novel 3-5R parallel mechanism family whose limb consists of a 2R and a 3R parallel subchain is performed by the aid of screw theory. A mobility criterion applicable to such 3-leg parallel mechanisms in which each kinematic chain contains five kinematic pairs is proposed. It is shown that under different structural conditions, the 3-5R parallel mechanism can have 3, 4, or 5 DOF (degrees of freedom). The structural conditions that guarantee the full-cycle mobility are analyzed. The analysis and the method presented in this paper will be helpful in using such a 3-5R parallel mechanism family and introduce new insights into the mobility analysis of parallel mechanisms.
Two Basic Features of Instantaneous Conjugate Motion and Their Importance in Facilitating Motion Analysis
Authors: Chen Chih-Hsin , Chen Janet Hong-Jian
Published: March 2004

Two basic features of instantaneous conjugate motion, which distinguishes it from instantaneous free body motion, are pointed out. Their influences on the geometrical constraints requisite for surface/line conjugation are discussed. Their importance in facilitating motion analysis of mechanical systems through linearization of relevant equations is clarified. Two illustrative examples are cited.
A GA Based Configuration Design Optimization Method
Authors: Grignon Pierre M. , Fadel Georges M.
Published: March 2004

This work presents a methodology for optimizing multiple system level assembly characteristics of complex mechanical assemblies by placement of their components. It addresses any component shape (including nonconvex, hollow, sharp edges) connected together by functional constraints. This method presents the designer with multiple solutions to the engineering configuration design problem (ECDP) using a Pareto Genetic Algorithm working on a population of sets instead of a population of individual points and thus results in a more informed a posteriori decision on the tradeoff issues between the various objectives. This paper addresses the definition of the assembly components and their relationships (ECDP), the definition of the configuration design optimization method (CDOM), and shows the application of the CDOM to one academic and two engineering test cases.
Type Synthesis of 3-DOF Translational Parallel Manipulators Based on Screw Theory
Authors: Kong Xianwen , Gosselin Cle´ment M.
Published: March 2004

A method is proposed for the type synthesis of 3-DOF (degree-of-freedom) translational parallel manipulators (TPMs) based on screw theory. The wrench systems of a translational parallel kinematic chain (TPKC) and its legs are first analyzed. A general procedure is then proposed for the type synthesis of TPMs. The type synthesis of legs for TPKCs, the type synthesis of TPKCs as well as the selection of actuated joints of TPMs are dealt with in sequence. An approach to derive the full-cycle mobility conditions for legs for TPKCs is proposed based on screw theory and the displacement analysis of serial kinematic chains undergoing small joint motions. In addition to the TPKCs proposed in the literature, TPKCs with inactive joints are synthesized. The phenomenon of dependent joint groups in a TPKC is revealed systematically. The validity condition of actuated joints of TPMs is also proposed. Finally, linear TPMs, which are TPMs whose forward displacement analysis can be performed by solving a set of linear equations, are also revealed.
Layout Optimization of Shapeable Components With Extended Pattern Search Applied to Transmission Design
Authors: Yin Su , Cagan Jonathan , Hodges Peter
Published: March 2004

An extended pattern search algorithm is presented for the placement of shapeable components within a product layout. Shapeable octrees are used to evaluate the amount of overlap between pairs of components, extending previous technology that requires fixed-size components. The method is used to conceptualize the layout of the cross-section of an automatic transmission.
Locally Linearized Dynamic Analysis of Parallel Manipulators and Application of Input Shaping to Reduce Vibrations
Authors: Kozak Kris , Ebert-Uphoff Imme , Singhose William
Published: March 2004

Input Shaping is a technique that seeks to reduce residual vibrations through modification of the reference command given to a system. Namely the reference command is convolved with a suitable train of impulses. Input shaping has proven to be successful in reducing the vibrations of a great variety of linear systems. This article seeks to apply input shaping to robotic manipulators of parallel architecture. Such systems have multiple degrees-of-freedom and non-linear dynamics and therefore standard input shaping techniques cannot be readily applied. In order to apply standard input shaping techniques to such systems, this article linearizes the dynamic equations of the system locally and determines the configuration-dependent natural frequencies and damping ratios throughout its workspace. Techniques are developed to derive the dynamic equations directly in linearized form. The method is demonstrated for a sample manipulator with two degrees-of-freedom. A linearized dynamic model is derived and input shaping is locally tuned according to the linearized dynamic model. Simulation results are provided and discussed.
Modeling of Swash Plate Axial Piston Pumps With Conical Cylinder Blocks
Authors: Khalil M. K. Bahr , Svoboda J. , Bhat R. B.
Published: March 2004

Electrically controlled swash plate axial piston pumps with conical cylinder blocks are recently used in the industry in view of their superior performance. Several studies have been carried out to study the characteristics of such novel pump mechanism. In these studies, partial mathematical modeling is conducted relevant to the points discussed. In the present study, a comprehensive pump mathematical model is developed and experimentally validated. The model could be used as a design tool in order to fully exploit the advantages of the new design.
An Agent Based Optimization Approach to Manufacturing Process Planning
Authors: Deshpande Saurabh , Cagan Jonathan
Published: March 2004

Many optimization problems, such as manufacturing process planning optimization, are difficult problems due to the large number of potential configurations (process sequences) and associated (process) parameters. In addition, the search space is highly discontinuous and multi-modal. This paper introduces an agent based optimization algorithm that combines stochastic optimization techniques with knowledge based search. The motivation is that such a merging takes advantage of the benefits of stochastic optimization and accelerates the search process using domain knowledge. The result of applying this algorithm to computerized manufacturing process models is presented.
Kinematic Analysis and Design of Kinematically Redundant Parallel Mechanisms
Authors: Wang Jing , Gosselin Cle´ment M.
Published: March 2004

This paper addresses the singularity analysis and the design of three new types of kinematically redundant parallel mechanisms, i.e., the four-degree-of-freedom planar and spherical parallel mechanisms and the seven-degree-of-freedom spatial Stewart platform. The main idea in the design of these parallel manipulators is the addition of one redundant degree of freedom in one of the kinematic chains of the nonredundant manipulator. Such manipulators can be used to avoid the singularities inside the workspace of nonredundant manipulators. After describing the geometry of the manipulators, the velocity equations are derived and the expressions for the Jacobian matrices are obtained. Then, the singularity conditions are discussed. Finally, the expressions of the singularity loci of the kinematically redundant mechanisms are obtained and the singularity loci of the nonredundant and redundant manipulators are compared. It is shown here that the conditions for the singularity of the redundant manipulators are reduced drastically relative to the nonredundant ones. As a result, the proposed kinematically redundant parallel manipulators may be of great interest in several applications.