bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexor Origin Release and Functional Prehension in Adult Spastic Hand Deformity
Authors: PINZUR M. S.
Published: August 2005

Eighteen adult patients with spastic hand deformities underwent release of the flexor-pronator origin and step-cut lengthening of the flexor pollicis longus to improve prehensile hand function. The goal of surgery was to provide active grasp release in order to improve hand function. Using a previously published grading scale, patients were graded before and after operation. At follow-up after an average of 35 months (range 24–64 months), all had improved by at least two functional levels.
Pollicisation of the Index Finger in Congenital Anomalies
Authors: SYKES P. J. , CHANDRAPRAKASAM T. , PERCIVAL N. J.
Published: August 2005

Between 1977 and 1988, 30 pollicisations were performed on 22 children with hypoplasia or aplasia of the thumb. A review was undertaken to grade the results. 73% were graded good or excellent, 17% fair and ten % poor. 36% required secondary surgery to achieve a satisfactory result. Better results were obtained in Blauth III or IV deformities, with poorer outcomes in Blauth V or patients with associated radial hypoplasia. Good functional and cosmetic results were found in patients operated upon at an early age. The presence of previously unreported bony spikes was a significant cause of poor mobility and was amenable to secondary surgery.
Free Toe Pulp Transfer in Thumb Reconstruction
Authors: RATCLIFFE R. J. , McGROUTHER D. A.
Published: August 2005

We report a detailed evaluation of 13 patients who have undergone free toe pulp transfer in thumb reconstruction at the West of Scotland Regional Plastic Surgery Unit. Using the lateral aspect of the great toe pulp, the average time for transfer was 7.5 hours and the average moving 2 P.D. achieved in the thumb reconstructions was 9.6 mm. Morbidity in the donor toe was minimal, but pain and hypersensitivity limited the usefulness of some reconstructed thumbs and cold intolerance was frequent (73%).
Reconstruction of the Distal Phalanx of the Fingers by Free Toe-to-Hand Transfer
Authors: ŠPOKEVIČIUS S. , VITKUS K.
Published: August 2005

Anatomical examination of the blood-vessels in the distal phalanges of the foot show that the arteries and veins of this region are thick enough to be anastomosed by microsurgical means. This makes it possible to perform free toe-to-hand transfer, reconstructing defects of the distal phalanx and suturing arteries and veins at the level of the middle or even distal phalanxes. Eleven distal parts of the fingers have been reconstructed. All the transfers were successful, and good cosmetic and functional results were obtained.
Simultaneous Carpal Tunnel Release and Dupuytren’s Fasciectomy
Authors: GONZALEZ F. , WATSON H. KIRK
Published: August 2005

Simultaneous operations for carpal tunnel syndrome and Dupuytren’s disease have been reported in only one study which recommended staged treatment because there was an 87% complication rate with simultaneous treatment. The present study reviewed simultaneous treatment of 30 patients during a 20-year period. Complications and unfavourable results were compared to similar groups of patients who underwent either Dupuytren’s fasciectomy or carpal tunnel release as sole procedures. Early complications (13%) were far less than in previous studies and were easily corrected. The incidence of recurrence and extension (20%) was lower than in the Dupuytren’s fasciectomy group and much lower than in previous reports. Simultaneous carpal tunnel release and Dupuytren’s fasciectomy are strongly recommended when these conditions are both present in the same hand.
Heterotopic Ossification in a Finger Following Head Injury
Authors: SPENCER R. F.
Published: August 2005

A case of digital periarticular heterotopic ossification is described. Such cases are extremely rare and diagnosis may be delayed. Spasticity, possibly in association with minor trauma, may contribute to the development of the process. Little experience exists of the management of such problems and a mobile joint may be difficult to achieve.
Neuro‐hormonal activation predicts ventilatory response to exercise and functional capacity in patients with heart failure
Authors: Passino Claudio , Poletti Roberta , Bramanti Francesca , Prontera Concetta , Clerico Aldo , Emdin Michele
Published: August 2005

Background:

Heart failure (HF) is characterised by reduced tolerance to effort, associated with progressive fatigue and dyspnoea. Neuro‐hormonal activation is a hallmark of HF and influences its clinical evolution.

Aim:

To evaluate the relationship between neuro‐hormonal activation, exercise capacity and ventilatory efficiency.

Methods and results:

154 HF patients (127 males, 62±1 years) underwent cardiopulmonary exercise testing and resting blood sampling for assay of plasma brain natriuretic peptide (BNP), NT‐proBNP, norepinephrine, epinephrine, aldosterone and plasma renin activity (PRA). BNP and NT‐proBNP levels correlated with peak oxygen consumption (VO2) (both R=−0.53, p<0.001), VE/VCO2 slope (R=0.56; p<0.001 and R=0.58; p<0.001, respectively) and maximum workload (R=−0.49; p<0.001 and R=−0.47; p<0.001, respectively). Norepinephrine correlated slightly less with peak VO2 (R=−0.38, p<0.001), VE/VCO2 (R=0.45; p<0.001) and maximum workload (R=−0.35; p<0.001). There was a significant inverse correlation between left ventricular ejection fraction and BNP (R=−0.48, p<0.001), NT‐proBNP (R=−0.42; p<0.001) and norepinephrine (R=−0.43; p<0.001). Weaker correlations were found for PRA, exercise parameters and ejection fraction. ROC curves showed that BNP was able to identify patients with peak VO2<14 ml/min/kg (cut‐off 98 pg/ml, AUC 0.775) and a VE/VCO2>35 (cut‐off 183 pg/ml, AUC 0.797), as well as NT‐proBNP (cut‐off 537 pg/ml, AUC 0.799 and cut‐off 1010 pg/ml, AUC 0.768, respectively) and norepinephrine (cut‐off 454 pg/ml, AUC 0.716 and cut‐off 575 pg/ml, AUC 0.783, respectively).

Conclusion:

Haemodynamic impairment (as indicated by BNP and NT‐proBNP plasma values) and sympathetic activation predict exercise capacity and ventilatory efficiency in HF patients.
Circulating levels of tumor necrosis factor‐α correlate positively with severity of peripheral oedema in patients with right heart failure
Authors: Odeh Majed , Sabo Edmond , Oliven Arie
Published: August 2005

Background:

Several previous studies have shown that circulating levels of tumor necrosis factor‐α (TNF) are elevated in patients with advanced congestive heart failure. However, the relationship between circulating levels of TNF and severity of peripheral oedema in these patients has not been previously evaluated.

Aims:

To investigate the relationship between circulating levels of TNF, and severity of peripheral oedema in patients with right‐sided heart failure (RHF).

Methods and results:

Circulating levels of TNF were measured in 15 healthy volunteers, and in 83 patients with RHF with various levels of peripheral oedema. At presentation, 13 patients had no peripheral oedema (grade 0), 22 patients had mild peripheral oedema (grade 1), 23 patients had moderate peripheral oedema (grade 2), and 25 patients had severe peripheral oedema (grade 3). The values of circulating TNF levels (mean±S.E.M.) at presentation in the control group and in the RHF patients (oedema grades 0—3) were 2.98±0.21, 4.22±0.55, 4.67±0.29, 7.66±0.44, and 10.94±0.67 pg/mL respectively. There was a significant difference between the groups (p<0.0001, ANOVA), and a significant positive correlation was found between circulating TNF levels and severity of peripheral oedema (r=0.77, p<0.0001).

Conclusion:

A significant relationship is present between circulating levels of TNF and severity of peripheral oedema in patients with RHF.
Activation of the NF‐κB system in peripheral blood leukocytes from patients with chronic heart failure
Authors: Jankowska Ewa A. , von Haehling Stephan , Czarny Anna , Zaczynska Ewa , Kus Agnieszka , Anker Stefan D. , Banasiak Waldemar , Ponikowski Piotr
Published: August 2005

Aim:

To evaluate the activation of transcriptional nuclear factor kappa‐B (NF‐κB) in peripheral blood leukocytes (PBL) from patients with chronic heart failure (CHF). In vitro experiments were used to elucidate the role of lipopolysaccharide (LPS) as a stimulus for the NF‐κB system in PBL.

Methods and results:

We examined 46 CHF patients (age: 62±1 years, LVEF: 31±1%, NYHA class: 2.7±0.1), 11 coronary artery disease (CAD) patients without CHF, and 13 healthy young subjects. The immunocytochemical localisation of NF‐κB in PBL was assessed using a polyclonal rabbit IgG anti‐c‐Rel‐subunit antibody. NF‐κB activation was expressed as the percentage of PBL nuclei stained positively for c‐Rel (NF‐κB(+)cell). PBL from healthy controls were exposed in vitro to the following concentrations of LPS from Escherichia coli (strain O111:B4): 0.1, 10 and 5000 ng/mL. CHF patients demonstrated the highest NF‐κB activation in PBL (NF‐κB(+)cells [%]: 37.1±1.5) as compared to CAD patients (29.1±3.0%) and controls (12.6±1.5%) (all p<0.05). There were three main clinical determinants of NF‐κB activation in PBL from CHF patients: peak oxygen consumption (r=0.53, p=0.025), presence of peripheral oedema (r=0.37, p<0.05) and serum C‐reactive protein (r=0.40, p=0.02). In PBL from healthy subjects, LPS at all concentrations increased NF‐κB activity towards the pattern detected in CHF.

Conclusions:

The NF‐κB system is highly overactive in PBL from CHF patients. LPS at low concentrations in peripheral blood may be involved in NF‐κB activation in PBL, and is a potential target for future therapeutic applications.
The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule
Authors: Bork Kaya , Reutter Werner , Gerardy-Schahn Rita , Horstkorte Rüdiger
Published: August 2005

Sialic acids are expressed as terminal sugars in many glycoconjugates and play an important role during development and regeneration, as they are involved as polysialic acid in a variety of cell–cell interactions mediated by the neural cell adhesion molecule NCAM. The key enzyme for the biosynthesis of sialic acid is the UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine‐kinase (GNE). Mutations in the binding site of the feedback inhibitor CMP‐sialic acid of the GNE leads to sialuria, a disease in which patients produce sialic acid in gram scale. Here, we report on the consequences after expression of a sialuria‐mutated GNE. Expression of the sialuria‐mutated GNE leads to a dramatic increase of both cellular sialic acid and polysialic acid on NCAM. This could also be achieved by application of the sialic acid precursor N‐acetylmannosamine. Our data suggest that biosynthesis of sialic acid regulates and limits the synthesis of polysialic acid.
Arthroscopic Triangular Fibrocartilage Complex Debridement Using Radiofrequency Probes
Authors: DARLIS N. A. , WEISER R. W. , SOTEREANOS D. G.
Published: August 2005

The initial results of using radiofrequency probes for debridement of a torn triangular fibrocartilage complex were studied in 20 patients with a mean age of 44 (range 27–56) years presenting with ulnar-sided wrist pain. On arthroscopic examination, 18 central and two radial triangular fibrocartilage complex tears were identified and debrided to a stable rim using radiofrequency probes. The mean follow-up was 22 (range 9–35) months. Seventeen patients experienced substantial pain relief. In three, the pain was unchanged. The mean flexion extension arc was 132°, pronosupination arc 155° and mean grip strength was 83% of that of the unaffected side. Using the modified Mayo wrist score, there were ten excellent, seven good and three fair results. No perioperative complications occurred. Radiofrequency probes were found to be safe and effective for use in triangular fibrocartilage complex debridement. These results compare favourably with other standard methods of treatment of this problem.
Focal adhesions as mechanosensors: A physical mechanism
Authors: Shemesh Tom , Geiger Benjamin , Bershadsky Alexander D. , Kozlov Michael M.
Published: August 2005

Focal adhesions (FA) are large, multiprotein complexes that provide a mechanical link between the cytoskeletal contractile machinery and the extracellular matrix. FA exhibit mechanosensitive properties; they self-assemble and elongate upon application of pulling forces and dissociate when these forces are decreased. We propose a thermodynamic model for the mechanosensitivity of FA, according to which a molecular aggregate, subjected to pulling forces, tends to grow in the direction of force application by incorporating additional molecules. We demonstrate that this principle is consistent with the phenomenology of FA dynamics by considering a one-dimensional protein aggregate subjected to pulling forces and anchored to the substrate. Depending on the force level, force distribution along the aggregate, and the character of its anchoring to the substrate, the aggregate is predicted to exhibit distinct modes of assembly that are largely consistent with the experimentally observed FA behavior. We define here specific conditions that can lead to the different regimes of FA assembly, including growth, steady state, and disassembly.
Novel CIPK1-Associated Proteins in Arabidopsis Contain an Evolutionarily Conserved C-Terminal Region That Mediates Nuclear Localization
Authors: Ok Sung Han , Jeong Hye Jin , Bae Jung Myung , Shin Jeong-Sheop , Luan Sheng , Kim Kyung-Nam
Published: August 2005

Environmental stimuli, including light, pathogens, hormones, and abiotic stresses, elicit changes in the cytosolic Ca2+ signatures of plant cells. However, little is known about the molecular mechanisms by which plants sense and transmit the specific cytoplasmic Ca2+ signal into the nucleus, where gene regulation occurs to respond appropriately to the stress. In this study, we have identified two novel Arabidopsis (Arabidopsis thaliana) proteins specifically associated with Calcineurin B-Like-Interacting Protein Kinase1 (CIPK1), a member of Ser/Thr protein kinases that interact with the calcineurin B-like Ca2+-binding proteins. These two proteins contain a very similar C-terminal region (180 amino acids in length, 81% similarity), which is required and sufficient for both interaction with CIPK1 and translocation to the nucleus. Interestingly, the conserved C-terminal region was also found in many proteins from various eukaryotic organisms, including humans. However, none of them have been characterized so far. Taken together, these findings suggest that the two proteins containing the evolutionarily conserved C-terminal region (ECT1 and ECT2) may play a critical role in relaying the cytosolic Ca2+ signals to the nucleus, thereby regulating gene expression.
An Auxilin-Like J-Domain Protein, JAC1, Regulates Phototropin-Mediated Chloroplast Movement in Arabidopsis
Authors: Suetsugu Noriyuki , Kagawa Takatoshi , Wada Masamitsu
Published: August 2005

The ambient-light conditions mediate chloroplast relocation in plant cells. Under the low-light conditions, chloroplasts accumulate in the light (accumulation response), while under the high-light conditions, they avoid the light (avoidance response). In Arabidopsis (Arabidopsis thaliana), the accumulation response is mediated by two blue-light receptors, termed phototropins (phot1 and phot2) that act redundantly, and the avoidance response is mediated by phot2 alone. A mutant, J-domain protein required for chloroplast accumulation response 1 (jac1), lacks the accumulation response under weak blue light but shows a normal avoidance response under strong blue light. In dark-adapted wild-type cells, chloroplasts accumulate on the bottom of cells. Both the jac1 and phot2 mutants are defective in this chloroplast movement in darkness. Positional cloning of JAC1 reveals that this gene encodes a J-domain protein, resembling clathrin-uncoating factor auxilin at its C terminus. The amounts of JAC1 transcripts and JAC1 proteins are not regulated by light and by phototropins. A green fluorescent protein-JAC1 fusion protein showed a similar localization pattern to green fluorescent protein alone in a transient expression assay using Arabidopsis mesophyll cells and onion (Allium cepa) epidermal cells, suggesting that the JAC1 protein may be a soluble cytosolic protein. Together, these results suggest that JAC1 is an essential component of phototropin-mediated chloroplast movement.
Differential effects of trans‐crotononitrile and 3‐acetylpyridine on inferior olive integrity and behavioural performance in the rat
Authors: Seoane A. , Apps R. , Balbuena E. , Herrero L. , Llorens J.
Published: August 2005

The inferior olive climbing fibre projection is key to cerebellar contributions to motor control. Here we present evidence for a novel tool, trans‐crotononitrile (TCN), to selectively inactivate the olive to study its functions. Anatomical, electrophysiological and behavioural techniques have been used in rats to assess the CNS effects of TCN, with a focus on the olivocerebellar projection. These findings were compared with those obtained with 3‐acetylpyridine (plus nicotinamide administered 3.5 h later, 3AP + 3.5 h). Fluoro‐Jade B cell labelling showed that TCN and 3AP + 3.5 h induce neurodegeneration primarily within the inferior olive, with no other targets in common. Recordings of evoked field potentials on the cerebellar cortical surface showed that both neurotoxins can reduce transmission in climbing fibre but not mossy fibre pathways. Both histological and electrophysiological differences suggest that TCN and 3AP have distinct mechanisms of action. Estimates of the numbers of surviving cells within individual subdivisions of the olive indicate that TCN and 3AP + 3.5 h cause different patterns of subtotal olivary lesion: most surviving neurons are present in the rostral (TCN) or caudal (3AP + 3.5 h) parts of the medial accessory olive, which are associated with two different cerebellar modules: the C2 and A modules, respectively. In behavioural studies, TCN and 3AP + 3.5 h produced differences in motor deficits consistent with the notion that these cerebellar modules have distinct functional responsibilities. Thus, studies using TCN as compared with 3AP + 3.5 h have the potential to shed light on the contributions of different cerebellar modules in motor control.
Tissue‐specific expression of tryptophan hydroxylase mRNAs in the rat midbrain: anatomical evidence and daily profiles
Authors: Malek Zeina S. , Dardente Hugues , Pevet Paul , Raison Sylvie
Published: August 2005

Serotonin (5‐HT) is involved in both photic and non‐photic synchronization of the mammalian biological clock located in the suprachiasmatic nuclei (SCN). We have previously demonstrated that tryptophan hydroxylase protein (TPH), the rate‐limiting enzyme of 5‐HT synthesis, shows circadian rhythmicity in the pathways projecting from the raphe nuclei to the intergeniculate leaflets of the thalamus on one hand, and to the SCN on the other hand. In this study, we investigate whether the circadian rhythmicity in TPH protein could result from the rhythmic expression of tph gene in the raphe nuclei. We thus cloned specific tph1 and tph2 partial cDNAs and assessed the daily profiles of TPH mRNA levels by in situ hybridization in the rat raphe nuclei. Our results demonstrate that: (i) tph2 gene is exclusively expressed in the raphe nuclei, whereas tph1 gene is expressed in the pineal gland; (ii) under light–dark cycle (LD), TPH2 mRNA levels present daily variation within both median and dorsal raphe nuclei; (iii) under constant darkness TPH2 mRNA levels in both nuclei exhibit the same variation reported under LD cycle.

These data show that the circadian 5‐HT synthesis within the serotonergic neurons projecting to the circadian system might be explained by the rhythmic transcription of the tph2 gene in raphe nuclei. Taking our result with previous data into consideration, we further suggest that 5‐HT synthesis and release within the circadian system could be directly or indirectly under the control of the SCN.
Impacts of lesion severity and tyrosine kinase receptor B deficiency on functional outcome of femoral nerve injury assessed by a novel single‐frame motion analysis in mice
Authors: Irintchev Andrey , Simova Olga , Eberhardt Kirsten A. , Morellini Fabio , Schachner Melitta
Published: August 2005

Functional recovery after peripheral nerve injury is often poor. Comprehension of cellular and molecular mechanisms limiting or promoting restoration of function and design of efficient therapeutic approaches remain serious challenges for neuroscience and medicine. Progress has been restricted by the lack of reliable methods for evaluation of motor functions in laboratory animals. We describe a novel approach for assessment of muscle function in mice after femoral nerve damage, an injury causing impairment of knee extension. The functional deficit can be precisely estimated by angle and distance measurements on single video frames recorded during movements of the animals with or without body weight support. Using this method we describe here the precise time‐course and degree of functional recovery after femoral nerve crush and transection. In addition, we show that restoration of function is considerably impaired in mice with a reduced expression level of the tyrosine kinase receptor B, a cognate receptor for the neurotrophin brain‐derived neurotrophic factor. This finding is consistent with known functions of brain‐derived neurotrophic factor and tyrosine kinase receptor B and demonstrates the potential of the method. The principles of the approach are highly relevant for the development of novel functional assays in other peripheral and, in particular, central nervous system injury paradigms.
Tetrodotoxin‐resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A
Authors: Ou Shao‐Wu , Kameyama Asako , Hao Li‐Ying , Horiuchi Masahisa , Minobe Etsuko , Wang Wu‐Yang , Makita Naomasa , Kameyama Masaki
Published: August 2005

Both tetrodotoxin‐sensitive (TTX‐S) and TTX‐resistant (TTX‐R) voltage‐dependent Na+ channels are expressed in the human neuroblastoma cell line NB‐1, but a gene encoding the TTX‐R Na+ channel has not been identified. In this study, we have cloned cDNA encoding the α subunit of the TTX‐R Na+ channel in NB‐1 cells and designated it hNbR1. The longest open reading frame of hNbR1 (accession no. AB158469) encodes 2016 amino acid residues. Sequence analysis has indicated that hNbR1 is highly homologous with human cardiac Nav1.5/SCN5A with > 99% amino acid identity. The presence of a cysteine residue (Cys373) in the pore‐loop region of domain I is consistent with the supposition that hNbR1 is resistant to TTX. Analysis of the genomic sequence of SCN5A revealed a new exon encoding S3 and S4 of domain I (exon 6A). In addition, an alternative splicing variant, lacking exon 18, that encodes 54 amino acids in the intracellular loop between domains II and III was found (hNbR1‐2; accession no. AB158470). Na+ currents in human embryonic kidney cells (HEK293) transfected with hNbR1 or hNbR1‐2 showed electrophysiological properties similar to those for TTX‐R INa in NB‐1 cells. The IC50 for the TTX block was ≈ 8 µm in both variants. These results suggest that SCN5A has a newly identified exon for alternative splicing and is more widely expressed than previously thought.
Timed hypocaloric feeding and melatonin synchronize the suprachiasmatic clockwork in rats, but with opposite timing of behavioral output
Authors: Caldelas Ivette , Feillet Celine A. , Dardente Hugues , Eclancher Françoise , Malan André , Gourmelen Sylviane , Pévet Paul , Challet Etienne
Published: August 2005

Temporal organization of the molecular clockwork and behavioral output were investigated in nocturnal rats housed in constant darkness and synchronized to nonphotic cues (daily normocaloric or hypocaloric feeding and melatonin infusion) or light (light–dark cycle and daily 1‐h light exposure). Clock gene (Per1, Per2 and Bmal1) and clock‐controlled gene (Vasopressin) expression in the suprachiasmatic nuclei was assessed over 24 h. Light and exogenous melatonin synchronized the molecular clock, signaling, respectively, ‘daytime’ and ‘nighttime’, without affecting temporal organization of behavioral output (rest/activity rhythm). By contrast, synchronization to hypocaloric feeding led to a striking temporal change between gene expression in the suprachiasmatic clock and waveform of locomotor activity rhythm, rats then becoming active during the subjective day (diurnal‐like temporal organization). When the time of feeding coincided with activity offset, normocaloric feeding also synchronized the locomotor activity rhythm with no apparent switch in temporal organization. Peak of Per2 expression in the piriform cortex occurred between the beginning and the middle of the activity/feeding period, depending on the synchronizer. These data demonstrate that even though the suprachiasmatic clockwork can be synchronized to nonphotic cues, hypocaloric feeding likely acts downstream from clock gene oscillations in the suprachiasmatic nuclei to yield a stable yet opposite organization of the rest/activity cycle.
Extracellular signal‐regulated kinases (ERKs) modulate cocaine‐induced gene expression in the mouse amygdala
Authors: Radwanska Kasia , Caboche Jocelyne , Kaczmarek Leszek
Published: August 2005

It is known that acute cocaine administration activates the extracellular signal‐regulated kinase (ERK) pathway in the striatum, and results in transcription and translation of immediate early genes (IEGs). In the present study we investigated a possible involvement of ERK in the regulation of IEG expression in the amygdala, another brain structure known to be related to an addicted state. The patterns of cocaine‐induced c‐Fos, JunB and Zif268 protein expression were investigated, using an immunohistochemical approach, within distinct nuclei of the amygdala, either in the presence or absence of a selective inhibitor of the ERK pathway, SL327. Although these IEGs were similarly activated in the various nuclei of the amygdala after acute administration of cocaine, they showed different patterns after chronic injections. They also showed selective sensitivities to ERK inhibition. In particular, whereas c‐Fos and JunB expressions were augmented following chronic cocaine treatment, as compared with acute treatment, Zif268 expression was decreased by this chronic treatment. Additionally, chronic blocking of ERK activation affected cocaine‐induced c‐Fos and JunB but not Zif268 expression. Thus, the differential involvement of ERK in chronic vs. acute regulation of IEGs may account for its specific role in addiction‐related behavioral alterations, such as sensitization and tolerance.
Response of tree seedlings to the abiotic heterogeneity generated by nurse shrubs: an experimental approach at different scales
Authors: Gómez‐Aparicio Lorena , Valladares Fernando , Zamora Regino , Luis Quero José
Published: August 2005

Spatial heterogeneity of abiotic factors influences patterns of seedling establishment at different scales. In stress‐prone ecosystems such as Mediterranean ones, heterogeneity generated by shrubs has been shown to facilitate the establishment of tree species. However, how this facilitation is affected by spatial scale remains poorly understood. We have experimentally analysed the consequences of the abiotic heterogeneity generated by pioneer shrubs on survival, growth and physiology of seedlings of three important tree species from Mediterranean mountains (Acer opalus ssp. granatense, Quercus pyrenaica and Quercus ilex). Patterns of abiotic heterogeneity and seedling performance were studied at two scales differing in grain: 1) the microhabitat scale, by using open interspaces as controls of the effect of different shrub species, and 2) the microsite scale, analysing the effects of fine‐grain heterogeneity (within‐microhabitat heterogeneity). Results showed that, at the microhabitat scale, seedling establishment of the three tree species significantly benefited from the modification of the abiotic environment by nurse shrubs. However, we found shrub‐seedling interactions to be species‐specific, due to differential modification of both aboveground (light availability) and belowground (soil compaction, water content, and fertility) abiotic factors by nurse shrub species. Heterogeneity at the within‐microhabitat scale was rather high, although it did not significantly affect seedling performance of any of the tree species. The study demonstrates that the effects of the abiotic heterogeneity generated by shrubs are not consistent across the range of spatial scales considered. The regeneration niche of tree species becomes very complex at fine spatial scales, and thereby estimators of abiotic heterogeneity are valuable descriptors of spatial patterns of seedling establishment only when microsite “noise” is averaged out at greater scales.
Spatial and temporal patterns of roost use by tree‐dwelling barbastelle batsBarbastella barbastellus
Authors: Russo Danilo , Cistrone Luca , Jones Gareth
Published: August 2005

We evaluated the spatial and temporal patterns of roost switching behaviour by a tree‐dwelling population of barbastelle batsBarbastella barbastellusin a beech forest of central Italy. Switching behaviour was common to both sexes and did not depend on group size. We observed both individual and group switching, the latter often involving the abandonment of a roost tree on a single night. We suggest that behaviours such as flight activity around roosts or cavity inspection by bats play a role in recruiting group mates and coordinating their occupation of another site. Bats almost never crossed mountain ridges to use roosts located beyond them, possibly because ridges are regarded as boundaries delimiting main roosting areas. The rate of switching was lowest during the middle of the lactation period, probably to minimise problems related to the transportation of non‐volant young by their mothers. Although the maintenance of social relationship among bats spread over large forest areas may partly explain the occurrence of roost switching, the persistence of this behaviour in solitary bats and the movement of entire groups best fit the hypothesis that roost switching represents a way to maintain or increase knowledge of alternative roosts.
Asymmetrical dimethylarginine plasma clearance persists after acute total nephrectomy in rats
Authors: Carello Katari A. , Whitesall Steven E. , Lloyd Mary C. , Billecke Scott S. , D'Alecy Louis G.
Published: August 2005

Elevated plasma concentrations of symmetrical dimethylarginine (SDMA) and asymmetrical dimethylarginine (ADMA) are repeatedly associated with kidney failure. Both ADMA and SDMA can be excreted in urine. We tested whether renal excretion is necessary for acute, short-term maintenance of plasma ADMA and SDMA. Sprague-Dawley rats underwent sham operation, bilateral nephrectomy (NPX), ureteral ligation, or ureteral section under isoflurane anesthesia. Tail-snip blood samples (250 μl) were taken before and at 6- or 12-h intervals for 72 h after operation. Plasma clearance was assessed in intact and NPX rats. High-performance liquid chromatography determined SDMA and ADMA concentrations. Sodium, potassium, creatinine, blood urea nitrogen (BUN), and body weight were also measured. Forty-eight hours after NPX, SDMA increased 25 times (0.23 ± 0.03 to 5.68 ± 0.30 μM), whereas ADMA decreased (1.17 ± 0.08 to 0.73 ± 0.08 μM) by 38%. Creatinine and BUN increased, paralleling SDMA. Sham-operated animals showed no significant changes. Increased SDMA confirms continuous systemic production of SDMA and its obligatory renal excretion, much like creatinine. In contrast, decreased plasma ADMA suggests that acute total NPX either reduced systemic ADMA formation and/or systemic hydrolysis of ADMA increased 48-h post-NPX. However, plasma clearance of ADMA appeared unchanged 48 h after NPX. We conclude that renal excretory function is needed for SDMA elimination but not needed for acute, short-term ADMA elimination in that systemic hydrolysis is fully capable of clearing plasma ADMA.
Systemic venous circulation. Waves propagating on a windkessel: relation of arterial and venous windkessels to systemic vascular resistance
Authors: Wang Jiun-Jr , Flewitt Jacqueline A. , Shrive Nigel G. , Parker Kim H. , Tyberg John V.
Published: August 2005

Compared with arterial hemodynamics, there has been relatively little study of venous hemodynamics. We propose that the venous system behaves just like the arterial system: waves propagate on a time-varying reservoir, the windkessel, which functions as the reverse of the arterial windkessel. During later diastole, pressure increases exponentially to approach an asymptotic value as inflow continues in the absence of outflow. Our study in eight open-chest dogs showed that windkessel-related arterial resistance was ∼62% of total systemic vascular resistance, whereas windkessel-related venous resistance was only ∼7%. Total venous compliance was found to be 21 times larger than arterial compliance ( n = 3). Inferior vena caval compliance (0.32 ± 0.015 ml·mmHg−1·kg−1; mean ± SE) was ∼14 times the aortic compliance (0.023 ± 0.002 ml·mmHg−1·kg−1; n = 8). Despite greater venous compliance, the variation in venous windkessel volume (i.e., compliance × windkessel pulse pressure; 7.8 ± 1.1 ml) was only ∼32% of the variation in aortic windkessel volume (24.3 ± 2.9 ml) because of the larger arterial pressure variation. In addition, and contrary to previous understanding, waves generated by the right heart propagated upstream as far as the femoral vein, but excellent proportionality between the excess pressure and venous outflow suggests that no reflected waves returned to the right atrium. Thus the venous windkessel model not only successfully accounts for variations in the venous pressure and flow waveforms but also, in combination with the arterial windkessel, provides a coherent view of the systemic circulation.
Overexpression of prolylcarboxypeptidase enhances plasma prekallikrein activation on Chinese hamster ovary cells
Authors: Shariat-Madar Z. , Rahimy E. , Mahdi F. , Schmaier A. H.
Published: August 2005

Plasma prekallikrein (PK) complexes with its receptor, high-molecular-weight kininogen (HK), on human umbilical vein endothelial cells (HUVEC). When assembled on endothelial cells, PK is activated to plasma kallikrein independent of factor XIIa by the serine protease prolylcarboxypeptidase (PRCP, Km= 9 nM). PRCP was shown to be a PK activator when isolated from HUVEC ( J Biol Chem 277: 17962–17969, 2002) and produced as a recombinant protein ( Blood 103: 4554–4561, 2004). To additionally confirm that human PRCP is a physiological PK activator, PRCP was overexpressed in Chinese hamster ovary (CHO) cells. CHO cells were transfected with full-length PRCP under the control of a cytomegalovirus promoter, and CHO recombinant PRCP was expressed as a fusion protein with COOH-terminal enhanced green fluorescence protein (EGFP). The presence of recombinant PRCP in transfected CHO cells was detected by real-time RT-PCR, immunoblot, and immunoprecipitation. PRCP mRNA and PK activation were two- to threefold higher in transfected than in control CHO cells. The increase in PRCP-induced PK activation in the transfected CHO cells paralleled the increase in PRCP antigen expression, as determined by anti-PRCP and anti-green fluorescence protein antibodies. PK activation of the transfected cells was blocked by small interfering RNA to PRCP. Anti-PRCP antibody and Z-Pro-Pro-aldehyde dimethyl acetate also blocked PK activation (IC50= 0.01 and 7.0 mM, respectively). Localization of PRCP in intact cells observed via confocal microscopy and flow cytometry also confirmed overexpression of PRCP on the external membrane. These investigations independently confirm that PRCP is expressed on cell membranes and that PRCP expression increases PK activation.
Inositol trisphosphate receptor calcium release is required for cerebral artery smooth muscle cell proliferation
Authors: Wilkerson M. Keith , Heppner Thomas J. , Bonev Adrian D. , Nelson Mark T.
Published: August 2005

Vascular damage signals smooth muscle cells to proliferate, often exacerbating existing pathologies. Although the role of changes in “global” Ca2+in vascular smooth muscle (VSM) cell dedifferentiation has been studied, the role of specific Ca2+signals in determining VSM phenotype remains relatively unexplored. Earlier work with cultured VSM cells suggests that inositol 1,4,5-trisphosphate receptor (IP3R) expression and sarcoplasmic reticulum (SR) Ca2+release may be linked to VSM cell proliferation in native tissue. Thus we hypothesized that SR Ca2+release through IP3Rs in the form of discrete transient signals is necessary for VSM cell proliferation. To investigate this hypothesis, we used mouse cerebral arteries to design an organ culture system that permitted examination of Ca2+dynamics in native tissue. Explanted arteries were cultured in normal medium with 10% FBS, and appearance of individual VSM cells migrating from explanted arteries (outgrowth cells) was tracked daily. Initial exposure to 10% FBS increased Ca2+waves in myocytes in the arteries that were blocked by the IP3R antagonist 2-aminoethoxydiphenylborate (2-APB). Inhibition of IP3R opening (via 100 μM 2-APB, 10 μM xestospongin C, or 25 μM U-73122) dramatically reduced outgrowth cell number compared with untreated or ryanodine-treated (10 μM) arteries. Consistent with this finding, 2-APB inhibited cell proliferation, as measured by reduced proliferating cell nuclear antigen immunostaining within 48 h of culture but did not inhibit cell migration. These results indicate that activation of IP3R Ca2+release is required for VSM cell proliferation in these arteries.
Prostaglandin E2protects lower airways against bronchoconstriction
Authors: Hartney John M. , Coggins Kenneth G. , Tilley Stephen L. , Jania Leigh A. , Lovgren Alysia Kern , Audoly Laurent P. , Koller Beverly H.
Published: August 2005

Prostaglandin E2(PGE2), similar to β-adrenergic receptor agonists, can protect airways from bronchoconstriction and resulting increase in airway resistance induced by a number of agents, including cholinergic receptor agonists and antigen. We examined the impact of sustained alterations in PGE2pathways on changes in airway resistance. Genetic methods were utilized to alter PGE2metabolism and signal transduction in the murine lung. PGE2levels were elevated by generating mice lacking 15-hydroxyprostaglandin ( Hpgd−/−), the major catabolic enzyme of PGE2, and by generating a transgenic line in which mouse PGE2synthase ( Ptges) expression is driven by a human lung-specific promoter, hSP-C. Conversely, to determine the impact of loss of PGE2on airway reactivity, we examined mice lacking this synthase ( Ptges−/−) and receptors that mediate the actions of PGE2, particularly the PGE2EP2receptor ( Ptger2). Diminished capacity to produce and respond to PGE2did not alter the response of mice to cholinergic stimuli. In contrast, the responsiveness to cholinergic stimulation was dramatically altered in animals with elevated PGE2levels. The Hpgd−/−and hSP- C- Ptges transgenic lines both showed attenuated airway responsiveness to methacholine as measured by lung resistance. Thus, whereas compromise of the Ptges/PGE2/ Ptger2 pathway does not alter airway responsiveness, genetic modulation that elevates PGE2levels in the lung attenuates airway responsiveness.
The Third World and Global Environmental Negotiations: Interests, Institutions and Ideas
Authors: Williams Marc
Published: August 2005

Marian Miller provided an engaging and persuasive analysis of the role of Third World states in global environmental negotiations. While Miller focused on the strategies of individual states, this article examines the collective agency of the Third World in global environmental negotiations. The first part of the article explores the debates on the continuing relevance of the Third World as a concept, and contends that the Third World retains relevance in the context of global bargaining processes. The second part of the article highlights the role of ideas and institutions in the continued reproduction of the Third World as an actor in global environmental politics. The final part of the article explores the ways in which the negotiations on climate change have tended to reproduce a distinctive Southern perspective.
Reverse transcriptional profiling: non-correspondence of transcript level variation and proximal promoter polymorphism
Authors: Brown Rebecca Petersen , Feder Martin E
Published: August 2005

Background

Variation in gene expression between two Drosophila melanogaster strains, as revealed by transcriptional profiling, seldom corresponded to variation in proximal promoter sequence for 34 genes analyzed. Two sets of protein-coding genes were selected from pre-existing microarray data: (1) those whose expression varied significantly and reproducibly between strains, and (2) those whose transcript levels did not vary. Only genes whose regulation of expression was uncharacterized were chosen. At least one kB of the proximal promoters of 15–19 genes in each set was sequenced and compared between strains (Oregon R and Russian 2b).

Results

Of the many promoter polymorphisms, 89.6% were SNPs and 10.4% were indels, including homopolymer tracts, microsatellite repeats, and putative transposable element footprints. More than half of the SNPs were changes within a nucleotide class. Hypothetically, genes differing in expression between the two strains should have more proximal promoter polymorphisms than those whose expression is similar. The number, frequency, and type of polymorphism, however, were the same in both sets of genes. In fact, the promoters of six genes with significantly different mRNA expression were identical in sequence.

Conclusion

For these genes, sequences external to the proximal promoter, such as enhancers or in trans, must play a greater role than the proximal promoter in transcriptomic variation between D. melanogaster strains.
A priori postulated and real power in cluster randomized trials: mind the gap
Authors: Guittet Lydia , Giraudeau Bruno , Ravaud Philippe
Published: August 2005

Background

Cluster randomization design is increasingly used for the evaluation of health-care, screening or educational interventions. The intraclass correlation coefficient (ICC) defines the clustering effect and be specified during planning. The aim of this work is to study the influence of the ICC on power in cluster randomized trials.

Methods

Power contour graphs were drawn to illustrate the loss in power induced by an underestimation of the ICC when planning trials. We also derived the maximum achievable power given a specified ICC.

Results

The magnitude of the ICC can have a major impact on power, and with low numbers of clusters, 80% power may not be achievable.

Conclusion

Underestimating the ICC during planning cluster randomized trials can lead to a seriously underpowered trial. Publication of a priori postulated and a posteriori estimated ICCs is necessary for a more objective reading: negative trial results may be the consequence of a loss of power due to a mis-specification of the ICC.
Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection
Authors: Neves-Souza Patrícia CF , Azeredo Elzinandes L , Zagne Sonia MO , Valls-de-Souza Rogério , Reis Sonia RNI , Cerqueira Denise IS , Nogueira Rita MR , Kubelka Claire F
Published: August 2005

Mononuclear phagocytes are considered to be main targets for Dengue Virus (DENV) replication. These cells are activated after infection, producing proinflammatory mediators, including tumour-necrosis factor-α, which has also been detected in vivo. Nitric oxide (NO), usually produced by activated mononuclear phagocytes, has antimicrobial and antiviral activities.

Methods

The expression of DENV antigens and inducible nitric oxide synthase (iNOS) in human blood isolated monocytes were analysed by flow cytometry using cells either from patients with acute Dengue Fever or after DENV-1 in vitro infection. DENV-1 susceptibility to iNOS inhibition and NO production was investigated using NG-methyl L-Arginine (NGMLA) as an iNOS inhibitor, which was added to DENV-1 infected human monocytes, and sodium nitroprussiate (SNP), a NO donor, added to infected C6/36 mosquito cell clone. Viral antigens after treatments were detected by flow cytometry analysis.

Results

INOS expression in activated monocytes was observed in 10 out of 21 patients with Dengue Fever and was absent in cells from ten healthy individuals. DENV antigens detected in 25 out of 35 patients, were observed early during in vitro infection (3 days), significantly diminished with time, indicating that virus replicated, however monocytes controlled the infection. On the other hand, the iNOS expression was detected at increasing frequency in in vitro infected monocytes from three to six days, exhibiting an inverse relationship to DENV antigen expression. We demonstrated that the detection of the DENV-1 antigen was enhanced during monocyte treatment with NGMLA. In the mosquito cell line C6/36, virus detection was significantly reduced in the presence of SNP, when compared to that of untreated cells.

Conclusion

This study is the first to reveal the activation of DENV infected monocytes based on induction of iNOS both in vivo and in vitro, as well as the susceptibility of DENV-1 to a NO production.
Enhanced efficacy of gemcitabine in combination with anti-CD20 monoclonal antibody against CD20+ non-Hodgkin's lymphoma cell lines in vitro and in scidmice
Authors: Smith Mitchell R , Joshi Indira , Jin Fang , Obasaju Coleman
Published: August 2005

Background

Despite exciting new targeted therapeutics against non-Hodgkin's lymphoma (NHL), chemotherapy remains a cornerstone of therapy. While purine nucleoside analogs have significant activity in low grade NHL, the pyrimidine nucleoside analog gemcitabine has been less extensively studied, but has important activity. Use of the anti-CD20 monoclonal antibody rituximab in combination with chemotherapy for B-NHL is becoming prevalent in clinical practice, but has not been extensively studied in pre-clinical models.

Methods

We have tested the activity of gemcitabine ± rituximabin vitroand inscid/human NHL xenograft models. We used two t(14;18)+, CD20+ follicular B cell NHL cell lines, DoHH2 a transformed NHL line and WSU-FSCCL isolated from pleural fluid of a patient with indolent NHL.

Results

Gemcitabine is cytotoxic to DoHH2 and WSU-FSCCL cellsin vitro, and the IC50is 2–3 fold lower in the presence of rituximab. Apoptosis is also enhanced in the presence of rituximab. Clearance of NHL cells from ascites inscidmice is prolonged by the combination, as compared with either agent alone. Most importantly, survival ofscidmice bearing human NHL cells is significantly prolonged by the combination of gemcitabine + rituximab.

Conclusion

Based on our pre-clinical data showing prolonged survival of mice bearing human lymphoma cell line xenografts after treatment with gemcitabine + anti-CD20 antibody, this combination, expected to have non-overlapping toxicity profiles, should be explored in clinical trials.