bluuebunny/crossref_metadata_2025 huggingface dataset:
A proteasomal stress response: pre‐treatment with proteasome inhibitors increases proteasome activity and reduces neuronal vulnerability to oxidative injury
Authors: Lee Chul‐Sang , Tee Lee Y. , Warmke Timothy , Vinjamoori Anant , Cai AiLi , Fagan Anne M. , Snider B. Joy
Published: November 2004

We report here that exposure to low concentrations of proteasome inhibitors (e.g. 10–100 nmMG‐132, 0.1–3 nmepoxomicin or 10–30 nmclasto‐lactacystin β‐lactone) resulted in an enhancement, rather than an inhibition, of proteasome activity in cultured neocortical neurons. Size‐fractionation chromatography confirmed that the enhanced peptide cleavage activity was associated with proteasome‐sized complexes. This sub toxic exposure reduced neuronal death caused by subsequent exposure to oxidative stress (100–200 µmH2O2for 30 min, 24‐h exposure to 100 µmparaquat or 7.5 µmmenadione), but did not alter vulnerability to excitotoxicity (5‐min exposure to 30–100 µmNMDA or 24 exposure to 12 µmNMDA). Sub toxic proteasome inhibitor exposure caused an increase in levels of proteasome core subunit proteins and mRNAs, but not in levels of potentially cytoprotective heat shock proteins (hsp70, hsp90 and hsp40). The neuroprotective effects of proteasome inhibitor pre‐treatment were blocked by coapplication of proteasome inhibitors during the oxidative insult. These findings support a model in which sublethal proteasome inhibition induces neurons to increase proteasome activity and promotes resistance to oxidative injury and suggests that enhancement of proteasome activity is a potential therapeutic target for diseases in which oxidative stress has been implicated.
Pulmonary gas exchange during exercise in Fontan patients at a long‐term follow‐up
Authors: Strömvall‐Larsson Eva , Eriksson Bengt O. , Holmgren Daniel , Sixt Rune
Published: November 2004

Desaturation during exercise in the Fontan type of circulation may be due to known right‐to‐left shunts in some patients, while in others there are no obvious signs of shunts.

Aim:  To evaluate the gas exchange and exercise capacity in patients with Fontan circulation.

Material and methods:  Twenty patients with the Fontan type of circulation, median age at operation 7·5 years (3·0–35 years), follow‐up time 12·1 years (8·3–20·4 years), were included. The intrapulmonary gas mixing (N2‐slope) and diffusion capacity for carbon monoxide (DLCO) was evaluated and determination of cardiac output was performed at rest and during exercise with measurements of ventilation, oxygen uptake, respiratory rate, carbon dioxide production and heart rate. Samples for blood gases (PaO2, SaO2) were obtained at rest and at the end of each work load.

Results:  The median exercise capacity was 1·47 l min−1. During exercise, all the patients had an alveolar–arterial oxygen partial pressure difference (PA–aO2) above 2 SD. Patients with known right‐to‐left shunts had lower PaO2 and SaO2 values and higher PA–aO2 values both at rest, median 7·5 kPa, 90%, and 7·2 kPa, respectively, and during exercise, median 5·8 kPa, 77% and 10·1 kPa, compared with those with no shunts, median 11·2 kPa, 97% and 4·1, respectively, at rest and 9·7 kPa, 94%, and 6·3 during exercise (P<0·01).

No correlation was found between cardiac index, the N2‐slope or the DLCO at rest and the PaO2 and SaO2 at rest or during exercise.

Conclusion:  In patients with the Fontan type of circulation, right‐to‐left shunts are the major cause of desaturation during exercise.
Is muscle power output a key factor in the age‐related decline in physical performance? A comparison of muscle cross section, chair‐rising test and jumping power
Authors: Runge Martin , Rittweger Jörn , Russo Cosimo Roberto , Schiessl Hans , Felsenberg Dieter
Published: November 2004

Ageing compromises locomotor capacity and is associated with an increased risk of falls. Several lines of evidence indicate that both changes in muscle mass and performance are causative. Most studies, however, do not discern between effects of ageing, sedentarism and comorbidity. The present study compares the age effects in muscle cross section, force and power in physically competent self‐selected subjects of different age groups. A total of 169 women and 89 men between 18 and 88 years, without any disease, impairment or medication affecting the musculoskeletal system were enrolled in this study. Calf muscle cross‐sectional area was assessed by computed tomography. Muscle force and power were assessed by jumping mechanography. No significant correlation between muscle cross section and age was found in the men. A weak correlation in the women disappeared after correction for height. Close correlations with age, however, were found for peak force and peak power. Correction for muscle cross section or body weight further increased these correlation coefficients, particularly for peak power specific to body weight (r = 0.81 in women and r = 0.86 in men). The non‐sedentarian population investigated here depicted a reduction of >50% between the age of 20 and 80 without a reduction in muscle cross section. This suggests a crucial role for muscular power in the ageing process. Possibly, the jumping mechanography as a measurement of anti‐gravitational power output is a promising extension of the chair‐rising test, known to be predictive for immobilization and the risk of falls.
Arterial concentration of 99mTc‐sestamibi at rest, during peak exercise and after dipyridamole infusion
Authors: Sand Niels Peter Rønnow , Juelsgaard Palle , Rasmussen Karin , Flø Christian , Thuesen Leif , Bagger Jens Peder , Nielsen Torsten Toftegaard , Rehling Michael
Published: November 2004

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial 99mTc‐sestamibi (MIBI) time‐activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one‐vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by 99mTc‐sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5–30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.
Non‐invasive assessment of endothelial function – relation between vasodilatory responses in skin microcirculation and brachial artery
Authors: Hansell Jimmy , Henareh Loghman , Agewall Stefan , Norman Mikael
Published: November 2004

Objective:  To compare different non‐invasive methods for determination of human endothelial function in peripheral circulation.

Design:  Observational, cross‐sectional study in 39 healthy subjects (21 females, age 17–56 years).

Setting:  Vascular research laboratory at university hospital.

Methods:  Laser Doppler (LD) flowmetry was used to compare skin microvascular perfusion changes during postocclusive reactive hyperaemia with those induced by iontophoretic administration of acetylcholine (ACh), an endothelial‐dependent vasodilator. LD measurements were compared with ultrasonographic measurements of postocclusive flow‐mediated dilatation (FMD) in the brachial artery (n = 21).

Results:  Local ACh induced a larger and more sustained skin perfusion increase than reactive hyperaemia after 4 min of regional arterial occlusion (P<0·001). A significant correlation was found between the magnitude of ACh‐induced vasodilatation and peak reactive hyperaemia, both in absolute (r = 0·62, P<0·001) and relative terms (r = 0·58, P<0·001). A correlation was also found between brachial artery FMD and the magnitude of ACh‐induced skin perfusion increase (r = 0·43, P<0·05) but not between FMD and reactive hyperaemia.

Conclusion:  Endothelial function, an early marker of cardiovascular risk, can be non‐invasively assessed and graded by LD and FMD‐measurements and despite inherent differences, both methods do correlate.
The validity and reliability of the Perometer in evaluating human knee volume
Authors: Man Ivy O. W. , Markland Kate L. , Morrissey Matthew C.
Published: November 2004

Background:  Accurate knee swelling evaluation is important in monitoring the progress of a patient's condition and rehabilitation. Water volumetry is the current gold standard of volume assessment but can be time consuming and unsuitable for assessing patients with open wounds. No previous study has reported the potential use of an optoelectronic device in assessing knee volume.

Objectives:  To evaluate an optoelectronic device, the Perometer® in knee volume assessment in uninjured subjects and compare it to the current gold standard of volume assessment – water displacement.

Materials and methods:  Bilateral knee measurements were measured in 20 uninjured individuals with both methods on two separate days using a one‐way repeated measures design. A cylindrical object was also measured 10 times with both tools.

Results:  The mathematically calculated volume of the cylinder was 1568 ml. The mean volume obtained by the Perometer was 1602 and 1620 ml by the volumeter. This represented an over‐estimation of the true volume of 2·2% by the Perometer and 3·4% by the volumeter. A high correlation was found for repeated measures of knee volumes with both methods (r = 0·94, P<0·01). Limits of agreement (LOA) were calculated to assess the amount of agreement between the two methods and these ranged from −130 to 207 ml indicating a low degree of agreement.

Conclusions:  The results indicate that the Perometer is as reliable as the knee volumeter in assessing knee volume. However, the wide LOA suggest the two methods should not be used interchangeably.
Effect of body position on foot and ankle volume in healthy subjects
Authors: Man Ivy O. W. , Glover Katie , Nixon Peter , Poyton Ross , Terre Rosie , Morrissey Matthew C.
Published: November 2004

Physical therapy treatments for and evaluation of lower limb swelling are usually performed in supine lying position. However, the limb is usually treated or assessed in the dependent position, i.e. sitting or standing. The purpose of this study was to determine the possible confounding effect of subject positioning on foot and ankle volume.

Sixty healthy individuals were randomly positioned into motionless standing, sitting or supine lying for 30 min. Volumetric measurements of the dominant leg were taken with a foot and ankle volumeter before and after 30 min of positioning. A significant difference between the three groups for foot and ankle volume change (F2,53 = 35·41, P<0·001) was found. A post‐hoc Tukey HSD test revealed that the difference was statistically significant between sitting and standing as well as supine lying and standing (P<0·001). No statistical significance was found between sitting and supine lying (P = 0·90).

Standing caused the greatest increase in foot and ankle volume followed by sitting then supine lying. The results indicate that treating or assessing a limb with the subject in a sitting position would not be significantly different from a subject who is positioned in supine lying. However, it is not known whether the height and the distance from the heart to the feet were comparable between the groups, and so it is recommended that, where possible, treatment and assessment of lower leg swelling should be undertaken with the leg in a non‐dependent position and definitely not in standing.
Subjective norms and the prediction of romantic relationship state and fate
Authors: Etcheverry Paul E. , Agnew Christopher R.
Published: November 2004

This study examined whether subjective norms are associated with commitment to a romantic relationship and with remaining in that relationship over time. Subjective norms are defined in the context of relationships as the perceived normative beliefs of a social network member regarding a given relationship weighted by the motivation to comply with that network member. In a longitudinal study of college students involved in dating relationships, subjective norms were found to be a significant predictor of romantic relationship commitment level, alone and in multiple regression analyses including satisfaction level, quality of alternatives, and investment size. Longitudinal analyses indicated that commitment mediated the effect of subjective norms on remaining in the relationship approximately 8 months later. Finally, level of dependence on a romantic relationship moderated the predictive value of subjective norms, with lower relationship dependence yielding greatest predictive value for subjective norms.
When the sexes need not differ: Emotional responses to the sexual and emotional aspects of infidelity
Authors: Vaughn Becker D. , Sagarin Brad J. , Guadagno Rosanna E. , Millevoi Allison , Nicastle Lionel D.
Published: November 2004

This study assessed whether previously reported sex differences in jealousy could be accounted for by other related emotions. Participants were presented with hypothetical scenarios involving both a sexual and an emotional infidelity, then were asked how jealous, angry, hurt, and disgusted they would be (using continuous scales). The results replicate the sex difference in response to sexual and emotional infidelity, demonstrate that it is robust when continuous measures are used, and confirm that it is unique to jealousy. Sex differences did not emerge for anger, hurt, or disgust. Instead, sexual infidelity elicited greater anger and disgust, and less hurt, than emotional infidelity, for both women and men. The results also suggest that it is the jealous response to an emotional infidelity that best discriminates women from men, and that both women and those participants in a serious, committed relationship reported significantly greater intensity in their emotional reactions, as compared to men and those not in a committed relationship.
Suspended Equilibrium in Iran's Political System
Authors: Kamrava Mehran , Hassan‐Yari Houchang
Published: November 2004

Two sets of power relationships have emerged in the political system of the Islamic Republic of Iran: official, institutional relationships outlined in the Constitution, and unofficial, informal ones existing between and within groups and clusters of powerful individuals and institutions. The juxtaposition of informal factional alliances with the formal institutions of power has resulted in the development of a precarious balance within the state, as ‘hardliners’ and ‘softliners’ vie for greater influence and the adoption of their agendas as official state policy. The ensuing results have been two‐fold. On the one hand, the emergence of multiple centers of power has enhanced the extent and reach of the state in relation to various social strata, thus bestowing it with considerable durability and staying power. On the other hand, the existence of multiple official and unofficial venues for competition has sharpened the tenor and substance of factional rivalries. For the most part, each of the factions has so far been able to balance out the influence and agendas of the other. At the same time, however, since the ‘softliners’ by and large advocate greater political liberalization, these very factional rivalries have had some modest consequences in opening up the Iranian polity. Ultimately, the pace and direction of political liberalization in Iran will depend on the outcome of the ongoing rivalry that is currently being played out within official state institutions and unofficial power‐cliques.
The Haiku and the Double Helix
Authors: GARDELS NATHAN
Published: November 2004

The Changing Global Order: World Leaders Reflect“ illumines the human prospect as few works of its kind do,” the eminent Cambridge political historian Ralph Buultjens wrote ofNPQ's last collection in theBoston Review of Books. But he also properly identified one shortcoming: a lack of coverage of the biosciences “that will surely shape the world to come.” For a variety of reasons, NPQ's many pieces over the years on science didn't fit into the geo‐cultural and geo‐political framework of that project. This special issue serves as a corrective to that shortcoming.
Culture, risk factors and suicide in rural China: a psychological autopsy case control study
Authors: Zhang J. , Conwell Y. , Zhou L. , Jiang C.
Published: November 2004

Objective:  Previous research on sociocultural factors for Chinese suicide have been basically limited to single case studies or qualitative research with ethnographic methodology. The current study examines the major risk factors and some cultural uniqueness related to Chinese rural suicide using a quantitative design.

Method:  This is a case control study with 66 completed suicides and 66 living controls obtained from psychological autopsy interviews in rural China.

Results:  Both bivariate analyses and the multiple regression model have found that the Chinese rural suicide patterns are basically similar to those in most other cultures in the world: strong predictors of rural Chinese suicide are the psychopathological, psychological, and physical health variables, followed by social support and negative and stressful life events. Other significant correlates include lower education, poverty, religion, and family disputes.

Conclusion:  Culture has an important impact on suicide patterns in a society.
Features of extramedullary and extraosseous multiple myeloma: a report of 19 patients from a single center
Authors: Damaj G. , Mohty M. , Vey N. , Dincan E. , Bouabdallah R. , Faucher C. , Stoppa A. M. , Gastaut J. A.
Published: November 2004

Extramedullary (EM) localizations at diagnosis or during the course of multiple myeloma (MM) are rare. We conducted a large retrospective study to more accurately describe the clinical and laboratory features of this entity, and the outcome of these manifestations. The charts of 19 eligible patients out of 432 patients with MM were retrieved from the hematology department of the Institut Paoli‐Calmettes Cancer Center. Median age was 61 (range: 39–79) with a female/male sex ratio of 8/11. Ten patients were found to have EM and extraosseous tumor at the time of MM diagnosis, and nine patients developed EM tumor during the course of the disease. Neither the stage of the disease, the LDH level, or the type of immunoglobulin (Ig) was found to be associated with the development of EM disease. Patients who developed EM tumor during the course of MM had a lower serum Ig and a higher monoclonal Bence–Jones proteinuria at the diagnosis of MM than patients who presented with EM tumor at diagnosis. Multiple sites were usually involved. Resistance to chemotherapy was frequent and response to thalidomide was poor. Eight out of the 19 patients responded to high‐dose chemotherapy. The remaining 11 patients progressed while on therapy. With a median follow‐up of 13 months (range: 2–65), six patients are alive, four patients are in partial remission and two patients in present progressive disease. In conclusion, EM tumors are a rare manifestation of MM, with a cumulative incidence of 4.6% of MM. Multiple sites are usually involved. The response to chemotherapy is very poor with a very low response rate to thalidomide. The prognosis is very poor, especially when the diagnosis of EM tumor is concurrent with the diagnosis of MM.
Alemtuzumab: effective monotherapy for simultaneous B‐cell chronic lymphocytic leukaemia and Sézary syndrome
Authors: Gibbs Simon D. J. , Herbert Kirsten E. , McCormack Christopher , Seymour John F. , Prince H. Miles
Published: November 2004

The simultaneous presentation of chronic lymphocytic leukaemia (CLL) and cutaneous T‐cell lymphoma (CTCL) is a very rare occurrence where optimal treatment is unknown. We present the case of a 65‐yr‐old man who was successfully treated with alemtuzumab monotherapy for both disorders, but at a cost of severe infectious morbidity and prolonged pancytopenia.
VH gene mutation status and cellular drug resistance in chronic lymphocytic leukaemia
Authors: Åleskog Anna , Tobin Gerard , Laurell Anna , Thunberg Ulf , Lindhagen Elin , Roos Göran , Nilsson Kenneth , Nygren Peter , Sundström Christer , Höglund Martin , Larsson Rolf , Rosenquist Richard
Published: November 2004

Objective: B‐cell chronic lymphocytic leukaemia (B‐CLL) can be divided into two clinical entities based on the immunoglobulin variable heavy chain (VH) gene mutation status, as cases with unmutated VH genes display a more aggressive disease with shorter survival time than mutated cases. The aim of this study was to investigate whether differences in cellular drug resistance could give an explanation for these divergent clinical courses. Methods: The VH gene mutation status was analysed in patients with previously untreated B‐CLL using VH gene family‐specific PCR amplification and nucleotide sequencing. In vitro sensitivity to cytarabine, fludarabine, cladribine, doxorubicin, idarubicin, vincristine, cyclophosphamide, melphalan and prednisolone was assessed using the non‐clonogenic in vitro assay, fluorometric microculture cytotoxicity assay. Results: The VH genes and in vitro drug resistance were successfully analysed in 46 cases, revealing that 25 (54%) cases showed unmutated and 21 (46%) cases mutated VH genes. Interestingly, the unmutated group generally tended to be more chemosensitive than the mutated group with significant differences for cytarabine and prednisolone (P ≤ 0.01). Conclusion: The propensity of inferior drug response in mutated B‐CLL may reflect a more differentiated disease than in unmutated B‐CLL. We conclude that the difference in prognosis between B‐CLL cases with unmutated and mutated VH genes could not be explained by difference in cellular drug resistance.
The influence of farnesyl protein transferase inhibitor R115777 (Zarnestra) alone and in combination with purine nucleoside analogs on acute myeloid leukemia progenitors in vitro
Authors: Korycka Anna , Smolewski Piotr , Robak Tadeusz
Published: November 2004

R115777 (Tipifarnib, Zarnestra) – farnesyl transferase inhibitor belongs to the new class of signal transduction inhibitors which seems to be yielding results in the treatment of patients with solid tumors. Recently it has also been considered as a drug of promise in hematologic malignancies such as acute myeloid leukemia (AML), especially in older patients, in chronic myelogenous leukemia (CML) as well as myelodysplastic syndromes (MDS). The aim of our study was to evaluate the influence of R115777 used alone or with purine nucleoside analogs (PNA): cladribine (2‐CdA) and fludarabine (F‐ara‐A) on leukemic progenitors [colony‐forming unit‐leukemia (CFU)‐L] from AML patients. Our studies were based on the methods of semisolid leukemic CFU‐L and normal granulocyte–macrophage progenitor (CFU‐GM) cultures in vitro. R115777 was added to the culture alone or in combinations with PNA. We showed that R115777 used alone or together with PNA at all combinations significantly inhibited the colony growth of AML CFU‐L, when compared with normal CFU‐GM (P < 0.01). In addition, the drugs used in combinations of two higher concentrations in significantly higher degree inhibited CFU‐L colony growth, when compared either with R115777 or with any of PNA used alone (P < 0.04). IC50 for R115777 were 67.1 and 121.9 nm for AML CFU‐L and normal CFU‐GM, respectively. Furthermore, in the case of AML the combination index was 0.89 and 1.16, respectively, for the combination of R115777 with 2‐CdA and R115777 with F‐ara‐A. An additive effect on AML CFU‐L cells and subadditive effect on normal CFU‐GM were seen. To assess a proapoptotic effect, the drugs were added to the liquid cultures at the same concentrations as for clonogenic assays. A significant increase in the rate of apoptosis induced by combinations of drugs in comparison with single agents was observed. In conclusion, the combination of R115777 with both PNA could be more effective than the drugs used alone. However, further experimental studies on the usefulness of these combinations in the treatment of myeloid leukemia patients are warranted.
The Function of the Endocytic Scaffold Protein Pan1p Depends on Multiple Domains
Authors: Miliaras Nicholas B. , Park Jin‐Hyouk , Wendland Beverly
Published: November 2004

Pan1p is an essential protein of the yeast Saccharomyces cerevisiae that is required for the internalization step of endocytosis and organization of the actin cytoskeleton. Pan1p, which binds several other endocytic proteins, is composed of multiple protein–protein interaction domains including two Eps15 Homology (EH) domains, a coiled‐coil domain, an acidic Arp2/3‐activating region, and a proline‐rich domain. In this study, we have induced high‐level expression of various domains of Pan1p in wild‐type cells to assess the dominant consequences on viability, endocytosis, and actin organization. We found that the most severe phenotypes, with blocked endocytosis and aggregated actin, required expression of nearly full length Pan1p, and also required the endocytic regulatory protein kinase Prk1p. The central coiled‐coil domain was the smallest fragment whose overexpression caused any dominant effects; these effects were more pronounced by inclusion of the second EH domain. Co‐overexpressing nonoverlapping amino‐ and carboxy‐terminal fragments did not mimic the effects of the intact protein, whereas fragments that overlapped within the coiled‐coil region could. Yeast two‐hybrid and in vivo coimmunoprecipitation analyses suggest that Pan1 may form dimers or higher order oligomers. Collectively, our data support a view of Pan1p as a dimeric/oligomeric scaffold whose functions require both the amino‐ and carboxy‐termini, linked by the central region.
Disease‐causing V2 Vasopressin Receptors are Retained in Different Compartments of the Early Secretory Pathway
Authors: Hermosilla Ricardo , Oueslati Morad , Donalies Ute , Schönenberger Eva , Krause Eberhard , Oksche Alexander , Rosenthal Walter , Schülein Ralf
Published: November 2004

The G protein‐coupled V2 vasopressin receptor is crucially involved in water reabsorption in the renal collecting duct. Mutations in the human V2 vasopressin receptor gene cause nephrogenic diabetes insipidus. Many of the disease‐causing mutants are retained intracellularly by the quality control system of the early secretory pathway. It was previously thought that quality control system is restricted to the endoplasmic reticulum (ER). Here, we have examined the retention mechanisms of eight V2 vasopressin receptor mutants. We show that mutants L62P, ΔL62‐R64 and S167L are trapped exclusively in the ER. In contrast, mutants R143P, Y205C, InsQ292, V226E and R337X reach the ER/Golgi intermediate compartment (ERGIC) and are rerouted to the ER. The ability of the mutant receptors to reach the ERGIC is independent of their expression levels. Instead, it is determined by their folding state. Mutant receptors in the ERGIC may be sorted into retrograde transport vesicles by an interaction of an RXR motif in the third intracellular loop with the coatomer complex I. Our data show that disease‐causing mutants of a particular membrane protein may be retained in different compartments of the early secretory pathway and that the folding states of the proteins determine their retention mechanism.
Ncr1p, the Yeast Ortholog of Mammalian Niemann Pick C1 Protein, is Dispensable for Endocytic Transport
Authors: Zhang Shaochong , Ren Jihui , Li Hongzhe , Zhang Qian , Armstrong Jeffery S. , Munn Alan L. , Yang Hongyuan
Published: November 2004

The Niemann Pick C1 protein localizes to late endosomes and plays a key role in the intracellular transport of cholesterol in mammalian cells. Cholesterol and other lipids accumulate in a lysosomal or late endosomal compartment in cells lacking normal NPC1 function. Other than accumulation of lipids, defects in lysosomal retroendocytosis, sorting of a multifunctional receptor and endosomal movement have also been detected in NPC1 mutant cells. Ncr1p is an ortholog of NPC1 in the budding yeast Saccharomyces cerevisiae. In this study, we show that Ncr1p is a vacuolar membrane protein that transits through the biosynthetic vacuolar protein sorting pathway, and that it can be solubilized by Triton X‐100 at 4 °C. Using well‐established assays, we demonstrate that the absence of Ncr1p had no effect on fluid phase and receptor‐ mediated endocytosis, biosynthetic delivery to the vacuole, retrograde transport from endosome to Golgi and ubiquitin‐ and nonubiquitin‐dependent multivesicular body sorting. We conclude that Ncr1p does not have an essential role in known endocytic transport pathways in yeast.
The effect on osteogenesis of type I collagen applied to experimental bone defects
Authors: Gungormus Metin
Published: November 2004

Abstract –  The purpose of the present investigation was to evaluate the effects of type I collagen sponge on the healing of bone defects. In this study, six adult male rabbits were used. After the induction of general anesthesia with intraperitoneal kethamine, the anterior surfaces of tibias of the rabbits were surgically exposed, and two holes with 4 mm in diameter were prepared on each tibia for the investigation. Only one hole in each tibia was filled with type I collagen, the other unfilled hole was used as control. During the study, radiopacity changes in the radiographs of the tibias of the rabbits were evaluated. The animals were killed on the 28th day, and histologic sections of the tibias were prepared. On the 28th day, it was histopathologically observed that collagen cavities were filled with new bone. In addition, it was determined that there was an increase in radiopacity of the defect areas from 14 to 28 days in both groups, and there were statistically a significant difference between control and collagen groups (P = 0.0001). In this study, consequently, it was determined that type I collagen sponge in the experimental cavities provides a more rapid regeneration of bone defects compared with non‐filled cavities.
Non‐surgical treatment of sports‐related temporomandibular joint disorders in basketball players
Authors: Muhtaroğullari Mehmet , Demiralp Burak , Ertan Atila
Published: November 2004

Abstract –  In this study, 18 basketball players (11 female, seven male; age range 14–32 years) with temporomandibular joint (TMJ) problems who had a history of sport injuries related to head or jaw region were evaluated and the results of the treatment were presented. A standardized functional examination of the masticatory system was performed including measurement of maximal jaw movements, recording of joint sounds, pain on movement of the jaw as well as tenderness to palpation of the both TMJ or masticatory muscles. Patients were also evaluated periodontally. Diagnosis was made according the criteria, described by Okeson, and appropriate treatment was applied using different kind of splints. At the end of treatment only one patient continued with right TMJ reduction with slight pain. Except for that patient, none of the patients had pain after treatment. The maximum opening of the jaws and the maximal jaw movements were statistically increased after treatment. Patients with TMJ problems also showed periodontal problems, most likely due to inadequate oral hygiene because of the limited jaw movements and pain. Periodontal parameters including probing depth (PD), Plaque index (PI), and Sulcus Bleeding Index (SBI) improved after treatment. Sports‐related TMJ injuries may result in complex problems such as pain, TMJ sounds, limitation in maximal jaw movements and maximum opening of the mouth, difficulty in chewing. With the appropriate diagnosis this could be treated non‐surgically in 6–8 months. This study also showed that the TMJ disorders may cause periodontal problems, which may affect all teeth and also the general health of the athlete.
Sociocultural influences on infant feeding decisions among HIV‐infected women in rural Kwa‐Zulu Natal, South Africa
Authors: Thairu Lucy N. , Pelto Gretel H. , Rollins Nigel C. , Bland Ruth M. , Ntshangase Ncamisile
Published: November 2004

The promotion of exclusive breastfeeding for 6 months, followed by rapid transition to alternative food sources may be an important public health approach to the reduction of mother‐to‐child transmission of HIV through breastmilk. The basic ethical principle of ‘informed choice’ requires that HIV positive women are provided with adequate information about their options. However, information is only one factor that affects their decisions. The objective of this ethnographic study was to identify sociocultural influences on infant feeding decisions in the context of a large cohort study designed to assess the impact of a breastfeeding counselling and support strategy to promote exclusive breastfeeding on postnatal transmission of HIV in African women. Following an initial period of exploratory interviewing, ethnographic techniques were used to interview 22 HIV positive women about their views on infant feeding and health. Interviews were tape‐recorded, transcribed and analysed with a text analysis program. Five themes of influences on feeding decisions emerged: (1) social stigma of HIV infection; (2) maternal age and family influences on feeding practices; (3) economic circumstances; (4) beliefs about HIV transmission through breastmilk; and (5) beliefs about the quality of breastmilk compared to formula. The study highlights the role of cultural, social, economic and psychological factors that affect HIV positive women's infant feeding decisions and behaviour.
Evaluation of the use of health care assistants to support disadvantaged women breastfeeding in the community
Authors: Beake Sarah , McCourt Christine , Rowan Cathy , Taylor Jane
Published: November 2004

There is little experience of the use of health care assistants in the community to support breastfeeding in the UK. The aim of this project was to evaluate the implementation of a small‐scale pilot project using health care assistants in the community to support disadvantaged women breastfeeding. The evaluation was funded as part of the Department of Health's Infant Feeding Initiative. A longitudinal observational and quasi‐experimental design was used. The project involved women, who had recently given birth, living in an area of London identified by the government's Sure Start scheme as socio‐economically disadvantaged. This paper focuses mainly on the findings drawn from the qualitative data focusing on the process of implementation, the role of the Support Worker and women's perceptions of the support. The findings suggest that the use of health care assistants in the community may offer a practical and encouraging approach in supporting breastfeeding which is acceptable to both breastfeeding women and health care professionals. More research is needed to establish whether the intervention significantly increases breastfeeding rates.
The research career of Richard B. Stein (1940–)
Authors: Stuart D G
Published: November 2004

This report reviews the research and mentoring career of Richard B. Stein (1940–). In 1962, he completed a B.S. degree in physics at the Massachusetts Institute of Technology, USA, and thereafter an M.A. (1964), Ph.D. (1966), and postdoctoral training (1966–68) at the University of Oxford, UK. He subsequently assumed a faculty position at the University of Alberta (Canada), where he is currently an active researcher and mentor. To this point in 2004, Stein has trained and collaborated closely with over 160 scientists, largely neuroscientists and biomedical engineers, from 27 countries. He and his former trainees and collaborators have made important contributions on topics that span the cellular-to-behavioral spectrum of movement and rehabilitation–prosthetics neuroscience. His mentors, trainees, and collaborators include scientists whose countries of origin are: Australia, 2; Austria, 1; Belgium, 1; Bulgaria, 1; Canada, 64; China, 6; Denmark, 1; Germany, 1; Great Britain, 16; Hong Kong, 4; India, 5; Iraq, 2; Italy, 2; Japan, 10; Kenya, 1; New Zealand, 4; Pakistan, 1; Palestine, 1; Poland, 1; Romania, 1; South Africa, 1; Sri Lanka, 1; The Netherlands, 1; Turkey, 1; Uruguay, 1; USA, 21; and Yugoslavia, 6. In all instances, Stein's research collaborations and mentoring have advanced the careers of his trainees and junior collaborators, a well-deserved and important compliment to a stellar movement neuroscientist.Key words: movement neuroscience, rehabilitation neuroscience, prosthetics.
Rate-coding of spinal motoneurons with high-frequency magnetic stimulation of human motor cortex
Authors: Bawa Parveen , Calancie Blair
Published: November 2004

Rate-coding in spinal motoneurons was studied using high-frequency magnetic stimulation of the human motor cortex. The subject made a weak contraction to cause rhythmic (i.e., tonic) discharge of a single motor unit in flexor (or extensor) carpi radialis or tibialis anterior, while the motor cortical representation of that muscle was stimulated with brief trains of pulses from a Pyramid stimulator (4 Magstim units connected by 3 BiStim modules). An "m@n" stimulus train consisted of m number of pulses (1–4), with an interpulse interval (IPI) of n ms (1–6). Peristimulus time histograms were constructed for each stimulus condition of a given motor unit, and related to the average rectified surface electromyography (EMG) from that muscle. Surface EMG responses showed markedly more facilitation than single-pulse stimulation, with increasing numbers of pulses in the train; responses also tended to increase in magnitude for the longer IPI values (4 and 6 ms) tested. Motor-unit response probability increased in a manner comparable to that of surface EMG. In particular, motoneurons frequently responded twice to a given stimulus train. In addition to recruitment of new motor units, the increased surface EMG responses were, in part, a direct consequence of short-term rate-coding within the tonically discharging motoneuron. Our results suggest that human corticomotoneurons are capable of reliably following high-frequency magnetic stimulation rates, and that this activity pattern is carried over to the spinal motoneuron, enabling it to discharge at extremely high rates for brief periods of time, a pattern known to be optimal for force generation at the onset of a muscle contraction.Key words: Human, single motor unit, repetitive transcranial magnetic stimulation, rate-coding, high-frequency stimulation, corticomotoneuron, peri-stimulus time histogram.
Infant stepping: a window to the behaviour of the human pattern generator for walking
Authors: Yang Jaynie F , Lam Tania , Pang Marco Y.C , Lamont Erin , Musselman Kristin , Seinen Elizabeth
Published: November 2004

The aim of this paper is to provide evidence, both published and new, to support the notion that human infants are particularly good subjects for the study of the pattern generator for walking. We and others have shown that stepping can be initiated by sensory input from the legs or by general heightened excitability of the infant. New results are presented here to suggest that weight support through the feet and rapid extension of the legs are important proprioceptive inputs to initiate stepping. Our previous work has shown that infants can step at many different speeds when supported on a treadmill. The step cycle duration shortens as the speed increases, with the changes coming largely from the stance phase, just as in most other terrestrial animals. Moreover, we have shown that infants will step in all directions. Regardless of the direction of stepping, the step cycle changes in the same way with walking speed, suggesting the circuitry that controls different directions of walking share common elements. We have also shown that infant stepping is highly organized. Sensory inputs, whether proprioceptive or touch, are gated in a functional way so that only important sensory inputs generate a response. For example, touch to the lateral surface of the foot elicits a response only in sideways walking, and only in the leading limb. New data is presented here to show that the pattern generators from each limb can operate somewhat independently. On a split-belt treadmill with the 2 belts running at different speeds or in different directions, the legs showed considerable independence in behaviour. Yet, the pattern generators on each side interact to ensure that swing phase does not occur at the same time. These studies have provided insight into the organization of the pattern generator for walking in humans. It will be interesting in the future to study how maturation of the descending tracts changes walking behaviour to allow independent bipedal walking.Key words: locomotion, central pattern generator, human, infant.
Ankle extensor proprioceptors contribute to the enhancement of the soleus EMG during the stance phase of human walking
Authors: Grey Michael J , Mazzaro Nazarena , Nielsen Jens Bo , Sinkjær Thomas
Published: November 2004

A rapid plantar flexion perturbation applied to the ankle during the stance phase of the step cycle during human walking unloads the ankle extensors and produces a marked decline in the soleus EMG. This demonstrates that sensory activity contributes importantly to the enhancement of the ankle extensor muscle activation during human walking. On average, the EMG begins to decline approximately 52 ms after the perturbation. In contrast, a rapid dorsi flex ion perturbation produces a group Ia mediated short-latency stretch reflex burst with an onset latency of approximately 36 ms. The transmission of sensory traffic from the foot and ankle was suppressed in 10 subjects by an anaesthetic nerve block produced with local injections of lidocaine hydrochloride. The anaesthetic block had no effect on the stance phase soleus EMG, the latencies of the EMG responses, or the magnitude of the EMG decline following the plantar flexion perturbation. Therefore, it is more likely that proprioceptive afferents, rather than cutaneous afferents, contribute to the background soleus EMG during the late stance phase of the step cycle. The large difference in onset latencies between the short-latency reflex and unload responses suggests that the largest of the active group Ia afferents might not contribute strongly to the background soleus EMG, although it remains to be determined which of the proprioceptive pathways provide the more important contributions.Key words: afferent feedback, gait, locomotion, stretch reflex.
Functional electrical stimulation using microstimulators to correct foot drop: a case study
Authors: Weber D J , Stein R B , Chan K M , Loeb G E , Richmond F J.R , Rolf R , James K , Chong S L , Thompson Aiko Kido , Misiaszek J
Published: November 2004

This paper presents a case study that tested the feasibility and efficacy of using injectable microstimulators (BIONs®) in a functional electrical stimulation (FES) device to correct foot drop. Compared with surface stimulation of the common peroneal nerve, stimulation with BIONs provides more selective activation of specific muscles. For example, stimulation of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles with BIONs produces ankle flexion without excessive inversion or eversion of the foot (i.e., balanced flexion). Efficacy was assessed using a 3-dimensional motion analysis of the ankle and foot trajectories during walking with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. BION stimulation of the TA muscle and deep peroneal nerve (which innervates TA and EDL) elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the less affected leg. The physiological cost index (PCI) measured effort during walking. The PCI equals the change in heart rate (from rest to activity) divided by the walking speed; units are beats per metre. The PCI is high without stimulation (2.29 ± 0.37, mean ± SD) and greatly reduced with surface (1.29 ± 0.10) and BIONic stimulation (1.46 ± 0.24). Also, walking speed increased from 9.4 ± 0.4 m/min without stimulation to 19.6 ± 2.0 m/min with surface and 17.8 ± 0.7 m/min with BIONic stimulation. These results suggest that FES delivered by a BION is an alternative to surface stimulation and provides selective control of muscle activation.Key words: FES, BION, foot drop, stroke, spinal cord injury.
Vestibulospinal influences on lower limb motoneurons
Authors: Kennedy Paul M , Cresswell Andrew G , Chua Romeo , Inglis J Timothy
Published: November 2004

Galvanic vestibular stimulation (GVS) is a research tool used to activate the vestibular system in human subjects. When a low-intensity stimulus (1–4 mA) is delivered percutaneously to the vestibular nerve, a transient electromyographic response is observed a short time later in lower limb muscles. Typically, galvanically evoked responses are present when the test muscle is actively engaged in controlling standing balance. However, there is evidence to suggest that GVS may be able to modulate the activity of lower limb muscles when subjects are not in a free-standing situation. The purpose of this review is to examine 2 studies from our laboratory that examined the effects of GVS on the lower limb motoneuron pool. For instance, a monopolar monaural galvanic stimulus modified the amplitude of the ipsilateral soleus H-reflex. Furthermore, bipolar binaural GVS significantly altered the onset of activation and the initial firing frequency of gastrocnemius motor units. The following paper examines the effects of GVS on muscles that are not being used to maintain balance. We propose that GVS is modulating motor output by influencing the activity of presynaptic inhibitory mechanisms that act on the motoneuron pool.Key words: galvanic vestibular stimulation, h-reflex, motor unit, vestibulospinal, human.