bluuebunny/crossref_metadata_2025 huggingface dataset:
VARIATION OF MQW DESIGN PARAMETERS IN A GaAs/InP-BASED LW-VCSEL AND ITS EFFECTS ON THE SPECTRAL LINEWIDTH
Authors: MENON P. SUSTHITHA , KANDIAH KUMARAJAH , SHAARI SAHBUDIN
Published: August 2010

This paper reports on the simulative and comparative study on the effects of multi quantum well (MQW) design parameters on the spectral linewidth of a wafer-bonded GaAs/InP -based, 1.5 μm long-wavelength vertical-cavity surface-emitting laser (LW-VCSEL). The device employs InGaAsP MQWs sandwiched between GaAs/AlGaAs and GaAs/AlAs distributed Bragg reflectors (DBR) and utilizes a bottom-emitting, air-post design for current confinement. Among the modeled LW-VCSEL devices, the best linewidth achieved was 41.29 MHz at a peak wavelength of 1.57 μm for 8 MQWs with well thicknesses of 5.5 nm each and barrier thicknesses of 8 nm; equivalent to the experimental device developed in the past. Comparison of linewidth values calculated using developed analytical equations that link the MQW parameters to the spectral linewidth versus the actual linewidth from fabricated devices yields error ratios of ~ 6% proving a robust approximation has been achieved.
Improvement in β-cell function in patients with normal and hyperglycemia following Roux-en-Y gastric bypass surgery
Authors: Lin Edward , Liang Zhe , Frediani Jennifer , Davis Scott S. , Sweeney John F. , Ziegler Thomas R. , Phillips Lawrence S. , Gletsu-Miller Nana
Published: August 2010

Glycemic disorders resolve following Roux-en-Y gastric bypass (RYGB) surgery, but early and longer-term mechanisms regarding effects on β-cell dysfunction as well as relationships with decreasing adiposity are not well understood. We evaluated longitudinal changes in peripheral insulin sensitivity (Si), the acute insulin response to glucose (AIRg), and the composite estimate of β-cell function, the disposition index (DI), over 24 mo via frequently sampled intravenous glucose tolerance testing in severely obese women who had fasting normoglycemia ( n = 16) and hyperglycemia ( n = 11) before RYGB surgery; homeostatic model assessment (HOMA-IR) estimated insulin resistance; air displacement plethysmography determined adipose tissue mass. At baseline, subjects with normoglycemia had adequate DI associated with elevated AIRg, but DI was markedly reduced in subjects with hyperglycemia. Within 1–6 mo post-RYGB, glycemic control was normalized in subjects with hyperglycemia related to reduced HOMA-IR (−54% at 1 mo, P < 0.005) and increased DI (23-fold at 6 mo vs. baseline, P < 0.05). Over 24 mo, DI improved in subjects with hyperglycemia (15-fold vs. baseline, P < 0.005) and also modestly in subjects with normoglycemia (58%, P < 0.05), due largely to increased Si. Decreasing adiposity correlated with longer-term HOMA-IR and Si values at 6 and 24 mo, respectively. In patients exhibiting fasting hyperglycemia before surgery, β-cell function improved early following RYGB, due largely to increases in insulin secretion. For both normoglycemic and hyperglycemic subjects, further improvement or stabilization of β-cell function over the 2 yr is due largely to improved Si associated with reduced adiposity.
Hypertension Induced by Angiotensin II and a High Salt Diet Involves Reduced SK Current and Increased Excitability of RVLM Projecting PVN Neurons
Authors: Chen Qing-Hui , Andrade Mary Ann , Calderon Alfredo S. , Toney Glenn M.
Published: August 2010

Although evidence indicates that activation of presympathetic paraventricular nucleus (PVN) neurons contributes to the pathogenesis of salt-sensitive hypertension, the underlying cellular mechanisms are not fully understood. Recent evidence indicates that small conductance Ca2+-activated K+ (SK) channels play a significant role in regulating the excitability of a key group of sympathetic regulatory PVN neurons, those with axonal projections to the rostral ventrolateral medulla (RVLM; i.e., PVN-RVLM neurons). In the present study, rats consuming a high salt (2% NaCl) diet were made hypertensive by systemic infusion of angiotensin II (AngII), and whole cell patch-clamp recordings were made in brain slice from retrogradely labeled PVN-RVLM neurons. To determine if the amplitude of SK current was altered in neurons from hypertensive rats, voltage-clamp recordings were performed to isolate SK current. Results indicate that SK current amplitude ( P < 0.05) and density ( P < 0.01) were significantly smaller in the hypertensive group. To investigate the impact of this on intrinsic excitability, current-clamp recordings were performed in separate groups of PVN-RVLM neurons. Results indicate that the frequency of spikes evoked by current injection was significantly higher in the hypertensive group ( P < 0.05–0.01). Whereas bath application of the SK channel blocker apamin significantly increased discharge of neurons from normotensive rats ( P < 0.05–0.01), no effect was observed in the hypertensive group. In response to ramp current injections, subthreshold depolarizing input resistance was greater in the hypertensive group compared with the normotensive group ( P < 0.05). Blockade of SK channels increased depolarizing input resistance in normotensive controls ( P < 0.05) but had no effect in the hypertensive group. On termination of current pulses, a medium afterhyperpolarization potential (mAHP) was observed in most neurons of the normotensive group. In the hypertensive group, the mAHP was either small or absent. In the latter case, an afterdepolarization potential (ADP) was observed that was unaffected by apamin. Apamin treatment in the normotensive group blocked the mAHP and revealed an ADP resembling that seen in the hypertensive group. We conclude that diminished SK current likely underlies the absence of mAHPs in PVN-RVLM neurons from hypertensive rats. Both the ADP and greater depolarizing input resistance likely contribute to increased excitability of PVN-RVLM neurons from rats with AngII-Salt hypertension.
H55N polymorphism as a likely cause of variation in citrate synthase activity of mouse skeletal muscle
Authors: Ratkevicius Aivaras , Carroll Andrew M. , Kilikevicius Audrius , Venckunas Tomas , McDermott Kevin T. , Gray Stuart R. , Wackerhage Henning , Lionikas Arimantas
Published: August 2010

Citrate synthase (CS) is an enzyme of the Krebs cycle that plays a key role in mitochondrial metabolism. The aim of this study was to investigate the mechanisms underlying low activity of citrate synthase (CS) in A/J mice compared with other inbred strains of mice. Enzyme activity, protein content, and mRNA levels of CS were studied in the quadriceps muscles of A/J, BALB/cByJ, C57BL/6J, C3H/HeJ, DBA/2J, and PWD/PhJ strains of mice. Cytochrome c protein content was also measured. The results of the study indicate that A/J mice have a 50–65% reduction in CS activity compared with other strains despite similar levels of Cs mRNA and lack of differences in CS and cytochrome c protein content. CS from A/J mice also showed lower Michaelis constant ( Km) for both acetyl CoA and oxaloacetate compared with the other strains of mice. In silico analysis of the genomic sequence identified a nonsynonymous single nucleotide polymorphism (SNP) (rs29358506, H55N) in Cs gene occurring near the site of the protein interacting with acetyl CoA. Allelic variants of the polymorphism segregated with the catalytic properties of CS enzyme among the strains. In summary, H55N polymorphism in Cs could be the underlying cause of low CS activity and its high affinity for substrates in A/J mice compared with other strains. This SNP might also play a role in resistance to obesity of A/J mice.
Negative energy balance and hepatic gene expression patterns in high-yielding dairy cows during the early postpartum period: a global approach
Authors: McCarthy S. D. , Waters S. M. , Kenny D. A. , Diskin M. G. , Fitzpatrick R. , Patton J. , Wathes D. C. , Morris D. G.
Published: August 2010

In high-yielding dairy cows the liver undergoes extensive physiological and biochemical changes during the early postpartum period in an effort to re-establish metabolic homeostasis and to counteract the adverse effects of negative energy balance (NEB). These adaptations are likely to be mediated by significant alterations in hepatic gene expression. To gain new insights into these events an energy balance model was created using differential feeding and milking regimes to produce two groups of cows with either a mild (MNEB) or severe NEB (SNEB) status. Cows were slaughtered and liver tissues collected on days 6–7 of the first follicular wave postpartum. Using an Affymetrix 23k oligonucleotide bovine array to determine global gene expression in hepatic tissue of these cows, we found a total of 416 genes (189 up- and 227 downregulated) to be altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with widespread changes in gene expression classified into 36 gene networks including those associated with lipid metabolism, connective tissue development and function, cell signaling, cell cycle, and metabolic diseases, the three most significant of which are discussed in detail. SNEB cows displayed reduced expression of transcription activators and signal transducers that regulate the expression of genes and gene networks associated with cell signaling and tissue repair. These alterations are linked with increased expression of abnormal cell cycle and cellular proliferation associated pathways. This study provides new information and insights on the effect of SNEB on gene expression in high-yielding Holstein Friesian dairy cows in the early postpartum period.
Defining a rat blood pressure quantitative trait locus to a <81.8 kb congenic segment: comprehensive sequencing and renal transcriptome analysis
Authors: Gopalakrishnan K. , Saikumar J. , Peters C. G. , Kumarasamy S. , Farms P. , Yerga-Woolwine S. , Toland E. J. , Schnackel W. , Giovannucci D. R. , Joe B.
Published: August 2010

Evidence from multiple linkage and genome-wide association studies suggest that human chromosome 2 (HSA2) contains alleles that influence blood pressure (BP). Homologous to a large segment of HSA2 is rat chromosome 9 (RNO9), to which a BP quantitative trait locus (QTL) was previously mapped. The objective of the current study was to further resolve this BP QTL. Eleven congenic strains with introgressed segments spanning <81.8 kb to <1.33 Mb were developed by introgressing genomic segments of RNO9 from the Dahl salt-resistant (R) rat onto the genome of the Dahl salt-sensitive (S) rat and tested for BP. The congenic strain with the shortest introgressed segment spanning <81.8 kb significantly lowered BP of the hypertensive S rat by 25 mmHg and significantly increased its mean survival by 45 days. In contrast, two other congenic strains had increased BP compared with the S. We focused on the <81.8 kb congenic strain, which represents the shortest genomic segment to which a BP QTL has been mapped to date in any species. Sequencing of this entire region in both S and R rats detected 563 variants. The region did not contain any known or predicted rat protein coding genes. Furthermore, a whole genome renal transcriptome analysis between S and the <81.8 kb S.R congenic strain revealed alterations in several critical genes implicated in renal homeostasis. Taken together, our results provide the basis for future studies to examine the relationship between the candidate variants within the QTL region and the renal differentially expressed genes as potential causal mechanisms for BP regulation.
The Enigma of Tripeptidyl-Peptidase II: Dual Roles in Housekeeping and Stress
Authors: Preta Giulio , de Klark Rainier , Gavioli Riccardo , Glas Rickard
Published: August 2010

The tripeptidyl-peptidase II complex consists of repeated 138 kDa subunits, assembled into two twisted strands that form a high molecular weight complex (>5 MDa). TPPII, like many other cytosolic peptidases, plays a role in the ubiquitin-proteasome pathway downstream of the proteasome as well as in the production and destruction of MHC class I antigens and degradation of neuropeptides. Tripeptidyl-peptidase II activity is increased in cells with an increased demand for protein degradation, but whether degradation of cytosolic peptides is the only cell biological role for TPPII has remained unclear. Recent data indicated that TPPII translocates into the nucleus to control DNA damage responses in malignant cells, supporting that cytosolic “housekeeping peptidases” may have additional roles in cell biology, besides their contribution to protein turnover. Overall, TPPII has an emerging importance in several cancer-related fields, such as metabolism, cell death control, and control of genome integrity; roles that are not understood in detail. The present paper reviews the cell biology of TPPII and discusses distinct roles for TPPII in the nucleus and cytosol.
A Study on Degree of Approximation by (E, 1) Summability Means of the Fourier‐Laguerre Expansion
Authors: Nigam H. K. , Sharma Ajay
Published: August 2010

A very new theorem on the degree of approximation of the generating function by (E, 1) means of its Fourier‐Laguerre series at the frontier point x = 0 is obtained.
Pseudoxanthoma Elasticum Papillary Dermal Elastolysis: A Case Report
Authors: Alves Rubina , Ferreira Lurdes , Vale Esmeralda , Bordalo Olívia
Published: August 2010

PXE‐PDE is a rare clinicopathological entity with few cases reported. It affects more often elderly women and is characterized by asymptomatic bilateral and symmetrical yellowish papules localized predominantly on the neck and supraclavicular regions. It is clinically similar to Pseudoxanthoma Elasticum. The authors report a case of a 64‐year‐old woman presenting asymptomatic, yellowish, non‐follicular papules, affecting the occipital and the posterior region of the neck for 1 year. The patient denied pruritic or inflammatory changes, marked solar exposition or trauma on the affected areas. Routine laboratory studies: thoracic x‐ray and ophthalmologic examination were normal. The histopathologic examination of a biopsy of one of the cutaneous lesions showed an absence of elastic fibers in the papillary dermis.The diagnosis of Pseudoxanthoma Elasticum—like Papillary Dermal Elastolysis (PXE‐PDE) was made. Of great importance is the differential diagnosis with Pseudoxanthoma elasticum (PXE), but we have also to consider other elastolytic disorders: mid‐dermal elastolysis (MDE), linear focal elastosis (LFE) and white fibrous papulosis of the neck (WFPN). Until know, there is no effective treatment for this pathology.
Intranasal Immunization with Chitosan/pCAGGS-flaA Nanoparticles InhibitsCampylobacter jejuniin a White Leghorn Model
Authors: Huang Jin-lin , Yin Yan-Xin , Pan Zhi-ming , Zhang Gong , Zhu Ai-ping , Liu Xiu-fan , Jiao Xin-an
Published: August 2010

Campylobacter jejuniis the most common zoonotic bacterium associated with human diarrhea, and chickens are considered to be one of the most important sources for human infection, with no effective prophylactic treatment available. We describe here a prophylactic strategy using chitosan-DNA intranasal immunization to induce specific immune responses. The chitosan used for intranasal administration is a natural mucus absorption enhancer, which results in transgenic DNA expression in chicken nasopharynx. Chickens immunized with chitosan-DNA nanoparticles, which carried a gene for the major structural protein FlaA, produced significantly increased levels of serum anti-Campylobacter jejuniIgG and intestinal mucosal antibody (IgA), compared to those treated with chitosan-DNA (pCAGGS). Chitosan-pCAGGS-flaA intranasal immunization induced reductions of bacterial expellation by 2-3log10and 2log10in large intestine and cecum of chickens, respectively, when administered with the isolatedC. jejunistrain. This study demonstrated that intranasal delivery of chitosan-DNA vaccine successfully induced effective immune response and might be a promising vaccine candidate againstC. jejuniinfection.
Thermal Temperature Measurements of Plasma Torch by Alexandrite Effect Spectropyrometer
Authors: Wang Peir-Jyh , Tzeng Chin-Ching , Liu Yan
Published: August 2010

An alexandrite effect spectropyrometer is used to directly measure the thermal temperature of an argon gas plasma jet from a 100 kW DC plasma torch, and the directly measured thermal temperature of the plasma is  K. By using the spectral correction function to delete the spectral lines and to correct its underlying spectrum of the relative spectral power distribution of the plasma jet, the remaining continuum spectral power distribution represents the thermal spectral emission of the plasma jet. The calculated thermal temperature of the corrected relative continuum spectral power distribution by the spectropyrometer is 10106 K  K, which is the true thermal temperature of the plasma jet. The blackbody level (BL) of the thermal plasma jet is defined as the ratio of the true thermal temperature to the directly measured temperature, and the blackbody level is a measure of how well the thermal plasma jet approaches a blackbody. The accuracy of directly measured thermal temperature depends on the blackbody level, the higher the blackbody level, and the higher the thermal temperature measurement accuracy.
S100B Protein, a Damage-Associated Molecular Pattern Protein in the Brain and Heart, and Beyond
Authors: Sorci Guglielmo , Bianchi Roberta , Riuzzi Francesca , Tubaro Claudia , Arcuri Cataldo , Giambanco Ileana , Donato Rosario
Published: August 2010

S100B belongs to a multigenic family of -binding proteins of the EF-hand type and is expressed in high abundance in the brain. S100B interacts with target proteins within cells thereby altering their functions once secreted/released with the multiligand receptor RAGE. As an intracellular regulator, S100B affects protein phosphorylation, energy metabolism, the dynamics of cytoskeleton constituents (and hence, of cell shape and migration), homeostasis, and cell proliferation and differentiation. As an extracellular signal, at low, physiological concentrations, S100B protects neurons against apoptosis, stimulates neurite outgrowth and astrocyte proliferation, and negatively regulates astrocytic and microglial responses to neurotoxic agents, while at high doses S100B causes neuronal death and exhibits properties of a damage-associated molecular pattern protein. S100B also exerts effects outside the brain; as an intracellular regulator, S100B inhibits the postinfarction hypertrophic response in cardiomyocytes, while as an extracellular signal, (high) S100B causes cardiomyocyte death, activates endothelial cells, and stimulates vascular smooth muscle cell proliferation.
Clinical Indication as an Ethical Appraisal: The Example of Imaging before Middle Ear Surgery
Authors: Hurst Samia A.
Published: August 2010

Purpose of the Study: Asking whether imaging is indicated before middle ear surgery requires us to examine the question of indication more generally. Procedures: Clinical indication integrates different levels, which are distinguished in this paper. As deciding whether or not an intervention is indicated requires different approaches on each of these levels, these approaches are also explored. Results: Even when sufficient data are available to determine whether an intervention brings some benefit, knowing whether or not this intervention is indicated still requires us to answer 3 additional questions: (1) Is the intervention sufficiently beneficial to be clinically relevant? (2) Is the intervention ‘reasonable’ in terms of its opportunity costs? (3) How are we to decide which interventions ‘make the cut’, and which do not? Although we may all have an informed opinion on this topic, the question of the thresholds we ought to apply to very marginal benefits is one where the best answer can only be the one we have all agreed on. This requires a guideline integrating elements of procedural fairness, developed in conditions of protection from the risks of conflicts of interests. Conclusion: Although some of these questions integrate considerations of costs, not all do. However, all integrate value judgements, making clinical indication in part a question of ethical appraisal.
What the Surgeon Cannot See and Needs to See before Middle Ear Surgery
Authors: Schmerber Sébastien , Lefournier Virginie , Karkas Alexandre
Published: August 2010

Objective: To define the utility of imaging prior to middle ear surgery. Methods: Different middle ear pathologies are subsequently described: conductive hearing loss with a normal tympanic membrane, labyrinthine fistulae, tegmen anomalies, opacified tympanic membrane, cholesteatoma, temporal bone fractures and glomus tumors. We discuss the indications and benefits of imaging in each of these pathologies. Results: Preoperative imaging shows interesting features and can be very helpful in the differential diagnosis and in surgical decision-making and planning. However, it is not mandatory and should not be systematic in every middle ear surgery. Conclusion: The modern radiological era provides the otological surgeon with numerous imaging technologies. Yet, these techniques should by no means replace the surgeon’s anatomical knowledge, clinical sense and surgical skills.
Quality Management in Middle Ear Surgery: Controversies Regarding Preoperative Imaging
Authors: Zahnert T. , Offergeld C.
Published: August 2010

Today a large variety of different imaging techniques are available for middle ear investigation. However, imaging is not suitable to give essential information in every case on the surgical strategy to be chosen. This article discusses the most frequent indications for preoperative imaging and the relevant techniques. CT scanning, MRI and rotational tomography are taken into consideration as well as traditional X-ray investigations like e.g. ‘Schüller’s view’. In general, preoperative imaging should only be performed in a patient if certain specific questions can be answered. The experience of the investigator to interpret the images may influence the choice of imaging as well as the equipment he has access to.
The Use of Radiology in Middle Ear and Temporal Bone Surgery
Authors: Bagger-Sjöbäck Dan , Papatziamos Georgios
Published: August 2010

A nationwide survey was performed in Sweden regarding the way that practicing otosurgeons utilize radiological imaging before and after performing surgery of the middle ear and temporal bone. Sixty-six surgeons from 30 different otorhinolaryngology departments participated in the study. These represented all hospitals in Sweden where ear surgery is performed to some degree. A questionnaire was designed consisting of 18 questions that were assigned to 4 different groups. Questions in group 1 assessed the general conditions regarding imaging services in the local hospital. Questions in group 2 illuminated the level of tuition and competence development when it comes to judging radiological examinations. Group 3 questions mirrored the clinical routines when ordering various specific investigations. In group 4, the questions were aimed at describing which type of information the surgeons wanted to obtain from the imaging investigations. The answers gave a good picture of how Swedish otosurgeons use the services offered by their local radiological departments. One of the conclusions is that, although there is consensus regarding certain types of examinations in specific conditions, there is a great variation in how surgeons utilize radiological imaging in many of the most common clinical conditions. It is obvious that the routines regarding the use of radiology in conjunction with ear surgery vary from place to place and also between different surgeons. Whether a consensus can be reached in the future regarding this issue remains to be seen.
Interstitial Deletions at 6q14.1–q15 Associated with Obesity, Developmental Delay and a Distinct Clinical Phenotype
Authors: Wentzel C. , Lynch S.A. , Stattin E.-L. , Sharkey F.H. , Annerén G. , Thuresson A.-C.
Published: August 2010

Background: Interstitial deletions of the long arm of chromosome 6 have been described in several patients with obesity and a Prader-Willi-like phenotype. Haploinsufficiency of the SIM1 gene located at 6q16.3 is suggested as being responsible for the regulation of body weight. Here we report on 2 patients with interstitial deletions at 6q14.1–q15 presenting with obesity and symptoms strikingly similar to those reported for deletions involving the SIM1 gene despite not having a deletion of this gene. Methods: Array comparative genomic hybridisation was used to diagnose 2 children with obesity and developmental delay, revealing 2 interstitial deletions at 6q14.1–q15 of 8.73 and 4.50 Mb, respectively, and a region of overlap of 4.2-Mb. Results: The similar phenotype in the 2 patients was most likely due to a 4.2-Mb common microdeletion at 6q14.1–q15. Another patient has previously been described with an overlapping deletion. The 3 patients share several features, such as developmental delay, obesity, hernia, rounded face with full cheeks, epicanthal folds, short palpebral fissures, bulbous nose, large ears, and syndactyly between toes II and III. Conclusions: Together with a previously reported patient, our study suggests that the detected deletions may represent a novel clinically recognisable microdeletion syndrome caused by haploinsufficiency of dosage-sensitive genes in the 6q14.1–q15 region.
Steroids and the Management of Macular Edema
Authors: Golan Shani , Loewenstein Anat
Published: August 2010

Macular edema (ME) is a condition which is usually secondary to an underlying disease process. It is most commonly seen following venous occlusive disease, diabetic retinopathy and posterior segment inflammatory disease. The treatment of ME varies, depending upon the underlying etiology, and has led to varying degrees of success. Traditionally, the main treatment options have included topical and systemic steroids, due to their known antiangiogenic, antiedematous, antiinflammatory and antiproliferative effects. This comprehensive review outlines the current use of steroids and highlights the ever-growing indications for steroids in ME secondary to various ocular conditions as well as the recent breakthrough results of the efficacy of this treatment.
Juvenile Muscular Atrophy of a Unilateral Upper Extremity (Hirayama Disease) in a Patient with CHARGE Syndrome
Authors: Yagihashi T. , Hatori K. , Ishii K. , Torii C. , Momoshima S. , Takahashi T. , Kosaki K.
Published: August 2010

CHARGE syndrome is an autosomal dominant congenital anomaly syndrome, and the causative gene is CHD7. We report a patient with a CHD7 mutation who presented with juvenile muscular atrophy of a unilateral upper extremity, a presumably heterogeneous condition that is also known as Hirayama disease. This association has not been previously described. Weakness and atrophy of the hands should be carefully examined in patients with CHARGE syndrome, since Hirayama disease might be a possible complication in adolescent patients with this syndrome.
Lack of Activation of the Unfolded Protein Response in Mouse and Cellular Models of Niemann-Pick Type C Disease
Authors: Klein Andres , Mosqueira Matías , Martínez Gabriela , Robledo Fermín , González Marcela , Caballero Benjamín , Cancino Gonzalo I. , Alvarez Alejandra R. , Hetz Claudio , Zanlungo Silvana
Published: August 2010

Background: Niemann-Pick type C (NPC) disease is a fatal lysosomal storage disease related to progressive neurodegeneration secondary to abnormal intracellular accumulation of cholesterol. Signs of endoplasmic reticulum (ER) stress have been reported in other lipidoses. Adaptation to ER stress is mediated by the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates stress or triggers apoptosis of irreversibly damaged cells. Objective: To investigate the possible engagement of ER stress responses in NPC models. Methods: We used NPC1 deficient mice and an NPC cell-based model by knocking down the expression of NPC1 to measure several UPR markers through different approaches. Results: Despite expectations that the UPR will be activated in NPC, our results indicate a lack of ER stress reactions in the cerebellum of symptomatic mice. Similarly, knocking down NPC1 in Neuro2a cells leads to clear cholesterol accumulation without evidence of UPR activation. Conclusion: Our results suggest that cholesterol overload and neuronal dysfunction in NPC is not associated with ER stress, which contrasts with recent reports suggesting the activation of the UPR in other lysosomal storage diseases.
Ischemic Stroke in Young Asian Women: Risk Factors, Subtypes and Outcome
Authors: Wasay Mohammad , Kaul Subhash , Menon Bindu , Venketasubramanian Narayanaswamy , Gunaratne Padma , Khalifa Ahmed , Poungvarin Niphon , Saadatnia Mohammad , Gan Robert Ngo , Dai Alper , Mehndiratta M.M.
Published: August 2010

Background and Objective: The objective of our study was to describe risk factors, mechanisms and outcome of young Asian women with ischemic stroke. Methods: Twelve tertiary-care centers in 8 Asian countries participated. Women aged 15–45 years were included if they had an ischemic stroke supported by neuroimaging. Data on age, risk factor history, stroke mechanism and discharge status were collected. Results: A total of 958 subjects were included, their mean age was 34 years. Large-vessel thrombosis comprised 24%, cerebral venous thrombosis 21%, cardioembolism 19% and small-vessel thrombosis 15%. The stroke risk factors included hypertension (29%), diabetes (14%), pregnancy (11%), valvular heart disease (10%) and cigarette smoking (3%). Anemia was found in 42%, and mortality was 4%; at discharge, 17% had modified Rankin score (mRS) >4 and 83% mRS 0–3. Conclusion: Unlike among Caucasians, large-vessel thrombosis, cerebral venous thrombosis and cardioembolism are common among young Asian women with stroke. A high proportion are pregnancy-related. More studies are needed.
Health-Related Quality of Life in Patients with Subarachnoid Haemorrhage
Authors: Meyer Bernhard , Ringel Florian , Winter Yaroslav , Spottke Annika , Gharevi Nadir , Dams Judith , Balzer-Geldsetzer Monika , Mueller Ines K. , Klockgether Thomas , Schramm Johannes , Urbach Horst , Dodel Richard
Published: August 2010

Background: Aneurysmal subarachnoid haemorrhage (SAH) is a devastating disease with high mortality and disability. The data from large longitudinal studies on health-related quality of life (HRQoL) in patients with SAH are limited. The objective was to investigate HRQoL in patients after SAH and to identify predictors of HRQoL. Methods: 113 patients with aneurysmal SAH were assigned to either neurosurgery (n = 57) or endovascular coiling (n = 56). Clinical assessments (Barthel Index, modified Rankin Scale) and evaluation of HRQoL [36-Item Short-Form Survey, EuroQol (EQ5D), EQ visual analogue scale (EQ VAS)] were performed at discharge, and at 6 and 12 months of follow-up. Independent predictors of HRQoL were determined using multiple regression analysis. Results: HRQoL in SAH patients was considerably reduced compared to the normal population. At discharge, 92.2% of the patients had moderate or severe problems on the EQ5D. The EQ VAS score was 57.8 ± 19.3. However, HRQoL still showed improvement from 3 months up to 1 year. At 12 months after SAH, the EQ VAS score was approximately 12–14% higher than at discharge. The independent predictors of decreased HRQoL included female gender, severe SAH, functional disability, depression, a lower level of education and the lack of a stable partnership. Conclusions: The long-term HRQoL outcome after SAH is unfavourable. HRQoL outcome measures should be included in future studies to provide better evidence of the long-term outcomes after SAH. In addition, the independent determinants of HRQoL identified in this study should be considered in the healthcare programmes aimed at increasing the HRQoL in SAH survivors.
Pyoderma Gangrenosum of the Eyelid: Report of Two Cases and Review of the Literature
Authors: Saito N. , Yanagi T. , Akiyama M. , Lin H.Y. , Kasai S. , Fujita Y. , Yamane N. , Inokuma D. , Kase S. , Ono K. , Minakawa H. , Shimizu H.
Published: August 2010

Pyoderma gangrenosum (PG) of the eyelid is extremely rare, and its proper management is essential for the preservation of visual function. Here, we report 2 cases of PG of the eyelid with intraorbital involvement. In both cases, the skin and intraorbital lesions improved after systemic immunosuppressive therapies; however, corneal perforation occurred in 1 case. In order to assess the clinical features of PG of the eyelid and to obtain clues for optimal treatment, we reviewed 15 well-documented cases in the literature, including the present cases. Corneal perforation occurred in 4 cases and defective ocular motility in 1 case. Three patients eventually underwent enucleation of the affected eye. Our cases and the literature review clearly indicate that MRI is a powerful tool for evaluating the extent of extracutaneous PG lesions around the eye and that early diagnosis and immediate immunosuppressive therapy are crucial for the preservation of visual acuity.
Serum Adiponectin, TNF-α, IL-12p70, and IL-13 Levels in Multiple Sclerosis and the Effects of Different Therapy Regimens
Authors: Musabak Ugur , Demirkaya Seref , Genç Gencer , Ilikci Rahsan Sagkan , Odabasi Zeki
Published: August 2010

Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the human central nervous system. In the present study, we aimed to determine adiponectin, tumor necrosis factor-α, interleukin (IL)-12p70, and IL-13 levels in the sera of patients with MS and to investigate the effects of interferon (IFN), glatiramer acetate (GA), and immunosuppressive treatment regimens on these parameters. Methods: Fifty-seven patients with MS and 34 healthy controls were enrolled into the study. Serum cytokine levels were measured using enzyme immunoassay. Results: Significantly elevated levels of IL-12p70 and IL-13 were found in the sera of patients with MS, but decreased adiponectin levels were found in patients’ sera compared to healthy controls. The levels of IL-12p70 and IL-13 in the IFN therapy group were higher than those of the healthy controls. However, the IL-12p70 and IL-13 levels in the GA therapy group were not different from those of the healthy controls. There were no differences with regard to adiponectin levels among the subgroups of patients with MS according to therapy regimen and the healthy controls. At the end of a 2-year follow-up period, Expanded Disability Status Scale (EDSS) values were found to be increased in the IFN therapy group but unchanged in the GA therapy group. Conclusions: These findings suggest that adiponectin, IL-12p70, and IL-13 may play a role in the pathogenesis of MS. Additionally, GA therapy regimens in MS are more effective than IFN therapy with respect to decreasing the levels of IL-12p70 and IL-13 and stabilizing the EDSS value.
Modulation of C6 Glioma Cell Proliferation by Ureido-Calix[8]arenes
Authors: Viola Santa , Merlo Sara , Consoli Grazia M.L. , Drago Filippo , Geraci Corrada , Sortino Maria Angela
Published: August 2010

Calixarenes are synthetic macrocyclic compounds that may serve as scaffolds for biologically active molecules and have been proposed as potential anticancer agents. We synthesized a ureido-calix[8]arene carrying N-acetyl-D-glucosamine residue (compound 1) and had previously demonstrated that it inhibits C6 glioma cell migration and proliferation, with divergent mechanisms. In the present work we explored in more detail the antiproliferative effect of compound 1, comparing it to related compounds lacking either the sugar moieties (compound 2), the multiple ureido groups (compound 3) or both (compound 4). The results show that the action of compound 1 is independent of the N-acetyl-D-glucosamine residues, requires the presence of multiple ureido groups and does not seem to involve focal adhesion kinase signaling. Inhibition of proliferation is reduced by preincubation with epidermal growth factor (EGF) and vascular endothelial growth factor (20 ng/ml) with compound 1, and extracellular-related kinase phosphorylation is reduced by treatment with compound 1 in both basal and EGF-stimulated conditions, suggesting that the observed effect depends on a direct interference with growth factor signaling.
Positive Effect of HPA Lanolin versus Expressed Breastmilk on Painful and Damaged Nipples during Lactation
Authors: Abou-Dakn M. , Fluhr J.W. , Gensch M. , Wöckel A.
Published: August 2010

Painful and/or damaged nipples associated with breastfeeding are common and represent a challenge for both the persons experiencing nipple pain and/or trauma and for those providing treatment. However, evidence-based data has been insufficient to demonstrably minimize these common reasons for failure to initiate or continue successful breastfeeding. The aim of this study was to evaluate the efficacy of specific-grade highly purified anhydrous (HPA) lanolin versus expressed breastmilk (EBM) for the treatment of painful and damaged nipples associated with breastfeeding in a prospective controlled clinical trial evaluating 84 lactating mothers. Nipple trauma and healing rates were rated by the Nipple Trauma Score. Nipple pain intensity was assessed on a visual analog scale. Outcome parameters were in favor of the HPA lanolin group, reaching statistical significance for healing rates, nipple trauma and nipple pain. In our study, we found HPA lanolin more effective than EBM, inducing faster healing of nipple trauma (absolute risk reduction of 0.43) and reducing nipple pain (absolute risk reduction of 0.61 on day 3). We concluded that HPA lanolin, combined with breastfeeding education, was more effective than EBM, combined with breastfeeding education, in reducing nipple pain and promoting healing of nipple trauma.
Intrauterine Growth Restriction following Ligation of the Uterine Arteries Leads to More Severe Glomerulosclerosis after Mesangioproliferative Glomerulonephritis in the Offspring
Authors: Plank Christian , Nüsken Kai-Dietrich , Menendez-Castro Carlos , Hartner Andrea , Östreicher Iris , Amann Kerstin , Baumann Pia , Peters Harm , Rascher Wolfgang , Dötsch Jörg
Published: August 2010

Background: Low birth weight is a risk factor for the development of a more severe course of secondary renal diseases. We tested the hypothesis that experimental mesangioproliferative glomerulonephritis (GN) shows an aggravated course in rats inflicted with experimental uteroplacental insufficiency during gestation. Methods: Intrauterine growth restriction (IUGR) was induced by ligation of both uterine arteries on day 19 in pregnant Wistar rat dams. GN was induced in male offspring at the age of 9 weeks by intravenous injection of an anti-Thy-1.1 antibody. At day 14 of GN, kidneys were taken and analyzed for glomerular morphometry, markers of inflammation, glomerulosclerosis and tubulointerstitial fibrosis. Results: Despite a similar extent of mesangiolysis, former IUGR animals presented with a higher level of glomerulosclerosis and increased deposition of glomerular collagens I and IV compared to nephritic control animals. Arterial blood pressure, renal function, and proteinuria after 14 days of GN were not influenced by former IUGR. Conclusion: Ligation of the uterine arteries in the rat leads to more pronounced sclerotic changes in the glomerulus in the offspring suffering from acute GN. This finding supports the hypothesis that former IUGR increases the susceptibility for a more severe course of secondary renal diseases.
Cystatin C as a Parameter of Glomerular Filtration Rate in Patients with Ovarian Cancer
Authors: Bodnar Lubomir , Wcislo Gabriel Benedykt , Smoter Marta , Gasowska-Bodnar Agnieszka , Stec Rafał , Synowiec Agnieszka , Szczylik Cezary
Published: August 2010

Aims: To evaluate the potential role of serum cystatin C as a marker of renal function in patients with ovarian cancer. Methods: Treatment of consecutive ovarian cancer patients who were eligible for chemotherapy with paclitaxel (135 mg/m2/24 h) and cisplatin (75 mg/m2) every 3 weeks in 6 cycles. Glomerular filtration rate (GFR) markers, i.e. serum levels of creatinine and cystatin C, estimated by the Cockcroft-Gault and Modification of Diet in Renal Disease formulas, were recorded before each cycle and 3 weeks after the 6th course. Results: The median age of 34 patients was 54 years. In the initial stage of treatment, we did not observe any correlation between cystatin C and other GFR markers. We noted a significant association between cystatin C and tumor extent on spiral CT scans (diameter: >1 cm) performed at baseline (p = 0.004), and after the 1st (p = 0.03) and 2nd cycle (p = 0.026). We observed a correlation between cystatin C and CA-125 level before chemotherapy (R = 0.4; p = 0.02) and after the 1st cycle (R = 0.43; p = 0.04). Conclusion: The results of our study suggest that cystatin C is not a reliable marker of the GFR in ovarian cancer patients, probably due to its nature as a cysteine protease inhibitor.
Gender Differences in Cognitive Ability Associated with Genetic Variants of NLGN4
Authors: Zhang Kejin , Gao Xiaocai , Qi Hongbin , Li Jing , Zheng Zijian , Zhang Fuchang
Published: August 2010

Neuroligin-4 (NL4), encoded by the NLGN4 gene on the X chromosome, is a neuronal-specific brain membrane protein which plays an important role in the formation of functional presynaptic elements and axon specialization. The genetic variants of NLGN4 affect the biological function of NL4, resulting in the manifestation of different psychiatric disorders. The present study investigates the influence of these genetic variants on cognitive performance. The cognitive abilities of 351 subjects were evaluated using the Chinese Wechsler Intelligence Scale Children. The haplotypes were assigned with the PHASE program. The ANOVA method was applied to investigate the relationship between single SNP, the identified target haplotypes and cognitive performance in a random sample. We observed that the XC allele of rs5916271 and XA allele of the re6638575 carriers had significantly higher cognitive ability performances than the noncarrier boys (p < 0.05). The target haplotype composed of 2 allele (XCA+) carriers also displayed a higher cognitive performance than that of the noncarriers boys. The genetic polymorphism of NLGN4 also had a significant effect on the boys’ cognitive ability and other intelligence factors. Future research will involve determining the relationship between NLGN4 and personal cognitive ability.
Genetic Polymorphisms Associated with 5-Fluorouracil-Induced Neurotoxicity
Authors: Kim Suk-Ran , Park Chang-Hun , Park Silvia , Park Joon-Oh , Lee Jeeyun , Lee Soo-Youn
Published: August 2010

Background: Encephalopathy is a rare drug toxicity of fluorouracil therapy. Toxicity from fluorouracil therapy is known to be associated with the individual genetic background of the enzymes, thymidylate synthase and dihydropyrimidine dehydrogenase. Methods: Two patients with advanced gastric cancer and metastatic pancreatic cancer who received 5-fluorouracil-based chemotherapy presented with acute mental change and hyperammonemia. To evaluate the genetic background of the fluorouracil-associated hyperammonemic encephalopathy, analysis of the polymorphisms of the TYMS, DPYD and MTHFR genes was performed. Results: The patients revealed to be TYMS suppressors showing homogenous deletion of 6 bp in the 3′-UTR and 3RC/3RC genotype in the promoter enhancer region (TSER), respectively. Conclusion: Genetic polymorphisms of the TYMS gene would contribute to the 5-fluorouracil-associated hyperammonemic encephalopathy. The prospective validation of the clinical implication of TYMS gene polymorphisms is warranted.
Expression of Novel Podocyte-Associated Proteins sult1b1 and ankrd25
Authors: Xu Xiangjun , Patrakka Jaakko , Sistani Laleh , Uhlen Mathias , Jalanko Hannu , Betsholtz Christer , Tryggvason Karl
Published: August 2010

Background/Aims: Podocytes have a unique function in the renal ultrafiltration that is achieved by expressing proteins that are highly specific to podocytes. In this study, we identified two novel podocyte-associated proteins. Methods: The expression of sult1b1 and ankrd25 in mouse tissues was studied by RT-PCR. The protein expression was studied by generating polyclonal antibodies that were used in Western blotting and immunohistochemistry. Results: By RT-PCR we detected sult1b1 expression only in glomerular, liver and brain tissues. By immunohistochemistry, sult1b1 was detected in the kidney exclusively in the Golgi apparatus of the podocyte. No expression outside the glomerulus was observed in the kidney. The ankrd25 transcript was detected in most mouse tissues analyzed by RT-PCR. In the kidney, however, immunohistochemistry showed that this protein was expressed only by podocyte, mesangial, and smooth muscle cells. In podocytes, ankrd25 was localized to foot processes. Conclusions: Identification of these two novel glomerulus-associated proteins opens up possibilities to investigate their role in the renal filter physiology and diseases. We speculate that sult1b1 may be involved in the sulfonylation of podocyte protein podocalyxin, whereas ankrd25 may contribute to controlling actin dynamics in podocyte foot processes.
Sonic Hedgehog Signaling Induces Vascular Smooth Muscle Cell Proliferation via Induction of the G
1
Cyclin-Retinoblastoma Axis
Authors: Li Fenghe , Duman-Scheel Molly , Yang Dong , Du Wei , Zhang Jian , Zhao Chenchao , Qin Lingfeng , Xin Shijie
Published: August 2010

Objective—

Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in the pathogenesis of intimal hyperplasia, the main cause of restenosis following vascular reconstruction. Here, the impact of sonic hedgehog (Shh)/Gli family zinc finger 2 (Gli2) signaling on VSMC proliferation was assessed.

Methods and Results—

Increased Shh signaling was detected in VSMCs in the neointima of vein grafts obtained from mice undergoing restenosis. Comparable results were found in primary cultured human VSMCs (hVSMCs) obtained from patients undergoing coronary bypass surgery, which were used to further assess the impacts of Shh signaling on VSMC proliferation. Inhibition of Shh signaling in hVSMCs through treatment with cyclopamine or knockdown of
Gli2
results in G
1
arrest and reduced cyclin D1, cyclin E, and phosphorylated retinoblastoma (pRB) levels. In contrast, activation of Shh/Gli2 signaling in hVSMCs results in increased levels of G
1
cyclins and promotes G
1
-S transition. Stimulation of hVSMC proliferation by Shh is abolished by
cyclin D1
knockdown.

Conclusion—

Combined, these results demonstrate that Shh/Gli2 signaling stimulates VSMC proliferation via regulation of the G
1
cyclin-retinoblastoma axis and suggest that antagonists that target the Shh pathway may be therapeutically beneficial in the prevention of intimal hyperplasia.
International Criminal Law before the Supreme Court of Mexico
Authors: Dondé Matute Javier
Published: August 2010

This article explores different cases taken before the Supreme Court of Mexico concerning issues of international criminal law. The first part addresses the proposition of universal jurisdiction in the Cavallo case. The second part concerns the ex post facto application of the Inter-American Convention on Forced Disappearance of Persons and the issue of the statute of limitations regarding international crimes in the Forced Disappearance case and the Echeverría Appeal. The final part discusses the Atenco case, in which the doctrine of command responsibility was considered but ultimately not used in the final decision. The conclusion is that the methods of interpretation of the Supreme Court are still limited by the Constitution, which sometimes hinders developments consistent with international standards.
The Prosecution of International Crimes in Uruguay
Authors: Galain Palermo Pablo
Published: August 2010

This article discusses the criminal trials carried out in Uruguay against civilian, military, and political functionaries who committed crimes, including crimes against humanity, during the period of civilian-military dictatorship lasting from 1973 to 1985. These criminal proceedings are analyzed in the contexts of transitional justice and international criminal law. Therefore, the first part of this article addresses the diverse phases of transitional justice in Uruguay while the second part analyzes fundamental aspects of criminal trials against 'state terrorists'.