bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of MHC‐I and ‐II in Uterine Tissue from Early Pregnant Bitches
Authors: Schäfer‐Somi S , Beceriklisoy HB , Walter I , Sabitzer S , Klein D , Kanca H , Kaya D , Agaoglu AR , İzgür H , Aslan S
Published: July 2009

Contents

The aim of the study was to investigate the expression of major histocompatibility complex (MHC)‐I and ‐II in uterine tissues from pregnant and non‐pregnant bitches, taken at different time periods after mating. The pregnant bitches were ovariohysterectomized during the pre‐implantation (group 1, n = 4), implantation (group 2, n = 7) and placentation stage (group 3, n = 7). Non‐pregnant animals in diestrus served as controls (group 4, n = 7). The expression of MHC‐ I and ‐II in salpinx, apex, middle horn, corpus uteri and at implantation sites was investigated by immunohistochemistry as well as qualitative and quantitative RT‐PCR; MHC‐I mRNA was detected in all tissues and with quantitative RT‐PCR, and no significant changes were detected until placentation. Immunohistologically, at the apex and corpus site, the average number of MHC‐II positive cells increased from the pre‐implantation to the post‐implantation stage (apex: 1.54 ± 1.21 to 3.82 ± 2.93; corpus: 1.62 ± 1.9 to 5.04 ± 4.95; p < 0.05). The greatest numbers of MHC‐II positive cells were observed at placentation sites (6.64 ± 5.9). In parallel, a marked increase in the relative mRNA expression of MHC‐II in uterine tissues was assessed from the pre‐implantation to the placentation stage (relative to Glycerinaldehyd‐3‐phosphate‐Dehydrogenase (GAPDH): 6.9 ± 9.5, 8.4 ± 5.8, p > 0.05). Immunohistologically, in the salpinx, significantly greater numbers of MHC‐II positive cells were found in the tissues of pregnant animals than in the control group (p < 0.05). It is proposed that the increase in MHC‐II is pregnancy‐related, even though the impact on maintenance of canine pregnancy is still unclear.
Cortical serotonin and norepinephrine denervation in parkinsonism: preferential loss of the beaded serotonin innervation
Authors: Nayyar Tultul , Bubser Michael , Ferguson Marcus C. , Diana Neely M. , Shawn Goodwin J. , Montine Thomas J. , Deutch Ariel Y. , Ansah Twum A.
Published: July 2009

Parkinson’s Disease (PD) is marked by prominent motor symptoms that reflect striatal dopamine insufficiency. However, non‐motor symptoms, including depression, are common in PD. It has been suggested that these changes reflect pathological involvement of non‐dopaminergic systems. We examined regional changes in serotonin (5‐HT) and norepinephrine (NE) systems in mice treated with two different 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) treatment paradigms, at survival times of 3 or 16 weeks after the last MPTP injection. MPTP caused a decrease in striatal dopamine concentration, the magnitude of which depended on the treatment regimen and survival interval after MPTP treatment. There was significant involvement of other subcortical areas receiving a dopamine innervation, but no consistent changes in 5‐HT or NE levels in subcortical sites. In contrast, we observed an enduring decrease in 5‐HT and NE concentrations in both the somatosensory cortex and medial prefrontal cortex (PFC). Immunohistochemical studies also revealed a decrease in the density of PFC NE and 5‐HT axons. The decrease in the cortical serotonergic innervation preferentially involved the thick beaded but not smooth fine 5‐HT axons. Similar changes in the 5‐HT innervation of post‐mortem samples of the PFC from idiopathic PD cases were seen. Our findings point to a major loss of the 5‐HT and NE innervations of the cortex in MPTP‐induced parkinsonism, and suggest that loss of the beaded cortical 5‐HT innervation is associated with a predisposition to the development of depression in PD.
Long‐term follow‐up of 3‐month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial
Authors: Yee David S. , Lowrance William T. , Eastham James A. , Maschino Alexandra C. , Cronin Angel M. , Rabbani Farhang
Published: July 2009

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

To report our long‐term follow‐up of an institutional randomized prospective trial of radical prostatectomy (RP) with or without a 3‐month course of neoadjuvant hormone therapy (NHT), which results in pathological downstaging, but generally no reduction in biochemical recurrence (BCR) on early follow‐up (at 3 years).

PATIENTS AND METHODS

From December 1992 to June 1996, 148 patients with clinically localized prostate cancer were randomized to RP only or 3 months of goserelin acetate and flutamide before RP. BCR was defined as a detectable serum prostate specific antigen level (>0.1 ng/mL) at least 6 weeks after surgery, with a confirmatory increase.

RESULTS

The median follow‐up for BCR‐free patients was 8 years. There was no significant difference in BCR‐free probabilities between groups (P = 0.7). The BCR‐free probability at 7 years was 78% for patients undergoing RP only and 80% for patients undergoing NHT and RP (difference of 2%; 95% confidence interval, CI, 12–16%). A Cox regression showed no significant relationship between NHT and BCR (hazard ratio 1.16; 95% CI, 0.56–2.39, P = 0.7). Overall, two patients had local recurrence and six developed metastases, and were evenly distributed among the RP only and NHT groups.

CONCLUSION

Although our study was not originally powered to detect differences in BCR, there was no overall benefit in BCR‐free probability, local recurrence or metastasis with 3 months of NHT at 8 years of follow‐up. Pending evidence of improvement in patient outcomes, NHT before RP appears to be unjustified outside of clinical trials.
The role of lymphangiogenesis in lymphatic tumour spread of urological cancers
Authors: Bolenz Christian , Fernández Mario I. , Tilki Derya , Herrmann Edwin , Heinzelbecker Julia , Ergün Süleyman , Ströbel Philipp , Reich Oliver , Michel Maurice S. , Trojan Lutz
Published: July 2009

Metastases to regional lymph nodes are a common early event in many malignant diseases and have a poor prognosis, including in urological cancers. Molecular pathways contributing to lymphatic tumour dissemination and lymph node metastasis remain poorly understood. Besides the process of lymphovascular invasion (LVI), recent studies suggested de novo lymphatic vessel formation (i.e. lymphangiogenesis) as a potential mechanism of lymphatic tumour spread. Specific markers for lymphatic endothelium have recently been discovered, enabling basic morphological studies on lymphatic vessel density. There is a gap in the knowledge of the functional relationship between tumoral lymphatic vessels, LVI, lymphangiogenesis and the formation of lymph node metastases. The identification of lymph‐specific growth factors (e.g. vascular endothelial growth factor‐C and ‐D) as promoters of lymphatic metastasis has resulted in the interesting idea of targeting the pathways involved in lymphatic tumour progression. We summarize preliminary evidence on the role of lymphangiogenesis during the formation of lymphatic metastasis in the most common urological cancers.
Natural history of benign prostatic enlargement: long‐term longitudinal population‐based study of prostate volume doubling times
Authors: Lieber Michael M. , Rhodes Thomas , Jacobson Debra J. , McGree Michaela E. , Girman Cynthia J. , Jacobsen Steven J. , St. Sauver Jennifer L.
Published: July 2009

Study Type – Prognosis (cohort) Level of Evidence 2a

OBJECTIVES

To measure prostate volume doubling times (PVDTs) for a large sample of community men followed serially by transrectal ultrasonography (TRUS), and to determine whether specific characteristics are associated with a rapid PVDT.

SUBJECTS AND METHODS

A subsample of 446 subjects from a larger cohort of American white men aged 40–79 years were evaluated biennially for a median (range) follow‐up of 10 (3–14) years. Mixed‐effects regression models were used to estimate prostate growth rates and PVDT for subjects with three or more or with five or more serial biennial TRUS PV measurements.

RESULTS

The median (25–75th percentile) PVDT was 32.6 (24.6–44.0) years. The average annual increase in PV was 2.2%. The PVDT distribution was constant in men of all age groups studied (r < 0.001, P = 0.99). The factor most strongly associated with PVDT was baseline transition zone volume (r = −0.55, P < 0.001). Baseline total prostate‐specific antigen (PSA) level, free PSA and total PV were also significantly inversely associated with PVDT (r = −0.30, −0.44 and −0.32, respectively, all P < 0.001). Age, baseline anthropomorphic measurements, hormone levels and specific lifestyle characteristics were not significantly correlated with PVDT.

CONCLUSION

These data indicate that PVDT might be a useful future measure of benign prostatic growth. They provide a basis to forecast PV at 10, 20, or 30 years later, after one baseline TRUS measurement of prostate volume, and can be presented in a simple nomogram.
How are Methodologies and Tools Framing Managers' Strategizing Practice in Competitive Strategy Development?
Authors: Jarratt Denise , Stiles David
Published: July 2009

Criticisms have been levelled at the use of traditional strategic tools such as SWOT, PEST and BCG in contemporary business environments. In light of these criticisms, the objective of this research is to understand how senior executives engage with methodologies and tools as they develop competitive strategy. Within a broader strategy‐as‐practice approach, we use an activity theory framework to capture strategizing insights of senior executives in the UK responsible for competitive strategy. Our sample includes executives leading manufacturing organizations embedded in networks and CEOs reported in the financial press as adopting innovative business models. Our data suggest there is no one preferred practice approach by these highly regarded executives. Rather, methods and tools are adapted as they are contextualized in alternative practices. Three dominant strategizing practice models emerged from the data reflecting alternative applications of methodologies and tools. The first model captures routinized behaviour adopted by those who view their future as predictable, and an extension of the current environment. The second model posits reflective interaction between the strategist, organizational processes, culture, relationships and practice, and the final model shows an imposed engagement with strategizing methodologies and tools that bypass the organization's collective structures. These practice models suggest strategy leaders' activities depend upon their interpretation of the operating environment.
ACCOUNTING FOR CHANGES IN THE HOMEOWNERSHIP RATE*
Authors: Chambers Matthew , Garriga Carlos , Schlagenhauf Don E.
Published: July 2009

This article accounts for the boom in homeownership from 1994 to 2005 by examining the roles of demographic changes and mortgage innovations. To measure the impact of these factors, we construct a quantitative general equilibrium overlapping generation model with housing. In the long‐run, mortgage innovation accounts for between 56 and 70% of the increase whereas demographics account for a much smaller portion. We test this result by considering changes in mortgages after 1940. We find that the introduction of the conventional fixed rate mortgage accounts for at least 50% of the observed increase in homeownership during that period.
Increased risk of adverse pregnancy outcomes for women with migraines: A nationwide population-based study
Authors: Chen H-M , Chen S-F , Chen Y-H , Lin H-C
Published: July 2009

Using a 3-year nationwide population-based database, this study aims to examine the risk of adverse pregnancy outcomes in women with migraines, including low birthweight (LBW), preterm birth, infants born small for gestational age, Caesarean section (CS) and pre-eclampsia. We identified a total of 4911 women with migraines who gave birth from 2001 to 2003, together with 24 555 matched women as a comparison cohort. Multivariate logistic regression analyses showed that after adjusting for potential confounders, the odds ratios were 1.16 [95% confidence intervals (CI) = 1.03–1.31, P = 0.014] for LBW, 1.24 (95% CI = 1.13–1.39, P < 0.001) for preterm births, 1.16 (95% CI = 1.07–1.24, P < 0.001) for CS and 1.34 (95% CI = 1.02–1.77, P = 0.027) for pre-eclampsia for women with migraines compared with unaffected mothers. We conclude that women with migraines were at increased risk of having LBW, preterm babies, pre-eclampsia and delivery by CS, compared with unaffected mothers.
Markers and mapping revisited: finding your gene
Authors: Jones Neil , Ougham Helen , Thomas Howard , Pašakinskienė Izolda
Published: July 2009

Contents

Summary
935

I.
Introduction
936

II.
Survey of genetic variation – sources and resources
936

III.
Survey of molecular marker types
939

IV.
Mapping approaches and tools
948

V.
Survey of bioinformatics and computer resources
954

VI.
Bringing it all together: stay‐green gene case study
961

VII.
The future of mapping
962

Acknowledgements
962

References
962
Fistula Function and Dialysis Adequacy During Ozonotherapy in Chronically Hemodialyzed Patients
Authors: Tylicki Leszek , Biedunkiewicz Bogdan , Nieweglowski Tomasz , Grabowska Malgorzata , Chamienia Andrzej , Slizien Alicja Debska , Rutkowski Boleslaw
Published: July 2009

Abstract:  There are a variety of complications related to chronic hemodialysis treatment, including thrombosis in hemodialysis access leading to blood recirculation, and in turn to the deterioration in hemodialysis effectiveness. Given that ozone decreases blood viscosity, increases erythrocyte deformability, and inhibits coagulation, the periodic blood ozonation may be of benefit in the attenuation of these disturbances. To gain insight into this issue, we originally evaluated the impact of ozonated autohemotherapy on recirculation in arteriovenous fistula, hemodialysis adequacy, and the frequency of dialyzer reuse. Twelve chronically hemodialyzed patients with peripheral arterial disease were enrolled in the prospective, placebo‐controlled study. Nine sessions of autohemotherapy with the exposure of blood to oxygen, as a control, and nine sessions of autohemotherapy where the blood is exposed to ozone in a concentration of 50 µg/mL are administered in a single‐blind manner. Access recirculation is measured by means of spectral technology (Crit Line Monitor, HemaMetrics, Kaysville, UT, U.S.A.), and hemodialysis adequacy is calculated using the Dau‐girdas formula and expressed as the Kt/V index. The Kt/V index and the frequency of dialyzer reuse do not change after ozonated autohemotherapy. Recirculation decreases after ozonotherapy in the majority of patients, on average by 35.3%, but the change does not reach the level of statistical significance (P = 0.064). We demonstrate that ozonated autohemotherapy does not influence dialysis adequacy and the frequency of dialyzer reuse. The improvement of fistula function, expressed as a decrease in recirculation, is not significant, although seen in  the  majority  of  patients.
T‐Wave Morphology in Short QT Syndrome
Authors: Anttonen Olli , Junttila Juhani , Giustetto Carla , Gaita Fiorenzo , Linna Eeva , Karsikas Mari , Seppänen Tapio , Perkiömäki Juha S. , Mäkikallio Timo H. , Brugada Ramon , Huikuri Heikki V.
Published: July 2009

Background: Short QT syndrome (SQTS) is an inherited disorder characterized by a short QT interval and vulnerability to ventricular tachyarrhythmias. The diagnostic criteria for this syndrome are not well defined, since there is uncertainty about the lowest normal limits for the corrected QT (QTc) interval.

Objective: The aim of this study was to determine whether T‐wave morphology parameters are abnormal in short QT subjects and whether those parameters can help in the diagnosis of SQTS.

Methods and Results: We describe three families (10 patients) with short QT intervals (QTc 310 ± 32 ms). Seven subjects had suffered serious arrhythmic events and three were asymptomatic. T‐wave morphology was assessed using the principal component analysis (PCA). QTc was significantly shorter and T‐wave amplitude in lead V2 higher in the short QT subjects compared to healthy controls (n = 149), (P < 0.001 for both). The total cosine of the angle between the main vectors of the QRS and T‐wave loops (TCRT) was markedly abnormal among the symptomatic patients with short QT syndrome (n = 7) (TCRT –0.14 ± 0.55 vs 0.36 ± 0.51, P = 0.019). None of the three asymptomatic patients with short QT but without a history of arrhythmic events had an abnormally low TCRT.

Conclusion: Our observations suggest that patients with a short QT interval and a history of arrhythmic events have abnormal T‐wave loop parameters. These electrocardiogram (ECG) features may help in the diagnosis of SQTS in addition to the measurement of the duration of QT interval from the 12‐lead ECG.
Post‐tooth extraction sepsis without locoregional infection – a population‐based study in Taiwan
Authors: Lee J‐J , Hahn L‐J , Kao T‐P , Liu C‐H , Cheng S‐J , Cheng S‐L , Chang H‐H , Jeng J‐H , Kok S‐H
Published: July 2009

Objective:  To investigate the incidence and risk factors of post‐tooth extraction sepsis in patients without locoregional infection.

Subjects and Methods:  We assessed all claim records of the Taiwanese National Health Insurance program in 2005. Admissions for patients aged ≥16 years containing a discharge diagnosis of sepsis, and who received tooth extraction within 14 days before the admission were identified. Patient charts were reviewed to confirm the diagnosis of sepsis and rule out other infection sources. The relationship between postextraction sepsis (PES) and clinical parameters was analyzed.

Results:  Thirty‐three of the 2 223 971 extraction cases met the criteria of PES, an incidence of 1.48 per 100 000, and seven patients (21.2%) died of the disease. Aging significantly increased the risk of PES (P < 0.001). Pre‐existing comorbidities were found in 20 of the 33 cases, with diabetes mellitus and hematologic diseases the most common. The method, number, and position of extraction had no influence on PES incidence. Blood cultures were positive in 25 patients (75.8%) and isolates included species of the Streptococcus, Actinomyces, Klebsiella, Bacteroides, Prevotella, and Enterococcus genera.

Conclusion:  Tooth extraction is associated with a low but significant risk of postoperative sepsis, especially in the elderly and patients with underlying diseases.
V.A.C.® Therapy in the management of paediatric wounds: clinical review and experience
Authors: Baharestani Mona , Amjad Ibrahim , Bookout Kim , Fleck Tatjana , Gabriel Allen , Kaufman David , McCord Shannon Stone , Moores Donald C. , Olutoye Oluyinka O. , Salazar Jorge D. , Song David H. , Teich Steven , Gupta Subhas
Published: July 2009

Usage of negative pressure wound therapy (NPWT) in the management of acute and chronic wounds has grown exponentially in the past decade. Hundreds of studies have been published regarding outcomes and methods of therapy used for adult wounds. This treatment is increasingly being used to manage difficult‐to‐treat paediatric wounds arising from congenital defects, trauma, infection, tumour, burns, pressure ulceration and postsurgical complications in children, although relatively few studies have been aimed at this population. Given the anatomical and physiological differences between adults and children, a multidisciplinary expert advisory panel was convened to determine appropriate use of NPWT with reticulated open cell foam (NPWT/ROCF) as delivered by Vacuum Assisted Closure® (V.A.C.® Therapy, KCI Licensing, Inc., San Antonio, TX) for the treatment of paediatric wounds.

The primary objectives of the expert advisory panel were to exchange state‐of‐practice information on paediatric wound care, review the published data regarding the use of NPWT/ROCF in paediatric wounds, evaluate the strength of the existing data and establish guidelines on best practices with NPWT/ROCF for the paediatric population. The proposed paediatrics‐specific clinical practice guidelines are meant to provide practitioners an evidence base from which decisions could be made regarding the safe and efficacious selection of pressure settings, foam type, dressing change frequency and use of interposing contact layer selections. The guidelines reflect the state of knowledge on effective and appropriate wound care at the time of publication. They are the result of consensus reached by expert advisory panel members based on their individual clinical and published experiences related to the use of NPWT/ROCF in treating paediatric wounds. Best practices are described herein for novice and advanced users of NPWT/ROCF. Recommendations by the expert panel may not be appropriate for use in all circumstances. Decisions to adopt any particular recommendation must be made by the collaborating medical team, including the surgeon and wound care specialist based on available resources, individual patient circumstances and experience with the V.A.C.® Therapy System.
Effect of Bacillus thuringiensis on Habrobracon hebetor during combined biological control of Plodia interpunctella
Authors: Oluwafemi Akinkurolere Rotimi , Rao Qiong , Wang Xi‐Qiao , Zhang Hong‐Yu
Published: July 2009

Abstract  The suitability of combining microbial pesticides and an insect parasitoid for pest management of stored cereal in China was evaluated using laboratory assays. For this purpose, interactions between Bacillus thuringiensis (Bt), Bt‐intoxicated host larvae and the parasitoid Habrobracon hebetor (Say) (Hymenoptera: Braconidae) were tested against Plodia interpunctella Hübner (Lepidoptera: Pyralidae). Bt or H. hebetor alone caused 41.67% and 35.35%P. interpunctella larval mortality respectively. The Bt–parasitoid combined treatment significantly increased mortality of P. interpunctella (86%). Progeny development of H. hebetor was dependent upon its susceptibility to Bt. Fewer parasitoids emerged from Bt–parasitoid combined treatment than in non‐Bt treatments. However, since Bt did not prevent parasitoid development, a combined treatment with Bt and parasitoid release could produce better protection against P. interpunctella than either treatments when used singly, because their lethal effects were additive to each other.
Investigating Population and Topological Evolution in a Complex Adaptive Supply Network*
Authors: PATHAK SURYA D. , DILTS DAVID M. , MAHADEVAN SANKARAN
Published: July 2009

This paper investigates the dynamics of a complex adaptive supply network (CASN), focusing on understanding stability of the structural evolution of a supply network and supplier population emergence. Supply network evolution data collected from simulated responses of the U.S. automobile industry are used in multivariate statistics and time series analysis to identify patterns of network evolution. This analysis reveals that the type of environment a supply network evolves in appears to be a major factor in determining critical timing of structural changes during the evolution of a CASN. Further, time series analysis of firm population evolution highlights how supply networks evolve due to path dependencies in the CASN system. Information about these two aspects of supply network evolution can prove useful to a decision maker in determining how to respond to supply network changes.
Control of Growth and Differentiation of the Endometrium: The Role of Tissue Interactions
Authors: BIGSBY ROBERT M.
Published: July 2009

Abstract: Early work with neonatal mice showed that estrogen receptor‐negative uterine epithelium responded to estrogen treatment. Since the underlying mesenchymal cells were estrogen receptor‐positive, it was suggested that these cells mediated the hormonal response through elaboration of a paracrine factor. Cell culture work showed that mesenchymal cells produced soluble factors that stimulate uterine epithelium, but hormonal regulation was absent or minimal. The paracrine hypothesis of estrogen action has been proved by the use of tissue recombinant studies in which epithelium from estrogen receptor‐alpha knockout mice was combined with wild‐type mesenchyme; estrogen stimulated the ERα‐negative epithelium if the underlying stromal cells were receptor‐positive. Also, it is hypothesized that there is a reciprocal paracrine interaction during stimulation with progesterone and estrogen. Accordingly, under progesterone dominance, the epithelium elaborates factors that direct the underlying stroma to proliferate when estrogen is administered. Although this hypothesis needs further testing, it has been shown that the uterine epithelium is required for stromal responsiveness to hormones. The question arises: What are the factors that mediate the effects of the steroid hormones in the uterus? Several peptide growth factors are regulated by estrogen and/or progesterone. Use of knockout animals will allow a determination of the role that these factors play in the uterus. However, ablation of many of these growth factor genes has proved lethal to the newborn animals, making it impossible to study hormonal effects using standard techniques. Tissue xenograft and tissue recombination studies offer a means of defining the role of specific growth factors in uterine physiology.
Circulating Ovarian Steroids and Endometrial Matrix Metalloproteinases (MMPs)
Authors: HENRIET PATRICK , CORNET PATRICIA B. , LEMOINE PASCALE , GALANT CHRISTINE , SINGER CHRISTIAN F. , COURTOY PIERRE J. , EECKHOUT YVES , MARBAIX ETIENNE
Published: July 2009

Abstract: Recent studies strongly suggest that matrix metalloproteinases (MMPs) play a key role in the initiation of menstrual bleeding in the human endometrium upon the fall of ovarian steroid serum concentrations by inducing the degradation of the extracellular matrix of this mucosa. MMPs are also involved in abnormal endometrial bleeding and have been identified in endometriotic foci. In all cases, they are associated with areas of extracellular matrix breakdown. This paper reviews the literature on the regulation by estradiol and progesterone of the expression and activation of MMPs, and of the expression of their tissue inhibitors (TIMPs), (i) in the endometrium in situ during normal cycle, (ii) during artificial cycles in spayed monkeys, and (iii) in cultures of endometrial explants or purified cells. Whereas progesterone consistently decreases the activity of endometrial MMPs, its effects vary in intensity, duration, and pattern between MMPs as well as among experimental systems. The contribution and limitations of the various investigations are therefore discussed. The focal heterogeneity points to additional local controls of the expression and activation of MMPs in human endometrium, acting beyond the general inhibitory role of progesterone, for example, by cytokines. Focal changes in type or abundance of sex steroid receptors also could be responsible for spatial variation in the expression of MMPs in the endometrium and endometriotic lesions.
Mechanics of Eye Movements: Implications of the “Orbital Revolution”
Authors: HASLWANTER THOMAS
Published: July 2009

Abstract: Our understanding of the functional structure of extraocular muscles has undergone a profound change: while these muscles used to be represented by strings running straight from their origin in the posterior orbita to their insertion on the globe, we now know that their paths and pulling directions are dominated by fibromuscular pulley structures, keeping them close to the orbital wall for most of their path. An overview is presented of recent models that have been developed to understand the implications of muscle pulleys for the neural control of eye movements and the applications of such models to the interpretation of experimental data.
Calcium Channelopathy Mutants and Their Role in Ocular Motor Research
Authors: STAHL JOHN S.
Published: July 2009

Abstract: Thanks to technical advances in eye movement recording, the mouse is destined to become increasingly important in ocular motor research. An advantage of this species is the wide range of existing mutant strains and techniques to generate new mutations affecting specific cell types. Mutations of ion channels may be used to modulate the intrinsic properties of neurons, and this approach may generate insight into the degree to which neuronal computations depend upon those intrinsic properties as opposed to the properties of circuits of neurons. Dendritic calcium currents carried by P‐type voltage‐activated calcium channels have been widely postulated to perform important computational functions in cerebellar Purkinje cells. Mutations of this channel lead to human diseases, and several ataxic strains of mice are now known to harbor mutations of this calcium channel. Murine P‐channel mutants such as rocker are ataxic, but have normal or near‐normal numbers of cerebellar Purkinje cells and thus offer the opportunity to study the effects of biophysical perturbations as opposed to outright cell destruction or inactivation. Initial studies of rocker mice reveal an array of ocular motor abnormalities, including static hyperdeviation of the eyes and an attenuation of vestibulo‐ocular reflex gains at high stimulus frequencies. The pattern of gain and phase abnormalities is entirely different in lurcher, an ataxic mutant in which Purkinje cells degenerate. The ocular motor abnormalities of rocker progress with animal age, underscoring the importance of careful attention to animal age when performing ocular motor studies in this short‐lived species.
The Contribution of Midbrain Circuits in the Control of Gaze
Authors: BÜTTNER ULRICH , BÜUTTNER‐ENNEVER JEAN A. , RAMBOLD HOLGER , HELMCHEN CHRISTOPH
Published: July 2009

Abstract: The midbrain contains several structures important for the generation of torsional and vertical eye movements including the rostral interstitial nucleus of the MLF (riMLF) and the interstitial nucleus of Cajal (iC). While the riMLF is the immediate premotor structure for the generation of torsional and vertical saccades, the iC is considered a major part of the neural integrator for torsional and vertical eye movements. Experiments in monkeys show that a unilateral inactivation of the riMLF with muscimol leads to spontaneous contralesional torsional nystagmus, whereas an iC inactivation causes ipsilesional torsional nystagmus. In addition, inactivation of either structure leads to a tonic ocular torsion to the contralesional side. While the deficits after a riMLF lesion are thought to result from an imbalance of the saccade generator, a vestibular imbalance probably causes the deficits after an iC lesion. Contralesional and ipsilesional torsional nystagmus is also found in patients with unilateral mesencephalic lesions. A detailed analysis of the lesions from MRI scans shows a preferential involvement of the riMLF for patients with contralesional torsional nystagmus, and a major involvement of iC in cases with ipsilesional torsional nystagmus. Thus, the direction of torsional nystagmus appears to be a valuable topodiagnostic sign for patients with midbrain lesions.
The Role of the Lateral Intraparietal Area of the Monkey in the Generation of Saccades and Visuospatial Attention
Authors: GOLDBERG MICHAEL E. , BISLEY JAMES , POWELL KEITH D. , GOTTLIEB JACQUELINE , KUSUNOKI MAKOTO
Published: July 2009

Abstract: The brain cannot monitor or react towards the entire world at a given time. Instead, using the process of attention, it selects objects in the world for further analysis. Neuronal activity in the monkey intraparietal area has the properties appropriate for a neuronal substrate of attention: instead of all objects being represented in the parietal cortex, only salient objects are. Such objects can be salient because of their physical properties (recently flashed objects or moving objects) or because they can be made important to the animal by virtue of a task. Although lateral intraparietal area (LIP) neurons respond through the delay period of a memory‐guided saccade, they also respond in an enhanced manner to distractors flashed during the delay period of a memory‐guided saccade being generated to a position outside the receptive field. This activity parallels the monkey's psychophysical attentional process: attention is ordinarily pinned at the goal of a memory‐guided saccade, but it shifts briefly to the locus of a task‐irrelevant distractor flashed briefly during the delay period and then returns to the goal. Although neurons in LIP have been implicated as being directly involved in the generation of saccadic eye movements, their activity does not predict where, when, or if a saccade will occur. The ensemble of activity in LIP, however, does accurately describe the locus of attention.
Scanpaths: The Path to Understanding Abnormal Cognitive Processing in Neurological Disease
Authors: KENNARD CHRISTOPHER
Published: July 2009

Abstract: Scanpaths, the sequence of saccades and fixations during visual search, provide the means to study a range of cognitive activities: planning, visuospatial attention, and spatial working memory. By measuring scanpaths, we have been able to identify impairment of working memory in patients with spatial hemineglect. Scanpaths during cognitively demanding tasks indicate a defect of working memory in patients with Parkinson's disease. Studies of scanpaths in patients with homonymous hemianopia have provided the means to develop a new strategy for visual rehabilitation.
Adaptive Control of Vergence in Humans
Authors: SCHOR CLIFTON M. , MAXWELL JAMES S. , McCANDLESS JEFREY , GRAF ERICH
Published: July 2009

Abstract: Vergence eye alignment minimizes horizontal, vertical, and cyclodisparities to optimize stereo‐depth perception. Only the horizontal component of vergence is under voluntary control. Couplings with voluntary version and horizontal vergence guide vertical vergence and cyclovergence. Can these couplings be modified in response to sensory demands on binocular vision? We have modified vertical vergence and cyclovergence in response to optical changes in disparity. Vertical vergence was stimulated with aniseikonic lenses that exaggerated vertical disparity in tertiary gaze. Vertical vergence adapted in an hour to produce nonconcomitant changes in vertical phoria that varied with vertical eye position in tertiary gaze. Cyclovergence was stimulated with cyclodisparities that varied with gaze elevation and convergence angle. Cyclovergence adapted within 2 hours to produce nonconcomitant changes in cyclophoria that varied with gaze elevation and convergence. The adaptive couplings for vertical vergence and cyclovergence are modeled as a combination of passive orbital mechanics and active gain control of the vertical recti and obliques. Vergence adaptation is a calibration process that adjusts the innervation for horizontal, vertical, and torsion components of vergence to the physical constraints set by the extraocular muscles and orbital connective tissues. Passive orbital mechanics simplify the neural control for precise vertical vergence and cyclovergence that are needed to achieve binocular alignment under open‐loop conditions in response to perceived spatial location.
Balancing the Risks and Benefits of Moderate Drinking
Authors: ELLISON R. CURTIS
Published: July 2009

Abstract: The risks of excessive alcohol intake are well known, and heavy drinkers should decrease their intake or stop drinking. On the other hand, in comparison with non‐drinkers, moderate drinkers are at much lower risk of cardiovascular disease and certain other diseases and have lower total mortality. Thus, middle‐aged or older men and post‐menopausal women with no contraindications to alcohol use should be informed that they have, on average, net health benefits from the regular consumption of small‐to‐moderate amounts of alcohol.
Alcohol, Type of Alcohol, and All‐Cause and Coronary Heart Disease Mortality
Authors: GRØNBÆK MORTEN
Published: July 2009

Abstract: Many studies from a variety of countries have shown a U‐ or J‐shaped relation between alcohol intake and mortality from all causes. It is now quite well documented from epidemiologic as well as clinical and experimental studies that the descending leg of the curve results from a decreased risk of cardiovascular disease among those with light‐to‐moderate alcohol consumption. The findings that wine drinkers are at a decreased risk of mortality from cardiovascular disease compared to non‐wine drinkers suggest that substances present in wine are responsible for a beneficial effect on the outcome, in addition to that from a light intake of ethanol. Several potential confounding factors still remain to be excluded, however.
Wine, Biodiversity, Technology, and Antioxidants
Authors: MATTIVI FULVIO , ZULIAN CHRISTIAN , NICOLINI GIORGIO , VALENTI LEONARDO
Published: July 2009

Abstract: Two chemical classes of flavonoids, the flavan‐3‐ols (catechins and proanthocyanidins) and the anthocyanins, are the natural antioxidants present at the highest concentration in red grape and wine. In the berry, the anthocyanins are localized in the skins, similarly to other highly bioactive phenolics of grape such as the resveratrols and the flavonols, while the flavan‐3‐ols are contained both in the skins and seeds. During winemaking, only a fraction of the grape flavonoids are selectively extracted into the wine, with a time course and a final yield strongly depending on the grape variety. The knowledge of the diverse and cultivar‐specific characteristics of the grape is therefore critical to the appropriate design of the winemaking process. By means of a selective extraction method specifically designed to mimic the winemaking process, it was possible to analyze the “phenolic potential of red grape,” thus obtaining quantitative information about amount and localization of the extractable flavonoids in the grape. Twenty‐five high‐quality red grape cultivars (V. vinifera) were studied, including 4 of the worldwide leading cultivars and 21 Italian cultivars with the highest reputation for the production of both young and aged premium red wines. The results clearly indicate that the grape variety plays a central role in determining both the absolute amount of the flavonoids, and the distribution between the berry skin and seeds of the flavan‐3‐ols. The very high biodiversity of the red grape cultivars in terms of flavonoids indicate a largely under‐exploited opportunity to produce a range of diverse premium wines with optimized levels of natural antioxidants.
Wine Polyphenols and Optimal Nutrition
Authors: URSINI FULVIO , SEVANIAN ALEX
Published: July 2009

Abstract: One of the key elements of Mediterranean diet is the use of wine, usually taken with foods. Besides the evidence from human experience and ancient medicine, modern experimental data support the notion that the most striking effect of wine in protecting against cardiovascular disease involves the reduction of oxidative damage to plasma lipoproteins. This oxidative damage is thought to be mediated by eating foods containing oxidized lipids. In fact, eating a meal containing oxidized lipids increases the plasma level of lipid hydroperoxides and increases the susceptibility to oxidation of LDL. The postprandial increase of LDL‐, an oxidatively modified form of LDL, where apoB is unfolded and sinking in the core of the particle, is a valuable biomarker for this food‐derived oxidative stress in plasma. Wine, taken with foods minimizes the postprandial rise of lipid hydroperoxides and LDL‐ and abolishes the increase of LDL oxidability. Among wine antioxidants, the best candidates for providing an antioxidant effect are procyanidins. These compounds are considered better antioxidants than the corresponding monomers containing catechol groups. This is due to the hydrogen transfer mechanism for the radical‐scavenging reaction, which renders the reaction more specific for peroxyl radicals and pH independent. Moreover, the fast intramolecular disproportion among aroxyl radicals pulls the antioxidant reaction by both decreasing the oxidation potential and increasing the rate of the reaction. Apparently, wine procyanidins are active in preventing lipid oxidation of foods while in the digestive tract, thus preventing the postprandial plasma rise in oxidants. The likely limited bioavailability of these compounds, therefore, does not affect their relevance as key elements for optimizing nutrition and reducing risk of atherogenesis. Accordingly, studies with rabbits fed a high cholesterol diet show that grapeseed procyanidins are strongly protective not only in terms of reducing plasma lipid peroxides, but they also markedly inhibit lipid‐laden foam‐cell deposition. Drinking wine at meals provides this kind of protection, and the final benefits are realized by the prevention of the development of atheromatous lesions even under conditions of hypercholesterolemia.
Cancer Chemopreventive Activity of Resveratrol
Authors: BHAT KRISHNA P.L. , PEZZUTO JOHN M.
Published: July 2009

Abstract:Cancer chemopreventive agents are designed to reduce the incidence of tumorigenesis by intervening at one or more stages of carcinogenesis. Recently, resveratrol, a natural product found in the diet of humans, has been shown to function as a cancer chemopreventive agent. Resveratrol was first shown to act as an antioxidant and antimutagenic agent, thus acting as an anti‐initiation agent. Further evidence indicated that resveratrol selectively suppresses the transcriptional activation of cytochrome P‐450 1A1 and inhibits the formation of carcinogen‐induced preneoplastic lesions in a mouse mammary organ culture model. Resveratrol also inhibits the formation of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐promoted mouse skin tumors in the two‐stage model. The enzymatic activities of COX‐1 and ‐2 are inhibited by resveratrol in cell‐free models, andCOX‐2mRNA and TPA‐induced activation of protein kinase C and AP‐1‐mediated gene expression are suppressed by resveratrol in mammary epithelial cells. In addition, resveratrol strongly inhibits nitric oxide generation and inducible nitric oxide synthase protein expression. NFκB is strongly linked to inflammatory and immune responses and is associated with oncogenesis in certain models of cancer, and resveratrol suppresses the induction of this transcription factor by a number of agents. The mechanism may involve decreasing the phosphorylation and degradation of IκBα. At the cellular level, resveratrol also induces apoptosis, cell cycle delay or a block in the G1→ S transition phase in a number of cell lines. Thus, resveratrol holds great promise for future development as a chemopreventive agent that may be useful for several disorders. Preclinical toxicity studies are underway that should be followed by human clinical trials.
Oxygen, Oxidants, and Antioxidants in Wound Healing
Authors: SEN CHANDAN K. , KHANNA SAVITA , GORDILLO GAYLE , BAGCHI DEBASIS , BAGCHI MANASHI , ROY SASHWATI
Published: July 2009

Abstract:Disrupted vasculature and high energy‐demand by regenerating tissue results in wound hypoxia. Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of hyperbaric oxygen in promoting wound healing is sketchy, however. Topical oxygen therapy involves local administration of pure oxygen. The advantages of topical oxygen therapy include low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this modality of wound care is of outstanding interest, it clearly lacks the support of mechanism‐oriented studies. The search for mechanisms by which oxygen supports wound healing has now taken another step. Respiratory burst‐derived oxidants support healing. Oxidants serve as cellular messengers to promote healing. Although this information is of outstanding significance to the practice of oxygen therapy, it remains largely unexplored. The search for “natural remedies” has drawn attention to herbals. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are likely to be of outstanding significance in wound healing.
Preservation of Paraoxonase Activity by Wine Flavonoids
Authors: FUHRMAN BIANCA , AVIRAM MICHAEL
Published: July 2009

Abstract: Paraoxonase is an esterase physically associated with HDL, and its activity has been shown to be inversely related to the risk of cardiovascular diseases. We have shown that paraoxonase can hydrolyze specific lipid peroxides in oxidized lipoproteins and in atherosclerotic lesions. Paroxonase was shown to be inactivated by oxidative stress. Consumption of wine flavonoids was shown to preserve paraoxonase activity by reducing the oxidative stress in apolipoprotein E‐deficient mice, thereby contributing to paraoxonase hydrolytic activity on lipid peroxides in oxidized lipoproteins and atherosclerotic lesions.
The Cardioprotective Effect of Wine on Human Blood Chemistry
Authors: Van VELDEN DAVID P. , MANSVELT ERNA P.G. , FOURIE ELBA , ROSSOUW MARIETJIE , MARAIS A. DAVID
Published: July 2009

Abstract: We investigated the in vivo effects of regular consumption of red and white wine on the serum lipid profile, plasma plasminogen activator‐1, homocysteine levels, and total antioxidant status. This study confirmed that moderate consumption of wine, red more than white, exerts cardioprotective effects through beneficial changes in lipid profiles and plasma total antioxidant status.
Tissue Engineering and Reparative Medicine
Authors: SIPE JEAN D.
Published: July 2009

Abstract:Reparative medicine is a critical frontier in biomedical and clinical research. The National Institutes of Health Bioengineering Consortium (BECON) convened a symposium titled “Reparative Medicine: Growing Tissues and Organs,” which was held on June 25 and 26, 2001 in Bethesda, Maryland. The relevant realms of cells, molecular signaling, extracellular matrix, engineering design principles, vascular assembly, bioreactors, storage and translation, and host remodeling and the immune response that are essential to tissue engineering were discussed. This overview of the scientific program summarizes the plenary talks, extended poster presentations and breakout session reports with an emphasis on scientific and technical hurdles that must be overcome to achieve the promise of restoring, replacing, or enhancing tissue and organ function that tissue engineering offers.
Biomaterials and Scaffolds in Reparative Medicine
Authors: CHAIKOF ELLIO L. , MATTHEW HOWARD , KOHN JOACHIM , MIKOS ANTONIO G. , PRESTWICH GLENN D. , YIP CHRISTOPHER M.
Published: July 2009

Abstract: Most approaches currently pursued or contemplated within the framework of reparative medicine, including cell‐based therapies, artificial organs, and engineered living tissues, are dependent on our ability to synthesize or otherwise generate novel materials, fabricate or assemble materials into appropriate 2‐D and 3‐D forms, and precisely tailor material‐related physical and biological properties so as to achieve a desired clinical response. This paper summarizes the scientific and technological opportunities within the fields of biomaterials science and molecular engineering that will likely establish new enabling technologies for cellular and molecular therapies directed at the repair, replacement, or reconstruction of diseased or damaged organs and tissues.
Biological Response of Chondrocytes to Hydrogels
Authors: ELISSEEFF J. H. , LEE A. , KLEINMAN H. K. , YAMADA Y.
Published: July 2009

Abstract: Primary bovine chondrocytes were encapsulated in alginate and alginate combined with cartilage matrix extract, Cartrigel, for the purpose of cartilage tissue engineering. The cell constructs were incubated in vitro and gene expression of cartilage‐specific extracellular matrix molecules was quantitated and localized with in situ hybridization with a decrease in expression observed in the alginate‐Cartrigel constructs. Further understanding of cell response to scaffolds will allow rational design and development of hydrogels for cartilage tissue engineering.