bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐resolution Melting Facilitates Mutation Screening of PYGM in Patients with McArdle Disease
Authors: Duno Morten , Quinlivan Ros , Vissing John , Schwartz Marianne
Published: March 2009

Mutations in PYGM, encoding the muscle‐specific glycogen phosphorylase (myophosphorylase), are responsible for McArdle disease. Among Caucasians, a large proportion of patients are homozygous for the R50X mutation, but other mutations can affect all the 20 exons of PYGM, making mutation detection laborious.

We have developed a high‐resolution melting (HRM) assay for mutation detection in PYGM. Twelve McArdle patients were investigated, in whom pre‐screening had ruled out homozygosity or compound heterozygosity for the two common G205S and R50X mutations. In total, we identified 16 different variations. Thirteen of these are pathogenic, and three were classified as polymorphisms. Nine variations had not previously been described. One of the novel mutations, c.2430C > T, was initially predicted to result in a silent G810G change, but cDNA analysis demonstrated that the mutation led to abnormal mRNA processing.

The HRM protocol reduced the need for direct sequencing by approximately 85%, and is a good approach to search for new mutations in PYGM.
Drivers of megaherbivore demographic fluctuations: inference from elephants
Authors: Trimble M. J. , Ferreira S. M. , Van Aarde R. J.
Published: March 2009

Environmentally induced variation in survival and fecundity generates demographic fluctuations that affect population growth rate. However, a general pattern of the comparative influence of variation in fecundity and juvenile survival on elephant population dynamics has not been investigated at a broad scale. We evaluated the relative importance of conception, gestation, first year survival and subsequent survivorship for controlling demographic variation by exploring the relationship between past environmental conditions determined by integrated normalized difference vegetation index (INDVI) and the shape of age distributions at 17 sites across Africa. We showed that, generally, INDVI during gestation best explained anomalies in age structure. However, in areas with low mean annual rainfall, INDVI during the first year of life was critical. The results challenge Eberhardt's paradigm for population analysis that suggests that populations respond to limited resource availability through a sequential decrease in juvenile survival, reproductive rate and adult survival. Contrastingly, elephants appear to respond first through a reduction in reproductive rate. We conclude that this discrepancy is likely due to the evolutionary significance of extremely large body size – an adaptation that increases survival rate but decreases reproductive potential. Other megaherbivores may respond similarly to resource limitation due to similarities in population dynamics. Knowing how vital rates vary with changing environmental conditions will permit better forecasts of the trajectories of megaherbivore populations.
Conditions for successfully implementing resident‐oriented care in nursing homes
Authors: Berkhout Afke JMB , Boumans Nicolle PG , Mur Ingrid , Nijhuis Frans JN
Published: March 2009

This study reports an investigation of the conditions for a successful introduction of a resident‐oriented care model on six somatic and psychogeriatric intervention wards in three Dutch nursing homes. This study aims to answer the following research question: ‘What are the conditions for successfully implementing resident‐oriented care?’ To answer the research question, the organisational change process was monitored by using the ‘7‐S’ model of Peters and Waterman as a diagnostic framework. Based on this model, the following change characteristics were studied: structure, strategy, systems, staff, skills, style and shared values. Our study involved a one group pretest/post‐test design. To measure the conditions for change, we operationalised the factors of the 7‐S model serving as a diagnostic framework and studied their presence and nature on the intervention wards. For this purpose qualitative interviews were held with the change agents of the nursing homes and the wards’ supervisors. To determine the degree of ‘success’ of the implementation, we measured the extent to which resident‐oriented care was implemented. For this purpose a quantitative questionnaire was filled in by the nurses of the intervention wards. By relating the extent to which resident‐oriented care was implemented to the differences in change conditions, we were able to distinguish the ‘most’ from the ‘least’ successful intervention ward and so, pointing out the conditions contributing to a successful implementation of resident‐oriented care. The results showed that, in contrast to the least successful intervention ward, the most successful intervention ward was characterised by success conditions related to the 7‐S model factors strategy, systems, staff and skills. The factor structure did not contribute to the success of the implementation. Success conditions appeared to be related to the ward level and not to the organisational or project level. Especially the supervisors’ role appeared to be crucial for a successful implementation.
Quantitative analysis of the scientific literature on acetaminophen in medicine and biology: a 2003–2005 study†
Authors: Robert Claude , Saenz‐Feijoo Rosa , Gaudy Jean‐François , Arreto Charles‐Daniel
Published: March 2009

This study quantifies the utilization of acetaminophen in life sciences and clinical medicine using bibliometric indicators. A total of 1626 documents involving acetaminophen published by 74 countries during 2003–2005 in the Thompson‐Scientific Life sciences and Clinical Medicine collections were identified and analyzed. The USA leads in the number of publications followed by the UK, and industrialized countries, including France, Japan and Germany; the presence of countries such as China, India and Turkey among the top 15 countries deserves to be noticed. The European Union stands as a comparable contributor to the USA, both in terms of number of publications and in terms of profile of papers distributed among subcategories of Life Sciences and Clinical Medicine disciplines. All documents were published in 539 different journals. The most prolific journals were related to pharmacology and/or pharmaceutics. All aspects of acetaminophen (chemistry, pharmacokinetics, metabolism, etc.) were studied with primary interest for therapeutic use (42%) and adverse effects (28%) comprising a large part of publications focusing on acetaminophen hepatotoxicity. This quantitative overview provides as to the interest of the scientific community in this analgesic and completes the various review documents that regularly appear in the scientific literature.
Age‐related myelin dynamics revealed by increased oligodendrogenesis and short internodes
Authors: Lasiene Jurate , Matsui Aya , Sawa Yuhito , Wong Fernando , Horner Philip J.
Published: March 2009

Aging is associated with many functional and morphological central nervous system changes. It is important to distinguish between changes created by normal aging and those caused by disease. In the present study we characterized myelin changes within the murine rubrospinal tract and found that internode lengths significantly decrease as a function of age which suggests active remyelination. We also analyzed the proliferation, distribution and phenotypic fate of dividing cells with Bromodeoxyuridine (5‐bromo‐2‐deoxyuridine, BrdU). The data reveal a decrease in glial cell proliferation from 1 to 6, 14 and 21 months of age in gray matter 4 weeks post‐BrdU injections. However, we found an increase in gliogenesis at 21st  month in white matter of the spinal cord. Half of newly generated cells expressed NG2. Most cells were positive for the early oligodendrocyte marker Olig2 and a few also expressed CC1. Very few cells ever became positive for the astrocytic markers S100β or GFAP. These data demonstrate ongoing oligodendrogenesis and myelinogenesis as a function of age in the spinal cord.
Identification of paraxanthine as the most potent caffeine‐derived inhibitor of connective tissue growth factor expression in liver parenchymal cells
Authors: Gressner Olav A. , Lahme Birgit , Siluschek Monika , Gressner Axel M.
Published: March 2009

Background: Recently, we identified hepatocytes as the major cellular source of profibrogenic connective tissue growth factor (CTGF/CCN2) in the liver. Based on reports of a hepatoprotective effect of coffee consumption, we were the first to provide evidence that caffeine suppresses transforming growth factor (TGF)‐β dependent and ‐independent CTGF expression in hepatocytes in vitro and in vivo, thus suggesting this xanthine‐alkaloid as a potential therapeutic agent.

Aim: This study aims at comparing the inhibitory capacities of caffeine and its three demethylated derivates paraxanthine, theophylline and theobromine on CTGF expression in hepatocytes and hepatic stellate cells (HSC).

Results: Our data suggest paraxanthine as the most important pharmacological repressor of hepatocellular CTGF expression among the caffeine‐derived metabolic methylxanthines with an inhibitory dosage (ID)50 of 1.15 mM, i.e. 3.84‐fold lower than what is observed for caffeine. In addition, paraxanthine displayed the least cell toxicity as proven by the water‐soluble tetrazolium‐1 cell vitality assay. However, caffeine or any of the metabolites did not inhibit CTGF expression in HSC. At the toxicological threshold concentration of 1 mM for paraxanthine, we observed an inhibition of hepatocellular CTGF synthesis by 44%, which was strongly reverted in the presence of the specific competitive cyclic adenosine monophosphate inhibitor Rp‐adenosine 3′,5‐cyclic monophosphorothioate triethylammonium salt. Furthermore, CTGF protein expression induced by various concentrations of TGF‐β (0.13–1 ng/ml) is still reduced by, on average, 27%/45% in the presence of paraxanthine (1.25 mM/2.5 mM).

Conclusion: Our data provide an evidence‐based suggestion of the caffeine‐derived primary metabolite paraxanthine as a potentially powerful antifibrotic drug by its inhibitory effect on (hepatocellular) CTGF synthesis.
Clinical Assessment and Rest and Stress Echocardiography for Prediction of Long‐Term Prognosis in African Americans with Known or Suspected Coronary Artery Disease
Authors: Sawada Stephen G. , Sayyed Samer , Raiesdana Azad , Gradus‐Pizlo Irmina , Mahenthiran Jothiharan , Feigenbaum Harvey
Published: March 2009

Background: There is limited information on noninvasive risk stratification of African Americans, a high‐risk group for cardiovascular events. We investigated the value of clinical assessment and echocardiography for the prediction of a long‐term prognosis in African Americans. Methods: Dobutamine echocardiography was performed in 324 African Americans. Two‐dimensional measurements were performed at rest, and rest and stress wall motion was assessed. A retrospective follow‐up was conducted for cardiac events: myocardial infarction (MI) or cardiac death (CD). Results: The mean age was 59 ± 12 years, and 83% of patients had hypertension. The follow‐up was obtained in 318 (98%) patients for a mean of 5.3 years. The events occurred in 107 (33%) subjects. The independent predictors of events were history of MI (P = 0.001, risk ratio [RR] 2.04), ischemia (P = 0.007, RR 1.97), fractional shortening (P = 0.033, RR 0.08), and left atrial (LA) dimension (P = 0.034, RR 1.39). An LA size of 3.6 cm and a fractional shortening of 0.30 were the best cutoff values for the prediction of events. Prior MI, ischemia, LA size >3.6 cm, and fractional shortening <0.30 were each considered independent risk predictors for events. The event rates were 13%, 21%, 38%, 59%, and 57% in patients with 0, 1, 2, 3, and 4 risk predictors, respectively. Event‐free survival progressively worsened with an increasing number of predictors: 0 or 1 versus 2 predictors, P < 0.001; 2 versus 3 or 4 predictors, P = 0.003. Conclusion: The long‐term prognosis of African Americans can be accurately predicted by clinical assessment combined with rest and stress echocardiography.
Complementary Roles of Transthoracic Two‐Dimensional Color Doppler Imaging and Myocardial Contrast Echocardiography in Diagnosis of Endomyocardial Fibrosis
Authors: Diaz Rienzi A. , Aranguiz Ernesto , Pedemonte Oneglio
Published: March 2009

Endomyocardial fibrosis (EMF) is a rare progressive restrictive cardiomyopathy of unknown etiology that mainly presents with heart failure. The presence of a small ventricle with obliteration of the apex and a large atrium are two‐dimensional echocardiographic findings that are highly suggestive of EMF. Cardiac magnetic resonance with delayed enhancement allows detection of subendocardial fibrosis with good histopathological correlation, providing a noninvasive modality for diagnosing EMF. We herein report a case of EMF in which the complementary role of two‐dimensional color Doppler imaging and myocardial contrast echocardiography proved to be useful in the diagnosis of this clinical entity, which was later confirmed by cardiac magnetic resonance, surgery, and histopathology.
A Comparison of Echocardiographic Techniques in Determination of Arterial Elasticity in the Pediatric Population
Authors: Fahey Michael , Ko H. Helen , Srivastava Shubhika , Lai Wyman W. , Chatterjee Samprit , Parness Ira A. , Lytrivi Irene D.
Published: March 2009

Background: Many methods are used to measure arterial elasticity in children using echocardiography. There is no data to support the equivalence of the different techniques. The goal of this study was to evaluate the reproducibility of several techniques used to measure arterial elasticity using echocardiography. Methods: Aortic distension in two different sites (arterial distension) through the cardiac cycle was measured by (four) two‐dimensional (2D) and M‐mode echocardiographic techniques in 20 children without significant structural heart disease. These measurements combined with noninvasive blood pressure measurements were used to calculate arterial elastic indices. Arterial elasticity was expressed in terms of distensibility and stiffness. Data were collected by two sonographers and interpreted by two reviewers. Paired Student's t‐test and Pitman's test for equality of variance for correlated observations were used to detect differences between different sonographers, different reviewers, and different techniques. Results: No significant difference in the measured elasticity between sonographers or reviewers was observed. There was a somewhat increased variance in two of the four techniques evaluated. There was no significant difference in elasticity measured using different techniques to evaluate the same arterial site, although a significantly decreased elasticity was noted from measurements taken in the proximal ascending aorta as compared with the distal ascending aorta. Conclusions: Many echocardiographic techniques produce reproducible measurements of arterial elasticity. There may be intrinsic differences in arterial elasticity between different segments of the ascending aorta, which have not been previously described in children with normal cardiac anatomy. Comparisons of data from separate studies must take these differences into account.
Folic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double‐blind randomized controlled trial
Authors: Behzadi A. H. , Omrani Z. , Chalian M. , Asadi S. , Ghadiri M.
Published: March 2009

Objective:  The purpose of this study was to evaluate the efficacy of adding folic acid to sodium valproate in the acute phase of mania.

Method:  Following a double‐blind randomized controlled trial, 88 clinically manic patients with diagnosis of type I bipolar disorder (BID) were divided randomly into two groups (case and control). The case group was treated with folic acid and sodium valproate and the control group with sodium valproate and placebo. The severity of mania was assessed using the Young Mania Rating Scale (YMRS) at the beginning and end of the first, second and third weeks of the study.

Results:  The case group’s mean manic YMRS measurements (SD) before the initiation of therapy and in the first, second and third weeks of treatment were 34.0 ± 7.7, 26.7 ± 2.1, 18.1 ± 2.1 and 7.1 ± 0.9 respectively. The control group’s measurements were 34.7 ± 3.8, 27.3 ± 2.3, 20.7 ± 2.5 and 10.1 ± 1.1. There was a statistically significant difference in YMRS scaling results between the case and control groups after 3 weeks of treatment (7.1 ± 0.9 vs. 10.1 ± 1.1, P = 0.005).

Conclusion:  Based on our findings, folic acid seems to be an effective adjuvant to sodium valproate in the treatment of the acute phase of mania in patients with bipolar disorder.
In‐patient suicide – a 13‐year assessment
Authors: Ajdacic‐Gross V. , Lauber C. , Baumgartner M. , Malti T. , Rössler W.
Published: March 2009

Objective:  To describe the suicide rates of psychiatric in‐patients in the canton of Zurich for the period 1992–2004, and to determine putative risk factors.

Method:  The data were derived from the psychiatric case register of the canton Zurich. The analyses were based on person‐years calculations and standardised mortality ratios. Additional information was assessed via case records.

Results:  During the 13‐year period the standardised mortality ratio was 48.9. The risk of suicide was particularly high in patients with personality and affective disorders. Most suicides occurred during regular leave periods, despite the fact that clinical assessment had indicated there was no suicide risk for the patient.

Conclusion:  The suicide risk of in‐patients is distinctly higher than in the general population. A better assessment of suicide risk before regular leave periods could lead to a decrease of suicides in in‐patient settings, as well as a more rigorous treatment of borderline cases, and of affective and psychotic symptoms.
Shopping Beyond the Parenthesis. An Equivalence of Books and Bottled Ketchup
Authors: Frost Simon R.
Published: March 2009

Words have been made public in very many ways: spoken as improvisation, recited from memory, written down and published or read aloud to an audience. Those printed have had very many formats: draft, (broad)sheet, part and periodical. Bound single and multiple volumes are merely one option. If a Gutenberg parenthesis is to make sense at all, then it is as a perception, of the bound volume format retaining a certain sanctity – regardless of what the material history of print culture might say. The question would then be, who held this perception and when? Or more precisely, if we assume the perception, under what conditions did alternatives emerge? Of the many contexts in which the hegemony of the bound volume has been debunked,1 commodification is one. This essay2 will examine, therefore, an early example of an industrialised literary Artwork in an emergent commodity culture, George Eliot’s Middlemarch, to see whether there may have been other ways of treating the volume’s otherwise hegemonic unified text; other ways of interpreting, or of readers profiting from, a commodity reading.
p53 protein expression in skin with different levels of photoaging
Authors: De Castro Inês Alencar , Schütz Larissa , Capp Edison , Cartell André , Meurer Luise , Bakos Lucio
Published: March 2009

In non‐melanoma skin cancer, keratinocytes show marked p53 protein expression. Considering photoaging as a background for skin cancer, p53 protein expression by immunohistochemistry was evaluated in normal skin with different levels of photoaging. The difference in p53 expression between mild and severe levels of photoaging was not statistically significant (P=0.169).
Effects of near‐infrared laser exposure in a cellular model of wound healing
Authors: Skopin Mark D. , Molitor Scott C.
Published: March 2009

Background: Clinical studies have demonstrated beneficial outcomes for low‐level laser therapy (LLLT) using near‐infrared (NIR) wavelengths. It has been hypothesized that the benefits of NIR LLLT are due in part to the thermal effects of NIR exposure. However, it is not clear whether photochemical interactions between NIR light and superficial tissues contribute to beneficial outcomes. To investigate the photochemical effects of NIR exposure, the efficacy of 980 nm NIR LLLT on human fibroblast growth rates is investigated using an in vitro model of wound healing.

Methods: A small pipette is used to induce a wound in fibroblast cell cultures, which are imaged at specific time intervals over 48 h and exposed to a range of laser doses (1.5–66 J/cm2) selected to encompass the range of doses used during other in vivo and in vitro studies. For each image acquired, wound sizes were quantified using a novel application of existing image processing algorithms.

Results: Cell growth rates were compared across different laser exposure intensities with the same exposure duration, and across different laser exposure durations with the same exposure intensity. Exposure to low‐ and medium‐intensity laser light accelerates cell growth, whereas high‐intensity light negated the beneficial effects of laser exposure. Cell growth was accelerated over a wide range of exposure durations using medium‐intensity laser light, with no significant inhibition of cell growth at the longest exposure durations used in this study.

Conclusion: Low‐level exposure to 980 nm laser light can accelerate wound healing in vitro without measurable temperature increases. However, these results also demonstrate the need for appropriate supervision of laser therapy sessions to prevent overexposure to NIR laser light that may inhibit cell growth rates observed in response to lower intensity laser exposure.
Tanning salons in Santiago, Chile: the knowledge of the staff in charge and the quality of information provided to potential clients before and after a new regulatory law
Authors: Salomone Claudia , Majerson Daniela , Molgó Montserrat , Sáenz de Santa María Mariá Luisa , Romero William
Published: March 2009

Introduction: In recent years, the use of artificial tanning devices has become very popular in Chile. In April, 2007, a new law was established to regulate the non‐medical use of tanning beds and tanning booths. The aim of this study was to evaluate the level and quality of information provided by tanning salon staff to clients before deciding on using the services. This information was collected before and 6 months after the law was enacted by researchers visiting tanning salons posing as potential clients.

Methods: Using a previously designed questionnaire, 24 tanning salons in Santiago, Chile, were evaluated by researchers acting as potential customers without experience with artificial tanning devices. Employees were questioned using a hidden questionnaire before and 6 months after enactment of the law.

Results: Before the law, 25% of the establishments gave spontaneous information about the risks of using tanning beds, which increased to 45.8% after enactment of the law. Clients never received written information, either before or after enactment of the law. On both evaluations, more than 1/3 of the employees affirmed that there were no risks in using tanning beds. Before enactment of the law, only 12.5% of the tanning salons required the use of goggles, while after the law, this increased to 25% (P=NS). Only two establishments required that clients sign an informed consent form after enactment of the law.

Discussion: The level of knowledge among employees in tanning salons was very low and the quality of the information they provided to the clients was very poor. It was important to legislate on ultraviolet tanning services, but at present, the impact of the law has been very limited.
Failure of short‐term psoralen and ultraviolet A light maintenance treatment to prevent early relapse in patients with chronic recurring plaque‐type psoriasis
Authors: Radakovic Sonja , Seeber Arno , Hönigsmann Herbert , Tanew Adrian
Published: March 2009

Background: Photochemotherapy using psoralen and ultraviolet A light (PUVA) is a highly effective treatment option for patients with severe psoriasis. Maintenance treatment has been advocated to provide for sustained remission. However, only a few studies have been conducted to assess the efficacy of maintenance treatment and these have provided inconsistent results.

Methods: We performed a prospective intrapatient left–right comparison study in 34 patients with chronic relapsing plaque psoriasis. PUVA treatment for clearing was given four times weekly. After complete or near‐complete clearing, all patients were placed on a halfside maintenance schedule with irradiation twice weekly and then once weekly for 4 weeks each. The psoriasis area and severity index score was determined at baseline, end of the clearing phase and at 2‐monthly intervals after discontinuation of treatment.

Results: Using a short‐term maintenance protocol, a moderate delay in relapse of psoriasis was observed in only three patients (8.8%; 95% CI: 1.8–23.6%). In the remaining patients (91.2%), maintenance treatment had no effect on the length of remission. The mean time interval until relapse without and with maintenance irradiation was 4.5 ± 3.4 and 4.6 ± 3.4 months, respectively.

Conclusion: Our data indicate that short‐term maintenance treatment is not effective in preventing early relapse of psoriasis and should be avoided.
Landscape‐scale detection and mapping of invasive African Olive (Olea europaea L. ssp. cuspidata Wall ex G. Don Ciferri) in SW Sydney, Australia using satellite remote sensing
Authors: Cuneo P. , Jacobson C.R. , Leishman M.R.
Published: March 2009

Question: Is satellite imagery an effective tool for mapping and examining the distribution of the invasive species Olea europaea L. ssp. cuspidata at a regional landscape scale?

Location: Southwest Sydney, Australia.

Methods: Remote sensing software was used to classify pixels of Olea europaea L. ssp. cuspidata (African Olive) and major vegetation types from satellite imagery, using a “supervised classification” technique across a 721 km2 study area in the Cumberland Plain region of western Sydney. A map of African Olive distribution was produced from the image analysis and checked for accuracy at 337 random locations using ground observation and comparison with existing vegetation maps. The African Olive distribution data were then used in a GIS analysis with additional spatial datasets to investigate the relationship between the distribution of African Olive and environmental factors, and to quantify the conservation threat to endangered native vegetation.

Results: A total area of 1907 ha of dense African Olive infestation was identified, with an omission error of 7.5% and a commission error of 5.4%. African Olive was found to occur on the steepest slopes (mean slope 14.3°) of the vegetation classes examined, with aspect analysis identifying a high prevalence on south‐ and southwest‐facing slopes. The analysis also quantified the level of African Olive infestation in endangered ecological communities, with Western Sydney Dry Rainforest (25% affected) and Moist Shale Woodland (28% affected) identified as most vulnerable to African Olive invasion.

Conclusion: The distribution of African Olive can be efficiently mapped at a landscape scale. This technique, used in association with additional spatial datasets, identified African Olive as a significant environmental weed in SW Sydney, occupying a greater area than previously recognised and threatening several endangered native vegetation communities.
Should edentulous patients be constrained to removable complete dentures? The use of dental implants to improve the quality of life for edentulous patients
Authors: Turkyilmaz Ilser , Company Andrea M. , McGlumphy Edwin A.
Published: March 2009

doi:10.1111/j.1741‐2358.2009.00294.x
 
Should edentulous patients be constrained to removable complete dentures? The use of dental implants to improve the quality of life for edentulous patients

Background:  Nowadays, there is some speculation among dental educators that the need for complete dentures will significantly decrease in the future and that training in their provision should be removed from the dental curriculum.

Objective:  To sensitise the reader to the functional shortcomings of complete denture therapy in the edentulous patient and present restorative options including implants to improve edentulous quality of life in these patients.

Methods:  Information retrieval followed a systematic approach using PubMed. English articles published from 1964 to 2008, in which the masticatory performance of patients with implant‐supported dentures was assessed by objective methods and compared with performance with conventional dentures, were included.

Results:  National epidemiological survey data suggested that the adult population in need of one or two complete dentures will increase from 35.4 million adults in 2000 to 37.9 million adults in 2020. Clinical studies have showed that the ratings of general satisfaction were significantly better in the patients treated with implant overdentures post‐delivery compared with the complete denture users. In addition, the implant group gave significantly higher ratings on comfort, stability and ability to chew. Furthermore, patients who received mandibular implant overdentures had significantly fewer oral health‐related quality of life problems than did the conventional group.

Conclusion:  Implant‐supported dentures including either complete overdentures or a hybrid prosthesis significantly improve the quality of life for edentulous patients compared with conventional removable complete dentures. Therefore, the contemporary dental practitioner should consider other options as well as conventional removable complete dentures to restore edentulous patients.
α‐1 Antitrypsin binds preprohepcidin intracellularly and prohepcidin in the serum
Authors: Pandur Edina , Nagy Judit , Poór Viktor S. , Sarnyai Ákos , Huszár András , Miseta Attila , Sipos Katalin
Published: March 2009

Recent discoveries have indicated that the hormone hepcidin plays a major role in the control of iron homeostasis. Hepcidin regulates the iron level in the blood through the interaction with ferroportin, an iron exporter molecule, causing its internalization and degradation. As a result, hepcidin increases cellular iron sequestration, and decreases the iron concentration in the plasma. Only mature hepcidin (result of the cleavage of prohepcidin by furin proteases) has biological activity; however, prohepcidin, the prohormone form, is also present in the plasma. In this study, we aimed to identify new protein–protein interactions of preprohepcidin, prohepcidin and hepcidin using the BacterioMatch two‐hybrid system. Screening assays were carried out on a human liver cDNA library. Preprohepcidin screening gave the following results: α‐1 antitrypsin, transthyretin and α‐1‐acid glycoprotein showed strong interactions with preprohepcidin. We further confirmed and examined the α‐1 antitrypsin binding in vitro (glutathione S‐transferase, pull down, coimmunoprecipitation, MALDI‐TOF) and in vivo (ELISA, cross‐linking assay). Our results demonstrated that the serine protease inhibitor α‐1 antitrypsin binds preprohepcidin within the cell during maturation. Furthermore, α‐1 antitrypsin binds prohepcidin significantly in the plasma. This observation may explain the presence of prohormone in the circulation, as well as the post‐translational regulation of the mature hormone level in the blood. In addition, the lack of cleavage protection in patients with α‐1 antitrypsin deficiency may be the reason for the disturbance in their iron homeostasis.
The hemoglobins of the sub‐Antarctic fish Cottoperca gobio, a phyletically basal species – oxygen‐binding equilibria, kinetics and molecular dynamics
Authors: Giordano Daniela , Boechi Leonardo , Vergara Alessandro , Martí Marcelo A. , Samuni Uri , Dantsker David , Grassi Luigi , Estrin Darío A. , Friedman Joel M. , Mazzarella Lelio , di Prisco Guido , Verde Cinzia
Published: March 2009

The dominant perciform suborder Notothenioidei is an excellent study group for assessing the evolution and functional importance of biochemical adaptations to temperature. The availability of notothenioid taxa in a wide range of latitudes (Antarctic and non‐Antarctic) provides a tool to enable identification of physiological and biochemical characteristics gained and lost during evolutionary history. Non‐Antarctic notothenioids belonging to the most basal families are a crucial source for understanding the evolution of hemoglobin in high‐Antarctic cold‐adapted fish. This paper focuses on the structure, function and evolution of the oxygen‐transport system of Cottoperca gobio, a sub‐Antarctic notothenioid fish of the family Bovichtidae, probably derived from ancestral species that evolved in the Antarctic region and later migrated to lower latitudes. Unlike most high‐Antarctic notothenioids, but similar to many other acanthomorph teleosts, C. gobio has two major hemoglobins having the β chain in common. The oxygen‐binding equilibria and kinetics of the two hemoglobins have been measured. Hb1 and Hb2 show strong modulation of oxygen‐binding equilibria and kinetics by heterotropic effectors, with marked Bohr and Root effects. In Hb1 and Hb2, oxygen affinity and subunit cooperativity are slightly higher than in most high‐Antarctic notothenioid hemoglobins. Hb1 and Hb2 show similar rebinding rates, but also show significant dynamic differences that are likely to have functional consequences. Molecular dynamic simulations of C. gobio Hb1 were performed on the dimeric protein in order to obtain a better understanding of the molecular basis of structure/function relationships.
The in vitro nuclear aggregates of polyamines
Authors: Di Luccia Aldo , Picariello Gianluca , Iacomino Giuseppe , Formisano Annarita , Paduano Luigi , D’Agostino Luciano
Published: March 2009

Natural polyamines (putrescine, spermidine, and spermine) self‐assemble in a simulated physiological environment (50 mm sodium phosphate buffer, pH 7.2), generating in vitro nuclear aggregates of polyamines (ivNAPs). These supramolecular compounds are similar in structure and molecular mass to naturally occurring cellular nuclear aggregates of polyamines, and they share the ability of NAPs to interact with and protect the genomic DNA against nuclease degradation. Three main ivNAP compounds were separated by gel permeation chromatography. Their elution was carried out with 50 mm sodium phosphate buffer supplemented with 150 mm NaCl. Freezing and thawing of selected chromatographic fractions obtained by GPC runs in which the mobile phase was sodium phosphate buffer not supplemented with NaCl yielded three different microcrystallites, specifically corresponding to the ivNAPs, all of which were able to bind DNA. In this study, we demonstrated that in vitro self‐assembly of polyamines and phosphates is a spontaneous, reproducible and inexpensive event, and provided the indications for the production of the ivNAPs as a new tool for manipulating the genomic DNA machinery.
A Case Report of Darbepoetin Treatment in a Patient With Sickle Cell Disease and Chronic Renal Failure Undergoing Regular Hemodialysis Procedures That Induce a Dose‐Dependent Extension of Blood Transfusion Intervals
Authors: Schettler Volker , Wieland Eberhard
Published: March 2009

Abstract:  In this case, a female Nigerian patient suffered from sickle cell disease (SCD, hemoglobin SS)‐induced chronic renal failure and was undergoing hemodialysis treatment. Due to SCD crisis and renal anemia the patient received regular blood transfusions when the hemoglobin concentration fell below 5.0 g/L. Blood transfusion associated iron‐overload was noticed. To reduce the iron‐overload side effects, we started an erythropoietin therapy (darbepoetin) to extend the blood transfusion interval, using 30–150 µg/week. As a result of our investigation we observed that darbepoetin can significantly extend blood transfusion intervals without increasing SCD crisis. To substantiate our observation, further investigations are needed with more SCD patients undergoing regular hemodialysis treatment.
Ratio of Platelet Reduction is an Early Predictive Factor for the Effectiveness of Leukocytapheresis for Ulcerative Colitis Patients
Authors: Takemoto Koji , Kuriyama Motoaki , Kato Jun , Suzuki Hideyuki , Ishikawa Shin , Hiraoka Sakiko , Yamamoto Kazuhide
Published: March 2009

Abstract:  Leukocytapheresis is effective for ulcerative colitis (UC), and both peripheral leukocyte and platelet counts decrease during apheresis. While leukocyte counts increase and overshoot after finishing the apheresis procedure, platelet reduction continues even after apheresis. The aim of this study is to elucidate the impact of the overshoot of leukocyte and continuous platelet reduction on the efficacy of leukocytapheresis for UC. Leukocyte and platelet counts before and one hour after each leukocytapheresis session of 43 UC cases were examined (31 entered remission, but 12 did not). The correlation between the efficacy of leukocytapheresis and leukocyte overshoot or platelet reduction was examined. The average increase ratio of leukocytes in the initial five sessions of the responders was not significantly different from that of the non‐responders (95% vs. 92%, P = 0.28). In contrast, the average decrease ratio of platelets in the initial five sessions of the responders was significantly higher than that of the non‐responders (34% vs. 27%, P = 0.0041). Moreover, the platelet reduction at the third and fourth apheresis sessions in the responders was remarkably greater than that in the non‐responders (33% vs. 20%, P = 0.0018). The efficiency of platelet reduction could be a predictive factor for the efficacy of leukocytapheresis.
Feasibility of Five Days of Consecutive Leukocytapheresis for the Treatment of Ulcerative Colitis: A Preliminary Study
Authors: Tsujikawa Tomoyuki , Andoh Akira , Ogaẃa Atsuhiro , Sonoda Ayano , Yagi Yuhki , Hata Kazuori , Sasaki Masaya , Saito Yasaharu , Fujiyama Yoshihide
Published: March 2009

Abstract:  Leukocytapheresis (LCAP) has been applied for the treatment of steroid refractory ulcerative colitis (UC). A standard protocol employs one or two sessions of LCAP per week. Our aim was to determine whether five consecutive LCAP sessions can be performed safely and effectively for UC patients. Six patients with moderately active UC were enrolled. The patients received five days of consecutive LCAP in which the processing volume of blood was limited to 1500 mL per session. The hemoglobin levels in each patient gradually decreased, and the platelet count by the fifth session reached half of the value before the first session. The clinical activity index in two patients improved daily, and they went into remission with an improvement in the colonic endoscopic appearance after one week. This preliminary study showed that five consecutive LCAP sessions are safe and feasible for active UC patients. The therapeutic efficacy and suitable patients for this treatment protocol should be confirmed by further studies.
Characterization of nine novel microsatellite markers from Brandt's vole (Lasiopodomys brandtii)
Authors: YUE LING‐FEN , WANG DA‐WEI , HUANG BAO‐HUAN , LIU XIAO‐HUI
Published: March 2009

Highly polymorphic microsatellite markers are the most powerful tools to infer kinship relations. In this study, a library enriched for (AC)n (AG)n and (AGAT)n was constructed for screening microsatellite markers in Brandt's vole (Lasiopodomys brandtii), and nine novel polymorphic microsatellite markers were developed and characterized. The number of alleles ranged from 4 to 11 per locus and the mean polymorphism information content was 0.7535. The observed and the expected heterozygosity values averaged 0.760 (0.554–0.908) and 0.7914 (0.718–0.845), respectively. Average nonexclusion probability for one candidate parent varied from 0.485 to 0.716. These nine novel markers are highly polymorphic and powerful enough for our future kinship analysis.
Microsatellite markers for the tetraploid halophyte Suaeda maritima (L.) Dumort. (Chenopodiaceae) and cross‐species amplification in related taxa
Authors: PRINZ KATHLEEN , HENSEN ISABELL , SCHIE STEPHAN , DEBENER THOMAS , WEISING KURT
Published: March 2009

We developed 12 polymorphic microsatellite markers for the tetraploid halophyte Suaeda maritima (Chenopodiaceae). Population genetic parameters were estimated for three populations from different habitats (coastal and inland), using the program Tetrasat. Between two and 15 alleles per locus were observed. Mean expected heterozygosities (HE) and Shannon‐Wiener Diversity Indices (H′) per locus and population ranged from zero to 0.852, and from zero to 2.990, respectively. The two inland populations were less diverse than the coastal one at most of the loci. All markers cross‐amplified in the closely related Suaeda salsa, and all but one were transferable to Suaeda spicata and Suaeda salinaria.
Forecast Updating and Supplier Coordination for Complementary Component Purchases
Authors: Thomas Douglas J. , Warsing Donald P. , Zhang Xueyi
Published: March 2009

We study a supply chain where an original equipment manufacturer (OEM) buys subassemblies, comprised of two complementary sets of components, from a contract manufacturer (CM). The OEM provides a demand forecast at the time when the CM must order the long lead‐time set of components, but must decide whether or not to provide updated forecasts as a matter of practice. Forecast updates affect the CM's short lead‐time purchase decision, and the anticipation of updates may also affect the long lead‐time purchase decision. While the OEM and CM both incur lost sales costs, the OEM can decide whether or not to share the overage costs otherwise fully borne by the CM. We investigate when the OEM is better served by committing to provide updated forecasts and/or committing to share overage costs. For a distribution‐free, two‐stage forecast‐update model, we show that (1) the practice of providing forecast updates may be harmful to the OEM and (2) at the OEM's optimal levels of overage risk sharing, the CM undersupplies relative to the supply chain optimal quantity. For a specific forecast‐update model, we computationally investigate conditions under which forecast updating and risk sharing are in the best interest of the OEM.
A Rapid Detection Method for the Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses
Authors: Nieto J.E. , Aleman M.
Published: March 2009

Background:Anesthetic‐induced malignant hyperthermia has been documented in Quarter Horses and is caused by a single‐point mutation in the ryanodine receptor 1 gene at nucleotide C7360G generating a R2454G amino acid substitution. An accurate, faster molecular test that is less prone to contamination would facilitate screening for the mutation in horses intended for breeding, in those undergoing surgical procedures, and in those with clinical signs compatible with malignant hyperthermia.

Objective:To report a rapid and accurate method for the detection of the ryanodine receptor 1 C7360G mutation.

Animals:Eleven diseased, 10 healthy, and 225 randomly selected Quarter Horses.

Methods:This study included horses with the ryanodine receptor 1 C7360G mutation as detected by gene sequencing. Available genomic and complementary DNA extracted from whole blood, hair or skeletal muscle was used for genetic analysis. Real‐time polymerase chain reaction (RT‐PCR) melting curve analysis was performed by equine specific primers and 2 hybridization probes (sensor and anchor probes) that contain the site of the mutation. Results from this method were blinded and compared with nucleic acid sequencing for validation.

Results:A rapid genotyping assay with fluorescence resonance energy transfer probes and melting curve analysis was accurate (100% agreement,K= 1) for identification of affected horses. The prevalence of the mutation in a random population of Quarter Horses was 1.3%.

Conclusions and Clinical Importance:Malignant hyperthermia in Quarter Horses can be rapidly and accurately detected by RT‐PCR melting curve genotyping with hybridization probes.
AMP‐activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle
Authors: Thomson D.M. , Brown J.D. , Fillmore N. , Ellsworth S.K. , Jacobs D. L. , Winder W.W. , Fick C.A. , Gordon S.E.
Published: March 2009

One characteristic of ageing skeletal muscle is a decline in mitochondrial function. Activation of AMP‐activated protein kinase (AMPK) occurs in response to an increased AMP/ATP ratio, which is one potential result of mitochondrial dysfunction. We have previously observed higher AMPK activity in old (O; 30 months) vs young adult (YA; 8 months) fast‐twitch muscle in response to chronic overload. Here we tested the hypothesis that AMPK would also be hyperactivated in O vs YA fast‐twitch extensor digitorum longus muscles from Fischer344× Brown Norway (FBN) rats (n= 8 per group) in response to high‐frequency electrical stimulation of the sciatic nerve (HFES) or injection of AICAR, an activator of AMPK. Muscles were harvested immediately after HFES (10 sets of six 3‐s contractions, 10 s rest between contractions, 1 min rest between sets) or 1 h after AICAR injection (1 mg (g body weight)−1 subcutaneously). The phosphorylations of AMPKα and acetyl‐CoA carboxylase (ACC2; a downstream AMPK target) were both greatly increased (P≤ 0.05) in response to HFES in O muscles, but were either unresponsive (AMPK α) or much less responsive (ACC) in YA muscles. AMPK α2 activity was also greatly elevated in response to HFES in O muscles (but not YA muscles) despite a lower total AMPK α2 protein content in O vs YA muscles. In contrast, AMPK α2 activity was equally responsive to AICAR treatment in both age groups. Since mitochondrial content and/or efficiency could potentially underlie AMPK hyperactivation, we measured levels of mitochondrial proteins as well as citrate synthase (CS) activity. While CS activity was increased by 25% in O vs YA muscles, uncoupling protein‐3 (UCP‐3) protein level was upregulated with age by 353%. Thus, AMPK hyperactivation in response to contractile activity in aged fast‐twitch muscle may be the result of compromised cellular energetics and not necessarily due to an inherent defect in responsiveness of the AMPK molecule per se.
Development of an In Vitro Porcine Aorta Model to Study the Stability of Stent Grafts in Motor Vehicle Accidents
Authors: Darvish Kurosh , Shafieian Mehdi , Romanov Vasily , Rotella Vittorio , Salvatore Michael D. , Blebea John
Published: March 2009

Endovascular stent grafts for the treatment of thoracic aortic aneurysms have become increasingly utilized and yet their locational stability in moderate chest trauma is unknown. A high speed impact system was developed to study the stability of aortic endovascular stent grafts in vitro. A straight segment of porcine descending aorta with stent graft was constrained in a custom-made transparent urethane casing. The specimen was tested in a novel impact system at an anterior inclination of 45deg and an average deceleration of 55G, which represented a frontal automobile crash. Due to the shock of the impact, which was shown to be below the threshold of aortic injury, the stent graft moved 0.6mm longitudinally. This result was repeatable. The presented experimental model may be helpful in developing future grafts to withstand moderate shocks experienced in motor vehicle accidents or other dynamic loadings of the chest.