bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Changes in Ventricular Repolarization after Thrombolytic Therapy in Patients with Acute Myocardial Infarction as Indicators for Prediction of Epicardial Coronary Artery Reperfusion
Authors: Hegazy Aly Mohamad , Abdulkader Bader A. , Akbar Mousa A.J. , El-Enezi Laila Soud
Published: February 2007

Objectives: To investigate the relationship between early T-wave inversion after thrombolytic therapy and the likelihood of successful epicardial coronary reperfusion. Subjects and Methods: Thrombolytic therapy was given to 195 patients with ST segment elevation due to acute anterior myocardial infarction (AMI). Coronary angiography was performed. Receiver operating characteristic (ROC) curve (grade of sensitivity versus false positive) was calculated using likelihood ratio method to identify the ideal cut-off values of the ventricular repolarization variables. Results: Predictive indices showed 80% sensitivity, 83% specificity, 81% accuracy, 88% positive predictive value and 71% negative predictive value for early T-wave inversion after thrombolytic therapy. A good concordant agreement was noted between the data of coronary angiography and early T-wave inversion in the infarct-related ECG leads after thrombolysis (kappa coefficient ĸ= 0.876). Stepwise multivariate analysis revealed that early T-wave inversion after thrombolytic therapy of AMI was significantly associated with a history of preinfarction angina, residual infarct-related coronary artery stenosis >50%, short time to thrombolytic therapy <90 min, and evening time for occurrence of thrombolysis (p < 0.05). The ROC curve data analysis showed that early T-wave inversion amplitude after AMI had 87% sensitivity and 84% specificity for predicting successful reperfusion, with an ideal cut-off value of 7.2 mm, while time of T-wave inversion had 80% sensitivity and 79% specificity, with an ideal cut-off value of 120 min. Conclusion: The data indicate that early inversion of T wave after AMI is a statistically significant independent variable in predicting successful epicardial coronary thrombolysis status.
Bilateral Emphysematous Pyelonephritis and Emphysematous Cystitis with Autosomal-Dominant Polycystic Kidney Disease: Is Conservative Management Justified?
Authors: Arun Narayanaswamy , Hussain Abdullatif , Kapoor Madan Mohan , Abul Fawzi
Published: February 2007

Objective: To report a case of bilateral emphysematous pyelonephritis (EPN) and emphysematous cystitis in a 64-year-old diabetic male with autosomal-dominant polycystic kidney disease (ADPKD). Case Presentation and Intervention: A 64-year-old diabetic male presented with worsening of renal function and fluid overload. Diagnosis was confirmed by computerized tomography (CT scan) and conservative management with broad-spectrum antibiotics was instituted. There was good clinical response and repeated CT scan showed complete resolution. Conclusion: This case shows that conservative management is an acceptable alternative to surgery in EPN occurring with ADPKD. However, it is recommended that patients should be closely monitored, both clinically and radiologically, and percutaneous catheter drainage or surgical intervention carried out whenever deemed necessary.
Luteinizing Hormone-Releasing Hormone Analogue-Induced Cataract in a Patient with Prostate Cancer
Authors: Al-Enezi Ahmad , Kehinde Elijah O. , Behbehani Abdulla M. , Sheikh Zafar A.
Published: February 2007

Objective: To report a case of right posterior subcapsular cataract induced by 3-monthly depot luteinizing hormone-releasing hormone (LHRH) analogue therapy in a patient with early prostate cancer. Case Presentation: A 52-year-old male with static myopia of several years’ duration was given a 3-month depot LHRH analogue (goserelin 10.8 mg) as part of neoadjuvant treatment for early prostate cancer. Four weeks after the treatment, the patient developed right posterior subcapsular cataract commonly associated with steroid treatment. The patient had right eye cataract extraction followed by insertion of a new lens. Conclusion: This report shows a case of a posterior subcapsular cataract as an adverse reaction to depot goserelin acetate. This is a feature commonly seen in steroid-induced cataract. Patients with prostate cancer and poor vision if due to cataract may not be ideal patients for depot preparations of LHRH analogues.
Allogeneic HLA-Matched Donor Dendritic Cells Loaded with Patient Leukemic Blasts Preferentially Induce CD4-Positive Leukemia-Reactive Donor Lymphocytes
Authors: Thomas-Kaskel Anna-Katharina , Alves Portugal Tatiana Gil , Herchenbach Dieter , Houet Leonora , Veelken Hendrik , Finke Jürgen
Published: February 2007

Background: The therapeutic value of donor lymphocyte infusions in patients who relapse with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT) is limited by a low efficacy and the risk of graft-versus-host disease. We aimed at generating leukemia-reactive donor T cells for patients with AML. Methods: Peripheral blood mononuclear cells of the donor were stimulated with mature donor dendritic cells, pulsed with irradiated patient leukemic blasts (LB), or directly with cytokine-treated LB. After 3 weekly stimulations, donor cells were tested for anti-leukemic reactivity in an IFNγ Elispot. Results: In 5 of 6 donors, cells with reactivity against patient LB with low or absent reactivity against non-leukemic cells could be generated. T cell subset analyses in 2 donors indicated that specific anti-leukemic reactivity was mainly mediated by CD4+ T cells, which were also the predominant cell fraction in 4 of 6 donors. One leukemia-reactive donor T cell line was expanded with a recently developed system. One week of expansion resulted in a 10-fold increase in reactivity with sustained specificity of the resulting T cell line. Conclusions: Our results show the feasibility of the in vitro generation of leukemia-reactive donor lymphocytes, rendering this method a promising tool for post-HSCT immunotherapy.
Area under the Maximum Expiratory Flow-Volume Curve – A Sensitive Parameter in the Evaluation of Airway Patency
Authors: Zapletal Alois , Hladíková Marie , Chalupová Jana , Svobodová Tamara , Vávrová Véra
Published: February 2007

Background: The most frequently used parameters for assessing bronchoconstriction and bronchodilation are forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF). Objectives: To assess the sensitivity of other parameters after induced bronchoconstriction and bronchodilation. Methods: From maximum expiratory flow-volume (MEFV) curves, forced vital capacity, FEV1, PEF, maximum expiratory flows (MEF) at 25, 50 and 75% of vital capacity and the area under the MEFV curve (Aex) were measured in two groups of asthmatic children after induced bronchoconstriction and bronchodilation, and in children with cystic fibrosis (CF) after bronchodilation. Results: In 142 asthmatics without airway obstruction, bronchoconstriction was induced by inhalation of 1% histamine aerosol. The 20% fall in Aex compared to baseline was found in all asthmatics, while the 20 and 15% falls in FEV1 were noted in 36 and 65% of the patients, respectively. Other parameters were less sensitive or interpretation was problematic. Another110 asthmatics with mild-moderate airway obstruction were treated with various bronchodilators. The 20% increase in Aex was observed in all asthmatics, while the 20% increase in FEV1 was found in only 33% of the patients and the 15% increase in FEV1 in 51%. In 9CF children, the pattern of changes in Aex and FEV1 after bronchodilation was similar to that in asthmatics. Conclusions: Aex was a sensitive and less problematic parameter in the evaluation of airway patency in comparison with FEV1 and other parameters measured from the MEFV curve in our study patients.
Self-Application of Complementary and Alternative Medicine by Patients with Gynecologic Cancer
Authors: Akyuz Aygul , Dede Murat , Cetinturk Ayse , Yavan Tulay , Yenen Mufit Cemal , Sarici S. Umit , Dilek Saffet
Published: February 2007

Objectives: In this study we aimed to determine the epidemiology and demographic data on complementary and alternative medicine (CAM) use along with the medical/surgical treatment modalities in patients with gynecologic cancers in Turkey. Materials and Methods: A cross-sectional study was designed to determine demographic data on CAM use of patients with gynecologic cancers who had medical and/or surgical treatments. Semistructured questionnaires were used for collecting data from 126 patients. Results: When the CAM use ratio of patients was evaluated with respect to demographic characteristics, patients using any type of CAM were younger and more educated, and there were no significant differences between the patients who used and who did not use any type of CAM with respect to geographical region. There were no significant correlations between the use of CAM and the type of malignancy, treatment modality and time period after diagnosis. Conclusion: There is critical concern about the probable serious risks associated with non-educated CAM practitioners. Therefore, informed and educated healthcare professionals should inform and help in relieving patients in a more professional and multidisciplinary way.
Impedance Measurements of the Spinal Cord of Man and Animals
Authors: Vieira José F.S. , Shieff Colin , Nashold Jr. Blaine S. , Bullard Dennis E. , Cosman Eric
Published: February 2007

The measurement of electrical impedance of normal and pathologic tissue has not been fully utilized in neurosurgery. This is a report of electrical impedance measurement in the central nervous system of both man and animals. We show the results of the laboratory study done in animals, in the brain and in the spinal cord as well. Also we show the clinical experience of the impedance recordings in the DREZ procedure for some chronic pain conditions, correlating the measurements at the time of the operation with normal conditions, with comments about the findings.
Dorsal Root Entry Zone Lesions in the Treatment of Pain following Brachial Plexus Avulsion, Spinal Cord Injury and Herpes zoster
Authors: Friedman Allan H. , Bullitt Elisabeth
Published: February 2007

This paper details the long-term results in patients treated with dorsal root entry zone (DREZ) lesions for the treatment of pain following brachial plexus avulsion, spinal cord injury, and herpes zoster. With our current operative technique, 82% of patients with brachial plexus avulsion injuries were afforded long-term pain relief. Patients with pain confined to dermatomes just below the level of spinal injury also did well with DREZ lesions, although the results were less good in patients with diffuse pain or with sacral pain. The postoperative results in patients with postherpetic pain were disappointing.
The Hopkins Experience with Lesions of the Dorsal Horn (Nashold’s Operation) for Pain from Avulsion of the Brachial Plexus
Authors: Campbell James N. , Solomon Clifford T. , James Carol S.
Published: February 2007

Lesions of the dorsal horn (DREZ operation) have been reported to be useful in reducing pain secondary to avulsion of the brachial plexus. Ten patients had the DREZ operation for this condition at The Johns Hopkins Hospital by one of us (JNC) between 1981 and 1985. Radiofrequency heat lesions were made. The patients were interviewed 7–52 months after the operation by one of two individuals not involved in the procedure to assess pain relief and postoperative complications. The mean pain relief was 85%, and there were no significant complications. It is concluded that the DREZ operation is the treatment of choice for treatment of severe pain that results from avulsion of the brachial plexus.
Dorsal Root Entry Zone Lesions for Conus medullaris Root Avulsions
Authors: Moossy John J. , Nashold Jr. Blaine S.
Published: February 2007

We have found dorsal root entry zone (DREZ) lesions to be an effective treatment of chronic deafferentation pain in patients who have had avulsions of the dorsal rootlets from the spinal cord. Eight patients were operated in whom chronic pain of the lower extremity resulted from dorsal root avulsions from the conus medullaris. In 7 of the 8 patients, the mechanism of injury was a motor vehicle accident; all 7 sustained severe pelvic trauma. Seven of the 8 patients remained pain-free, off all narcotics, with an average follow-up of 33 months. All patients had DREZ lesions of the conus performed by radiofrequency techniques.
Dorsal Root Entry Zone Coagulation for Intractable Sciatica
Authors: Saris Stephen C. , Vieira José F.S. , Nashold Jr. Blaine S.
Published: February 2007

Chronic back and leg pain which is unresponsive to medical and/or surgical treatment is a common and difficult neurosurgical problem. Twelve patients with this condition underwent dorsal root entry zone coagulation of that region of the conus medullaris which correlated with the pain. Only 2 patients had a favorable result. The implications of this finding are discussed.
Involuntary Movements of the Lower Extremity following Dorsal Root Entry Zone Lesions in a Man Treated for Phantom Limb Pain
Authors: Tourian Ara , Iacono Robert , Nashold Blaine , Urban Bruno , Sanders Donald
Published: February 2007

A patient developed continuous patterned involuntary movements of abduction-adduction, flexion-extension of his right lower extremity following surgical placement of spinal dorsal root entry zone lesions for the treatment of phantom limb pain. The stereotype movements were monitored by video and electromyographic recording of quadriceps femoris and hamstring muscles. Administration of para-chloro-phenylbutyric acid (baclofen) dramatically stopped the involuntary movements and electromyographic silence ensued. Voluntary muscle movements were preserved. The theoretical implications of this unique movement disorder and central patterning of motor activity within the spinal cord are discussed.
Clinical Review of Nucleus Caudalis DorsaI Root Entry Zone Lesions for Facial Pain
Authors: Bernard Jr. Estrada J. , Nashold Jr. Blaine S. , Caputi Franco
Published: February 2007

Twenty-seven patients with intractable facial pain underwent dorsal root entry zone thermocoagulation lesion of the nucleus caudalis of the spinal trigeminal nucleus. Retrospective review revealed a success rate of 85 % in the immediate postoperative period declining to 52% on subsequent follow-up. The best results were in the subgroup of patients with postherpetic neuralgia, of which 67% achieved definite relief. There tended to be some correlation of satisfactory results and pain quality as well as extent of pain along trigeminal territory. The operative morbidity was low although most patients were observed to have a mild transient ipsilateral dysmetria.
Historical Development of Neural Transplantation
Authors: Borges Lawrence F.
Published: February 2007

The techniques of neural transplantation are almost 100 years old. As these techniques begin to be used to treat human neurological disorders, it is important to remember the contributions of the many investigators who have advanced this fascinating area of neurobiology.
Immunology of Transplantation in the Central Nervous Sylftem
Authors: Fuchs Herbert E. , Bullard Dennis E.
Published: February 2007

The brain has long been considered an immunologically privileged site. Tissue transplanted to the central nervous system (CNS) is immunologically better tolerated than grafts to other regions of the body. With improved graft survival, tissue transplantation may provide new treatment options for previously incurable CNS disorders. The normal immune response is reviewed, followed by a discussion of the factors responsible for graft rejection. The modification of these factors to allow successful CNS transplantation is discussed.
Intraoperative Electrical Stimulation of the Brain in Patients with Obsessive-Compulsive Neurosis
Authors: Laitinen Lauri V. , Singounas Evangelos
Published: February 2007

Twenty patients with intractable obsessive-compulsive neurosis were operated under local anesthesia. Each patient had a lesion produced in 1 of the 4 brain targets: anterior internal capsule, rostral cingulum, middle cingulum, and genu of the corpus callosum. Before destructive permanent lesions were produced, the target area was stimulated electrically. Stimulation gave subjective or objective reactions in 30% of the patients: diminished anxiety, 3 patients; increased anxiety, 1 patient, and motor responses, 2 patients. None experienced an obsessive reaction to stimulation. The clinical effect of surgery was usually good.
Investigation on Cerebrospinal Fluid Opioids and Neurotransmitters Related to Spinal Cord Stimulation
Authors: Tonelli L. , Setti T. , Falasca A. , Martignoni E. , Torcia E. , Calcaterra F.M. , Merli G.A. , Facchinetti F.
Published: February 2007

The purpose of this study was to assess the biochemical mechanisms underlying spinal cord stimulation (SCS). Seventeen patients with chronic pain were investigated by measuring cerebrospinal fluid concentrations of endogenous opioids and biogenic amines before and during dorsal column stimulation. BasaI cerebrospinal fluid β-endorphin levels were below the normal range. No significant change of norepinephrine, epinephrine, dopamine, β-endorphin, β-lipotropin, or adrenocorticotropic hormone levels were found after SCS. A 50% increase of cerebrospinal β-endorphin and β-lipotropin levels occurred in 6 out of 16 patients, namely those where SCS gave the major pain relief. These data confirm the derangement of the endogenous opioid system in chronic pain conditions and suggest that the β-endorphin response to SCS could have clinical value in predicting the success of treatment.
Developing an Appropriate Psychology through Culturally Sensitive Research Practices in the Arabic-Speaking World
Authors: Zebian Samar , Alamuddin Rayane , Maalouf Mariane , Chatila Yasmine
Published: February 2007

Contemporary psychologists in the Arabic-speaking world remain deeply concerned with many of the same foundational issues that have impeded the development of sustainable research traditions since at least the 1950s. As a means of assessing historical and current trends in regional research practices, the project reported in this article employs a content analysis method to assess the cultural sensitivity of peer-reviewed English-language empirical studies conducted on peoples of the Arabic-speaking world. Results suggest that cultural sensitivity is quite low on many of the dimensions assessed, including whether/how findings are applied to everyday settings, validity of methodological procedures employed, the way cultural contributions to psychological processes are discussed, the local relevance of conclusions drawn from empirical findings, and how theories and concepts are transferred from mainstream (Western) psychology. The current findings are used to suggest some strategic and potentially controversial connections between culturally sensitive research and developing an appropriate psychology.
Spiritual Well-Being as a Mediator of the Relation between Culture-Specific Coping and Quality of Life in a Community Sample of African Americans
Authors: Utsey Shawn O. , Bolden Mark A. , Williams Otis , Lee Angela , Lanier Yzette , Newsome Crystal
Published: February 2007

This study examines the antecedent factors affecting the quality of life of African Americans. A theoretical model is proposed that identifies the effects of culture-specific coping and spiritual well-being as predictors of quality of life. A sample of 281 African Americans was administered a battery of questionnaires that examined the constructs of interest. The theoretical model was tested within a structural equation—modeling framework to identify both direct and indirect effects. Results indicate overall model fit, with both culture-specific coping and spiritual well-being as significant predictors of quality of life. Spiritual well-being partially mediated the effects of culture-specific coping on quality of life. The article concludes with a discussion of the study's findings in relation to quality of life issues for African Americans.
Child-Rearing Values of Estonian and Finnish Mothers and Fathers
Authors: Tulviste Tiia , Ahtonen Maaret
Published: February 2007

This study compares the child-rearing values of mothers and fathers of 4 to 6-year-old children in Estonia and Finland. All samples assign the most value to characteristics related to benevolence, self-direction, and being trustworthy. Valuing smartness and politeness is specific to the Estonian culture, and valuing hedonism is specific to the Finnish culture. Compared with Estonian parents, Finnish parents tend to stress benevolence, hedonism, and bad habits rather than conformity and achievement; their child-rearing values are more homogeneous; and the values held by a mother and father from the same family reveal more similarities. Estonian mothers attach more importance to benevolence and conformity than do Estonian fathers. Child-rearing values do not differ according to the child's gender. The findings suggest that differences in child-rearing values related to parental gender depend on the cultural context.
Climatoeconomic Roots of Survival Versus Self-Expression Cultures
Authors: Van de Vliert Evert
Published: February 2007

The circumstances under which societies adapt their cultural values to cold, temperate, and hot climates include the availability of money to cope with climate. In a country-level study, collective income, household income, and economic growth were conceptualized as moderators of the climate-culture link because money is primarily used to satisfy homeostatic needs for thermal comfort, nutrition, and health. The results demonstrate that members of societies in more-demanding climates endorse survival values at the expense of self-expression values to the extent that they are poorer ( n= 74 nations), that household incomes in these lower-income societies are lower ( n = 66 nations), and that they face more economic recession ( n = 38 nations). In addition to theoretical implications, the findings have practical implications for the cultural consequences of global warming and the effectiveness of financing for human development.
The Making of Sophomores
Authors: Patterson Nancy C. , Beltyukova Svetlana A. , Berman Karen , Francis Anthony
Published: February 2007

America’s urban high schools are having trouble making sophomores, resulting in freshmen classes bulging with students repeating a grade. Research shows that these students are at high risk of failure and dropout. Urban districts have begun to respond to the notable “freshmen bulge” through school restructuring. This mixed-methods study examines first steps taken by one urban high school in Ohio to address the challenges of high levels of freshmen failure through a small schools model. The authors discuss freshman student, parent, and teacher reactions to a pilot program designed expressly for the making of sophomores.
The Place of the “Open House” in the School-Choice Process
Authors: Oplatka Izhar
Published: February 2007

The current study aimed at exploring the perceived significance of promotional events in secondary schools among Canadian parents, their children, and teachers and at determining the influence of these events on the school-choice process and school life. The findings suggest that both teachers and families displayed apparently contradictory perceptions of the open house with respect to its significance and influence, differing as well from one another in their understanding of the place of this event in school life and choice. In addition, four effective aspects of this promotional event have been subjectively identified by the respondents. Empirical and practical implications are suggested.
Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia
Authors: Wierda William G. , O'Brien Susan , Wang Xuemei , Faderl Stefan , Ferrajoli Alessandra , Do Kim-Anh , Cortes Jorge , Thomas Deborah , Garcia-Manero Guillermo , Koller Charles , Beran Miloslav , Giles Francis , Ravandi Farhad , Lerner Susan , Kantarjian Hagop , Keating Michael
Published: February 2007

The clinical course for patients with chronic lymphocytic leukemia is extremely heterogeneous. The Rai and Binet staging systems have been used to risk-stratify patients; most patients present with early-stage disease. We evaluated a group of previously untreated patients with chronic lymphocytic leukemia (CLL) at initial presentation to University of Texas M. D. Anderson Cancer Center to identify independent characteristics that predict for overall survival. Clinical and routine laboratory characteristics for 1674 previously untreated patients who presented for evaluation of CLL from 1981 to 2004 were included. Univariate and multivariate analyses identified several patient characteristics at presentation that predicted for overall survival in previously untreated patients with CLL. A multivariate Cox proportional hazards model was developed, including the following independent characteristics: age, β-2 microglobulin, absolute lymphocyte count, sex, Rai stage, and number of involved lymph node groups. Inclusion of patients from a single institution and the proportion of patients younger than 65 years may limit this model. A weighted prognostic model, or nomogram, predictive for overall survival was constructed using these 6 characteristics for 5- and 10-year survival probability and estimated median survival time. This prognostic model may help patients and clinicians in clinical decision making as well as in clinical research and clinical trial design.
Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival
Authors: Wiestner Adrian , Tehrani Mahsa , Chiorazzi Michael , Wright George , Gibellini Federica , Nakayama Kazutaka , Liu Hui , Rosenwald Andreas , Muller-Hermelink H. Konrad , Ott German , Chan Wing C. , Greiner Timothy C. , Weisenburger Dennis D. , Vose Julie , Armitage James O. , Gascoyne Randy D. , Connors Joseph M. , Campo Elias , Montserrat Emilio , Bosch Francesc , Smeland Erlend B. , Kvaloy Stein , Holte Harald , Delabie Jan , Fisher Richard I. , Grogan Thomas M. , Miller Thomas P. , Wilson Wyndham H. , Jaffe Elaine S. , Staudt Louis M.
Published: February 2007

A gene expression signature of tumor proliferation rate in mantle cell lymphoma (MCL) is an overriding molecular predictor of the length of survival following diagnosis. Many strongly proliferative MCL tumors have exceptionally high cyclin D1 mRNA levels and preferentially express short cyclin D1 mRNA isoforms. We demonstrate here that these short mRNAs are cyclin D1a isoforms with truncated 3′UTRs, not alternatively spliced cyclin D1b mRNA isoforms. Among 15 MCL tumors with truncated cyclin D1 mRNAs, 7 had genomic deletions in the CCND1 3′UTR region. In 3 others, CCND1 contained point mutations that created premature polyadenylation signals, giving rise to 1.5-kb mRNAs lacking most of the 3′UTR. Both types of genomic alteration created transcripts lacking mRNA destabilization elements present in the wild-type cyclin D1a mRNA. Premature polyadenylation due to a 3′UTR mutation also was present in the Z-138 MCL cell line, which expressed both truncated and full-length cyclin D1a mRNAs. In these cells, the half-life of the short cyclin D1a mRNA was much longer than that of the full-length mRNA. We conclude that alterations of CCND1 3′UTR structure can significantly increase its oncogenic effect and worsen the clinical course of MCL patients.
Ineffective erythropoiesis in β-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin
Authors: Gardenghi Sara , Marongiu Maria F. , Ramos Pedro , Guy Ella , Breda Laura , Chadburn Amy , Liu YiFang , Amariglio Ninette , Rechavi Gideon , Rachmilewitz Eliezer A. , Breuer William , Cabantchik Z. Ioav , Wrighting Diedra M. , Andrews Nancy C. , de Sousa Maria , Giardina Patricia J. , Grady Robert W. , Rivella Stefano
Published: February 2007

Progressive iron overload is the most salient and ultimately fatal complication of β-thalassemia. However, little is known about the relationship among ineffective erythropoiesis (IE), the role of iron-regulatory genes, and tissue iron distribution in β-thalassemia. We analyzed tissue iron content and iron-regulatory gene expression in the liver, duodenum, spleen, bone marrow, kidney, and heart of mice up to 1 year old that exhibit levels of iron overload and anemia consistent with both β-thalassemia intermedia (th3/+) and major (th3/th3). Here we show, for the first time, that tissue and cellular iron distribution are abnormal and different in th3/+ and th3/th3 mice, and that transfusion therapy can rescue mice affected by β-thalassemia major and modify both the absorption and distribution of iron. Our study reveals that the degree of IE dictates tissue iron distribution and that IE and iron content regulate hepcidin (Hamp1) and other iron-regulatory genes such as Hfe and Cebpa. In young th3/+ and th3/th3 mice, low Hamp1 levels are responsible for increased iron absorption. However, in 1-year-old th3/+ animals, Hamp1 levels rise and it is rather the increase of ferroportin (Fpn1) that sustains iron accumulation, thus revealing a fundamental role of this iron transporter in the iron overload of β-thalassemia.
Platelet-bound lipopolysaccharide enhances Fc receptor–mediated phagocytosis of IgG-opsonized platelets
Authors: Semple John W. , Aslam Rukhsana , Kim Michael , Speck Edwin R. , Freedman John
Published: February 2007

Platelets express Toll-like receptor 4 (TLR4), and this has been shown to be responsible for the thrombocytopenia induced by lipopolysaccharide (LPS) administration in vivo. We studied the role of LPS in mediating platelet phagocytosis by THP-1 cells in vitro by flow cytometry. Opsonization of platelets with an IgG monoclonal (W6/32) antibody or with IgG autoantibody-positive sera from patients with autoimmune thrombocytopenia (AITP) significantly enhanced platelet phagocytosis (P < .001). In contrast, platelet phagocytosis did not occur if platelets were bound with only LPS. If, however, the LPS-bound platelets were also opsonized with either W6/32 or autoantibody-positive sera with titers greater than 4, there was a significant and synergistic increase in Fc-dependent platelet phagocytosis (P < .001, P = .003, P = .048, and P = .047). These results suggest that, in the presence of antiplatelet antibodies, bacterial products can significantly alter platelet phagocytosis, and this may have relevance to how Gram-negative infections enhance platelet destruction in some patients with AITP.
A comparative study of the actions of alkylpyridinium salts from a marine sponge and related synthetic compounds in rat cultured hippocampal neurones
Authors: Koss David J , Hindley Kathleen P , David Kanola C , Mancini Ines , Guella Graziano , Sepčić Kristina , Turk Tom , Rebolj Katja , Riedel Gernot , Platt Bettina , Scott Roderick H
Published: February 2007

Background

Polymeric alkylpyridinium salts (poly-APS), are chemical defences produced by marine sponges including Reniera sarai. Poly-APS have previously been shown to effectively deliver macromolecules into cells. The efficiency of this closely follows the ability of poly-APS to form transient pores in membranes, providing strong support for a pore-based delivery mechanism. Recently, water soluble compounds have been synthesised that are structurally related to the natural polymers but bear a different number of pyridinium units. These compounds may share a number of bio-activities with poly-APS. Using electrophysiology, calcium imaging and 1,6-diphenyl-1,3,5-hexatriene imaging, the pore forming properties of poly-APS and four related synthetic oligomers have been tested on primary cultured rat hippocampal neurones.

Results

Acute application of poly-APS (0.5 μg/ml), reduced membrane potential, input resistance and suppressed action potential firing. Poly-APS evoked inward cation currents with linear current-voltage relationships similar to actions of pore formers on other cell types. Poly-APS (0.005–5 μg/ml) also produced Ca2+ transients in ~41% of neurones. The dose-dependence of poly-APS actions were complex, such that at 0.05 μg/ml and 5 μg/ml poly-APS produced varying magnitudes of membrane permeability depending on the order of application. Data from surface plasmon resonance analysis suggested accumulation of poly-APS in membranes and subsequent enhanced poly-APS binding. Even at 10–100 fold higher concentrations, none of the synthetic compounds produced changes in electrophysiological characteristics of the same magnitude as poly-APS. Of the synthetic oligomers tested compounds 1 (monomeric) and tetrameric 4 (5–50 μg/ml) induced small transient currents and 3 (trimeric) and 4 (tetrameric) produced significant Ca2+ transients in hippocampal neurones.

Conclusion

Poly-APS induced pore formation in hippocampal neurones and such pores were transient, with neurones recovering from exposure to these polymers. Synthetic structurally related oligomers were not potent pore formers when compared to poly-APS and affected a smaller percentage of the hippocampal neurone population. Poly-APS may have potential as agents for macromolecular delivery into CNS neurones however; the smaller synthetic oligomers tested in this study show little potential for such use. This comparative analysis indicated that the level of polymerisation giving rise to the supermolecular structure in the natural compounds, is likely to be responsible for the activity here reported.
Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance
Authors: Lin Pei-Yin , Fosmire Susan P , Park See-Hyoung , Park Jin-Young , Baksh Shairaz , Modiano Jaime F , Weiss Robert H
Published: February 2007

Background

The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC) is associated with frequent treatment failures (~90% in metastatic cases), and these tumors frequently contain PTEN abnormalities.

Results

Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis.

Conclusion

Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories.
Effects of Total Thyroid Ablation Versus Near-Total Thyroidectomy Alone on Mild to Moderate Graves’ Orbitopathy Treated with Intravenous Glucocorticoids
Authors: Menconi Francesca , Marinò Michele , Pinchera Aldo , Rocchi Roberto , Mazzi Barbara , Nardi Marco , Bartalena Luigi , Marcocci Claudio
Published: February 2007

Context: Graves’ orbitopathy (GO) is probably caused by autoimmune reactions against autoantigen(s) shared by thyroid and orbital tissues sustained by intrathyroidal autoreactive T-lymphocytes infiltrating the orbit. Total thyroid ablation (TTA) may be beneficial for GO through removal of shared antigen(s) and autoreactive T-lymphocytes, but randomized studies are lacking.

Objective: Our objective was to evaluate the effects of TTA in patients with GO treated with iv glucocorticoids (GC).

Design/Setting: A prospective, single-blind, randomized study was conducted at a referral center.

Patients/Interventions: Sixty patients with mild to moderate GO were randomized into: 1) near-total thyroidectomy (TX); or 2) TX plus 131I (TTA) groups, and then treated with iv GC. Patients were evaluated 3 and 9 months after iv GC.

Main Outcome Measure: Overall improvement of GO at 9 months was the main outcome measure.

Results: The distribution of GO outcome at 9 months was significantly more favorable in TTA than in TX patients (P = 0.0014 by χ2 test). A cumulative significant (P = 0.0054) difference between the two groups at 3 and 9 months was found using a generalized linear model. Radioiodine uptake test and thyroglobulin assay in a patient sample showed complete ablation in the majority of TTA, but not of TX patients.

Conclusions: Compared with thyroidectomy alone, TTA is followed by a better outcome of GO in patients given iv GC. Whether TTA maintains this advantage in the long-term remains to be established.
Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways
Authors: Weston Christi A. , Teressa Getu , Weeks Benjamin S. , Prives Joav
Published: February 2007

During neuromuscular junction formation, extracellular matrix-mediated signals cause muscle surface acetylcholine receptors (AChRs) to aggregate at synaptic sites. Two extracellular matrix proteins, agrin and laminin, have each been shown to initiate signaling pathways that culminate in AChR clustering in cultured muscle cells. Here we present evidence that laminin-induced AChR clustering is mediated by the activation of the Rho GTPases Cdc42, Rac and Rho. Clustering in response to laminin is blocked by the dominant negative mutants Cdc42N17, RacN17 and RhoN19, as well as by the Rho inhibitor C3 transferase. Moreover, laminin-induced AChR clustering is impaired by the Rho kinase inhibitor Y-27632. Agrin-induced AChR clustering has previously been shown to require activation of Cdc42, Rac and Rho. Therefore, although agrin and laminin use distinct transmembrane receptors to initiate AChR clustering, their signaling pathways converge at the level of Rho GTPase activation.
Mitochondrial bioenergetics and structural network organization
Authors: Benard Giovanni , Bellance Nadège , James Dominic , Parrone Philippe , Fernandez Helder , Letellier Thierry , Rossignol Rodrigue
Published: February 2007

Mitochondria form a dynamic network, and it remains unclear how the alternate configurations interact with bioenergetics properties. The metabolic signals that link mitochondrial structure to its functional states have not been fully characterized. In this report, we analyze the bidirectional relationships between mitochondrial morphology and function in living human cells. First, we determined the effect of mitochondrial fission on energy production by using small interfering RNA (siRNA) targeting DRP1, which revealed the importance of membrane fluidity on the control of bioenergetics. Second, we followed the effect of rotenone, a specific inhibitor of respiratory chain complex I, which causes large structural perturbations, once a threshold was reached. Last, we followed changes in the mitochondrial network configuration in human cells that had been treated with modulators of oxidative phosphorylation, and in fibroblasts from two patients with mitochondrial disease where the respiratory rate, ΔΨ and the generation of reactive oxygen species (ROS) were measured. Our data demonstrate that the relationship between mitochondrial network organization and bioenergetics is bidirectional, and we provide a model for analyzing the metabolic signals involved in this crosstalk.
Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes
Authors: Yao Ling-Ling , Wang Yong-Gang , Cai Wen-Jie , Yao Tai , Zhu Yi-Chun
Published: February 2007

Survivin is known to be essential for cell division and to inhibit apoptosis during embryonic development and in adult cancerous tissues. However, the cardiovascular role of survivin is unknown. We observed that in cardiomyocytes cultured under conditions of serum and glucose deprivation (DEPV), the levels of survivin, Bcl-2 and extracellular signal-regulated kinase (ERK) were positively correlated with the anti-apoptotic action of a δ-opioid receptor agonist, [D-Ala2, D-Leu5]-enkephalin acetate (DADLE). By contrast, Bax translocation, mitochondrial membrane damage and reactive oxygen species (ROS) production were inversely correlated with the changes of survivin and Bcl-2. The use of RNA interference (RNAi) targeting survivin increased DEPV-induced cardiomyocyte apoptosis, whereas the anti-apoptotic effect of DADLE was blunted by survivin RNAi. Moreover, survivin transfection and overexpression provided protection against DEPV-induced cardiomyocyte apoptosis. Inhibition of ERK prevented the DADLE-induced decrease in apoptosis and Bax translocation, and increase in survivin and Bcl-2. DADLE-induced increase in survivin was also blunted by phosphoinositol 3-kinase (PI 3-kinase) inhibition. In conclusion, the present study provides the first direct evidence of an anti-apoptotic role of survivin mediating the anti-apoptotic effect of δ-opioid receptor activation in cardiomyocytes. ERK and PI 3-kinase were found to be upstream regulators of survivin. Mitochondrial membranes as well as ROS, Bcl-2 and Bax were also involved in this anti-apoptotic action.
The Ambiguous Prospects for Eu Climate Policy — A Summary of Options
Authors: Wettestad Jørgen
Published: February 2007

The European Union is a key actor in international efforts to build an effective response to the challenge of global climate change. After the US, it is the second biggest emitter of greenhouse gases. In the 1997 Kyoto Protocol, the EU committed itself to an 8% reduction of a basket of greenhouse gases. However, EU climate policy so far must be characterised as more of a failure than a success. Not least worrisome, EU officials have recently projected that EU greenhouse gas emissions will increase 6–8% by the end of this decade. In light of the Kyoto commitments and EU climate policy ambitions, what is most probable – comforting emission cuts or embarrassing increases? What are the main, determining factors? On the basis of a summary and review of important developments and achievements in EU climate policy, including the more recent, post-Kyoto developments, the central discussion of key future perspectives are carried out; distinguishing between national, EU–level and global “lenses”. Domestic progress so far makes it tempting to adopt a pessimistic position. But complexity is very high and simple and sweeping assessments and answers should be treated with every bit of caution and suspicion.
Japan and Climate Change: Responses and Explanations
Authors: Kawashima Yasuko
Published: February 2007

The purpose of this paper is to assess Japan's response to climate change negotiation in the last decade, and to forecast it in the future. For Japan, hosting the 3rd Conference of the Parties (COP3) to the Convention was a significant milestone that changed Japan's response from reactive to proactive. Since then, Japan has been keen on taking a lead in the negotiation, but without much success. This failure is due to several reasons: (1) Japan's high standard on energy efficiency per GDP and thus its difficulty to make further improvement; (2) Japan's foreign policy has considered U.S.–Japan relation to be the most important, and (3) Japan's culture that cherishes harmony rather than becoming a leader. These features are likely to remain in the future as long as Japan's decision-making system itself remains the same.
Infectious Diseases: Pharmacologic Treatment Options for Nosocomial Pneumonia Involving Methicillin-Resistant Staphylococcus aureus
Authors: Maclayton Darego O , Hall Ronald G
Published: February 2007

Objective:

To discuss current and potential treatment options for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA).

Data Sources:

A MEDLINE search (1966–January 2007) was conducted to identify English-language literature on pharmacotherapy of nosocomial pneumonia and the bibliographies of pertinent articles. Programs and abstracts from infectious disease meetings were also searched. Search terms included MRSA, nosocomial pneumonia, pulmonary infections, vancomycin, quinupristin/dalfopristin, linezolid, daptomycin, tigecycline, dalbavancin, oritavancin, and ceftobiprole.

Data Selection and Data Extraction:

All articles were critically evaluated and all pertinent information was included in this review.

Data Synthesis:

Vancomycin has been the drug of choice for MRSA infections for many years. Recent data suggest that linezolid may be superior to vancomycin in the treatment of MRSA nosocomial pneumonia. However, there are limitations to the available data. Therefore, prospective, randomized studies are needed before linezolid is recommended as the preferred first-line therapy. Other approved agents for nosocomial MRSA infections, such as quinupristin/dalfopristin and daptomycin, should not be used in the treatment of MRSA pneumonia, as they were inferior in clinical trials. Tigecycline has excellent activity against MRSA in vitro, but should not be routinely used for the treatment of MRSA pneumonia, as clinical data are lacking. In a Phase III clinical trial, an anti-MRSA cephalosporin, ceftobiprole, is being evaluated for effectiveness against nosocomial pneumonia. Investigational glycopeptides may eventually have a role in the treatment of nosocomial pneumonia, but data are currently lacking.

Conclusions:

Vancomycin is still the drug of choice for treatment of MRSA pneumonia, and linezolid should be used as an alternative agent. Linezolid should carry strong consideration for patients with vancomycin-induced nephrotoxicity or a documented lack of response to vancomycin. Tigecycline and investigational agents with activity against MRSA may be future options for nosocomial pneumonia due to MRSA.