bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Antioxidants Interfere With Radiation Therapy for Cancer?
Authors: Moss Ralph W.
Published: August 2007

Despite recent comprehensive review articles concluding that supplemental antioxidants do not undermine the effectiveness of cytotoxic therapies, the use of antioxidants during cancer treatment remains controversial. Many oncologists take the position that antioxidants by their nature undermine the free radical mechanism of chemotherapy and radiotherapy and should therefore generally be avoided during treatment. For their part, many integrative practitioners believe that antioxidants taken during cancer treatment not only alleviate some of the adverse effects of that treatment but also enhance the efficacy of cancer therapy. Until recently, research attention has focused primarily on the interaction of antioxidants with chemotherapy; relatively little attention has been paid to the interaction of antioxidants with radiotherapy. This article reviews the clinical literature that has addressed whether antioxidants do in fact interfere with radiation therapy. Studies have variously investigated the use of α-tocopherol for the amelioration of radiation-induced mucositis; pentoxifylline and vitamin E to correct the adverse effects of radiotherapy; melatonin alongside radiotherapy in the treatment of brain cancer; retinol palmitate as a treatment for radiation-induced proctopathy; a combination of antioxidants (and other naturopathic treatments) and external beam radiation therapy as definitive treatment for prostate cancer; and the use of synthetic antioxidants, amifostine, dexrazoxane, and mesna as radioprotectants. With few exceptions, most of the studies draw positive conclusions about the interaction of antioxidants and radiotherapy. Although further studies are needed, the preponderance of evidence supports a provisional conclusion that dietary antioxidants do not conflict with the use of radiotherapy in the treatment of a wide variety of cancers and may significantly mitigate the adverse effects of that treatment.
Exercise Training Manages Cardiopulmonary Function and Fatigue During and Following Cancer Treatment in Male Cancer Survivors
Authors: Schneider Carole M. , Hsieh City C. , Sprod Lisa K. , Carter Susan D. , Hayward Reid
Published: August 2007

This investigation determined the cardiopulmonary function and fatigue alterations in male cancer survivors during treatment as well as following treatment utilizing similar exercise assessment protocols and individualized, prescriptive exercise interventions. The study included 45 male cancer survivors that were referred by local oncologists. Following a comprehensive screening and physical examination, cardiovascular endurance, pulmonary function, and fatigue were assessed leading to the development of 12-week individualized exercise prescriptions and exercise interventions. The cancer survivors were divided into during treatment (DTm) and following treatment (FTm) groups. Repeated-measures analysis of variance and analyses of covariance were used to compare pre- versus postintervention and between groups. Cardiopulmonary function was maintained in the DTm, whereas the FTm showed significant reductions in resting heart rate ( P < .05) with concurrent increases in predicted VO2max and time on treadmill ( P < .05) postexercise intervention. Fatigue levels did not increase in the DTm group, whereas the FTm group showed significant reductions in behavioral fatigue, affective fatigue, sensory fatigue, cognitive/mood fatigue, and total fatigue ( P < .05) after the exercise intervention. The results of the current study suggest that moderate intensity, individualized, prescriptive exercise intervention maintains or improves cardiovascular and pulmonary function with concomitant reductions in fatigue in cancer survivors during and following cancer treatment. Exercise appears to be a safe, efficacious strategy for improving physical fitness in cancer survivors during and following treatment.
The Neuroimmune Basis of Anti-inflammatory Acupuncture
Authors: Kavoussi Ben , Ross B. Evan
Published: August 2007

This review article presents the evidence that the antiinflammatory actions of acupuncture are mediated via the reflexive central inhibition of the innate immune system. Both laboratory and clinical evidence have recently shown the existence of a negative feedback loop between the autonomic nervous system and the innate immunity. There is also experimental evidence that the electrical stimulation of the vagus nerve inhibits macrophage activation and the production of TNF, IL-1β , IL-6, IL-18, and other proinflammatory cytokines. It is therefore conceivable that along with hypnosis, meditation, prayer, guided imagery, biofeedback, and the placebo effect, the systemic anti-inflammatory actions of traditional and electro-acupuncture are directly or indirectly mediated by the efferent vagus nerve activation and inflammatory macrophage deactivation. In view of this common physiological mediation, assessing the clinical efficacy of a specific acupuncture regimen using conventional double-blind placebo-controlled trials inherently lacks objectivity due to (1) the uncertainty of ancient rules for needle placement, (2) the diffuse noxious inhibitory control triggered by control-needling at irrelevant points, (3) the possibility of a dose-response relationship between stimulation and effects, and (4) the possibility of inadequate blinding using an inert sham procedure. A more objective assessment of its efficacy could perhaps consist of measuring its effects on the surrogate markers of autonomic tone and inflammation. The use of acupuncture as an adjunct therapy to conventional medical treatment for a number of chronic inflammatory and autoimmune diseases seems plausible and should be validated by confirming its cholinergicity.
β-Carotene Inhibits Tumor-Specific Angiogenesis by Altering the Cytokine Profile and Inhibits the Nuclear Translocation of Transcription Factors in B16F-10 Melanoma Cells
Authors: Guruvayoorappan C. , Kuttan Girija
Published: August 2007

Angiogenesis is the formation of new blood vessels out of the preexisting vascular network and involves a sequence of events that are of key importance in a broad array of physiological and pathological processes. The growth of tumor and metastasis are dependent on the formation of new blood vessels. The present study therefore aims at evaluating the antiangiogenic effect of β-carotene using in vivo and in vitro models. Male C57BL/6 mice as well as B16F-10 cells were used for the experimental study. The in vivo study includes the inhibitory effect of β-carotene on the formation of tumor-directed capillaries. Rat aortic ring assay, human umbilical vein endothelial cell proliferation, migration, and tube formation are used for assessing the in vitro antiangiogenic effect of β-carotene. The differential regulation of proinflammatory cytokines as well as the inhibitory effect of β-carotene on the activation and nuclear translocation of transcription factors are also assessed. β-Carotene treatment significantly reduces the number of tumor-directed capillaries accompanied by altered serum cytokine levels. β-Carotene is able to inhibit proliferation, migration, and tube formation of endothelial cells. β-Carotene treatment downregulates the expression of matrix metalloproteinase (MMP)—2, MMP-9, prolyl hydroxylase, and lysyl oxidase gene expression and upregulates the expression of tissue inhibitor of metalloproteinase (TIMP)—1 and TIMP-2. The study reveals that β-carotene treatment could alter proinflammatory cytokine production and could inhibit the activation and nuclear translocation of p65, p50, c-Rel subunits of nuclear factor-κ B, and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element—binding protein in B16F-10 melanoma cells. These observations show that β -carotene exerts its antiangiogenic effect by altering the cytokine profile and could inhibit the activation and nuclear translocation of transcription factors.
Hepatoprotective Effect of Andrographolide Against Hexachlorocyclohexane-Induced Oxidative Injury
Authors: Trivedi Neha P. , Rawal Upendra M. , Patel Beena P.
Published: August 2007

Many plant products are known to exert antioxidative effects by quenching various free radicals and singlet molecular oxygen. Andrographis paniculata (Kalmegh) is used extensively in the Indian traditional system of medicine as a hepatoprotective and hepatostimulative agent and has been reported to have antioxidant effects against different hepatotoxins. The present study aims to analyze antioxidant properties of an active component, andrographolide (ANDLE), extracted from A paniculata. This study investigates the effect of andrographolide on the hepatocellular antioxidant defense system and lipid peroxidation of control mice, mice treated with hexachlorocyclohexane (BHC) only, and andrographolide + BHC. Glutathione (GSH), glutathione-s-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GSH-Px), γ-glutamyl transpeptidase (γ-GTP), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) are studied by spectrophotometric methods. The BHC experimental model forms an irreversible liver tumor in male mice. The activities of GSH, GR, GSH-Px, SOD, and CAT show significant ( P ≤ .05) increases, while γ-GTP and GST show significant decreases ( P ≤ .05) in andrographolide-supplemented mice as compared with BHC-treated mice. This study indicates that the antioxidant effect of andrographolide could be due to its ability to activate antioxidant enzymes that catalyze the reaction of oxidants and are effective in severe liver damage.
Effects of an Integrated Yoga Program in Modulating Psychological Stress and Radiation-Induced Genotoxic Stress in Breast Cancer Patients Undergoing Radiotherapy
Authors: Banerjee Birendranath , Vadiraj H.S. , Ram Amritanshu , Rao Raghavendra , Jayapal Manikandan , Gopinath Kodaganur S. , Ramesh B.S. , Rao Nalini , Kumar Ajay , Raghuram Nagarathna , Hegde Sridevi , Nagendra H.R. , Prakash Hande M.
Published: August 2007

Effects of an integrated yoga program in modulating perceived stress levels, anxiety, as well as depression levels and radiation-induced DNA damage were studied in 68 breast cancer patients undergoing radiotherapy. Two psychological questionnaires—Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS)—and DNA damage assay were used in the study. There was a significant decrease in the HADS scores in the yoga intervention group, whereas the control group displayed an increase in these scores. Mean PSS was decreased in the yoga group, whereas the control group did not show any change pre- and postradiotherapy. Radiation-induced DNA damage was significantly elevated in both the yoga and control groups after radiotherapy, but the postradiotherapy DNA damage in the yoga group was slightly less when compared to the control group. An integrated approach of yoga intervention modulates the stress and DNA damage levels in breast cancer patients during radiotherapy.
State of the Art Review: Osteoarthritis and Therapeutic Exercise
Authors: Stitik Todd P. , Gazzillo Greg , Foye Patrick M.
Published: August 2007

Therapeutic exercise is an invaluable component to a compre hensive treatment program for patients with osteoarthritis. There are several major components to a complete therapeutic exercise program. Compliance with a long-term home exercise program after discharge from a physical therapy program is a very challenging but extremely important issue. Ideally, therapeutic exercise should be provided under the supervision of a physician who is knowledgeable in the use of exercise as a treatment for musculoskeletal conditions. Many practitioners of physical medicine and rehabilitation (physiatrists) can fill this important role for osteoarthritis patients.
Pharmacy Review: Reducing the Risks of Diabetes: The Pharmacist's Perspective
Authors: Brooks Nikki , Prevost Rebecca R.
Published: August 2007

Pharmacists are in a unique position to affect the lives of people living with diabetes. The pharmacist can identify people at risk, screen for pharmacotherapy problems, and give encouragement between physician visits. The medication knowledge that the clinical pharmacist brings to the health care team results in decreased costs, improved glycemic control, and greater adherence to ADA standards of care.
Nutrition Review: Diet and Nutrients in the Prevention and Treatment of Type 2 Diabetes
Authors: Melanson Kathleen J.
Published: August 2007

Lifestyle factors, including diet, are critical in the prevention and treatment of type 2 diabetes. Because weight gain increases diabetes risk, and even modest weight reduction reduces risk, weight management is paramount in lessening the occurrence and effects of diabetes. Weight loss interventions should include patient education, behavioral strategies, physical activity, energy intake deficits of 500 to 1000 kcal/day, and prevention of recidivism. Macronutrient distribution ranges of diets for diabetic patients follow those of the Dietary Reference Intakes, allowing for individualization according to a patient's metabolic responses, needs, and preferences. Nutrients to be limited include saturated fats, artificial trans fats, cholesterol, and sodium, whereas nutrients to be emphasized include monounsaturated fatty acids, omega-3 polyunsaturated fatty acids, fibers, antioxidants, and minerals, including potassium, magnesium, calcium, and chromium. Food sources are advised rather than supplements. Sugars can be isocalorically substituted for starches without detriments to glycemic control. Diets with low glycemic index or load may have modest benefits in managing type 2 diabetes. If a diabetic patient chooses to consume alcohol, he or she should do so in moderation. Foods advocated in type 2 diabetes are similar to those that are also beneficial in reducing risk for other chronic diseases.
A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice
Authors: Brown Brian D. , Cantore Alessio , Annoni Andrea , Sergi Lucia Sergi , Lombardo Angelo , Della Valle Patrizia , D'Angelo Armando , Naldini Luigi
Published: August 2007

A longstanding goal for the treatment of hemophilia B is the development of a gene transfer strategy that can maintain sustained production of clotting factor IX (F.IX) in the absence of an immune response. To this end, we have sought to use lentiviral vectors (LVs) as a means for systemic gene transfer. Unfortunately, initial evaluation of LVs expressing F.IX from hepatocyte-specific promoters failed to achieve sustained F.IX expression in hemophilia B mice due to the induction of an anti-F.IX cellular immune response. Further analysis suggested that this may be a result of off-target transgene expression in hematopoietic-lineage cells of the spleen. In order to overcome this problem, we modified our vector to contain a target sequence for the hematopoietic-specific microRNA, miR-142-3p. This eliminated off-target expression in hematopoietic cells, and enabled sustained gene transfer in hemophilia B mice for more than 280 days after injection. Treated mice had more than 10% normal F.IX activity, no detectable anti-F.IX antibodies, and were unresponsive to F.IX immunization. Importantly, the mice survived tail-clip challenge, thus demonstrating phenotypic correction of their bleeding diathesis. This work, which is among the first applications to exploit the microRNA regulatory pathway, provides the basis for a promising new therapy for the treatment of hemophilia B.
New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients
Authors: Haase Detlef , Germing Ulrich , Schanz Julie , Pfeilstöcker Michael , Nösslinger Thomas , Hildebrandt Barbara , Kundgen Andrea , Lübbert Michael , Kunzmann Regina , Giagounidis Aristoteles A. N. , Aul Carlo , Trümper Lorenz , Krieger Otto , Stauder Reinhard , Müller Thomas H. , Wimazal Friedrich , Valent Peter , Fonatsch Christa , Steidl Christian
Published: August 2007

We have generated a large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) at 4 institutions in Austria and 4 in Germany. Cytogenetic analyses were successfully performed in 2072 (97.6%) patients, revealing clonal abnormalities in 1084 (52.3%) patients. Numeric and structural chromosomal abnormalities were documented for each patient and subdivided further according to the number of additional abnormalities. Thus, 684 different cytogenetic categories were identified. The impact of the karyotype on the natural course of the disease was studied in 1286 patients treated with supportive care only. Median survival was 53.4 months for patients with normal karyotypes (n = 612) and 8.7 months for those with complex anomalies (n = 166). A total of 13 rare abnormalities were identified with good (+1/+1q, t(1q), t(7q), del(9q), del(12p), chromosome 15 anomalies, t(17q), monosomy 21, trisomy 21, and −X), intermediate (del(11q), chromosome 19 anomalies), or poor (t(5q)) prognostic impact, respectively. The prognostic relevance of additional abnormalities varied considerably depending on the chromosomes affected. For all World Health Organization (WHO) and French-American-British (FAB) classification system subtypes, the karyotype provided additional prognostic information. Our analyses offer new insights into the prognostic significance of rare chromosomal abnormalities and specific karyotypic combinations in MDS.
The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation
Authors: Shaw Bronwen E. , Gooley Theodore A. , Malkki Mari , Madrigal J. Alejandro , Begovich Ann B. , Horowitz Mary M. , Gratwohl Alois , Ringdén Olle , Marsh Steven G. E. , Petersdorf Effie W.
Published: August 2007

Hematopoietic cell transplantation (HCT) from an HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele–matched unrelated donor is a well-recognized life-saving treatment modality for patients with hematologic disorders. The morbidity and mortality from clinically significant acute graft-versus-host disease (aGVHD) remains a limitation. The extent to which transplantation outcome may be improved with donor matching for HLA-DP is not well defined. The risks of aGVHD, relapse, and mortality associated with HLA-DPB1 allele mismatching were determined in 5929 patients who received a myeloablative HCT from an HLA-A–, HLA-B–, HLA-C–, HLA-DRB1–, and HLA-DQB1–matched or –mismatched donor. There was a statistically significantly higher risk of both grades 2 to 4 aGVHD (odds ratio [OR] = 1.33; P < .001) and grades 3 to 4 aGVHD (OR = 1.26; P < .001) after HCT from an HLA-DPB1–mismatched donor compared with a matched donor. The increased risk of aGVHD was accompanied by a statistically significantly decrease in disease relapse (hazard ratio [HR] = 0.82; P = .01). HLA-DPB1 functions as a classical transplantation antigen. The increased risk of GVHD associated with HLA-DPB1 mismatching is accompanied by a lower risk of relapse. Knowledge of the DPB1 matching status prior to transplantation will aid in more precise risk stratification for the individual patient.
Duloxetine in the treatment of major depressive disorder: an open-label study
Authors: Hudson James I , Perahia David G , Gilaberte Inmaculada , Wang Fujun , Watkin John G , Detke Michael J
Published: August 2007

Background

Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.

Methods

Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17) total score ≥18 and a Clinical Global Impression of Severity (CGI-S) score ≥4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.

Results

The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.

Conclusion

In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.

Trial registration

NCT00036309.
How human practices have affected vector-borne diseases in the past: a study of malaria transmission in Alpine valleys
Authors: Sérandour Julien , Girel Jacky , Boyer Sebastien , Ravanel Patrick , Lemperière Guy , Raveton Muriel
Published: August 2007

Background

Malaria was endemic in the Rhône-Alpes area of eastern France in the 19thcentury and life expectancy was particularly shortened in Alpine valleys. This study was designed to determine how the disease affected people in the area and to identify the factors influencing malaria transmission.

Methods

Demographic data of the 19thcentury were collected from death registers of eight villages of the flood-plain of the river Isère. Correlations were performed between these demographic data and reconstructed meteorological data. Archive documents from medical practitioners gave information on symptoms of ill people. Engineer reports provided information on the hydraulic project developments in the Isère valley.

Results

Description of fevers was highly suggestive of endemic malaria transmission in the parishes neighbouring the river Isère. The current status of anopheline mosquitoes in the area supports this hypothesis. Mean temperature and precipitation were poorly correlated with demographic data, whereas the chronology of hydrological events correlated with fluctuations in death rates in the parishes.

Conclusion

Nowadays, most of the river development projects involve the creation of wet areas, enabling controlled flooding events. Flood-flow risk and the re-emergence of vector-borne diseases would probably be influenced by the climate change. The message is not to forget that human disturbance of any functioning hydrosystem has often been linked to malaria transmission in the past.
Studying the Hurdles of Insulin Prescription (SHIP©): development, scoring and initial validation of a new self-administered questionnaire
Authors: Martinez Luc , Consoli Silla M , Monnier Louis , Simon Dominique , Wong Olivier , Yomtov Bernard , Guéron Béatrice , Benmedjahed Khadra , Guillemin Isabelle , Arnould Benoit
Published: August 2007

Background

Although insulin therapy is well-accepted by symptomatic diabetic patients, it is still often delayed in less severe patients, in whom injectable insulin remains under-used. A better understanding of patients' perception of insulin would eventually help physicians to adopt the most appropriate dialogue when having to motivate patients to initiate or to intensify insulin injection.

Methods

The 'Studying the Hurdles of Insulin Prescription' (SHIP) questionnaire was developed based on a list of concepts derived from three diabetic patients' focus groups, and was included into two cross-sectional studies with similar design: SHIP Oral study and SHIP Premix study. Diabetic patients treated with oral hypoglycaemic agents (OHA; n = 1,494) and patients already treated with insulin (n = 1,150) completed the questionnaire at baseline, 6- and 12 months. Psychometric properties were assessed: 1) structure analysis by Principal Component Analysis (PCA) with Varimax rotation, 2) internal consistency reliability (Cronbach's alpha), and 3) concurrent validity (Spearman correlation coefficients with the Fear of Self-Injecting (FSI) score of the Diabetes Fear of Injecting and Self-testing Questionnaire. Reluctance/motivation towards insulin was assessed. Scores' ability to predict patients' insulin injection reluctance/motivation and initiation/intensification was evaluated with the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC).

Results

PCA analysis confirmed the structure of the 14 items grouped into 3 dimensions: 'acceptance and motivation', 'fear and constraints', and 'restraints and barriers' towards insulin injection. Internal consistency reliability was excellent (Cronbach's alpha > 0.70); concurrent validity was good. The three scores were significantly predictive of patients' reluctance/motivation towards insulin injection initiation, as they were of patients' actual switch, except for the 'restraints and barriers' dimension. 'Acceptance and motivation' and 'fears and constraints' dimensions were also significantly predictive of patients' reluctance/motivation towards insulin intensification. By the end of the 12-month study, 179 of the initially OHA-treated patients had started insulin injections; 186 of the patients already treated with insulin had increased their injections.

Conclusion

The SHIP questionnaire provides reliable and valid assessment of diabetic patients' attitude towards insulin and injections. The predictive power of scores for patients' reluctance/motivation and actual treatment decisions demonstrates encouraging potential for further application in clinical practice.
Modulation of CD1d-restricted NKT cell responses by CD4
Authors: Chen Xiuxu , Wang Xiaohua , Besra Gurdyal S , Gumperz Jenny E
Published: August 2007

CD4+ and CD4− NKT cell populations have been shown to be functionally distinct, but the role of CD4 molecules in NKT cell activation is not clear. Here, we have used human CD1d-restricted NKT cell clones to investigate the contribution of CD4 to NKT cell functional responses. Coligation of CD4 with the TCR/CD3 complex resulted in enhanced cytokine secretion and increased calcium flux by CD4+ NKT cell clones, indicating that CD4 is functionally active in these cells. CD4 blockade specifically inhibited cytokine secretion and proliferation of CD4+ NKT cell clones in response to CD1d+ APCs but did not affect cytotoxicity, suggesting that CD4 preferentially modulates some NKT cell functional responses and not others. Anti-CD4 mAb treatment inhibited NKT cell responses to both MHC class II+ and MHC class II− APCs, indicating that its effect was not due to blocking CD4 binding to MHC class II molecules on APCs. The inhibitory effect of the anti-CD4 mAb also did not require recognition of CD1d by the NKT cell, since calcium flux was reduced in response to anti-CD3 mAb stimulation. Western blot analysis revealed that anti-CD4 treatment resulted in increased phosphorylation of an inhibitory site of p56lck (tyrosine 505). Thus, CD4 blockade interferes with the course of CD3-mediated signaling events in NKT cells. These results indicate that CD4 can contribute to NKT cell activation independently of the presence of a CD4-ligand on APCs and suggest that it preferentially modulates cytokine and proliferative responses.
Adoptive transfer of murine syngeneic graft-vs.-host disease by CD4+ T cells
Authors: Bryson J Scott , Jennings C Darrell , Brandon Jason A , Perez Jacqueline , Caywood Betty E , Kaplan Alan M
Published: August 2007

Syngeneic graft-vs.-host disease (SGVHD) develops in rodents following the treatment of lethally irradiated, bone marrow (BM) reconstituted animals with a short course of the immunosuppressive agent cyclosporine A (CsA). Using an in vivo depletion approach, we recently demonstrated that CD4+, but not CD8+, T cells participated in inducing SGVHD. Studies were therefore undertaken to adoptively transfer SGVHD into lethally irradiated, syngeneic BM reconstituted secondary recipients. Whole T cell populations as well as purified CD4+T cells isolated from SGVHD, but not normal or transplant control, animals mediated the transfer of SGVHD into secondary recipients. These cells have an apparent specificity for enteric bacterial antigens. The pathologic process that developed was identical to that observed in the animals with de novo SGVHD after syngeneic BMT and CsA therapy. It was shown that a radiation-sensitive mechanism prevented the transfer of SGVHD into normal, nonirradiated secondary recipients. The ability to reproducibly transfer SGVHD into secondary recipients will enhance our ability to study regulatory mechanisms that are altered during CsA therapy and permit the development of murine CsA-induced SGVHD.
Mycobacterium bovisBCG disrupts the interaction of Rab7 with RILP contributing to inhibition of phagosome maturation
Authors: Sun Jim , Deghmane Ala-Eddine , Soualhine Hafid , Hong Thomas , Bucci Cecilia , Solodkin Anna , Hmama Zakaria
Published: August 2007

Phagosomes containing M. tuberculosis and M. bovis BCG interact normally with early endosomes but fail to fuse with late endosomes and lysosomes. Whereas many early events of mycobacterial phagosomes have been elucidated, the exact mechanism of the inhibition of fusion with lysosomes is still unclear. Several Rab GTPase proteins were shown to be involved in membrane fusion and vesicular transport. In particular, Rab7 associates with the phagosomal membrane and regulates the fusion between late endosomes and lysosomes. This function of Rab7 was shown to be mediated in epithelial cell models by the Rab7 effector RILP (Rab7-interacting lysosomal protein). However, the relevance of Rab7-RILP interaction to phagosome biogenesis in macrophage infected with mycobacteria is still unknown. In this study, cotransfection of RAW 264.7 cells with Rab7 and RILP revealed that Rab7-RILP interaction occurs in macrophages ingesting latex beads. Thereafter, this cell system model was used to demonstrate that infection with live but not killed M. bovis BCG inhibited RILP recruitment despite Rab7 acquisition by the phagosome. Further investigation using immobilized RILP to pull down active Rab7 (GTP-bound form) from macrophage lysates demonstrated that inactive Rab7 (GDP-bound form) predominates in cells infected with live BCG. In addition, cell-free system experiments demonstrated that BCG culture supernatant contains a factor that catalyzes the GTP/GDP switch on recombinant Rab7 molecules. Such a factor was shown to diffuse beyond BCG phagosomes and target other Rab7-positive compartments. These findings suggest that live mycobacteria express within the macrophage a Rab7 deactivating factor leading to abortion of RILP-mediated fusion with lysosomes.
Forecasting Probabilistic Seismic Shaking for Greater Tokyo from 400 Years of Intensity Observations
Authors: Bozkurt Serkan B. , Stein Ross S. , Toda Shinji
Published: August 2007

The long recorded history of earthquakes in Japan affords an opportunity to forecast seismic shaking exclusively from past shaking. We calculate the time-averaged (Poisson) probability of severe shaking by using more than 10,000 intensity observations recorded since AD 1600 in a 350 km-wide box centered on Tokyo. Unlike other hazard-assessment methods, source and site effects are included without modeling, and we do not need to know the size or location of any earthquake nor the location and slip rate of any fault. The two key assumptions are that the slope of the observed frequency-intensity relation at every site is the same, and that the 400-year record is long enough to encompass the full range of seismic behavior. Tests we conduct here suggest that both assumptions are sound. The resulting 30-year probability of IJMA≥6 shaking (∼ PGA≥0.4 g or MMI≥ IX) is 30%–40% in Tokyo, Kawasaki, and Yokohama, and 10%–15% in Chiba and Tsukuba. This result means that there is a 30% chance that 4 million people will be subjected to IJMA≥6 shaking during an average 30-year period. We also produce exceedance maps of PGA for building-code regulations, and calculate short-term hazard associated with a hypothetical catastrophe bond. Our results resemble an independent assessment developed from conventional seismic hazard analysis for greater Tokyo.
Analytical Seismic Fragility Curves for Typical Bridges in the Central and Southeastern United States
Authors: Nielson Bryant G. , DesRoches Reginald
Published: August 2007

Seismic fragility curves for classes of highway bridges are essential for risk assessment of highway transportation networks exposed to seismic hazards. This study develops seismic fragility curves for nine classes of bridges (common three-span, zero-skew bridges with non-integral abutments) common to the central and southeastern United States. The methodology adopted uses 3-D analytical models and nonlinear time-history analyses. An important aspect of the selected methodology is that it considers the contribution of multiple bridge components. The results show that multispan steel girder bridges are the most vulnerable of the considered bridge classes while single-span bridges tend to be the least vulnerable. A comparison of the proposed fragility curves with those currently found in HAZUS-MH shows a strong agreement for the multispan simply supported steel girder bridge class. However, for other simply supported bridge classes (concrete girder, slab), the proposed fragility curves suggest a lower vulnerability level than presented in HAZUS-MH.
Imaging Medullary Thyroid Carcinoma with Persistent Elevated Calcitonin Levels
Authors: Giraudet Anne Laure , Vanel Daniel , Leboulleux Sophie , Aupérin Anne , Dromain Clarisse , Chami Linda , Ny Tovo Noël , Lumbroso Jean , Lassau Nathalie , Bonniaud Guillaume , Hartl Dana , Travagli Jean-Paul , Baudin Eric , Schlumberger Martin
Published: August 2007

Purpose: Because calcitonin level remains elevated after initial treatment in many medullary thyroid carcinoma (MTC) patients without evidence of disease in the usual imaging work-up, there is a need to define optimal imaging procedures.

Patients and Methods: Fifty-five consecutive elevated calcitonin level MTC patients were enrolled to undergo neck and abdomen ultrasonography (US); neck, chest, and abdomen spiral computed tomography (CT); liver and whole-body magnetic resonance imaging (MRI); bone scintigraphy; and 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/CT scan (PET).

Results: Fifty patients underwent neck US, CT, and PET, and neck recurrence was demonstrated in 56, 42, and 32%, respectively. Lung and mediastinum lymph node metastases in the 55 patients were demonstrated in 35 and 31% by CT and in 15 and 20% by PET. Liver imaging with MRI, CT, US, and PET in 41 patients showed liver in 49, 44, 41, and 27% patients, respectively. Bone metastases in 55 patients were demonstrated in 35% by PET, 40% by bone scintigraphy, and 40% by MRI; bone scintigraphy was complementary with MRI for axial lesions but superior for the detection of peripheral lesions. Ten patients had no imaged tumor site despite elevated calcitonin level (median 196 pg/ml; range 39–816). FDG uptake in neoplastic foci was higher in progressive patients but with a considerable overlap with stable ones.

Conclusion: The most efficient imaging work-up for depicting MTC tumor sites would consist of a neck US, chest CT, liver MRI, bone scintigraphy, and axial skeleton MRI. FDG PET scan appeared to be less sensitive and of low prognostic value.
Increased Prevalence of Subclinical Hypothyroidism in Common Bile Duct Stone Patients
Authors: Laukkarinen Johanna , Kiudelis Gediminas , Lempinen Marko , Räty Sari , Pelli Hanna , Sand Juhani , Kemppainen Esko , Haglund Caj , Nordback Isto
Published: August 2007

Context: Earlier, we have shown an increased prevalence of previously diagnosed hypothyroidism in common bile duct (CBD) stone patients and a delayed emptying of the biliary tract in hypothyroidism, explained partly by the missing prorelaxing effect of T4 on the sphincter of Oddi contractility.

Objective: In this study, the prevalence of previously undiagnosed subclinical hypothyroidism in CBD stone patients was compared with nongallstone controls.

Patients: All patients were clinically euthyreotic and without a history of thyroid function abnormalities. CBD stones were diagnosed at endoscopic retrograde cholangiopancreatography (group 1; n = 303) or ruled out by previous medical history, liver function tests, and ultrasonography (control group II; n = 142).

Main Outcome Measures: Serum free FT4 and TSH (S-TSH) were analyzed; S-TSH above the normal range (>6.0 mU/liter) was considered as subclinical and S-TSH 5.0–6.0 mU/liter as borderline-subclinical hypothyroidism.

Results: A total of 5.3 and 5.0% (total 10.2%; 31 of 303) of the CBD stone patients were diagnosed to have subclinical and borderline-subclinical hypothyroidism, compared with 1.4% (P = 0.05) and 1.4% (total 2.8%, four of 142; P = 0.026) in the control group, respectively. In women older than 60 yr, the prevalence of subclinical hypothyroidism was 11.4% in CBD stone and 1.8% in control patients (P = 0.032) and subclinical plus borderline-subclinical hypothyroidism 23.8% in CBD stone and 1.8% in control patients (P = 0.012).

Conclusion: Subclinical hypothyroidism is more common in the CBD stone patients, compared with nongallstone controls, supporting our hypothesis that hypothyroidism might play a role in the forming of CBD stones. At minimum, women older than 60 yr with CBD stones should be screened for borderline or overt subclinical hypothyroidism.
Iraq and Vietnam: Some Unsettling Parallels
Authors: Carpenter Ted Galen
Published: August 2007

Ted Galen Carpenter, vice president for defense and foreign policy studies at the Cato Institute, is the author of seven books and more than 350 articles on international issues. He is a member of the Editorial Advisory Board of Mediterranean Quarterly.
NO-mediated apoptosis in yeast
Authors: Almeida Bruno , Buttner Sabrina , Ohlmeier Steffen , Silva Alexandra , Mesquita Ana , Sampaio-Marques Belém , Osório Nuno S. , Kollau Alexander , Mayer Bernhard , Leão Cecília , Laranjinha João , Rodrigues Fernando , Madeo Frank , Ludovico Paula
Published: August 2007

Nitric oxide (NO) is a small molecule with distinct roles in diverse physiological functions in biological systems, among them the control of the apoptotic signalling cascade. By combining proteomic, genetic and biochemical approaches we demonstrate that NO and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are crucial mediators of yeast apoptosis. Using indirect methodologies and a NO-selective electrode, we present results showing that H2O2-induced apoptotic cells synthesize NO that is associated to a nitric oxide synthase (NOS)-like activity as demonstrated by the use of a classical NOS kit assay. Additionally, our results show that yeast GAPDH is a target of extensive proteolysis upon H2O2-induced apoptosis and undergoes S-nitrosation. Blockage of NO synthesis with Nω-nitro-L-arginine methyl ester leads to a decrease of GAPDH S-nitrosation and of intracellular reactive oxygen species (ROS) accumulation, increasing survival. These results indicate that NO signalling and GAPDH S-nitrosation are linked with H2O2-induced apoptotic cell death. Evidence is presented showing that NO and GAPDH S-nitrosation also mediate cell death during chronological life span pointing to a physiological role of NO in yeast apoptosis.
Antagonistic action of harpin proteins: HrpWea from Erwinia amylovora suppresses HrpNea-induced cell death in Arabidopsis thaliana
Authors: Reboutier David , Frankart Cécile , Briand Joël , Biligui Bernadette , Rona Jean-Pierre , Haapalainen Minna , Barny Marie-Anne , Bouteau François
Published: August 2007

Harpins are proteins secreted by the type-three secretion system of phytopathogenic bacteria. They are known to induce a hypersensitive response (HR) in non-host plant leaf tissue. Erwinia amylovora, the fire blight pathogen of pear and apple trees, secretes two different harpins, HrpNea and HrpWea. In the present study, we showed that an Erwinia amylovora hrpWea mutant induces stronger electrolyte leakages in Arabidopsis thaliana foliar disks than the wild-type strain, thus suggesting that HrpWea could function as a HR negative modulator. We confirmed this result by using purified HrpWea and HrpNea. HrpWea has dual effects depending on its concentration. At 200 nM, HrpWea, like HrpNea, provoked the classical defense response – active oxygen species (AOS) production and cell death. However, at 0.2 nM, HrpWea inhibited cell death and AOS production provoked by HrpNea. HrpWea probably inhibits HrpNea-induced cell death by preventing anion channel inhibition, confirming that anion channel regulation is a determinant feature of the plant response to harpins. Collectively our data show that the HrpWea harpin can act antagonistically to the classical HrpNea harpin by suppressing plant defense mechanisms.
Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6–aPKC
Authors: Atwood Scott X. , Chabu Chiswili , Penkert Rhiannon R. , Doe Chris Q. , Prehoda Kenneth E.
Published: August 2007

Cdc42 recruits Par-6–aPKC to establish cell polarity from worms to mammals. Although Cdc42 is reported to have no function in Drosophila neuroblasts, a model for cell polarity and asymmetric cell division, we show that Cdc42 colocalizes with Par-6–aPKC at the apical cortex in a Bazooka-dependent manner, and is required for Par-6–aPKC localization. Loss of Cdc42 disrupts neuroblast polarity: cdc42 mutant neuroblasts have cytoplasmic Par-6–aPKC, and this phenotype is mimicked by neuroblast-specific expression of a dominant-negative Cdc42 protein or a Par-6 protein that lacks Cdc42-binding ability. Conversely, expression of constitutively active Cdc42 leads to ectopic Par-6–aPKC localization and corresponding cell polarity defects. Bazooka remains apically enriched in cdc42 mutants. Robust Cdc42 localization requires Par-6, indicating the presence of feedback in this pathway. In addition to regulating Par-6–aPKC localization, Cdc42 increases aPKC activity by relieving Par-6 inhibition. We conclude that Cdc42 regulates aPKC localization and activity downstream of Bazooka, thereby directing neuroblast cell polarity and asymmetric cell division.
Nucleocytoplasmic shuttling of persistently activated STAT3
Authors: Herrmann Andreas , Vogt Michael , Mönnigmann Martin , Clahsen Thomas , Sommer Ulrike , Haan Serge , Poli Valeria , Heinrich Peter C. , Müller-Newen Gerhard
Published: August 2007

Persistent activation of the transcription factor STAT3 has been detected in many types of cancer and plays an important role in tumor progression, immune evasion and metastasis. To analyze persistent STAT3 activation we coexpressed STAT3 with v-Src. We found that tyrosine phosphorylation of STAT3 by v-Src is independent of Janus kinases (Jaks), the canonical activators of STATs. The STAT3-induced feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), did not interfere with STAT3 activation by v-Src. However, the protein inhibitor of activated STAT3 (PIAS3) suppressed gene induction by persistently activated STAT3. We measured nucleocytoplasmic shuttling of STAT3 in single cells by bleaching the YFP moiety of double-labelled STAT3-CFP-YFP in the cytoplasm. Analysis of the subcellular distribution of CFP and YFP fluorescence over time by mathematical modeling and computational parameter estimation revealed that activated STAT3 shuttles more rapidly than non-activated STAT3. Inhibition of exportin-1-mediated nuclear export slowed down nucleocytoplasmic shuttling of v-Src-activated STAT3 resulting in reduced tyrosine phosphorylation, decreased induction of STAT3 target genes and increased apoptosis. We propose passage of persistently activated STAT3 through the nuclear pore complex as a new target for intervention in cancer.
Optimizing spot welding parameters in a sheet metal assembly by neural networks and genetic algorithm
Authors: Hamedi M , Shariatpanahi M , Mansourzadeh A
Published: August 2007

Deformation of the spot-welded sub-assemblies in assembly operations and the gap between the matching sub-assemblies have been quality concerns specifically in the automotive industry. Overall quality of the car body and its sub-assemblies, apart from quality of each stamped part, depends markedly on the welding process. This paper considers optimization of three important process parameters in the spot welding of the body components, namely welding current, welding time, and gun force. In this research, first the effects of these parameters on deformation of the sub-assemblies are experimentally investigated. Then neural networks and multi-objective genetic algorithms are utilized to select the optimum values of welding parameters that yield the least values of dimensional deviations in the sub-assemblies. Welding sub-assemblies with the optimized set of parameters brought all of them into the tolerance range. The proposed approach can be utilized in manufacturing sub-assemblies that can fit and match better with adjacent parts in the automotive body. It enhances quality of the joint and will result in improving overall quality of the body in white.
A servo-controller design based on non-linear adaptive robust control
Authors: Wang J P , Cho H S , Cao B G
Published: August 2007

Based on a non-linear model of a computer numerical control (CNC) system, a general adaptive robust controller (ARC) is presented in this paper. The ARC was used to treat problems including the compensation of friction non-linearity, parameter variation, and unmodelled dynamics in the design of a CNC system. It can enhance stability robustness and performance robustness. The simulation results show the effectiveness of the method.
A preliminary approach for modelling and planning the composition of engineering project teams
Authors: Coates G , Duffy A H B , Hills W , Whitfield R I
Published: August 2007

Managing engineering projects is a complex activity involving multiskilled engineers, who have varying levels of capability in these skills. This paper outlines a preliminary approach to modelling and planning the composition of engineering project teams, taking into consideration the skills and capabilities of engineers and the nature of the project work to be undertaken. The approach includes a simple means of identifying engineers' skills and then quantifying their level of capability in these skills. Subsequently, the approach uses a genetic algorithm along with a task-to-engineer allocation strategy to establish how best to utilize the mix of skills and capabilities of the team of engineers assigned to the project under consideration. The approach also provides a means of identifying imbalances or shortfalls in skill and capability within a team, and the formulation of an appropriate development strategy to redress/overcome them. An application of the approach to an industrial case study is presented, which led to significant potential reductions in expected project duration and labour cost. These potential reductions could be achieved by appropriately modelling engineers' skills and capabilities, and redressing the imbalance within the team through proposed changes to its composition.