bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet protein disulfide isomerase is localized in the dense tubular system and does not become surface expressed after activation
Authors: van Nispen tot Pannerden Hezder E. , van Dijk Suzanne M. , Du Vivian , Heijnen Harry F. G.
Published: October 2009

Evidence is accumulating that circulating tissue factor (TF) contributes to the initiation of coagulation and the formation of fibrin. The majority of circulating TF is cryptic, and it has been suggested that close vicinity with anionic phospholipids on the cell surface increases the active conformation of TF. Two recent papers have shown that encryption of TF and initiation of coagulation are facilitated by the enzyme protein disulfide isomerase (PDI), possibly on the surface of activated platelets or endothelial cells. In this brief report, we demonstrate that the majority of PDI in platelets is intracellular where it is exclusively located in the dense tubular system. On activation, PDI remains confined to the intracellular stores of the dense tubular system and is neither released nor targeted to the cell surface. Similar results were obtained in endothelium where PDI remains exclusively localized in the endoplasmic reticulum, both at steady state and after thrombin stimulation.
Kavosh: a new algorithm for finding network motifs
Authors: Kashani Zahra Razaghi Moghadam , Ahrabian Hayedeh , Elahi Elahe , Nowzari-Dalini Abbas , Ansari Elnaz Saberi , Asadi Sahar , Mohammadi Shahin , Schreiber Falk , Masoudi-Nejad Ali
Published: October 2009

Background

Complex networks are studied across many fields of science and are particularly important to understand biological processes. Motifs in networks are small connected sub-graphs that occur significantly in higher frequencies than in random networks. They have recently gathered much attention as a useful concept to uncover structural design principles of complex networks. Existing algorithms for finding network motifs are extremely costly in CPU time and memory consumption and have practically restrictions on the size of motifs.

Results

We present a new algorithm (Kavosh), for finding k-size network motifs with less memory and CPU time in comparison to other existing algorithms. Our algorithm is based on counting all k-size sub-graphs of a given graph (directed or undirected). We evaluated our algorithm on biological networks of E. coli and S. cereviciae, and also on non-biological networks: a social and an electronic network.

Conclusion

The efficiency of our algorithm is demonstrated by comparing the obtained results with three well-known motif finding tools. For comparison, the CPU time, memory usage and the similarities of obtained motifs are considered. Besides, Kavosh can be employed for finding motifs of size greater than eight, while most of the other algorithms have restriction on motifs with size greater than eight. The Kavosh source code and help files are freely available at: http://Lbb.ut.ac.ir/Download/LBBsoft/Kavosh/.
Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke
Authors: Matsukawa Noriyuki , Yasuhara Takao , Hara Koichi , Xu Lin , Maki Mina , Yu Guolong , Kaneko Yuji , Ojika Kosei , Hess David C , Borlongan Cesar V
Published: October 2009

Background

Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting.

Results

Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury.

Conclusion

The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.
Prevalence and risk factors for stunting and severe stunting among under-fives in North Maluku province of Indonesia
Authors: Ramli  , Agho Kingsley E , Inder Kerry J , Bowe Steven J , Jacobs Jennifer , Dibley Michael J
Published: October 2009

Background

Adequate nutrition is needed to ensure optimum growth and development of infants and young children. Understanding of the risk factors for stunting and severe stunting among children aged less than five years in North Maluku province is important to guide Indonesian government public health planners to develop nutrition programs and interventions in a post conflict area. The purpose of the current study was to assess the prevalence of and the risk factors associated with stunting and severe stunting among children aged less than five years in North Maluku province of Indonesia.

Methods

The health and nutritional status of children aged less than five years was assessed in North Maluku province of Indonesia in 2004 using a cross-sectional multi-stage survey conducted on 750 households from each of the four island groups in North Maluku province. A total of 2168 children aged 0-59 months were used in the analysis.

Results

Prevalence of stunting and severe stunting were 29% (95%CI: 26.0-32.2) and 14.1% (95%CI: 11.7-17.0) for children aged 0-23 months and 38.4% (95%CI: 35.9-41.0) and 18.4% (95%CI: 16.1-20.9) for children aged 0-59 months, respectively. After controlling for potential confounders, multivariate analysis revealed that the risk factors for stunted children were child's age in months, male sex and number of family meals per day (≤2 times), for children aged 0-23 months, and income (poorest and middle-class family), child's age in months and male sex for children aged 0-59 months. The risk factors for severe stunting in children aged 0-23 months were income (poorest family), male sex and child's age in months and for children aged 0-59 months were income (poorest family), father's occupation (not working), male sex and child's age in months.

Conclusion

Programmes aimed at improving stunting in North Maluku province of Indonesia should focus on children under two years of age, of male sex and from families of low socioeconomic status.
Influence of obstetric factors on osteogenic potential of umbilical cord-derived mesenchymal stem cells
Authors: Penolazzi Letizia , Vecchiatini Renata , Bignardi Stefania , Lambertini Elisabetta , Torreggiani Elena , Canella Alessandro , Franceschetti Tiziana , Calura Giorgio , Vesce Fortunato , Piva Roberta
Published: October 2009

Wharton's jelly from the umbilical cord is a noncontroversial source of mesenchymal stem cells (WJMSCs) with high plasticity, proliferation rate and ability to differentiate towards multiple lineages. WJMSCs from different donors have been characterized for their osteogenic potential. Although there is large evidence of WJMSCs plasticity, recently scientific debate has focused on MSCs selection, establishing predictable elements to discriminate the cells with most promising osteoprogenitor cell potential.

In the present study a comparative study between the presence of osteoblastic markers and different parameters that pertain to both the newborn and the mother was performed. Umbilical cords were collected after all patients signed the informed consent and local ethical commettee approved the study. Obstetric parameters, including baby's gender and birth weight, mother's age at delivery, gestational stage at parturition and mode of delivery were examined. After characterization and expansion, WJMSCs were analyzed for two osteoblastic markers, alkaline phosphatase (ALP) activity, and the expression level of RUNX-2 transcription factor, and for their ability to deposit mineralized matrix after osteogenic induction.

We found that osteoblastic potential was not influenced by baby's gender and mode of delivery. On the contrary, the highest degree of osteoblastic potential has been shown by WJMSCs with RUNX-2 high basal levels, selected from umbilical cords of the heaviest term babies.

Even if further evaluation is required, our hypothesis is that our findings may help in selecting the optimal umbilical cord donors and in collecting high potential Wharton's jelly-derived osteoprogenitors efficiently.
NADPH oxidase mediates β-amyloid peptide-induced activation of ERK in hippocampal organotypic cultures
Authors: Serrano Faridis , Chang Angela , Hernandez Caterina , Pautler Robia G , Sweatt J David , Klann Eric
Published: October 2009

Background

Previous studies have shown that beta amyloid (Aβ) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signal-regulated kinase (ERK) cascade. In this study we sought to characterize the cellular localization of phosphorylated, active ERK in organotypic hippocampal cultures after acute exposure to either Aβ (1-42) or nicotine.

Results

We observed that Aβ and nicotine increased the levels of active ERK in distinct cellular localizations. We also examined whether phospho-ERK was regulated by redox signaling mechanisms and found that increases in active ERK induced by Aβ and nicotine were blocked by inhibitors of NADPH oxidase.

Conclusion

Our findings indicate that NADPH oxidase-dependent redox signaling is required for Aβ-induced activation of ERK, and suggest a similar mechanism may occur during early stages of Alzheimer's disease.
XVII International AIDS Conference: From Evidence to Action ‐ Introduction
Authors: Kort Rodney
Published: October 2009

3‐8 August 2008, XVII International AIDS Conference, Mexico City, Mexico
XVII International AIDS Conference: From Evidence to Action ‐ Clinical and biomedical prevention science
Authors: Mascolini Mark , Kort Rodney , Gilden David
Published: October 2009

The question of whether to initiate ART at higher CD4+ cell counts than currently recommended by World Health Organization (WHO) treatment guidelines received much attention at the XVII International AIDS Conference (AIDS 2008). If studies presented at the conference ultimately lead to a revision of WHO treatment guidance, the estimated number of people who will need ART globally will increase substantially. Task‐shifting is emerging as an important strategy for dealing with the acute shortage of health care workers in many high‐burden countries, and several studies presented at AIDS 2008 demonstrated the impressive health system efficiencies garnered by using nurses or other health care providers to deliver HIV care and treatment. Other key presentations and discussion at the conference focused on the optimal time to start TB treatment in HIV‐infected patients, the growing risk of resistance in high‐burden countries, including its impact on future treatment options, and several large cohort trials testing optimal drug regimens in resource‐limited settings.

Biomedical prevention research continues to confirm the long‐term, protective benefits of circumcision. Several studies involving HIV serodiscordant heterosexual couples have produced data suggesting a strong protective effect of ART for HIV‐negative partners. Disappointing results from recent vaccine and non‐ARV based microbicides trials are nevertheless providing important data to this field, and the expanding number of pre‐exposure prophylaxis (PrEP) trials and ARV‐based microbicides appear to provide the best hope for a new, efficacious biomedical prevention intervention.

3‐8 August 2008, XVII International AIDS Conference, Mexico City, Mexico
Phenotypic and functional characterization of switch memory B cells from patients with oligoarticular juvenile idiopathic arthritis
Authors: Corcione Anna , Ferlito Francesca , Gattorno Marco , Gregorio Andrea , Pistorio Angela , Gastaldi Roberto , Gambini Claudio , Martini Alberto , Traggiai Elisabetta , Pistoia Vito
Published: October 2009

Introduction

In chronic inflammatory disorders, B cells can contribute to tissue damage by autoantibody production and antigen presentation to T cells. Here, we have characterized synovial fluid and tissue B-cell subsets in patients with oligoarticular juvenile idiopathic arthritis (JIA), an issue not addressed before in detail.

Methods

B cells from synovial fluid (SF) and peripheral blood (PB) of 25 JIA patients, as well as from PB of 20 controls of comparable age, were characterized by multicolor flow cytometry. Immunoglobulin-secreting cells were detected by ELISPOT. Immunohistochemical analyses of synovial tissue from three JIA patients were performed.

Results

JIA SF B cells were enriched in CD27+ and CD27- switch memory B cells, but not in CD27+ IgM memory B cells, compared with patient and control PB. Plasma blasts were more abundant in SF and secreted higher amounts of IgG. Lymphoid aggregates not organized in follicle-like structures were detected in synovial tissue sections and were surrounded by CD138+ plasma cells. Finally, transitional B cells were significantly increased in JIA PB versus SF or control PB. CCR5, CCR8, CXCR2, and CXCR3 were upregulated, whereas CCR6, CCR7, and CXCR5 were downregulated on SF CD27+ and CD27- switch memory B cells compared with their circulating counterparts. SF CD27+ and CD27- switch memory B cells expressed at high levels the costimulatory molecule CD86 and the activation marker CD69.

Conclusions

This study demonstrates for the first time an expansion of activated switch memory B cells and of IgG-secreting plasma blasts in the SF from oligoarticular JIA patients. Memory B cells belonged to either the CD27+or the CD27- subsets and expressed CD86, suggesting their involvement in antigen presentation to T cells. Patterns of chemokines-receptor expression on CD27+ and CD27- switch memory B cells delineated potential mechanisms for their recruitment to the inflamed joints.
Treatment of candidemia and invasive candidiasis in the intensive care unit: post hoc analysis of a randomized, controlled trial comparing micafungin and liposomal amphotericin B
Authors: Dupont Bertrand F , Lortholary Olivier , Ostrosky-Zeichner Luis , Stucker Flavie , Yeldandi Vijay
Published: October 2009

Introduction

Invasive candidiasis and candidemia are life-threatening nosocomial infections in intensive care patients.

Methods

A post hoc analysis of a phase 3 trial assessing micafungin (100 mg/day for subjects > 40 kg; 2 mg/kg/day for subjects ≤ 40 kg) versus liposomal amphotericin B (3 mg/kg/day). Subgroups were defined according to the type of ward on the first day of treatment: intensive care unit (ICU) or non-ICU. Multivariate regression was performed to identify factors associated with treatment success at end of therapy and all-cause mortality at days 8 and 30.

Results

In non-ICU subjects, treatment success was significantly higher for micafungin versus liposomal amphotericin B (85% (n = 108/127) versus 72.1% (n = 98/136); P = 0.0113). However, for ICU subjects, treatment success rates for micafungin versus liposomal amphotericin B were similar (62.5% (n = 75/120) versus 66.4% (n = 73/110); P = 0.5828). Overall, treatment success was significantly lower in ICU subjects compared with non-ICU subjects (64.3% (n = 148/230) versus 78.3% (n = 206/263); P = 0.0006). Multivariate regression analysis revealed a lower likelihood of treatment success for: ICU versus non-ICU subjects; persistent neutropenia; and high versus low Acute Physiology and Chronic Health Evaluation (APACHE) II scores. However, when interactions between potential explanatory factors were included in the analysis model, ICU status no longer emerged as a significant associated variable but the association between APACHE II score and treatment outcome remained. Further analyses indicated that the likelihood of mortality at day 8 and day 30 was lower for subjects with lower APACHE II scores. Renal function was significantly better in micafungin versus liposomal amphotericin B subjects: a difference (liposomal amphotericin B - micafungin in mean peak change in estimated glomerular filtration rate (ml/minute/1.73 m2) of -18.2 (P < 0.0001) and -17.7 (P = 0.0124) in non-ICU and ICU subjects, respectively.

Conclusions

Overall, ICU subjects had lower treatment success rates than non-ICU subjects for both liposomal amphotericin B and micafungin. Multivariate regression after controlling for potential confounding factors suggested the APACHE II score remained a potential explanatory factor associated with treatment success, mortality at day 8, and mortality at day 30.

Trial registration

Post hoc analysis - clinicaltrials.gov trial NCT00106288.
Effects of positive end-expiratory pressure on respiratory function and hemodynamics in patients with acute respiratory failure with and without intra-abdominal hypertension: a pilot study
Authors: Krebs Joerg , Pelosi Paolo , Tsagogiorgas Charalambos , Alb Markus , Luecke Thomas
Published: October 2009

Introduction

To investigate the effects of positive end-expiratory pressure (PEEP) on respiratory function and hemodynamics in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) with normal intra-abdominal pressure (IAP < 12 mmHg) and with intra-abdominal hypertension (IAH, defined as IAP ≥ 12 mmHg) during lung protective ventilation and a decremental PEEP, a prospective, observational clinical pilot study was performed.

Methods

Twenty patients with ALI/ARDS with normal IAP or IAH treated in the surgical intensive care unit in a university hospital were studied. The mean IAP in patients with IAH and normal IAP was 16 ± 3 mmHg and 8 ± 3 mmHg, respectively (P < 0.001). At different PEEP levels (5, 10, 15, 20 cmH2O) we measured respiratory mechanics, partitioned into its lung and chest wall components, alveolar recruitment, gas-exchange, hemodynamics, extravascular lung water index (EVLWI) and intrathoracic blood volume index (ITBVI).

Results

We found that ALI/ARDS patients with IAH, as compared to those with normal IAP, were characterized by: a) no differences in gas-exchange, respiratory mechanics, partitioned into its lung and chest wall components, as well as hemodynamics and EVLWI/ITBVI; b) decreased elastance of the respiratory system and the lung, but no differences in alveolar recruitment and oxygenation or hemodynamics, when PEEP was increased at 10 and 15cmH2O; c) at higher levels of PEEP, EVLWI was lower in ALI/ARDS patients with IAH as compared with those with normal IAP.

Conclusions

IAH, within the limits of IAP measured in the present study, does not affect interpretation of respiratory mechanics, alveolar recruitment and hemodynamics.
Defining the chromatin signature of inducible genes in T cells
Authors: Lim Pek S , Hardy Kristine , Bunting Karen L , Ma Lina , Peng Kaiman , Chen Xinxin , Shannon Mary F
Published: October 2009

Background

Specific chromatin characteristics, especially the modification status of the core histone proteins, are associated with active and inactive genes. There is growing evidence that genes that respond to environmental or developmental signals may possess distinct chromatin marks. Using a T cell model and both genome-wide and gene-focused approaches, we examined the chromatin characteristics of genes that respond to T cell activation.

Results

To facilitate comparison of genes with similar basal expression levels, we used expression-profiling data to bin genes according to their basal expression levels. We found that inducible genes in the lower basal expression bins, especially rapidly induced primary response genes, were more likely than their non-responsive counterparts to display the histone modifications of active genes, have RNA polymerase II (Pol II) at their promoters and show evidence of ongoing basal elongation. There was little or no evidence for the presence of active chromatin marks in the absence of promoter Pol II on these inducible genes. In addition, we identified a subgroup of genes with active promoter chromatin marks and promoter Pol II but no evidence of elongation. Following T cell activation, we find little evidence for a major shift in the active chromatin signature around inducible gene promoters but many genes recruit more Pol II and show increased evidence of elongation.

Conclusions

These results suggest that the majority of inducible genes are primed for activation by having an active chromatin signature and promoter Pol II with or without ongoing elongation.
Comparison of Iodine-123 Metaiodobenzylguanidine (MIBG) Scan and [18F]Fluorodeoxyglucose Positron Emission Tomography to Evaluate Response After Iodine-131 MIBG Therapy for Relapsed Neuroblastoma
Authors: Taggart Denah R. , Han Myo M. , Quach Alekist , Groshen Susan , Ye Wei , Villablanca Judith G. , Jackson Hollie A. , Mari Aparici Carina , Carlson David , Maris John , Hawkins Randall , Matthay Katherine K.
Published: October 2009

Purpose

Children with relapsed neuroblastoma have poor survival. It is crucial to have a reliable method for evaluating functional response to new therapies. In this study, we compared two functional imaging modalities for neuroblastoma: metaiodobenzylguanidine (MIBG) scan for uptake by the norepinephrine transporter and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake for glucose metabolic activity.

Patients and Methods

Patients enrolled onto a phase I study of sequential infusion of iodine-131 (131I) MIBG (NANT-2000-01) were eligible for inclusion if they had concomitant FDG-PET and MIBG scans. 131I-MIBG therapy was administered on days 0 and 14. For each patient, we compared all lesions identified on concomitant FDG-PET and MIBG scans and gave scans a semiquantitative score.

Results

The overall concordance of positive lesions on concomitant MIBG and FDG-PET scans was 39.6% when examining the 139 unique anatomic lesions. MIBG imaging was significantly more sensitive than FDG-PET overall and for the detection of bone lesions (P < .001). There was a trend for increased sensitivity of FDG-PET for detection of soft tissue lesions. Both modalities showed similar improvement in number of lesions identified from day 0 to day 56 scan and in semiquantitative scores that correlated with overall response. FDG-PET scans became completely negative more often than MIBG scans after treatment.

Conclusion

MIBG scan is significantly more sensitive for individual lesion detection in relapsed neuroblastoma than FDG-PET, though FDG-PET can sometimes play a complementary role, particularly in soft tissue lesions. Complete response by FDG-PET metabolic evaluation did not always correlate with complete response by MIBG uptake.
Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
Authors: Witzig Thomas E. , Wiernik Peter H. , Moore Timothy , Reeder Craig , Cole Craig , Justice Glen , Kaplan Henry , Voralia Michael , Pietronigro Dennis , Takeshita Kenichi , Ervin-Haynes Annette , Zeldis Jerome B. , Vose Julie M.
Published: October 2009

Purpose

Lenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL).

Patients and Methods

Patients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety.

Results

Forty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively).

Conclusion

Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.
Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
Authors: Schultz Kirk R. , Bowman W. Paul , Aledo Alexander , Slayton William B. , Sather Harland , Devidas Meenakshi , Wang Chenguang , Davies Stella M. , Gaynon Paul S. , Trigg Michael , Rutledge Robert , Burden Laura , Jorstad Dean , Carroll Andrew , Heerema Nyla A. , Winick Naomi , Borowitz Michael J. , Hunger Stephen P. , Carroll William L. , Camitta Bruce
Published: October 2009

Purpose

Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups.

Patients and Methods

We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph− ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) –identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT.

Results

Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction.

Conclusion

Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.
Longitudinal Cohort Study of Risk Factors in Cancer Patients of Bisphosphonate-Related Osteonecrosis of the Jaw
Authors: Vahtsevanos Konstantinos , Kyrgidis Athanassios , Verrou Evgenia , Katodritou Eirini , Triaridis Stefanos , Andreadis Charalampos G. , Boukovinas Ioannis , Koloutsos Georgios E. , Teleioudis Zisis , Kitikidou Kyriaki , Paraskevopoulos Panagiotis , Zervas Konstantinos , Antoniades Konstantinos
Published: October 2009

Purpose

The reported incidence of osteonecrosis of the jaw (ONJ) ranges from 0.94% to 18.6%. This cohort study aimed to calculate the incidence of and identify the risk factors for ONJ in patients with cancer treated with intravenous zoledronate, ibandronate, and pamidronate.

Patients and Methods

Data analyzed included age, sex, smoking status, underlying disease, medical and dental history, bisphosphonates (BP) type, and doses administered. Relative risks, crude and adjusted odds ratios (aORs), and cumulative hazard ratios for ONJ development were calculated.

Results

We included 1,621 patients who received 29,006 intravenous doses of BP, given monthly. Crude ONJ incidence was 8.5%, 3.1%, and 4.9% in patients with multiple myeloma, breast cancer, and prostate cancer, respectively. Patients with breast cancer demonstrated a reduced risk for ONJ development, which turned out to be nonsignificant after adjustment for other variables. Multivariate analysis demonstrated that use of dentures (aOR = 2.02; 95% CI, 1.03 to 3.96), history of dental extraction (aOR = 32.97; 95% CI, 18.02 to 60.31), having ever received zoledronate (aOR = 28.09; 95% CI, 5.74 to 137.43), and each zoledronate dose (aOR = 2.02; 95% CI, 1.15 to 3.56) were associated with increased risk for ONJ development. Smoking, periodontitis, and root canal treatment did not increase risk for ONJ in patients receiving BP.

Conclusion

The conclusions of this study validated dental extractions and use of dentures as risk factors for ONJ development. Ibandronate and pamidronate at the dosages and frequency used in this study seem to exhibit a safer drug profile concerning ONJ complication; however, randomized controlled trials are needed to validate these results. Before initiation of a bisphosphonate, patients should have a comprehensive dental examination. Patients with a challenging dental situation should have dental care attended to before initiation of these drugs.
Racial and Ethnic Disparities in the Use of Postmastectomy Breast Reconstruction: Results From a Population- Based Study
Authors: Alderman Amy K. , Hawley Sarah T. , Janz Nancy K. , Mujahid Mahasin S. , Morrow Monica , Hamilton Ann S. , Graff John J. , Katz Steven J.
Published: October 2009

Purpose

There is concern that minority women have limited access to breast reconstruction. We described patterns of use, experiences with clinicians, and patients' satisfaction with treatment decisions for women of different race/ethnicities.

Methods

A total of 3,252 patients with breast cancer from Los Angeles and Detroit Surveillance, Epidemiology, and End Results registries were surveyed near the time of diagnosis (n = 2,260, response rate 72.2%). The primary outcomes were receipt of reconstruction, access to information about reconstruction, and decisional satisfaction. The primary independent variable was race/ethnicity (white, African American [AA], highly acculturated Latina [Latina-high], and less acculturated Latina [Latina-low]). Control variables included other sociodemographic and clinical factors. χ2 and multivariate logistic regression were used for the analyses.

Results

Receipt of reconstruction varied significantly by patient race/ethnicity—40.9% of whites, 33.5% of AAs, 41.2% of Latina-high, and only 13.5% of Latina-low (P < .001)—and persisted when we controlled for demographic and clinical factors. Minority women were significantly less likely than whites to see a plastic surgeon before initial surgery and were more likely to desire more information about reconstruction (17.0% of whites v 27.0% of AAs, 30.0% of Latina-high, and 55.9% of Latina-low; P < .001). Decisional satisfaction was lowest among minority women without reconstruction (P < .001).

Conclusion

Minority women, particularly less acculturated Latinas, had low receipt of breast reconstruction, which may be related to limited information about the procedure and less access to plastic surgeons. Greater desire for information and lower satisfaction with surgical decisions among these patients motivate greater attention to treatment support for these patients.
Quality of Life of Patients With Endometrial Cancer Undergoing Laparoscopic International Federation of Gynecology and Obstetrics Staging Compared With Laparotomy: A Gynecologic Oncology Group Study
Authors: Kornblith Alice B. , Huang Helen Q. , Walker Joan L. , Spirtos Nick M. , Rotmensch Jacob , Cella David
Published: October 2009

Purpose

The study's objective was to compare the quality of life (QoL) of patients with endometrial cancer undergoing surgical staging via laparoscopy versus laparotomy.

Patients and Methods

The first 802 eligible patients (laparoscopy, n = 535; laparotomy, n = 267) participated in the QoL study in a Gynecologic Oncology Group (GOG) randomized trial of laparoscopy versus laparotomy (GOG 2222). Patients completed QoL assessments at baseline; at 1, 3, and 6 weeks; and at 6 months postsurgery.

Results

In an intent-to-treat analysis, laparoscopy patients reported significantly higher Functional Assessment of Cancer Therapy–General (FACT-G) scores (P = .001), better physical functioning (P = .006), better body image (BI; P < .001), less pain (P < .001) and its interference with QoL (P < .001), and an earlier resumption of normal activities (P = .003) and return to work (P = .04) over the 6-week postsurgery period, as compared with laparotomy patients. However, the differences in BI and return to work between groups were modest, and the adjusted FACT-G scores did not meet the minimally important difference (MID) between the two surgical arms over 6 weeks. By 6 months, except for better BI in laparoscopy patients (P < .001), the difference in QoL between the two surgical techniques was not statistically significant.

Conclusion

Although the FACT-G did not show a MID between the two surgical groups, and only modest differences in return to work and BI were found between the two groups, statistically significantly better QoL across many parameters in the laparoscopy arm at 6 weeks provides modest support for the QoL advantage of using laparoscopy to stage patients with early endometrial cancer.
Underweight and Breast Cancer Recurrence and Death: A Report From the Korean Breast Cancer Society
Authors: Moon Hyeong-Gon , Han Wonshik , Noh Dong-Young
Published: October 2009

Purpose

The association between body mass index and breast cancer outcome is controversial. Furthermore, the impact of underweight on breast cancer recurrence and death has not been adequately addressed.

Patients and Methods

We investigated this issue using a large nationwide database of 24,698 Korean breast cancer patients. The association between body weight status and breast cancer recurrence was further explored using a single-institution database containing information on 4,345 patients.

Results

The results from the nationwide database showed significantly lower overall survival (OS) and breast cancer-specific survival (BCSS) in underweight patients compared with survival in patients of normal weight after adjusting for known prognostic factors such as age, tumor size, lymph node metastasis, hormone receptor status, histologic grade, and lymphovascular invasion (hazard ratio [HR], 1.48; 95% CI, 1.15 to 1.90 for OS; HR, 1.49; 95% CI, 1.15 to 1.93 for BCSS), which were not observed in obese patients. In an analysis of recurrence data from the single institution, underweight women had a significantly higher risk of both distant metastasis and local recurrence of breast cancer (HR, 1.93; 95% CI, 1.04 to 3.58 and HR, 5.13; 95% CI, 2.66 to 9.90, respectively).

Conclusion

Our study suggests that underweight should be considered to be a high risk factor for death and recurrence after breast cancer surgery, especially in Asian breast cancer patients.
Timed Sequential Treatment With Cyclophosphamide, Doxorubicin, and an Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor–Secreting Breast Tumor Vaccine: A Chemotherapy Dose-Ranging Factorial Study of Safety and Immune Activation
Authors: Emens Leisha A. , Asquith Justin M. , Leatherman James M. , Kobrin Barry J. , Petrik Silvia , Laiko Marina , Levi Joy , Daphtary Maithili M. , Biedrzycki Barbara , Wolff Antonio C. , Stearns Vered , Disis Mary L. , Ye Xiaobu , Piantadosi Steven , Fetting John H. , Davidson Nancy E. , Jaffee Elizabeth M.
Published: October 2009

Purpose

Granulocyte-macrophage colony-stimulating factor (GM-CSF) –secreting tumor vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance vaccine-induced immunity in patients with breast cancer.

Patients and Methods

We conducted a 3 × 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF–secreting tumor vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity.

Results

Twenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received vaccine alone or with 200 mg/m2 CY. HER2-specific antibody responses were enhanced by 200 mg/m2 CY and 35 mg/m2 DOX, but higher CY doses suppressed immunity. Analyses revealed that CY at 200 mg/m2 and DOX at 35 mg/m2 is the combination that produced the highest antibody responses.

Conclusion

First, immunotherapy with an allogeneic, HER2-positive, GM-CSF–secreting breast tumor vaccine alone or with CY and DOX is safe and induces HER2-specific immunity in patients with metastatic breast cancer. Second, the immunomodulatory activity of low-dose CY has a narrow therapeutic window, with an optimal dose not exceeding 200 mg/m2. Third, factorial designs provide an opportunity to identify the most active combination of interacting drugs in patients. Further investigation of the impact of chemotherapy on vaccine-induced immunity is warranted.
Individual differences and reasoning: A study on personality traits
Authors: Bensi Luca , Giusberti Fiorella , Nori Raffaella , Gambetti Elisa
Published: October 2009

Personality can play a crucial role in how people reason and decide. Identifying individual differences related to how we actively gather information and use evidence could lead to a better comprehension and predictability of human reasoning. Recent findings have shown that some personality traits are related to similar decision‐making patterns showed by people with mental disorders. We performed research with the aim to investigate delusion‐proneness, obsessive‐like personality, anxiety (trait and state), and reasoning styles in individuals from the general population. We introduced personality trait and state anxiety scores in a regression model to explore specific associations with: (1) amount of data‐gathered prior to making a decision; and (2) the use of confirmatory and disconfirmatory evidence. Results showed that all our independent variables were positively or negatively associated with the amount of data collected in order to make simple probabilistic decisions. Anxiety and obsessiveness were the only predictors of the weight attributed to evidence in favour or against a hypothesis. Findings were discussed in relation to theoretical assumptions, predictions, and clinical implications. Personality traits can predict peculiar ways to reason and decide that, in turn, could be involved to some extent in the formation and/or maintenance of psychological disorders.
Reactive aggression in psychopathy and the role of frustration: Susceptibility, experience, and control
Authors: Harenski Carla L. , Kiehl Kent A.
Published: October 2009

This article is a commentary on ‘Psychopathy, frustration, and reactive aggression: The role of ventromedial prefrontal cortex’ (Blair, 2010).
Health of entrepreneurs versus employees in a national representative sample
Authors: Stephan Ute , Roesler Ulrike
Published: October 2009

Prior research has found entrepreneurs to experience significantly higher job control and job demands compared with employees. This suggests that entrepreneurs have so‐called active jobs and thus may benefit from positive health consequences. The present research compared entrepreneurs' health with employees' health in a national representative sample with regard to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD‐10) diagnoses of somatic diseases, the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM‐IV) diagnoses of mental disorders, blood pressure, well‐being (life‐satisfaction) as well as behavioural health indicators (sick days, physician visits). Entrepreneurs showed significantly lower overall somatic and mental morbidity, lower blood pressure, lower prevalence rates of hypertension, and somatoform disorders, as well as higher well‐being and more favourable behavioural health indicators. The results are discussed with regard to the active job hypothesis and recommendations for future research are provided.
Factors regulating tachyphylaxis triggered by N-terminal-modified angiotensin II analogs
Authors: Barros Alexandre J. , Ito Christian M. , Makino Elaine N. , Cembranelli Fernando A.M. , Moraes Francisco C. , Souza Sinval E.G. , Oliveira Laerte , Shimuta Suma I. , Nakaie Clovis R.
Published: October 2009

Binding of angiotensin II (DRVYIHPF, AngII) to its AT1receptor can trigger a process known as tachyphylaxis (loss of receptor response owing to repeated agonist stimulation). We propose a two-state binding model for tachyphylaxis where the N-terminal Asp1and Arg2residues of the peptide are supposed to initially bind to the N-terminal segment (Arg23) and to the EC-3 loop (Asp281) of an AT1molecule, respectively (state 1). Sequentially, a disruption of the salt bond between the AngII Asp1β-carboxyl function and the receptor Arg23can occur with release of the peptide N-terminal segment, favoring the binding of the Arg2residue to the EC-3 loop (Asp178,281, state 2). In the present study, we expanded this investigation by assaying pharmacological properties of different AngII analogs in guinea-pig ileum bearing modifications at positions 1 and 2. Most of these peptides were weak agonists but many of them had the ability to induce tachyphylaxis. These findings support the two-state model for tachyphylaxis, but alternative mechanisms were revealed where state 1 was no longer needed, depending on the chemical structure of AngII residue 1. Otherwise, any modification of the wild type AngII Arg2residue was deleterious for the tachyphylaxis mechanism.
Chemokines in tumor-associated angiogenesis
Authors: Gerber Peter Arne , Hippe Andreas , Buhren Bettina Alexandra , Müller Anja , Homey Bernhard
Published: October 2009

Tumor growth is dependent on several key factors. Apart from immune escape and an efficient blockade of apoptotic signals, tumors require oxygen and nutrients to grow past a diameter of 2 μm. Therefore, it is of vital importance for the tumor to facilitate tumor-associated angiogenesis, e.g., thede novoformation of new blood vessels. In addition to established and key angiogenic factors, such as vascular endothelial growth factor, chemokines, a superfamily of cytokine-like proteins that bind to seven transmembrane-spanning G-protein-coupled receptors, have been associated with angiogenesis under homeostatic conditions. Chemokines were initially identified as key factors that control the directional migration of leukocytes, stem cells and cancer cellsin vitroand which critically regulate their traffickingin vivo. Recently their role in establishing a favorable microenvironment for tumor-associated angiogenesis, a process that requires complex bidirectional interactions of the tumor and associated vessels, has been the focus of research. Chemokine-promoted angiogenesis not only facilitates tumor growth by supplying nutrients and oxygen but it is also a prerequisite to tumor metastasis. Hence, the pharmacologic control of tumor angiogenesis presents a promising strategy for novel anticancer therapeutics. Here, we discuss the current pathogenetic concepts of tumor-associated angiogenesis in the context of chemokines and their receptors and highlight promising therapeutic strategies.
Hexose-6-phosphate dehydrogenase in the endoplasmic reticulum
Authors: Senesi Silvia , Csala Miklos , Marcolongo Paola , Fulceri Rosella , Mandl Jozsef , Banhegyi Gabor , Benedetti Angelo
Published: October 2009

Hexose-6-phosphate dehydrogenase (H6PD) is a luminal enzyme of the endoplasmic reticulum that is distinguished from cytosolic glucose-6-phosphate dehydrogenase by several features. H6PD converts glucose-6-phosphate and NADP+to 6-phosphogluconate and NADPH, thereby catalyzing the first two reactions of the pentose-phosphate pathway. Because the endoplasmic reticulum has a separate pyridine nucleotide pool, H6PD provides NADPH for luminal reductases. One of these enzymes, 11β-hydroxysteroid dehydrogenase type 1 responsible for prereceptorial activation of glucocorticoids, has been the focus of much attention as a probable factor in the pathomechanism of several human diseases including insulin resistance and the metabolic syndrome. This review summarizes recent advances related to the functions of H6PD.
Crystal structure of 4-hydroxybutyrate CoA-transferase from Clostridium aminobutyricum
Authors: Macieira Sofia , Zhang Jin , Velarde Milko , Buckel Wolfgang , Messerschmidt Albrecht
Published: October 2009

4-Hydroxybutyrate CoA-transferases (4-HB-CoAT) takes part in the fermentation of 4-aminobutyrate to ammonia, acetate, and butyrate in anaerobic bacteria such as Clostridium aminobutyricum and Porphyromonas gingivalis or facultative anaerobic bacteria such as Shewanella oneidensis. Site-directed mutagenesis of the highly active enzyme has identified the catalytic glutamate residue as E238. Crystal structure of this enzyme has been determined at a resolution of 1.85 Å. The 438-amino acid residue polypeptide chain folds into two topologically similar domains with an open α/β-fold, which is also found in other CoAT family I and family II members. The data indicate that the members of CoAT families I and II are closely related; the latter only lacking the catalytic glutamate residue. A putative co-substrate binding site for the 4-HB-CoAT was identified, in which a 4-hydroxybutyrate molecule has been modeled. This site is also responsible for binding the acetyl group of acetyl-CoA or the succinyl group of succinyl-CoA in succinyl-CoA:3-oxoacid CoA-transferase from mammalian mitochondria. Mutations of relevant active site amino acid residues have been produced and their activities tested to corroborate the proposed structural model for substrate binding. 4-HB-CoAT from C. aminobutyricum represents the only functionally characterized 4-HB-CoAT present in the structural database.
Zustandsregelung linearer Systeme — Eine NeubetrachtungState Feedback Control of Linear Systems — a Renewed Approach
Authors: Roppenecker Günter
Published: October 2009

Die bislang übliche Struktur zur Zustandsregelung linearer Systeme besteht aus einer Zustandsrückführung und einer Führungsgrößenaufschaltung über ein konstantes Vorfilter. Im Unterschied zur bewährten klassischen Regelung enthält sie keinen Soll-Istwert-Vergleich und die Aufschaltung über das Vorfilter ist abhängig vom Zustandsregler. Dieser Beitrag zeigt, dass Zustandsregelungen auch in eine Struktur mit Soll-Istwert-Vergleich überführt werden können, die zudem eine vom Zustandsregler unabhängige Vorsteuerung zur Führungs- und gegebenenfalls auch Störgrößenaufschaltung ermöglicht. Letztendlich können somit Zustandsregelungen immer auch in Form einer gewöhnlichen Regelung mit Soll-Istwert-Vergleich für die Regelgröße realisiert werden. Bei Verwendung einer modellgestützten Vorsteuerung lassen sich dabei das Führungsverhalten, die Reaktion auf durch Messung bekannte Störgrößen und die Ausregelung der sonstigen Einflüsse jeweils getrennt voneinander einstellen.