bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoclonal antibody 4C5 prevents activation of MMP2 and MMP9 by disrupting their interaction with extracellular HSP90 and inhibits formation of metastatic breast cancer cell deposits
Authors: Stellas Dimitris , El Hamidieh Avraam , Patsavoudi Evangelia
Published: August 2010

Background

Heat shock protein 90 (HSP90) is a molecular chaperone that is considered a new target for the treatment of cancer. Increasing data reveal an extracellular chaperoning activity for HSP90. Here we investigate the interaction of the secreted isoforms of HSP90 with matrix metalloproteinases (MMP) MMP2 and MMP9. Moreover we examine the role of a monoclonal antibody (mAb) against HSP90, mAb 4C5, regarding these interactions and its value as a potential inhibitor of human breast cancer cell invasion and metastasis.

Results

Our results showed that both HSP90α and HSP90β are secreted by MDAMB453 human breast cancer cells and interact with MMP2 and MMP9. MAb 4C5, while not affecting the secretion of inactive MMPs, inhibits their activation by disrupting their interaction extracellularly with both isoforms of HSP90. The in vivo studies revealed that mAb 4C5 significantly inhibits the metastatic deposit formation of MDAMB453 cells into the lungs of SCID mice.

Conclusion

Both isoforms of HSP90 are secreted by MDAMB453 cells and interact with MMP2 and MMP9. MAb 4C5 prevents MMP2 and MMP9 activation, by disrupting their interaction with HSP90. Finally mAb 4C5 significantly inhibits the metastatic deposit formation of MDAMB453 cells, by preventing their extravasation and infiltration in the lung tissue and therefore it could be used as a potential therapeutic agent for cancer metastasis.
Gene encoding γ-carbonic anhydrase is cotranscribed with argC and induced in response to stationary phase and high CO2 in Azospirillum brasilense Sp7
Authors: Kaur Simarjot , Mishra Mukti N , Tripathi Anil K
Published: August 2010

Background

Carbonic anhydrase (CA) is a ubiquitous enzyme catalyzing the reversible hydration of CO2 to bicarbonate, a reaction underlying diverse biochemical and physiological processes. Gamma class carbonic anhydrases (γ-CAs) are widespread in prokaryotes but their physiological roles remain elusive. At present, only γ-CA of Methanosarcina thermophila (Cam) has been shown to have CA activity. Genome analysis of a rhizobacterium Azospirillum brasilense, revealed occurrence of ORFs encoding one β-CA and two γ-CAs.

Results

One of the putative γ-CA encoding genes of A. brasilense was cloned and overexpressed in E. coli. Electrometric assays for CA activity of the whole cell extracts overexpressing recombinant GCA1 did not show CO2 hydration activity. Reverse transcription-PCR analysis indicated that gca1 in A. brasilense is co-transcribed with its upstream gene annotated as argC, which encodes a putative N-acetyl-γ-glutamate-phosphate reductase. 5'-RACE also demonstrated that there was no transcription start site between argC and gca1, and the transcription start site located upstream of argC transcribed both the genes (argC-gca1). Using transcriptional fusions of argC-gca1 upstream region with promoterless lacZ, we further demonstrated that gca1 upstream region did not have any promoter and its transcription occurred from a promoter located in the argC upstream region. The transcription of argC-gca1 operon was upregulated in stationary phase and at elevated CO2 atmosphere.

Conclusions

This study shows lack of CO2 hydration activity in a recombinant protein expressed from a gene predicted to encode a γ-carbonic anhydrase in A. brasilense although it cross reacts with anti-Cam antibody raised against a well characterized γ-CA. The organization and regulation of this gene along with the putative argC gene suggests its involvement in arginine biosynthetic pathway instead of the predicted CO2 hydration.
Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias
Authors: Rocquain Julien , Carbuccia Nadine , Trouplin Virginie , Raynaud Stéphane , Murati Anne , Nezri Meyer , Tadrist Zoulika , Olschwang Sylviane , Vey Norbert , Birnbaum Daniel , Gelsi-Boyer Véronique , Mozziconacci Marie-Joelle
Published: August 2010

Background

Gene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.

Methods

We searched for mutations in the ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in 65 myelodysplastic syndromes (MDSs) and 64 acute myeloid leukemias (AMLs) without balanced translocation or complex karyotype.

Results

Mutations in ASXL1 and CBL were frequent in refractory anemia with excess of blasts. Mutations in TET2 occurred with similar frequency in MDSs and AMLs and associated equally with either ASXL1 or NPM1 mutations. Mutations of RUNX1 were mutually exclusive with TET2 and combined with ASXL1 but not with NPM1. Mutations in FLT3 (mutation and internal tandem duplication), IDH1, IDH2, NPM1 and WT1 occurred primarily in AMLs.

Conclusion

Only 14% MDSs but half AMLs had at least two mutations in the genes studied. Based on the observed combinations and exclusions we classified the 12 genes into four classes and propose a highly speculative model that at least a mutation in one of each class is necessary for developing AML with simple or normal karyotype.
Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar)
Authors: Ytteborg Elisabeth , Baeverfjord Grete , Torgersen Jacob , Hjelde Kirsti , Takle Harald
Published: August 2010

Background

Hyperthermia has been shown in a number of organisms to induce developmental defects as a result of changes in cell proliferation, differentiation and gene expression. In spite of this, salmon aquaculture commonly uses high water temperature to speed up developmental rate in intensive production systems, resulting in an increased frequency of skeletal deformities. In order to study the molecular pathology of vertebral deformities, Atlantic salmon was subjected to hyperthermic conditions from fertilization until after the juvenile stage.

Results

Fish exposed to the high temperature regime showed a markedly higher growth rate and a significant higher percentage of deformities in the spinal column than fish reared at low temperatures. By analyzing phenotypically normal spinal columns from the two temperature regimes, we found that the increased risk of developing vertebral deformities was linked to an altered gene transcription. In particular, down-regulation of extracellular matrix (ECM) genes such as col1a1, osteocalcin, osteonectin and decorin, indicated that maturation and mineralization of osteoblasts were restrained. Moreover, histological staining and in situ hybridization visualized areas with distorted chondrocytes and an increased population of hypertrophic cells. These findings were further confirmed by an up-regulation of mef2c and col10a, genes involved in chondrocyte hypertrophy.

Conclusion

The presented data strongly indicates that temperature induced fast growth is severely affecting gene transcription in osteoblasts and chondrocytes; hence change in the vertebral tissue structure and composition. A disrupted bone and cartilage production was detected, which most likely is involved in the higher rate of deformities developed in the high intensive group. Our results are of basic interest for bone metabolism and contribute to the understanding of the mechanisms involved in development of temperature induced vertebral pathology. The findings may further conduce to future molecular tools for assessing fish welfare in practical farming.
Structural motif screening reveals a novel, conserved carbohydrate-binding surface in the pathogenesis-related protein PR-5d
Authors: Doxey Andrew C , Cheng Zhenyu , Moffatt Barbara A , McConkey Brendan J
Published: August 2010

Background

Aromatic amino acids play a critical role in protein-glycan interactions. Clusters of surface aromatic residues and their features may therefore be useful in distinguishing glycan-binding sites as well as predicting novel glycan-binding proteins. In this work, a structural bioinformatics approach was used to screen the Protein Data Bank (PDB) for coplanar aromatic motifs similar to those found in known glycan-binding proteins.

Results

The proteins identified in the screen were significantly associated with carbohydrate-related functions according to gene ontology (GO) enrichment analysis, and predicted motifs were found frequently within novel folds and glycan-binding sites not included in the training set. In addition to numerous binding sites predicted in structural genomics proteins of unknown function, one novel prediction was a surface motif (W34/W36/W192) in the tobacco pathogenesis-related protein, PR-5d. Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily of PR-5 proteins from the Solanaceae family of plants, and is absent completely in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d was identified in the cellulose-binding fraction by mass spectrometry.

Conclusions

Based on the combined results, we propose that the putative binding site in PR-5d may be an evolutionary adaptation of Solanaceae plants including potato, tomato, and tobacco, towards defense against cellulose-containing pathogens such as species of the deadly oomycete genus,Phytophthora. More generally, the results demonstrate that coplanar aromatic clusters on protein surfaces are a structural signature of glycan-binding proteins, and can be used to computationally predict novel glycan-binding proteins from 3 D structure.
Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths
Authors: Herr Caroline EW , Dostal Miroslav , Ghosh Rakesh , Ashwood Paul , Lipsett Michael , Pinkerton Kent E , Sram Radim , Hertz-Picciotto Irva
Published: August 2010

Background

Toxic exposures have been shown to influence maturation of the immune system during gestation. This study investigates the association between cord blood lymphocyte proportions and maternal exposure to air pollution during each gestational month.

Methods

Cord blood was analyzed using a FACSort flow cytometer to determine proportions of T lymphocytes (CD3+ cells and their subsets, CD4+ and CD8+), B lymphocytes (CD19+) and natural killer (NK) cells. Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH) and particulate matter < 2.5 micrometer in diameter (PM2.5) were measured using fixed site monitors. Arithmetic means of these pollutants, calculated for each gestational month, were used as exposure metrics. Data on covariates were obtained from medical records and questionnaires. Multivariable linear regression models were fitted to estimate associations between monthly PAH or PM2.5 and cord blood lymphocytes, adjusting for year of birth and district of residence and, in further models, gestational season and number of prior live births.

Results

The adjusted models show significant associations between PAHs or PM2.5 during early gestation and increases in CD3+ and CD4+ lymphocytes percentages and decreases in CD19+ and NK cell percentages in cord blood. In contrast, exposures during late gestation were associated with decreases in CD3+ and CD4+ fractions and increases in CD19+ and NK cell fractions. There was no significant association between alterations in lymphocyte distribution and air pollution exposure during the mid gestation.

Conclusions

PAHs and PM2.5 in ambient air may influence fetal immune development via shifts in cord blood lymphocytes distributions. Associations appear to differ by exposure in early versus late gestation.
Functional interaction between Envoncogene from Jaagsiekte sheep retrovirus and tumor suppressor Sprouty2
Authors: Chitra Ebenezer , Lin Yi-Wen , Davamani Fabian , Hsiao Kuang-Nan , Sia Charles , Hsieh Shih-Yang , Wei Olivia L , Chen Jen-Hao , Chow Yen-Hung
Published: August 2010

Background

Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus capable of transforming target cells in vitro and in vivo. The Envelope (Env) gene from JSRV and from related retroviruses can induce oncogenic transformation, although the detailed mechanism is yet to be clearly understood. Host cell factors are envisaged to play a critical determining role in the regulation of Env-mediated cell transformation.

Results

JSRV Env-mediated transformation of a lung adenocarcinoma cell line induced rapid proliferation, anchorage-independent growth and tumor formation, but completely abrogated the migration ability. An analysis of the signaling scenario in the transformed cells suggested the involvement of the ERK pathway regulated by Sprouty2 in cell migration, and the PI3K-Akt and STAT3 pathways in proliferation and anchorage-independence. On the other hand, in a normal lung epithelial cell line, Env-mediated transformation only decreased the migration potential while the other functions remained unaltered. We observed that Env induced the expression of a tumor suppressor, Sprouty2, suggesting a correlation between Env-effect and Sprouty2 expression. Overexpression of Sprouty2 per se not only decreased the migratory potential and tumor formation potential of the target cells but also made them resistant to subsequent Env-mediated transformation. On the other hand, over expression of the functional mutants of Sprouty2 had no inhibitory effect, confirming the role of Sprouty2 as a tumor suppressor.

Conclusions

Our studies demonstrate that Env and Sprouty2 have a functional relationship, probably through shared signaling network. Sprouty2 functions as a tumor suppressor regulating oncogenic transformation of cells, and it therefore has the potential to be exploited as a therapeutic anti-cancer agent.
Redundant causation from a sufficient cause perspective
Authors: Gatto Nicolle M , Campbell Ulka B
Published: August 2010

Sufficient causes of disease are redundant when an individual acquires the components of two or more sufficient causes. In this circumstance, the individual still would have become diseased even if one of the sufficient causes had not been acquired. In the context of a study, when any individuals acquire components of more than one sufficient cause over the observation period, the etiologic effect of the exposure (defined as the absolute or relative difference between the proportion of the exposed who develop the disease by the end of the study period and the proportion of those individuals who would have developed the disease at the moment they did even in the absence of the exposure) may be underestimated. Even in the absence of confounding and bias, the observed effect estimate represents only a subset of the etiologic effect. This underestimation occurs regardless of the measure of effect used.

To some extent, redundancy of sufficient causes is always present, and under some circumstances, it may make a true cause of disease appear to be not causal. This problem is particularly relevant when the researcher's goal is to characterize the universe of sufficient causes of the disease, identify risk factors for targeted interventions, or construct causal diagrams. In this paper, we use the sufficient component cause model and the disease response type framework to show how redundant causation arises and the factors that determine the extent of its impact on epidemiologic effect measures.
Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise
Authors: Josse Andrea R , Sherriffs Scott S , Holwerda Andrew M , Andrews Richard , Staples Aaron W , Phillips Stuart M
Published: August 2010

Background

The thermogenic and metabolic properties of capsinoids appear to mimic those of the more pungent sister compound capsaicin. However, few data exist on how capsinoid ingestion affects energy expenditure in humans and no data exist on its interaction with exercise. We aimed to determine how ingestion of capsinoids affected energy expenditure, lipid oxidation and blood metabolites at rest and during moderate intensity exercise.

Methods

Twelve healthy young men (age = 24.3 ± 3 yr, BMI = 25.5 ± 1.7 kg·m-2) were studied on two occasions in a double-blind design following ingestion of either placebo or 10 mg of purified capsinoids at rest, after 90 min of cycling at 55% VO2 peak, and for 30 min into recovery. Subjects ingested the capsules 30 min prior to exercise.

Results

At rest, following ingestion of capsinoids, we observed increases in VO2 and plasma norepinephrine levels, and decreases in concentrations of serum free fatty acids, plasma glycerol and the respiratory exchange ratio (all P < 0.05). At exercise onset, we observed a blunted accumulation of blood lactate with capsinoid ingestion vs. placebo (P < 0.05). There were no other significant differences between the conditions during or post-exercise.

Conclusion

The ingestion of 10 mg of capsinoids increased adrenergic activity, energy expenditure, and resulted in a shift in substrate utilization toward lipid at rest but had little effect during exercise or recovery. The changes we observed confirm previous data on the thermogenic and metabolic effects of capsinoids at rest and further promote its potential role as an adjunct weight loss aid, in addition to diet and exercise.
Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report
Authors: Nicoletti Stefania , Papi Maximilian , Drudi Fabrizio , Fantini Manuela , Canuti Debora , Tamburini Emiliano , Possenti Cinzia , Pasquini Enzo , Brisigotti Massimo , Ravaioli Alberto
Published: August 2010

Introduction

Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites.

Case presentation

We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen.

Conclusions

It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.
Anti-glomerular basement membrane disease superimposed on membranous nephropathy: a case report and review of the literature
Authors: Patel Dhruval , Nivera Noel , Tunkel Allan R
Published: August 2010

Introduction

Anti-glomerular basement membrane disease is a rare autoimmune disorder characterized by pulmonary hemorrhage, crescentic glomerulonephritis and the presence of circulating anti-glomerular basement membrane antibodies. The simultaneous occurrence of both anti-glomerular basement membrane disease and membranous nephropathy is rare.

Case presentation

A 59-year-old Hispanic man presented with acute onset of nausea and vomiting and was found to have renal insufficiency. Work-up included a kidney biopsy, which revealed anti-glomerular basement membrane disease with underlying membranous nephropathy. He was treated with emergent hemodialysis, intravenous corticosteroids, plasmapheresis, and cyclophosphamide without improvement in his renal function.

Conclusion

Simultaneous anti-glomerular basement membrane disease and membranous nephropathy is very rare. There have been 16 previous case reports in the English language literature that have been associated with a high mortality and morbidity, and a very high rate of renal failure resulting in hemodialysis. Co-existence of membranous nephropathy and anti-glomerular basement membrane disease may be immune-mediated, although the exact mechanism is not clear.
Skull base approaches in neurosurgery
Authors: Scholz Martin , Parvin Richard , Thissen Jost , Löhnert Catharina , Harders Albrecht , Blaeser Klaus
Published: August 2010

The skull base surgery is one of the most demanding surgeries. There are different structures that can be injured easily, by operating in the skull base. It is very important for the neurosurgeon to choose the right approach in order to reach the lesion without harming the other intact structures. Due to the pioneering work of Cushing, Hirsch, Yasargil, Krause, Dandy and other dedicated neurosurgeons, it is possible to address the tumor and other lesions in the anterior, the mid-line and the posterior cranial base. With the transsphenoidal, the frontolateral, the pterional and the lateral suboccipital approach nearly every region of the skull base is exposable.

In the current state many different skull base approaches are described for various neurosurgical diseases during the last 20 years. The selection of an approach may differ from country to country, e.g., in the United States orbitozygomaticotomy for special lesions of the anterior skull base or petrosectomy for clivus meningiomas, are found more frequently than in Europe.

The reason for writing the review was the question: Are there keyhole approaches with which someone can deal with a vast variety of lesions in the neurosurgical field?

In my opinion the different surgical approaches mentioned above cover almost 95% of all skull base tumors and lesions. In the following text these approaches will be described.

These approaches are:

1) pterional approach

2) frontolateral approach

3) transsphenoidal approach

4) suboccipital lateral approach

These approaches can be extended and combined with each other. In the following we want to enhance this philosophy.
An endogenous F-box protein regulates ARGONAUTE1 in Arabidopsis thaliana
Authors: Earley K , Smith MR , Weber R , Gregory BD , Poethig RS
Published: August 2010

ARGONAUTE1 (AGO1) mediates microRNA- and small interfering RNA-directed posttranscriptional gene silencing in Arabidopsis thaliana. Mutant alleles of SQUINT (SQN) slightly reduce AGO1 activity and have weak effects on shoot morphology. A screen for mutations that suppress the sqn phenotype produced loss-of-function mutations in the F-box gene FBW2. Mutations in FBW2 not only suppress sqn but also suppress many of the developmental phenotypes of weak, but not null, alleles of AGO1 by increasing AGO1 protein levels. Conversely, over-expression of FBW2 decreases the abundance of the AGO1 protein but not AGO1 messenger RNA, further indicating that FBW2 regulates AGO1 protein levels. fbw2 mutants have no obvious morphological phenotype, but display a reduced sensitivity to abscisic acid (ABA) that can be attributed to increased AGO1 activity. Our results indicate that FBW2 is a novel negative regulator of AGO1 and suggest that it plays a role in ABA signalling and/or response.
Glucarpidase, Leucovorin, and Thymidine for High-Dose Methotrexate-Induced Renal Dysfunction: Clinical and Pharmacologic Factors Affecting Outcome
Authors: Widemann Brigitte C. , Balis Frank M. , Kim AeRang , Boron Matthew , Jayaprakash Nalini , Shalabi Aiman , O'Brien Michelle , Eby Michelle , Cole Diane E. , Murphy Robert F. , Fox Elizabeth , Ivy Percy , Adamson Peter C.
Published: August 2010

Purpose

To assess the role of the recombinant bacterial enzyme, glucarpidase (carboxypeptidase-G2), leucovorin, and thymidine in the management and outcome of patients with high-dose methotrexate (HDMTX) –induced nephrotoxicity.

Methods

Patients with HDMTX-induced nephrotoxicity received one to three doses of intravenous (IV) glucarpidase and leucovorin rescue. The initial cohort (n = 35) also received thymidine by continuous IV infusion. Subsequently, thymidine was restricted to patients with prolonged exposure (> 96 hours) to methotrexate (MTX) or with substantial MTX toxicity at study entry. Plasma MTX, leucovorin, and 5-methyltetrahydrofolate (5-mTHF) concentrations were measured pre- and postglucarpidase. Toxicities were monitored, and logistic regression analysis was used to assess the relationship of baseline characteristics to the development of severe toxicity and death.

Results

Glucarpidase was administered at a median of 96 hours (receiving thymidine, n = 44) and 66 hours (not receiving thymidine, n = 56) after the start of the MTX infusion. Plasma MTX concentrations decreased within 15 minutes of glucarpidase by 98.7%. Plasma 5-mTHF concentrations also decreased more than 98% after administration of glucarpidase. Of 12 deaths, six were directly attributed to irreversible MTX toxicity. Presence of grade 4 toxicity before administration of glucarpidase, inadequate initial increase in leucovorin dosing, and administration of glucarpidase more than 96 hours after the start of the MTX infusion were associated with development of grade 4 and 5 toxicity.

Conclusion

Early intervention with the combination of leucovorin and glucarpidase is highly effective in patients who develop HDMTX-induced renal dysfunction. Severe toxicity and mortality occurred in patients in whom glucarpidase rescue was delayed and occurred despite thymidine administration.
Patient-Reported Outcomes in Sentinel Node–Negative Adjuvant Breast Cancer Patients Receiving Sentinel-Node Biopsy or Axillary Dissection: National Surgical Adjuvant Breast and Bowel Project Phase III Protocol B-32
Authors: Land Stephanie R. , Kopec Jacek A. , Julian Thomas B. , Brown Ann M. , Anderson Stewart J. , Krag David N. , Christian Nicholas J. , Costantino Joseph P. , Wolmark Norman , Ganz Patricia A.
Published: August 2010

Purpose

Sentinel lymph node resection (SNR) may reduce morbidity while providing the same clinical utility as conventional axillary dissection (AD). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 is a randomized phase III trial comparing SNR immediately followed by AD (SNAD) to SNR and subsequent AD if SN is positive. We report the definitive patient-reported outcomes (PRO) comparisons.

Patients and Methods

Eligible patients had clinically node-negative, operable invasive breast cancer. The PRO substudy included all SN-negative participants enrolled May 2001 to February 2004 at community institutions in the United States (n = 749; 78% age ≥ 50; 87% clinical tumor size ≤ 2.0 cm; 84% lumpectomy; 87% white). They completed questionnaires presurgery, 1 and 2 to 3 weeks postoperatively, and every 6 months through year 3. Arm symptoms, arm use avoidance, activity limitations, and quality of life (QOL) were compared with intent-to-treat two-sample t-tests and repeated measures analyses.

Results

Arm symptoms were significantly more bothersome for SNAD compared with SNR patients at 6 months (mean, 4.8 v 3.0; P < .001) and at 12 months (3.6 v 2.5; P = .006). Longitudinally, SNAD patients were more likely to experience ipsilateral arm and breast symptoms, restricted work and social activity, and impaired QOL (P ≤ .002 all items). From 12 to 36 months, fewer than 15% of either SNAD or SNR patients reported moderate or greater severity of any given symptom or activity limitation.

Conclusion

Arm morbidity was greater with SNAD than with SNR. Despite considerable fears about complications from AD for breast cancer, this study demonstrates that initial problems with either surgery resolve over time.
Vinblastine in Children and Adolescents With High-Risk Anaplastic Large-Cell Lymphoma: Results of the Randomized ALCL99-Vinblastine Trial
Authors: Le Deley Marie-Cécile , Rosolen Angelo , Williams Denise M. , Horibe Keizo , Wrobel Grazyna , Attarbaschi Andishe , Zsiros Jozsef , Uyttebroeck Anne , Marky Ildiko M. , Lamant Laurence , Woessmann Wilhelm , Pillon Marta , Hobson Rachel , Mauguen Audrey , Reiter Alfred , Brugières Laurence
Published: August 2010

Purpose

The impact of adding vinblastine to a 4-month chemotherapy regimen, based on the Non-Hodgkin's Lymphoma Berlin-Frankfurt-Münster 90 protocol, in childhood high-risk anaplastic large-cell lymphoma (ALCL) was assessed.

Patients and Methods

Children and adolescents with high-risk ALCL, defined by mediastinal, lung, liver, spleen, or skin involvement, were eligible for the trial. After a prephase and one chemotherapy course, patients were randomly assigned to receive either five further chemotherapy courses without vinblastine or the same regimen with one vinblastine injection (6 mg/m2) during each course followed by weekly vinblastine to complete a total of 1 year of treatment. The primary end point was event-free survival (EFS), analyzed on the intent-to-treat population.

Results

Between November 1999 and June 2006, 110 patients were randomly assigned to receive vinblastine, and 107 were randomly assigned not to receive vinblastine. Median follow-up was 4.8 years. Patients in the vinblastine arm had a significantly reduced risk of events during the first year (hazard ratio [HR] = 0.31; 95% CI, 0.15 to 0.67; P = .002) followed by an increased risk thereafter (HR = 4.98; 95% CI, 1.65 to 15.0; P = .003). Consequently, EFS at 1 year differed significantly (91% in the vinblastine group v 74% in the no-vinblastine group), with no difference at 2 years (73% and 70%, respectively). Overall EFS curves did not differ significantly (HR = 0.91; 95% CI, 0.55 to 1.5; P = .71). Thirty-one percent of weekly doses of vinblastine were reduced as a result of hematologic toxicity, although vinblastine was discontinued for toxicity in only three patients.

Conclusion

Adding vinblastine during induction and as maintenance for a total treatment duration of 1 year significantly delayed the occurrence of relapses but did not reduce the risk of failure.
Comparison of haematology, coagulation and clinical chemistry parameters in blood samples from the sublingual vein and vena cava in Sprague–Dawley rats
Authors: Seibel J , Bodié K , Weber S , Bury D , Kron M , Blaich G
Published: August 2010

The investigation of clinical pathology parameters (haematology, clinical chemistry and coagulation) is an important part of the preclinical evaluation of drug safety. However, the blood sampling method employed should avoid or minimize stress and injury in laboratory animals. In the present study, we compared the clinical pathology results from blood samples collected terminally from the vena cava (VC) immediately before necropsy with samples taken from the sublingual vein (VS) also prior to necropsy in order to determine whether the sampling method has an influence on clinical pathology parameters. Forty-six 12-week-old male Sprague–Dawley rats were assigned to two groups (VC or VS; n = 23 each). All rats were anaesthetized with isoflurane prior to sampling. In the VC group, blood was withdrawn from the inferior VC. For VS sampling, the tongue was gently pulled out and the VS was punctured. The haematology, coagulation and clinical chemistry parameters were compared. Equivalence was established for 13 parameters, such as mean corpuscular volume, white blood cells and calcium. No equivalence was found for the remaining 26 parameters, although they were considered to be similar when compared with the historical data and normal ranges. The most conspicuous finding was that activated prothrombin time was 30.3% less in blood taken from the VC (16.6 ± 0.89 s) than that in the VS samples (23.8 ± 1.58 s). Summing up, blood sampling from the inferior VC prior to necropsy appears to be a suitable and reliable method for terminal blood sampling that reduces stress and injury to laboratory rats in preclinical drug safety studies.
Regulation of Jaw-specific Isoforms of Myosin-binding Protein-C and Tropomyosin in Regenerating Cat Temporalis Muscle Innervated by Limb Fast and Slow Motor Nerves
Authors: Kang Lucia H.D. , Hoh Joseph F.Y.
Published: August 2010

Cat jaw-closing muscles are a distinct muscle allotype characterized by the expression of masticatory-specific myofibrillar proteins. Transplantation studies showed that expression of masticatory myosin heavy chain (m-MyHC) is promoted by fast motor nerves, but suppressed by slow motor nerves. We investigated whether masticatory myosin-binding protein-C (m-MBP-C) and masticatory tropomyosin (m-Tm) are similarly regulated. Temporalis muscle strips were transplanted into limb muscle beds to allow innervation by fast or slow muscle nerve during regeneration. Regenerated muscles were examined postoperatively up to 168 days by peroxidase IHC using monoclonal antibodies to m-MyHC, m-MBP-C, and m-Tm. Regenerates in both muscle beds expressed fetal and slow MyHCs, m-MyHC, m-MBP-C, and m-Tm during the first 4 weeks. Longer-term regenerates innervated by fast nerve suppressed fetal and slow MyHCs, retaining m-MyHC, m-MBP-C, and m-Tm, whereas fibers innervated by slow nerve suppressed fetal MyHCs and the three masticatory-specific proteins, induced slow MyHC, and showed immunohistochemical characteristics of jaw-slow fibers. We concluded that expression of m-MBP-C and m-Tm is coregulated by m-MyHC and that neural impulses to limb slow muscle are capable of suppressing masticatory-specific proteins and to channel gene expression along the jaw-slow phenotype unique to jaw-closing muscle.
Liquid phase immunoassays utilizing magnetic markers and SQUID magnetometer
Authors: Kuma Hiroyuki , Oyamada Hiroko , Tsukamoto Akira , Mizoguchi Takako , Kandori Akihiko , Sugiura Yoshinori , Yoshinaga Kohji , Enpuku Keiji , Hamasaki Naotaka
Published: August 2010

Background: Immunoassays are one main detection system used in the field of clinical chemistry. Recent developments of a new detection method utilizing a magnetic marker and magnetic sensor have enabled rapid and sensitive immunoassay without the need for bound/free (BF) separation.

Methods: Newly-synthesized conjugated avidin was used as the magnetic marker for quantitative analysis of human interleukin-8 (hIL-8) and immunoglobulin E (hIgE) in several media. A superconducting quantum interference device sensor detected the magnetic fields from markers fixed to antigens by the sandwich method. Magnetic signals from unbound markers were nearly zero due to Brownian rotation.

Results: Our magnetic immunoassay could detect four attomoles of model proteins (hIL-8, hIgE) in phosphate buffer without BF separation. Using our standard curve, the range of protein detected ranged from 40 femtomoles to 4 attomoles, and we observed a strong association between protein amounts and magnetic signals from the bound markers. The homogeneous immunoassay could also quantify three hundred cells from the fungus Candida albicans in phosphate buffer.

Conclusions: The present study demonstrates the ability of magnetic markers for measuring biological targets without BF separation. This detection system has great potential for use as the next generation's analytical system.

Clin Chem Lab Med 2010;48:1263–9.
Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride
Authors: Yamana Kazutoshi , Labrie Fernand , Luu-The Van
Published: August 2010

5α-Reductases are crucial enzymes involved in the biosynthesis of dihydrotestosterone, the most potent natural androgen. To date, three types of 5α-reductases, chronologically named types 1, 2 and 3 5α-reductases (SRD5a-1, 2 and 3) have been described. In the present paper, we characterized the activity and compared the mRNA expression levels of SRD5a-3 with those of SRD5a-1 and 2 in various human tissues, and determined its sensitivity to finasteride and dutasteride. We have established HEK-293 cell line that stably expressed SRD5a-3 for studying its activity and the inhibitory effect of finasteride, using [14C]labeled steroids. mRNA expression levels were quantified using real-time PCR in many male and female human tissues including the prostate, adipose tissue, mammary gland, as well as breast and prostate cancer cell lines. Incubation of HEK-SRD5a-3 cells with [14C]4-androstenedione and [14C]testosterone allowed us to show that SRD5a-3 can catalyze very efficiently both substrates 4-androstenedione and testosterone into 5α-androstanedione and dihydrotestosterone, respectively. We observed that the affinity of the enzyme for 4-androstenedione is higher than for testosterone. The activity of SRD5a-3 and SRD5a-2 are similarly sensitive to finasteride, whereas dutasteride is a much more potent inhibitor of SRD5a-3 than SRD5a-2. Tissue distribution analysis shows that SRD5a-3 mRNA expression levels are higher than those of SRD5a-1 and SRD5a-2 in 20 analyzed tissues. In particular, it is highly expressed in the skin, brain, mammary gland and breast cancer cell lines, thus suggesting that SRD5a-3 could play an important role in the production of androgens in these and other peripheral tissues.
Applications of X-Ray Fluorescence to Confirm Sulfur Impact of Corrosive Drywall
Authors: Hejzlar Zdenek
Published: August 2010

A U.S. building boom that started in the late 1990s and peaked in early to mid 2000s resulted in imports of gypsum board, commonly known as drywall, from foreign sources particularly from China. Some of the homeowners began experiencing problems with homes built during this time. The complaints included sulfur based attack on the copper in the residences. The purpose of the paper is to present data obtained from a copper conductor exposure test designed to evaluate the use of X-ray fluorescence (XRF) in detecting and evaluating the sulfur impact on the exposed copper. In the experiment, small segments of copper were exposed to 45 different samples of drywall and evaluated using the XRF. The results show that the method can detect impacts on copper due to emissions from drywall and distinguish between corrosive and noncorrosive drywalls. The method affords corroborating evidence required by the interim guidance published in January 2010 by the Consumer Product Safety Commission and Department of Housing and Urban Development for homeowners in identifying homes with corrosion from problematic drywall. It also provides corroborating evidence for the Florida Department of Health Case Definition (12-18-09), Criteria 3.3.
Conductivity Study of Some Thiocyanate Salts in Aqueous Binary Mixtures of Tetrahydrofuran and 1,3-Dioxolane at 298.15 K
Authors: Chanda Riju , Roy Mahendra Nath
Published: August 2010

Electrical conductance measurements are reported for different thiocyanate salts, viz. ammonium thiocyanate (NH4CNS), sodium thiocyanate (NaCNS) and potassium thiocyanate (KCNS), sodium bromide (NaBr), sodium tetraphenylborate (NaBPh4) and tetrabutylammonium bromide (Bu4NBr) in different mole fraction of water-tetrahydrofuran (THF) and water-1,3-dioxolane (1,3-DXL) binary mixtures at 298.15 K. The conductance data have been analyzed by the Fuoss conductance equation in terms of the limiting molar conductance (Λ0
), the association constant (KA
) and the association diameter (R). The limiting ionic conductances have been estimated from the appropriate division of the limiting molar conductivity value of the “reference electrolyte” Bu4NBPh4. Slight ionic association was found for all these electrolytes in these solvent mixtures. The results have been interpreted in terms of the formation of ion-pairs of ion–solvent interactions and structural changes in the mixed solvents.
Effect of the Addition of In to Co/HMCM-49 Catalyst for the Selective Catalytic Reduction of NO Under Lean-burn Conditions
Authors: Li Fei , Xiao Dehai , Li Jing , Yang Xiangguang
Published: August 2010

Selective catalytic reduction (SCR) of NO with propane using bimetals (3Co2Ce, 3Co2Sr, 3Co2Sn and 3Co2In) loaded on HMCM-49 zeolite was studied under lean-burn condition. Only 3Co2In/HMCM-49 exhibited higher deNOx activity in a wide temperature range. The catalysts were characterized by N2-adsoption, X-ray diffraction (XRD), temperature-programmed surface reactions (TPSR) and temperature-programmed desorption (TPD) of NO. TPSR and TPD results exhibited that the addition of In inhibited the oxidation ability of Co on 3Co2In/HMCM-49 catalyst, but enhanced NOx adsorption.
The Quest for the Hydroxyl-Peroxy Radical
Authors: Smith Ian W. M. , Le Picard Sébastien D. , Tizniti Meryem , Canosa André , Sims Ian R.
Published: August 2010

The hydroxyl-peroxy radical, HO3, has been the subject of numerous theoretical and experimental studies, not least because of its potential importance in atmospheric chemistry. Nevertheless, it has proved difficult to establish its stability: that is, values of D
0(HO-O2), the HO-O2 bond dissociation energy or, equivalently, Δ
fH
o
298(HO3), its standard enthalpy of formation. In this short article, a review is given of the results of experiments and calculations on HO3, culminating in experiments performed at low temperatures (55.9–99.8 K) in a CRESU apparatus, which establish both (i) rate constants for the formation of HO3 in the three-body reaction, OH + O2 + M → HO3 + M, and (ii) equilibrium constants from which values of D0(HO-O2) and Δ
fH
o
298(HO3) can be derived – making use of spectroscopic data for HO3, from which partition functions and standard entropies can be calculated. It is shown that these absolute experimental values for D
0(HO-O2) and Δ
fH
o
298(HO3) are: (i) in agreement with the limiting values determined in experiments by Lester and co-workers, and (ii) in fair agreement with the most recent theoretical results. Furthermore, these thermodynamic data make it clear that only very small fractions of OH will be bound with O2 under the conditions found at all levels of the Earth’s atmosphere.
Studies of the Formation and Growth of Aerosol from Molecular Iodine Precursor
Authors: Saunders R. W. , Kumar R. , Gómez Martín J. C. , Mahajan A. S. , Murray B. J. , Plane J. M. C.
Published: August 2010

The formation and growth of iodine oxide particles (IOPs), originating from molecular iodine precursor, has been studied at room temperature as a function of water vapour, and sulphuric and oxalic acid vapours. A linear variation in total IOP mass was observed over a wide range of iodine atom production rates under both dry and humid formation conditions. Particle formation was also observed in the absence of ozone, and was found to be temperature sensitive, with elevated temperatures resulting in reduced particle number and mass. Electronic structure calculations are used to show that particle formation is initiated by polymerization of I2O4 with I2O3, or with itself. Formation of IOPs in humid conditions results in lower numbers and smaller particles than formed in the absence of water vapour, because H2O forms relatively stable complexes with molecules such as I2O3 and I2O4, inhibiting their polymerization. Addition of H2O to particles formed under dry conditions shows the collapse of fractal-like, aggregate particle structures. The uptake of sulphuric acid vapour onto humidified particles was studied over a wide range of relative humidity (RH) at room temperature, with the calculated accommodation coefficient (α) for this process increasing with RH to a value of 0.75±0.05 at RH = 90%. In contrast, growth of particles exposed to oxalic acid vapour was not observed on the experimental timescales employed, indicating an upper limit for α of 10−3.
Aqueous Phase Reactivity of Nitrate Radicals (NO3) Toward Dicarboxylic Acids
Authors: de Sémainville Ph. G. , D Anna B. , George Ch.
Published: August 2010

Laser photolysis technique was used to study the reactivity of nitrate radical towards four dicarboxylic acids. The temperature dependence of the reactions was investigated in the range from 278K to 318K. The effect of the acid-base equilibrium was examined by measuring the activation parameters of the dissociated and undissociated acids at different pH. For droplets or aerosols under moderate acidic conditions, the charge exchange reaction at the carboxylate group might compete with the oxidation by the hydroxyl radical. On liquid particles enriched in nitrate (such as a deliquescent ammonium nitrate), the lifetime of carboxylic groups towards the NO3 radical may be as short as few hours (or less).
Sex Peptide Is Required for the Efficient Release of Stored Sperm in Mated Drosophila Females
Authors: Avila Frank W , Ravi Ram K , Bloch Qazi Margaret C , Wolfner Mariana F
Published: August 2010

The Drosophila seminal fluid protein (SFP) sex peptide (SP) elicits numerous post-mating responses, including increased egg laying and decreased sexual receptivity, in the mated female. Unlike other SFPs, which are detectable in mated females for only a few hours post mating, SP is maintained—and its effects are sustained—for several days. The persistence of SP in the mated female's reproductive tract is thought to be a consequence of its binding to, and gradual release from, sperm in storage, which maintains SP's ability to act within the female reproductive tract. Recent studies have shown that several other SFPs, acting in a network, are needed for SP's localization to sperm and are necessary for the efficient release of sperm from storage. This result suggested an additional new role for SP modulating the release of sperm from storage. We tested for this possibility by examining sperm storage parameters in mated females that did not receive SP. We found that while sperm accumulation into storage was unaffected, sperm depletion from storage sites was significantly decreased (or impaired) in the absence of SP. Mates of males expressing a modified SP that is unable to be released from sperm showed a similar phenotype, indicating that release of sperm-bound SP is a necessary component of normal sperm depletion. Additionally, SP null males were more successful in a sperm competitive environment when they were first to mate, which is likely a consequence of higher retention of their sperm due to defective sperm release. Our findings illustrate a direct role for SP in the release of sperm from storage.