bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diethylcarbamazine activity against Brugia malayimicrofilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway
Authors: McGarry Helen F , Plant Leigh D , Taylor Mark J 
Published: June 2005

Abstract
Background
Diethylcarbamazine (DEC) has been used for many years in the treatment of human lymphatic filariasis. Its mode of action is not well understood, but it is known to interact with the arachidonic acid pathway. Here we have investigated the contribution of the nitric oxide and cyclooxygenase (COX) pathways to the activity of DEC against B. malayi microfilariae in mice.

Methods
B. malayi microfilariae were injected intravenously into mice and parasitaemia was measured 24 hours later. DEC was then administered to BALB/c mice with and without pre-treatment with indomethacin or dexamethasone and the parasitaemia monitored. To investigate a role for inducible nitric oxide in DEC's activity, DEC and ivermectin were administered to microfilaraemic iNOS-/- mice and their background strain (129/SV). Western blot analysis was used to determine any effect of DEC on the production of COX and inducible nitric-oxide synthase (iNOS) proteins.

Results
DEC administered alone to BALB/c mice resulted in a rapid and profound reduction in circulating microfilariae within five minutes of treatment. Microfilarial levels began to recover after 24 hours and returned to near pre-treatment levels two weeks later, suggesting that the sequestration of microfilariae occurs independently of parasite killing. Pre-treatment of animals with dexamethasone or indomethacin reduced DEC's efficacy by almost 90% or 56%, respectively, supporting a role for the arachidonic acid and cyclooxygenase pathways in vivo. Furthermore, experiments showed that treatment with DEC results in a reduction in the amount of COX-1 protein in peritoneal exudate cells. Additionally, in iNOS-/- mice infected with B. malayi microfilariae, DEC showed no activity, whereas the efficacy of another antifilarial drug, ivermectin, was unaffected.

Conclusion
These results confirm the important role of the arachidonic acid metabolic pathway in DEC's mechanism of action in vivo and show that in addition to its effects on the 5-lipoxygenase pathway, it targets the cyclooxygenase pathway and COX-1. Moreover, we show for the first time that inducible nitric oxide is essential for the rapid sequestration of microfilariae by DEC.
Long-term survival after an aggressive surgical resection and chemotherapy for stage IV pulmonary giant cell carcinoma
Authors: Shoji Fumihiro , Maruyama Riichiroh , Okamoto Tatsuro , Ikeda Jiro , Nakamura Tomomi , Wataya Hiroshi , Ichinose Yukito 
Published: June 2005

Abstract

Background
Pulmonary giant cell carcinoma is one of the rare histological subtypes with pleomorphic, sarcomatoid or sarcomatous elements. The prognosis of patients with this tumor tends to be poor, because surgery, irradiation and chemotherapy are not usually effective.

Case presentation
We herein report a patient with pulmonary giant cell carcinoma with stage IV disease in whom aggressive multi-modality therapy resulted in a long-term survival. A 51-year-old male underwent an emergent operation with a partial resection of small intestinal metastases due to bleeding from the tumor. The patient also underwent a left pneumonectomy due to hemothorax as a result of the rapid growth of the primary tumor. Thereafter, two different regimens of chemotherapy and a partial resection for other site of small intestinal metastases and a splenectomy for splenic metastases were performed. The patient is presently doing well without any evidence of recurrence for 3 years after the initial operation.

Conclusion
This is a first report of a rare case with stage IV pulmonary giant cell carcinoma who has survived long-term after undergoing aggressive surgical treatment and chemotherapy.
The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616]
Authors: van der Horst Iwan CC , Ottervanger Jan Paul , van 't Hof Arnoud WJ , Reiffers Stoffer , Miedema Kor , Hoorntje Jan CA , Dambrink Jan-Henk E , Gosselink AT Marcel , Nijsten Maarten WN , Suryapranata Harry , de Boer Menko-Jan , Zijlstra Felix 
Published: June 2005

Abstract
Background
Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial.

Methods
Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge.

Results
There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01).

Conclusion
Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients.
Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition
Authors: Croisier Emilie , Moran Linda B , Dexter David T , Pearce Ronald KB , Graeber Manuel B 
Published: June 2005

Abstract

Background
The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.

Methods
We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course.

Results
While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD.

Conclusion
While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution.
Identification of co-regulated transcripts affecting male body size in Drosophila
Authors: Coffman Cynthia J , Wayne Marta L , Nuzhdin Sergey V , Higgins Laura A , McIntyre Lauren M 
Published: June 2005

AbstractFactor analysis is an analytic approach that describes the covariation among a set of genes through the estimation of 'factors', which may be, for example, transcription factors, microRNAs (miRNAs), and so on, by which the genes are co-regulated. Factor analysis gives a direct mechanism by which to relate gene networks to complex traits. Using simulated data, we found that factor analysis clearly identifies the number and structure of factors and outperforms hierarchical cluster analysis. Noise genes, genes that are not correlated with any factor, can be distinguished even when factor structure is complex. Applied to body size in Drosophila simulans, an evolutionarily important complex trait, a factor was directly associated with body size.
Modulation of Calmodulin Gene Expression as a Novel Mechanism for Growth Hormone Feedback Control by Insulin-like Growth Factor in Grass Carp Pituitary Cells
Authors: Huo Longfei , Fu Guodong , Wang Xinyan , Ko Wendy K. W. , Wong Anderson O. L. 
Published: June 2005

AbstractCalmodulin (CaM), the Ca2+ sensor in living cells, is essential for biological functions mediated by Ca2+-dependent mechanisms. However, modulation of CaM gene expression at the pituitary level as a means to regulate pituitary hormone synthesis has not been characterized. In this study we examined the functional role of CaM in the feedback control of GH by IGF using grass carp pituitary cells as a cell model. To establish the structural identity of CaM expressed in the grass carp, a CaM cDNA, CaM-L, was isolated from the carp pituitary using 3′/5′ rapid amplification of cDNA ends. The open reading frame of this cDNA encodes a 149-amino acid protein sharing the same primary structure with CaMs reported in mammals, birds, and amphibians. This CaM cDNA is phylogenetically related to the CaM I gene family, and its transcripts are ubiquitously expressed in the grass carp. In carp pituitary cells, IGF-I and IGF-II induced CaM mRNA expression with a concurrent drop in GH transcript levels. These stimulatory effects on CaM mRNA levels were not mimicked by insulin and appeared to be a direct consequence of IGF activation of CaM gene transcription without altering CaM transcript stability. CaM antagonism and inactivation of calcineurin blocked the inhibitory effects of IGF-I and IGF-II on GH gene expression, and CaM overexpression also suppressed the 5′ promoter activity of the grass carp GH gene. These results, as a whole, provide evidence for the first time that IGF feedback on GH gene expression is mediated by activation of CaM gene expression at the pituitary level.
Prokineticins (Endocrine Gland-Derived Vascular Endothelial Growth Factor and BV8) in the Bovine Ovary: Expression and Role as Mitogens and Survival Factors for Corpus Luteum-Derived Endothelial Cells
Authors: Kisliouk Tatiana , Podlovni Helena , Spanel-Borowski Katharina , Ovadia Oded , Zhou Qun-Yong , Meidan Rina 
Published: June 2005

AbstractA highly vascular endocrine gland, the corpus luteum (CL) is an excellent model for the study of angiogenic factors. Prokineticins (PK-1 and -2), also termed endocrine-gland-derived vascular endothelial growth factor (VEGF) and BV8 are newly identified proteins described as selective angiogenic mitogens. We previously identified PK binding sites, two closely homologous G protein-coupled receptors (PK-R1 and PK-R2) in human and bovine ovarian cells, but their function remained unknown. In this study we examined the presence and effects of PK in CL-derived endothelial and steroidogenic cell types (LEC and LSC, respectively). PK-1 mRNA was identified in CL and follicles by real-time PCR, using primers specific for the bovine PK-1 sequence (retrieved from Bos taurus whole genome shotgun database). PK were potent angiogenic mitogens for LEC; they enhanced cell proliferation, elevated [3H]thymidine incorporation, MAPK activation, and c-jun/fos mRNA expression. The effects of PK proteins on cell survival were examined by nuclear morphology (4′,6-diamidino-2-phenylindole dihydrochloride staining), measurement of DNA fragmentation (terminal dUTP nucleotide end labeling assay), and caspase-3 cleavage. Results obtained by these techniques demonstrated that PK protected LEC from serum starvation-induced apoptosis. Stress conditions such as serum withdrawal, TNF-α, and hypoxia markedly increased PK-R2 expression, whereas mRNA levels of PK-R1 remained unchanged. These suggest that the antiapoptotic effect of PK-1 on LEC may be mediated via PK-R2. PK-1 increased VEGF mRNA expression by LSC, implying that it could also indirectly, via VEGF, affect luteal angiogenesis. Together, these findings suggest an important role for PK-1 in luteal function by acting as a mitogen and survival factor in LEC.
Short-Term Stimulation of Lipogenesis by 3,5-l-Diiodothyronine in Cultured Rat Hepatocytes
Authors: Giudetti Anna M. , Leo Monica , Geelen Math J. H. , Gnoni Gabriele V. 
Published: June 2005

AbstractShort-term effects of 3,5-l-diiodothyronine (T2) on lipid biosynthesis were studied in cultured hepatocytes from hypothyroid rats. A comparison with the effects of T3 was routinely carried out. After T2 addition to cell cultures, a distinct stimulation of fatty acid and cholesterol syntheses, measured as incorporation of [1-14C]acetate into these lipid fractions, was observed. The T2 dose-dependent effect on both metabolic pathways, already detectable at 10−8-10−9m, reached a 2-fold stimulation at 10−5m T2. At this concentration, the stimulatory effect was evident within 1 h of T2 addition to the hepatocytes and increased with time up to the length of the experimental period of 4 h. T2 stimulation of lipogenesis was also confirmed by incubating hepatocytes with [3H]H2O, used as an independent index of lipogenic activity. The effects of T2 are rather specific as 3,3′,5,5′-tetraiodo-d-thyronine and 3,5-diiodo-l-tyrosine were practically ineffective on both fatty acid and cholesterol synthesis. Analysis of various lipid fractions showed that T2 addition to the cells produced a significant stimulation of the incorporation of newly synthesized fatty acids into both neutral and polar lipids. By comparing the effects induced by T2 with those seen in the presence of T3, it appeared that T2 was able to mimic T3 effects. Experiments conducted in the presence of cycloheximide, a protein synthesis inhibitor, indicated that the T2 stimulatory effect on fatty acid and cholesterol synthesis was essentially independent of protein synthesis.
Shopping Centre Design, Decline and Crime
Authors: Poyser Sam 
Published: June 2005

It is now widely accepted that the design of buildings and their surroundings can influence the commission of crime and nuisance behaviour (Garrad, 1999) and that the proper design and effective use of the built environment can lead to a reduction in the fear and incidence of crime, and an improvement in the quality of life (Skogan, 1990a). This article reports on research undertaken to determine whether architects, designing shopping centres in the 1960s and late 1990s, were aware of the link between environmental design and criminal opportunity. It goes on to examine what relation that ignorance/awareness might have to criminal opportunity, nuisance behaviour, and fear of crime in users. The related issue of management/maintenance of centres is also examined. The design of two Portsmouth, England, shopping centres (the ‘Tricorn’—planned and built in the 1960s and ‘Gunwhaf Quays' — planned and built in the late 1990s) is compared. The research findings utilising interviews, questionnaires and examination of local newspaper reports suggest that users found the ‘Tricorn’ to be poorly designed, ill maintained, to attract crime and nuisance behaviour, and to make them feel unsafe whilst, in contrast, users felt that ‘Gunwharf Quays' is well designed and maintained. Many feel that these factors may be connected to their feelings of safety, and to what they observed as low levels of crime and nuisance behaviour. Overall, the findings indicate that design and maintenance are important elements in relation to levels of crime, nuisance, and fear of crime in shopping centres. Several recommendations are made in the light of these findings.
Organised Crime: Redefined for Social Policy
Authors: Clark Mark 
Published: June 2005

This article argues that the modern concept of problem-orientated policing requires that organised crime be redefined in sociological and political science terminology to identify opportunities for community-based policing initiatives to be utilised in undermining its institutional base. It seeks to redefine organised crime by its use of power and acts of victimisation. The article reviews a number of traditional organised crime groups by undertaking an historical power analysis process to substantiate this argument. It identifies the conditions and societies that gave rise to organised crime. It discusses the initial community or institutional purpose of the organised group and how it mutated to dominate by acts of criminal victimisation. The view is expressed that a victim-centred, problem-orientated policing policy is necessary to understand the legitimacy of organised crime in isolated communities and to remove barriers between the police and these communities. This view promotes the use of specially trained community police officers who are directly linked to other agencies engaged in suppressing organized crime to develop community capacity building to resist crime in isolated communities.
N-Terminal Pro-B-Type Natriuretic Peptide after High-Dose Chemotherapy: A Marker Predictive of Cardiac Dysfunction?
Authors: Sandri Maria T , Salvatici Michela , Cardinale Daniela , Zorzino Laura , Passerini Rita , Lentati Paola , Leon Maria , Civelli Maurizio , Martinelli Giovanni , Cipolla Carlo M 
Published: June 2005

Abstract
Background: Chronic cardiac dysfunction may develop after administration of aggressive chemotherapy, sometimes leading to development of congestive heart failure (CHF). Recently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was implicated as a marker of CHF. In this study we evaluated the predictive role of NT-proBNP in patients treated with high-dose chemotherapy (HDC).
Methods: NT-proBNP was measured after 62 chemotherapy treatments in 52 patients affected by aggressive malignancies. Blood samples were drawn before the start of HDC, at the end of HDC administration, and 12, 24, 36, and 72 h thereafter. In these patients, echocardiograms were performed regularly during a 1-year follow-up.
Results: Seventeen patients (33%) had persistently increased NT-proBNP, 19 patients (36%) had only transient increases (concentrations went back to baseline at 72 h), and 16 (31%) had no increases [mean (SD) values at 72 h, 1163 (936) ng/L vs 185 (101) ng/L vs 39 (19) ng/L, respectively; P &lt;0.0001]. Only patients with persistently increased NT-proBNP had a significant worsening of the left ventricular diastolic indexes from baseline to 12 months [ratio of peak early to peak late flow velocities from 1.42 (0.33) to 0.78 (0.11); P &lt;0.0001; isovolumetric relaxation time from 90 (15) to 141 (26) ms; P &lt;0.0001; E-wave deceleration time from 162 (17) to 224 (32) ms; P = 0.0004] and of the left ventricular ejection fraction [from 62.8 (3.4)% to 45.6 (11.5)%; P &lt;0.0001].
Conclusions: Persistently increased NT-proBNP early after administration of HDC is strongly associated with development of cardiac dysfunction. This finding has important implications for identifying patients at risk of developing chemotherapy-induced cardiotoxicity.
Calculation of Gibbs Energy of Interaction (ΔG
0
int) of Neutral Benzoic Acids and their Anions
Authors: Gumtya S. K. , Lahiri Sujit Chandra 
Published: June 2005

Abstract
Quantitative correlation of the solubility phenomena and understanding of the dissolution mechanism are complex due to interplay of different types of intermolecular forces in the solubilization processes.
Attempts have been made to understand the solubilization process by determining the ΔG
0
int terms for neutral benzoic acid and substituted benzoic acids using the solubility values of neutral acids reported from our laboratory and the scaled particle theory. Similarly, ΔG
0
int terms for the anions are also calculated. ΔG
0
int values for neutral (HA) and charged ions (A−) are opposite. Different aspects of solubility and dissociation processes for the substituted acids and the effects of substitution have been explained with success.
The limitations of the method have also been emphasized.
Sex Differentiation and Early Gonadal Development in Brook Trout
Authors: Sacobie Charles F D , Benfey Tillmann J 
Published: June 2005

Abstract
Gonadal differentiation in brook trout Salvelinus fontinalis, as determined from samples collected weekly from 42 to 1,572 degree-days (°C) posthatch, occurs between 393 and 464 degree-days posthatch. During this interval, the gonad transforms from a structure containing several developing primordial germ cells into either a gonad with well-developed perinucleolar oocytes or a gonad with cavities that ultimately develop into sperm ducts or the gonadal circulatory system. Brook trout demonstrate differentiated development, in which the gonad develops directly into a testis or an ovary, and anatomical differentiation precedes cytological differentiation in both ovaries and testes. The data provided by this study should aid in the development of techniques for hormonal sex reversal in brook trout.
Antiretroviral Therapy in Resource-Poor Countries: Illusions and Realities
Authors: Desvarieux Moïse , Landman Roland , Liautaud Bernard , Girard Pierre-Marie 
Published: June 2005

The prospects for antiretroviral therapy in resource-poor settings have changed recently and considerably with the availability of generic drugs, the drastic price reduction of brand-name drugs, and the simplification of treatment. However, such cost reductions, although allowing the implementation of large-scale donor programs, have yet to render treatment accessible and possible in the general population. Successfully providing HIV treatment in high-prevalence/high-caseload countries may require that we redefine the problem as a public health mass therapy program rather than a multiplication of clinical situations. The public health goal cannot simply be the reduction of morbidity and mortality for those treated but must be the reduction in morbidity and mortality for the many, that is, at a population level.
Outcome Evaluation of a Public Health Approach to Suicide Prevention in an American Indian Tribal Nation
Authors: May Philip A. , Serna Patricia , Hurt Lance , DeBruyn Lemyra M. 
Published: June 2005

Objectives. We evaluated the efficacy of 15 years of a public health–oriented suicidal-behavior prevention program among youths living on an American Indian reservation. Methods. All suicides, suicide attempts, and suicidal gestures were monitored. Age-specific analyses over time were used to assess outcomes. Results. Both descriptive and linear regression analyses indicated that a substantial drop occurred in suicidal gestures and attempts. Suicide deaths neither declined significantly nor increased, although the total number of self-destructive acts declined by 73% (P=.001). Conclusions. Data from this community-based approach document a remarkable downward trend—measured by both magnitude and temporal trends in the specifically targeted age cohorts—in suicidal acts. The sequential decrease in age-specific rates of suicide attempts and gestures is indicative of the program’s success.